U.S. patent application number 15/355082 was filed with the patent office on 2017-04-20 for novel ruthenium complexes and their uses in processes for formation and/or hydrogenation of esters, amides and derivatives thereof.
The applicant listed for this patent is YEDA RESEARCH AND DEVELOPMENT CO. LTD.. Invention is credited to Ekambaram Balaraman, Boopathy Gnanaprakasam, Chidambaram Gunanathan, David MILSTEIN, Jing Zhang.
Application Number | 20170107251 15/355082 |
Document ID | / |
Family ID | 45048155 |
Filed Date | 2017-04-20 |
United States Patent
Application |
20170107251 |
Kind Code |
A1 |
MILSTEIN; David ; et
al. |
April 20, 2017 |
NOVEL RUTHENIUM COMPLEXES AND THEIR USES IN PROCESSES FOR FORMATION
AND/OR HYDROGENATION OF ESTERS, AMIDES AND DERIVATIVES THEREOF
Abstract
The present invention relates to novel Ruthenium complexes and
related borohydride complexes, and their use for (1) hydrogenation
of amides (including polyamides) to alcohols and amines; (2)
preparing amides from alcohols with amines (including preparing
polyamides (e.g., polypeptides) by reacting dialcohols and diamines
or by polymerization of amino alcohols); (3) hydrogenation of
esters to alcohols (including hydrogenation of cyclic esters
(lactones), cyclic di-esters (di-lactones) or polyesters); (4)
hydrogenation of organic carbonates (including polycarbonates) to
alcohols and of carbamates (including polycarbamates) or urea
derivatives to alcohols and amines; (5) dehydrogenative coupling of
alcohols to esters; (6) hydrogenation of secondary alcohols to
ketones; (7) amidation of esters (synthesis of amides from esters
and amines); (8) acylation of alcohols using esters; (9) coupling
of alcohols with water to form carboxylic acids; and (10)
dehydrogenation of beta-amino alcohols to form pyrazines. The
present invention further relates to novel uses of certain pyridine
Ruthenium complexes.
Inventors: |
MILSTEIN; David; (Rehovot,
IL) ; Balaraman; Ekambaram; (Rehovot, IL) ;
Gunanathan; Chidambaram; (Rehovot, IL) ;
Gnanaprakasam; Boopathy; (Rehovot, IL) ; Zhang;
Jing; (Rehovot, IL) |
|
Applicant: |
Name |
City |
State |
Country |
Type |
YEDA RESEARCH AND DEVELOPMENT CO. LTD. |
Rehovot |
|
IL |
|
|
Family ID: |
45048155 |
Appl. No.: |
15/355082 |
Filed: |
November 18, 2016 |
Related U.S. Patent Documents
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Application
Number |
Filing Date |
Patent Number |
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14702641 |
May 1, 2015 |
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15355082 |
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13880328 |
Jun 11, 2013 |
9045381 |
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PCT/IL2011/000817 |
Oct 11, 2011 |
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14702641 |
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61394387 |
Oct 19, 2010 |
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Current U.S.
Class: |
1/1 |
Current CPC
Class: |
C07C 29/136 20130101;
C07C 51/00 20130101; C07C 67/03 20130101; C07F 15/0053 20130101;
B01J 2231/40 20130101; C07C 29/149 20130101; C07C 209/62 20130101;
C07B 43/06 20130101; B01J 2231/643 20130101; C07C 51/02 20130101;
C07D 305/06 20130101; C07F 15/0046 20130101; C07C 67/00 20130101;
B01J 31/2404 20130101; C07C 29/136 20130101; C07C 41/26 20130101;
C07K 5/12 20130101; C07C 29/177 20130101; B01J 31/18 20130101; C07C
209/62 20130101; C07C 213/00 20130101; C07D 295/185 20130101; C07C
51/02 20130101; C07C 51/295 20130101; C07C 67/00 20130101; C07C
51/295 20130101; C07C 51/23 20130101; C07C 231/02 20130101; C07C
41/16 20130101; C07D 307/33 20130101; C07D 207/08 20130101; C07D
241/12 20130101; C07C 29/149 20130101; C07C 209/00 20130101; C07C
51/295 20130101; C07C 67/03 20130101; C07C 209/62 20130101; C07K
1/00 20130101; B01J 31/248 20130101; B01J 2531/0244 20130101; C07C
51/02 20130101; B01J 31/189 20130101; B01J 31/2409 20130101; C07C
29/136 20130101; C07C 45/006 20130101; C07C 51/295 20130101; C07C
213/00 20130101; C07C 2601/10 20170501; C07D 211/12 20130101; C07D
307/44 20130101; C07C 45/006 20130101; C07C 51/02 20130101; C07C
209/62 20130101; C07C 231/10 20130101; C08G 69/00 20130101; C07C
29/149 20130101; C07C 29/149 20130101; C07C 67/03 20130101; C07D
207/06 20130101; C07C 29/149 20130101; C07B 41/02 20130101; C07C
29/149 20130101; C07C 51/02 20130101; C07C 51/295 20130101; C07C
231/10 20130101; C07C 2601/08 20170501; C07B 41/12 20130101; C07C
29/149 20130101; C07D 295/027 20130101; C07C 2601/14 20170501; C07C
51/02 20130101; C07C 31/202 20130101; C07C 31/12 20130101; C07C
49/10 20130101; C07C 63/06 20130101; C07C 69/24 20130101; C07C
31/04 20130101; C07C 211/27 20130101; C07C 69/75 20130101; C07C
53/126 20130101; C07C 31/125 20130101; C07C 69/78 20130101; C07C
211/10 20130101; C07C 209/62 20130101; C07C 29/177 20130101; C07C
231/10 20130101; C07F 9/65583 20130101; C07C 231/02 20130101; C07C
213/00 20130101; C07C 29/149 20130101; B01J 2231/49 20130101; C07C
67/00 20130101; C07D 309/30 20130101; C07C 209/62 20130101; C07C
51/295 20130101; C07D 307/14 20130101; C07D 241/08 20130101; C07F
9/58 20130101; C07B 41/08 20130101; C07C 41/16 20130101; C07C
45/006 20130101; C07C 231/10 20130101; B01J 2531/821 20130101; C07C
29/149 20130101; C07C 51/295 20130101; C07C 67/00 20130101; C07C
231/10 20130101; C07C 231/10 20130101; C07C 231/10 20130101; C07D
487/14 20130101; Y02P 20/52 20151101; C07C 65/21 20130101; C07C
49/08 20130101; C07C 217/58 20130101; C07C 235/16 20130101; C07C
53/124 20130101; C07C 49/403 20130101; C07C 59/125 20130101; C07C
53/124 20130101; C07C 211/46 20130101; C07C 215/28 20130101; C07C
43/13 20130101; C07C 31/205 20130101; C07C 65/21 20130101; C07C
233/07 20130101; C07C 33/22 20130101; C07C 49/78 20130101; C07C
53/126 20130101; C07C 57/30 20130101; C07C 69/14 20130101; C07C
211/07 20130101; C07C 57/32 20130101; C07C 31/08 20130101; C07C
31/04 20130101; C07C 31/205 20130101; C07C 57/32 20130101; C07C
33/20 20130101; C07C 49/04 20130101; C07C 61/08 20130101; C07C
31/1355 20130101; C07C 235/14 20130101; C07C 61/08 20130101; C07C
69/24 20130101; C07C 211/35 20130101; C07C 59/125 20130101; C07C
233/05 20130101; C07C 31/10 20130101; C07C 235/10 20130101; C07C
57/30 20130101; C07C 235/06 20130101; C07C 233/05 20130101; C07D
213/38 20130101; C07C 63/08 20130101; C07C 45/006 20130101; B01J
2231/763 20130101; C07C 45/006 20130101; C07C 51/02 20130101; C07C
51/02 20130101; C07B 43/04 20130101; C07C 51/295 20130101; C07D
295/023 20130101; C07D 307/52 20130101; C07C 45/006 20130101; C07C
51/02 20130101; C07C 67/297 20130101; C07C 213/02 20130101; B01J
31/2485 20130101; C07C 29/149 20130101; C07C 45/002 20130101; C07C
51/295 20130101; C07D 307/83 20130101 |
International
Class: |
C07K 5/12 20060101
C07K005/12; C07C 209/62 20060101 C07C209/62; C07D 305/06 20060101
C07D305/06; C07D 307/44 20060101 C07D307/44; C07C 29/149 20060101
C07C029/149; C07D 295/027 20060101 C07D295/027; C07D 207/06
20060101 C07D207/06; C07D 207/08 20060101 C07D207/08; C07D 211/12
20060101 C07D211/12; C07C 231/10 20060101 C07C231/10; C07D 307/52
20060101 C07D307/52; C07D 295/185 20060101 C07D295/185; C07C 67/00
20060101 C07C067/00; C07C 213/02 20060101 C07C213/02; C07C 51/00
20060101 C07C051/00; C07D 309/30 20060101 C07D309/30; C07D 307/33
20060101 C07D307/33; C07D 307/83 20060101 C07D307/83; C07C 67/297
20060101 C07C067/297; C07D 241/12 20060101 C07D241/12; C07B 41/02
20060101 C07B041/02; C07B 43/04 20060101 C07B043/04; C07B 41/08
20060101 C07B041/08; C07B 41/12 20060101 C07B041/12; C07B 43/06
20060101 C07B043/06; B01J 31/24 20060101 B01J031/24; C07C 41/26
20060101 C07C041/26 |
Claims
1. A process for hydrogenating an ester, organic carbonate,
carbamate or urea derivative to at least one alcohol, amine or
combination thereof; or hydrogenating an amide to an alcohol and an
amine, comprising the step of reacting the ester, organic
carbonate, carbamate, urea derivative or amide with molecular
hydrogen (H.sub.2) in the presence of a borane derivative of a
Ruthenium complex, wherein said borane derivative is represented by
the structure of formula F: ##STR00514## wherein each L.sup.1 is
independently selected from the group consisting of phosphine
(PR.sup.aR.sup.b), phosphite P(OR.sup.a)(OR.sup.b), phosphinite
P(OR.sup.a)(R.sup.b), amine (NR.sup.aR.sup.b), imine, oxazoline,
sulfide (SR.sup.a), sulfoxide (S(.dbd.O)R.sup.a), heteroaryl
containing at least one heteroatom selected from nitrogen and
sulfur; arsine (AsR.sup.aR.sup.b), stibine (SbR.sup.aR.sup.b) and a
N-heterocyclic carbene represented by the structures: ##STR00515##
L.sup.3 is absent or is a mono-dentate two-electron donor selected
from the group consisting of CO, PR.sup.aR.sup.bR.sup.c,
P(OR.sup.a)(OR.sup.b)(OR.sup.c), NO.sup.+, AsR.sup.aR.sup.bR.sup.c,
SbR.sup.aR.sup.bR.sup.c, SR.sup.aR.sup.b, nitrile (RCN), isonitrile
(RNC), N.sub.2, PF.sub.3, CS, heteroaryl and tetrahydrothiophene;
L.sup.4 is --CH.sub.2-L.sup.1- or a group of the formula:
##STR00516## R.sup.a, R.sup.b and R.sup.c are each independently
alkyl, cycloalkyl, aryl, heterocyclyl, heteroaryl, alkylcycloalkyl,
alkylaryl, alkylheterocyclyl or alkylheteroaryl; R, R.sup.1,
R.sup.2 and R.sup.3 are each independently H, alkyl, cycloalkyl,
aryl, heterocycyl, heteroaryl, alkylcycloalkyl, alkylaryl,
alkylheterocyclyl or alkylheteroaryl; X.sup.1 represents zero, one,
two or three substituents and X.sup.2 represents zero, one, two,
three or four substituents, wherein each such substituent is
independently selected from the group consisting of alkyl,
cycloalkyl, aryl, heterocyclyl, heteroaryl, alkylcycloalkyl,
alkylaryl, alkylheterocyclyl, alkylheteroaryl, halogen, nitro,
amide, ester, cyano, alkoxy, alkylamino, arylamino, an inorganic
support and a polymeric moiety.
2. The process according to claim 1, wherein the borane derivative
is represented by the structure of any of formulae G, H, D and E:
##STR00517## wherein each of L.sup.1, L.sup.3, X.sup.1, X.sup.2,
R.sup.a and R.sup.b is as defined in claim 1.
3. The process according to claim 1, wherein the borane derivative
is represented by the structure of any of formulae 2', 4', 6' and
8': ##STR00518##
4. The process according to claim 1, wherein X.sup.1 and/or X.sup.2
are absent, and the pyridyl or bipyridy moiety is
unsubstituted.
5. The process according to claim 1, wherein L.sup.1 is phosphine
(PR.sup.aR.sup.b).
6. The process of claim 1, comprising the step of hydrogenating an
ester represented by the formula R.sup.6C(.dbd.O)--OR.sup.7 to the
corresponding alcohol or alcohols: ##STR00519## wherein R.sup.6 is
selected from the group consisting of H, an unsubstituted or
substituted alkyl, alkoxyalkyl, cycloalkyl, aryl, alkylaryl,
heterocyclyl and heteroaryl; and R.sup.7 is selected from the group
consisting of an unsubstituted or substituted alkyl, alkoxyalkyl,
cycloalkyl, aryl, alkylaryl, heterocyclyl and heteroaryl.
7. The process of claim 1, comprising the step of hydrogenating a
carbonate represented by the formula R.sup.8O--C(.dbd.O)--OR.sup.8,
to the corresponding alcohols(s) and methanol: ##STR00520## wherein
R.sup.8 and R.sup.8' are the same or different and are selected
from the group consisting of an unsubstituted or substituted alkyl,
alkoxyalkyl, cycloalkyl, aryl, alkylaryl, heterocyclyl and
heteroaryl.
8. The process of claim 1, comprising the step of hydrogenating a
carbamate represented by the formula
R.sup.9O--C(.dbd.O)--NHR.sup.10 to the corresponding amine, alcohol
and methanol: ##STR00521## wherein R.sup.9 is selected from the
group consisting of an unsubstituted or substituted alkyl,
alkoxyalkyl, cycloalkyl, aryl alkylaryl, heterocyclyl and
heteroaryl; and R.sup.10 is selected from the group consisting of H
or an unsubstituted or substituted alkyl, alkoxyalkyl, cycloalkyl,
aryl, alkylaryl, heterocyclyl and heteroaryl.
9. The process of claim 1, comprising the step of hydrogenating a
urea derivative to the corresponding amine and methanol:
##STR00522## wherein each of R.sup.9a and R.sup.10a, which may be
the same or different, is selected from the group consisting of an
unsubstituted or substituted alkyl, alkoxyalkyl, cycloalkyl, aryl,
alkylaryl, and heterocyclyl, and each of R.sup.9b and R.sup.10b,
which may be the same or different, is selected from the group
consisting of H, an unsubstituted or substituted alkyl,
alkoxyalkyl, cycloalkyl, aryl, alkylaryl, and heterocyclyl; or
wherein at least one of R.sup.9a and R.sup.10a, and/or R.sup.9b and
R.sup.10b together with the nitrogen to which they are attached
form a heterocyclic ring.
10. A process for preparing an amide from amine and an alcohol,
comprising the step of reacting a primary or secondary amine with a
primary alcohol in the presence of a borane derivative of a
Ruthenium complex; or a process for preparing an ester by
dehydrogenative coupling of primary alcohols, comprising the step
of reacting a primary alcohol or a combination of primary alcohols
in the presence of a borane derivative of a Ruthenium complex; or a
process for preparing an ester by dehydrogenative coupling of a
primary alcohol and a secondary alcohol comprising the step of
reacting the primary and secondary alcohol in the presence of a
borane derivative of a Ruthenium complex; or a process for
preparing a ketone by dehydrogenation of a secondary alcohol,
comprising the step of reacting the secondary alcohol in the
presence of a borane derivative of a Ruthenium complex; or a
process for preparing an amide from amine and an ester, comprising
the step of reacting a primary or secondary amine with an ester in
the presence of a borane derivative of a Ruthenium complex; or a
process for preparing an ester from an alcohol and an ester, by
reacting a primary or secondary alcohol with an ester in the
presence of a borane derivative of a Ruthenium complex; or a
process for preparing a carboxylic acid comprising the step of
reacting a primary alcohol with water and a base in the presence of
a borane derivative of a Ruthenium complex, wherein said borane
derivative is represented by the structure of formula F:
##STR00523## wherein each L.sup.1 is independently selected from
the group consisting of phosphine (PR.sup.aR.sup.b), phosphite
P(OR.sup.a)(OR.sup.b), phosphinite P(OR.sup.a)(R.sup.b), amine
(NR.sup.aR.sup.b), imine, oxazoline, sulfide (SR.sup.a), sulfoxide
(S(.dbd.O)R.sup.a), heteroaryl containing at least one heteroatom
selected from nitrogen and sulfur; arsine (AsR.sup.aR.sup.b),
stibine (SbR.sup.aR.sup.b) and a N-heterocyclic carbene represented
by the structures: ##STR00524## L.sup.3 is absent or is a
mono-dentate two-electron donor selected from the group consisting
of CO, PR.sup.aR.sup.bR.sup.c, P(OR.sup.a)(OR.sup.b)(OR.sup.c),
NO.sup.+, AsR.sup.aR.sup.bR.sup.c, SbR.sup.aR.sup.bR.sup.c,
SR.sup.aR.sup.b, nitrile (RCN), isonitrile (RNC), N.sub.2,
PF.sub.3, CS, heteroaryl and tetrahydrothiophene; L.sup.4 is
--CH.sub.2-L.sup.1- or a group of the formula: ##STR00525##
R.sup.a, R.sup.b and R.sup.c are each independently alkyl,
cycloalkyl, aryl, heterocyclyl, heteroaryl, alkylcycloalkyl,
alkylaryl, alkylheterocyclyl or alkylheteroaryl; R, R.sup.1,
R.sup.2 and R.sup.3 are each independently H, alkyl, cycloalkyl,
aryl, heterocyclyl, heteroaryl, alkylcycloalkyl, alkylaryl,
alkylheterocyclyl or alkylheteroaryl; X.sup.1 represents zero, one,
two or three substituents and X.sup.2 represents zero, one, two,
three or four substituents, wherein each such substituent is
independently selected from the group consisting of alkyl,
cycloalkyl, aryl, heterocyclyl, heteroaryl, alkylcycloalkyl,
alkylaryl, alkylheterocyclyl, alkylheteroaryl, halogen, nitro,
amide, ester, cyano, alkoxy, alkylamino, arylamino, an inorganic
support and a polymeric moiety.
11. The process according to claim 10, wherein the borane
derivative is represented by the structure of any of formulae G, H,
D and E: ##STR00526## wherein each of L.sup.1, L.sup.3, X.sup.1,
X.sup.2, R.sup.a and R.sup.b is as defined in claim 1.
12. The process according to claim 10, wherein the borane
derivative is represented by the structure of any of formulae 2',
4', 6' and 8': ##STR00527##
13. The process according to claim 10, wherein X.sup.1 and/or
X.sup.2 are absent, and the pyridyl or bipyridy moiety is
unsubstituted.
14. The process according to claim 10, wherein L.sup.1 is phosphine
(PR.sup.aR.sup.b).
15. The process of claim 10, for preparing an amide from amine and
an alcohol, wherein said process comprises reacting an amine
represented by formula R.sup.11R.sup.11'NH with an alcohol
represented by the formula R.sup.12CH.sub.2OH to generate an amide
represented by the structure
R.sup.12--C(.dbd.O)--NR.sup.11R.sup.11': ##STR00528## wherein
R.sup.10, R.sup.11 and R.sup.12 are each independently selected
from the group consisting of H an unsubstituted or substituted
alkyl, alkoxyalkyl, cycloalkyl, aryl, alkylaryl, heterocyclyl and
heteroaryl.
16. The process of claim 10, for preparing an amide from amine and
an alcohol, wherein the process is for preparing a polypeptide or a
cyclic dipeptide, and wherein the primary or secondary amine and
the primary alcohol are a beta-aminoalcohol.
17. The process of claim 10, for preparing an ester by
dehydrogenative coupling of primary alcohols, wherein the process
comprises the step of converting a primary alcohol represented by
formula R.sup.13CH.sub.2OH to an ester by the structure
R.sup.13--C(.dbd.O)--OCH.sub.2R.sup.13: ##STR00529## wherein
R.sup.13 is selected from the group consisting of H, an
unsubstituted or substituted alkyl, alkoxyalkyl, cycloalkyl, aryl,
alkylaryl, heterocyclyl and heteroaryl; or wherein the process
comprises the steps of reacting a first primary alcohol represented
by formula R.sup.13CH.sub.2OH with a second alcohol represented by
formula R.sup.13'CH.sub.2OH so as to generate an ester by the
structure R.sup.13--C(.dbd.O)--OCH.sub.2R.sup.13' or an ester of
formula R.sup.13'--C(.dbd.O)--OCH.sub.2R.sup.13 ##STR00530##
wherein R.sup.13 and R.sup.13' are the same or different from each
other and are each independently selected is from the group
consisting of H, an unsubstituted or substituted alkyl,
alkoxyalkyl, cycloalkyl, aryl, alkylaryl, heterocyclyl and
heteroaryl.
18. The process of claim 10, for preparing an ester by
dehydrogenative coupling of a primary alcohol and a secondary
alcohol, wherein the process comprises the step of reacting a
primary alcohol represented by formula R.sup.13CH.sub.2OH with a
secondary alcohol of formula R.sup.13'R.sup.13'' CHOH so as to
generate an ester by the structure
R.sup.13--C(.dbd.O)--OCHR.sup.13'R.sup.13'': ##STR00531## wherein
R.sup.13, R.sup.13' and R.sup.13'' are each independently selected
from the group consisting of H, an unsubstituted or substituted
alkyl, alkoxyalkyl, cycloalkyl, aryl, alkylaryl, heterocyclyl and
heteroaryl.
19. the process of claim 10, for preparing a ketone by
dehydrogenation of a secondary alcohol, wherein the process
comprises the step of converting a secondary alcohol represented by
formula R.sup.14CH(OH)R.sup.14' to a ketone represented by the
structure R.sup.14--C(.dbd.O)--R.sup.14': ##STR00532##
20. The process of claim 10, for preparing an amide from amine and
an ester, wherein the process comprises the step of reacting an
amine represented by formula R.sup.15R.sup.15' NH with an ester
represented by the formula R.sup.16--C(.dbd.O)--OCH.sub.2R.sup.16'
to generate an amide represented by the structure
R.sup.16--C(.dbd.O)--NR.sup.15R.sup.15': ##STR00533## wherein
R.sup.15, R.sup.15', R.sup.16 and R.sup.16' are each independently
selected from the group consisting of H, an unsubstituted or
substituted alkyl, alkoxyalkyl, cycloalkyl, aryl, alkylaryl,
heterocyclyl and heteroaryl.
21. The process of claim 10 for preparing an ester from an alcohol
and an ester, wherein the process comprises the step of reacting a
primary or secondary alcohol represented by formula
R.sup.17R.sup.17'CHOH with an ester by the structure
R.sup.18--C(.dbd.O)--OCH.sub.2R.sup.18': ##STR00534## wherein
R.sup.17, R.sup.17', R.sup.18 and R.sup.18' are each independently
selected from the group consisting of H, an unsubstituted or
substituted alkyl, alkoxyalkyl, cycloalkyl, aryl, alkylaryl,
heterocyclyl and heteroaryl.
22. The process of claim 10, for preparing a carboxylic acid,
wherein the process comprises the step of reacting a primary
alcohol represented by formula R.sup.17CH.sub.2OH with water in the
presence of a base so as to generate a carboxylic acid salt
represented by the structure R.sup.17--C(.dbd.O)O.sup.- and,
optionally, if desired, converting the carboxylic acid salt to the
corresponding carboxylic acid of formula R.sup.17--C(.dbd.O)OH.
##STR00535## wherein R.sup.17 is selected from the group consisting
of H, an unsubstituted or substituted alkyl, alkoxyalkyl,
cycloalkyl, aryl, alkylaryl, heterocyclyl and heteroaryl.
Description
[0001] This application is a Divisional Application from U.S.
application Ser. No. 14/702,641 filed May 1, 2015, which is a
Divisional Application from U.S. application Ser. No. 13/880,328
filed Jun. 11, 2013 now U.S. Pat. No. 9,045,381, which is a
National Phase Application of PCT International Application no.
PCT/IL2011/000817 International Filing Date Oct. 11, 2011, claiming
priority from U.S. Provisional Application no. 61/394,387 filed
Oct. 19, 2010, which are hereby incorporated by reference
FIELD OF THE INVENTION
[0002] The present invention relates to novel Ruthenium complexes
and related borohydride complexes, and their use, inter alia, for
(1) hydrogenation of amides (including polyamides) to alcohols and
amines; (2) preparing amides from alcohols with amines (including
the preparation of polyamides (e.g., polypeptides) by reacting
dialcohols and diamines and/or by polymerization of amino
alcohols); (3) hydrogenation of esters to alcohols (including
hydrogenation of cyclic esters (lactones) or cyclic di-esters
(di-lactones), or polyesters); (4) hydrogenation of organic
carbonates (including polycarbonates) to alcohols and hydrogenation
of carbamates (including polycarbamates) or urea derivatives to
alcohols and amines; (5) dehydrogenative coupling of alcohols to
esters; (6) dehydrogenation of secondary alcohols to ketones; (7)
amidation of esters (i.e., synthesis of amides from esters and
amines); (8) acylation of alcohols using esters; (9) coupling of
alcohols with water and a base to form carboxylic acids; and (10)
dehydrogenation of beta-amino alcohols to form pyrazines. The
present invention further relates to the novel uses of certain
pyridine Ruthenium complexes.
BACKGROUND OF THE INVENTION
[0003] Reduction of carboxylic acids and their derivatives plays an
important role in organic synthesis, both in laboratory and
industrial processes. Traditionally, the reduction is performed
using stochiometric amounts of hydride reagents, generating
stochiometric amounts of waste (Seyden-Penne). A much more
attractive, atom-economical approach is a catalytic reaction using
H.sub.2; however, hydrogenation of carboxylic acid derivatives
under mild conditions is a very challenging task (Rylander;
Hartwig), with amides presenting the one of the highest challenges
among all classes of carbonyl compounds. A few examples of the
important hydrogenation of amides to amines, in which the C--O bond
is cleaved with the liberation of water (Scheme 1), were reported
(Hirosawa et al., N nez Magro et al., Beamson et al.). This
reaction can also be affected with silanes as reducing agents
(Fernandes et al., Das et al.). In addition, the interesting
hydrogenation of cyclic N-acylcarbamates and N-acylsolfonamides,
which involves cleavage of the C--N bond, but does not form amines
was recently reported (Ito et al., 2009).
[0004] On the other hand, selective, direct hydrogenation of amides
to form amines and alcohols has not been reported. Hydrogenation of
amides to amines (via C--O cleavage, generating water) can have
C--N cleavage as a side reaction, requiring the presence of water,
and resulting from catalytic hydrolysis of the amides to acids and
amines followed by hydrogenation of the acids to alcohols: see N
nez Magro et al. and Beamson et al) However, no amide C--N
hydrogenolysis to form alcohols and amines was reported in absence
of water.
[0005] Amines and alcohols are used extensively in the chemical,
pharmaceutical and agrichemical industries (Lawrence; Ricci; Kumara
et al.). Design of such a reaction is conceptually challenging,
since the first mechanistic step in amide hydrogenation is expected
to be H.sub.2 addition to the carbonyl group to form a very
unstable hemiaminal which, in the case of primary or secondary
amides, spontaneously liberates water to form an imine; further
hydrogenation of the imine then leads to amine formation (Scheme
1). For amine and alcohol formation, cleavage of the C--N bond in
preference to the C--O bond is required.
##STR00001##
[0006] The reverse reaction, i.e., amide formation from alcohols
and amines with liberation of H.sub.2, was previously reported by
inventors of the present invention, and later, by others
(Nordstrom; Ghosh; Shimizu) Formation of amides from alcohols and
amines by use of hydrogen acceptors was also reported recently
(Zweifel; Watson). The importance of amides in chemistry and
biology is well recognized and has been studied extensively (Sewald
et al.; Greenberg et al.; Smith and March; Bray). Although several
methods are known for the synthesis of amides, preparation under
neutral conditions and without generation of waste is a challenging
goal (Larock; Smith). Synthesis of amides is mostly based on
activated acid derivatives (acid chlorides, anhydrides) or
rearrangement reactions induced by acid or base which often involve
toxic chemical waste and tedious work-up (Smith). Transition-metal
catalyzed conversion of nitriles into amides was reported (Cobley
et al.; Murahashi et al. 1986 and 1992). Catalytic acylation of
amines by aldehydes in the presence of a stoichiometric amount of
oxidant and a base is known (Tamaru et al., Tillack et al.).
Recently, oxidative amide synthesis was achieved from terminal
alkynes (Chan et al.). Cu(I) catalyzed reaction of sulfonyl azides
with terminal alkynes is a facile method for the synthesis of
sulfonyl amides (Cho et al.; Cassidy et al.).
[0007] Polyamides are one of the most important polymer classes,
extensively used in fiber products, plastics and their derivatives,
with many applications, including in biomedical studies. Recently,
the synthesis of functional polyamides has received considerable
attention. Generally, polyamides are synthesized by condensation of
diamines and activated dicarboxylic acid derivatives and/or in the
presence of coupling reagents. In some cases, ring opening of
small-ring lactams at high temperatures leads to polyamides. To
avoid the use of activators, waste generation, or harsh conditions,
the development of economical, efficient and environmentally benign
protocols are desirable.
[0008] Transition metal borohydride complexes display extensive
reactivity with organic substrates and are useful starting
materials for the preparation of transition metal hydrides and
borides (Dick et al; White et al). They have found uses in
catalytic hydroboration (Burgess et al., Isagawa et al., Lee et
al); polymerization of olefins (Barbier-Baudry et al., Bonnet et
al, and Marks et al.) and cyclic esters (Palard et al.). Ruthenium
hydrido borohydride complexes based on bidentate phosphorus ligands
and diamines, reported by Ohkuma et al, Sandoval et al. and Guo et
al. are effective catalysts in asymmetric transfer hydrogenation of
ketones (Ohkuma et al., Sandoval et al., Guo et al) and
enantioselective Michael addition (Guo et al.). In addition,
borohydride complexes may represent plausible models for CH.sub.4
coordination in the transition state for C--H activation (Jensen et
al. 1986 and 1988).
[0009] Transition metal complexes of bulky, electron-rich
tridentate ligands have found useful applications in synthesis,
bond activation, and catalysis (see recent reviews: Van der Boom et
al., Albrecht et al., Vigalok et al., Jensen 1999 and Rybtchinski
et al.). The highly electron-donating .sup.tBu-PNP
(2,6-bis(di-tert-butylphosphinomethyl)pyridine) and its group 8
metal complexes have been explored by several groups (Kawatsura et
al., Stambuli et al., Gibson et al., and Kloek et al) as well as by
some of the inventors of the present invention (Hermann et al.,
Ben-Ari et al. 2003 and 2006, Zhang et al. 2004, 2005 and 2006, and
Feller et al).
[0010] Dehydrogenation of alcohols to carbonyl compounds without a
hydrogen acceptor or oxidant, with the evolution of molecular
hydrogen, is attractive economically and environmentally (Scheme
2), but homogeneous systems capable of thermally catalyzing
dehydrogenation of alcohols are relatively rare (Zhang et al. 2004
and 2005, Murahashi et al. 1987, Charman et al., Morton et al.,
Dobson et al., Jung et al., Ligthart et al., Shinodxia et al.,
Matsubara et al., Adair et al., Lin et al. 1997 and 1992, Blum et
al., and Zhao et al.).
##STR00002##
[0011] Catalytic hydrogenation of polar carbonyl bonds is a simple,
convenient, and sustainable method which plays a pivotal role in
both industrial processes and academic research. The hydrogenation
of esters to alcohols is an important transformation and remains a
challenging task in the perspective of "green and sustainable
chemistry (GSC)" where the transformation is atom-economic without
generating any large amount of metal waste. Despite well-documented
homogeneously catalyzed reductions of ketones and aldehydes, the
catalytic hydrogenation of esters to alcohols under mild and
homogeneous conditions is relatively underdeveloped, owing to the
poor hydridophilicity (electrophilicity) of the ester carbonyl
functionality. The common trend in the reactivity of carbonyl
groups towards hydrogenation reactions is
RC(O)H>RC(O)R'>>RC(O)OR'>RC(O)NR'.
[0012] Simple 1,2-diols, e.g., propylene glycol (PG) and ethylene
glycol (EG), are utilized as high value-added specialty chemical
intermediates, in the manufacture of biodegradable polyester
fibers, unsaturated polyester resins, antifreeze, pharmaceuticals
and other important products. Currently, these two vicinal diols
are industrially produced from petroleum-derived propylene and
ethylene via hydration of their corresponding epoxy alkanes.
However, as crude oil resources become limited, substitutes for
petroleum feedstocks are increasingly sought after, and as such the
synthesis 1,2-diols, indirectly from biomass derived resources is
of great interest. Alternative methods which proceed under mild
reaction conditions with stable and easy-to-handle homogeneous
catalysts and environmentally benign are desirable.
[0013] Glycolide and lactide are important classes of cyclic
di-esters (di-lactones) utilized as starting materials for
Lewis-acid catalyzed polymerization reactions to synthesize
biodegradable polymers. Since these compounds are produced from
biomass derived resources such as glycolic acid (derived from sugar
cane) and lactic acid (from fermentation of glucose) respectively
via self-esterification, their efficient hydrogenation can provide
alternative, mild approaches to the indirect transformation of
biomass to important synthetic building blocks. Although few
catalytic hydrogenations of (mono lactones) to diols are known in
the literature, the complete hydrogenation of cyclic di-esters to
the corresponding 1,2-diols (e.g. ethylene glycol and propylene
glycol) is extremely difficult due to presence of two ester
moieties and the chelating ability of the final product, 1,2-diol,
which may retard the catalytic activity of the catalyst. Indeed, to
the applicant's best knowledge, catalytic hydrogenation of these
important families of cyclic di-esters has never been reported, be
it under heterogeneous or homogeneous catalysis.
[0014] The applicants of the present invention have recently
reported on new catalytic reactions of alcohols, such as
dehydrogenative coupling of primary alcohols to esters and
dehydrogenation of secondary alcohols to ketones using
pyridine-based pincer complexes (Zhang et al. 2004, 2005, 2006 and
2007; Gunanathan 2007; Gnanaprakasam and Milstein) and acridine
(Gunanathan 2008 and 2009). The catalytic efficiency of the
reaction of the conversion of primary alcohols to ester was
enhanced with Ru(II) complexes of an analogous ligand having a
potentially "hemilabile" amine "arm", PNN
(2-(di-tert-butylphosphinomethyl)-6-(diethylaminomethyl)pyridine).
(PNN)Ru(II) complexes effectively catalyze the acceptorless
dehydrogenation of primary alcohols to the corresponding esters and
molecular hydrogen in high yields and turnover numbers, in the
presence of a catalytic amount of base. Mechanistic studies of this
reaction have led to the discovery of a PNN Ru hydrido carbonyl
complex, which does not require the presence of base, the catalytic
reaction proceeding very effectively under neutral, mild conditions
(Zhang et al. 2005).
[0015] The pyridine-based PNN Ru complex 1 (FIG. 1A) efficiently
catalyzes the dehydrogenative coupling of alcohols to form esters
(Zhang 2005, Zhang 2007 and Milstein), the hydrogenation of esters
to alcohols under mild conditions (Zhang 2006 and Milstein) and the
coupling of alcohols and amines to form amides and H.sub.2
(Gunanathan 2007 and Milstein). The PNP complex 2 (FIG. 1A) is an
efficient catalyst for the dehydrogenative coupling of alcohols and
amines to form imines (Gnanaprakasam 2010 and Milstein). Complex 1
is also effective in N--H activation (Khaskin et al.) and in the
unique light induced splitting of water to H.sub.2 and O.sub.2
(Kohl et al.).
[0016] US patent publication no. US 2009/0112005, to some of the
inventors of the present invention, describes methods for preparing
amides, by reacting a primary amine and a primary alcohol in the
presence of Ruthenium complexes, to generate the amide compound and
molecular hydrogen.
[0017] PCT patent publication no. WO 2010/018570, to some of the
inventors of the present invention, describes methods for preparing
primary amines from alcohols and ammonia in the presence of
Ruthenium complexes, to generate the amine and water.
[0018] Zeng et al., published after the priority date of the
present application, describes a process for preparation of
polyamides via catalytic dehydrogenation of diols and diamines
using PNN pincer ruthenium complexes.
[0019] Given the widespread importance of amines, alcohols, amides
and esters in biochemical and chemical systems, efficient syntheses
that avoid the shortcomings of prior art processes are highly
desirable.
SUMMARY OF THE INVENTION
[0020] The present invention relates to novel Ruthenium complexes
and related borohydride complexes, and the use of such complexes
(e.g., catalysts), inter alia, for (1) hydrogenation of amides
(including polyamides) to alcohols and amines; (2) preparing amides
from alcohols with amines (including the preparation of polyamides
(e.g., polypeptides) by reacting dialcohols and diamines and/or by
polymerization of amino alcohols); (3) hydrogenation of esters to
alcohols (including hydrogenation of cyclic esters (lactones) or
cyclic di-esters (di-lactones) or polyesters); (4) hydrogenation of
organic carbonates (including polycarbonates) to alcohols and
hydrogenation of carbamates (including polycarbamates) or urea
derivatives to alcohols and amines; (5) dehydrogenative coupling of
alcohols to esters; (6) dehydrogenation of secondary alcohols to
ketones; (7) amidation of esters (i.e., synthesis of amides from
esters and amines); (8) acylation of alcohols using esters; (9)
coupling of alcohols with water to form carboxylic acids; and (10)
dehydrogenation of beta-amino alcohols to form pyrazines. The
present invention further relates to the novel uses of certain
pyridine Ruthenium complexes.
[0021] The inventors have unexpectedly discovered new,
bipyridine-based pincer complexes of general formulae A1, A2 and A3
as described herein. Examples of such complexes include, but are
not limited to, compounds of general formulae B1, C1, B2 and C2,
and compounds represented by the structures 3, 4, 7 and 9. Also
unexpectedly discovered are borohydride complexes of said
bipyridine-based pincer complexes, represented by the structure of
general formulae D and E, as well as pyridine-based borohydride
complexes of general formulae F, G or H and some borohydride
complexes such as 2', 4', 6' and 8'. These compounds efficiently
catalyze various processes as described and exemplified herein. In
one embodiment, the complex is a pincer complex represented by the
structure of formula 3 (FIG. 1B). It has unexpectedly been
discovered that complex 3 efficiently catalyzes the unprecedented
selective hydrogenation of amides to form amines and alcohols
(Scheme 3). The reaction proceeds under mild pressure and neutral
conditions, with no additives being required. Since the reaction
proceeds well under anhydrous conditions, hydrolysis of the amide
is not involved in this process.
##STR00003##
[0022] Other reactions catalyzed by pincer complex 3 and the other
pincer complexes described herein, and their borohydride
derivatives, are described in more detail hereinbelow. The
simplicity, generality and excellent atom-economy of these
processes make them attractive for use both in small and large
scale applications.
[0023] In one embodiment, the Ruthenium complex is represented by
any one of formulae A1, A2 or A3:
##STR00004##
wherein
[0024] L.sup.1 is selected from the group consisting of phosphine
(PR.sup.aR.sup.b), phosphite P(OR.sup.a)(OR.sup.b), phosphinite
P(OR.sup.a)(R.sup.b), amine (NR.sup.aR.sup.b), imine, oxazoline,
sulfide (SR.sup.a), sulfoxide (S(.dbd.O)R.sup.a), heteroaryl
containing at least one heteroatom selected from nitrogen and
sulfur; arsine (AsR.sup.aR.sup.b), stibine (SbR.sup.aR.sup.b) and a
N-heterocyclic carbene represented by the structures:
##STR00005##
[0025] L.sup.2 is a mono-dentate two-electron donor selected from
the group consisting of CO, PR.sup.aR.sup.bR.sup.c,
P(OR.sup.a)(OR.sup.b)(OR.sup.c), NO.sup.+, AsR.sup.aR.sup.bR.sup.c,
SbR.sup.aR.sup.bR.sup.c, SR.sup.aR.sup.b, nitrile (RCN), isonitrile
(RNC), N.sub.2, PF.sub.3, CS, heteroaryl, tetrahydrothiophene,
alkene and alkyne;
[0026] L.sup.3 is absent or is L.sup.2;
[0027] Y and Z are each independently H or an anionic ligand
selected from the group consisting of H, halogen, OCOR,
OCOCF.sub.3, OSO.sub.2R, OSO.sub.2CF.sub.3, CN, OR, N(R).sub.2 and
RS;
[0028] R.sup.a, R.sup.b and R.sup.c are each independently alkyl,
cycloalkyl, aryl, heterocyclyl, heteroaryl, alkylcycloalkyl,
alkylaryl, alkylheterocyclyl or alkylheteroaryl;
[0029] R, R.sup.1, R.sup.2 and R.sup.3 are each independently H,
alkyl, cycloalkyl, aryl, heterocyclyl, heteroaryl, alkylcycloalkyl,
alkylaryl, alkylheterocyclyl or alkylheteroaryl;
[0030] X.sup.1 represents zero one, two or three substituents and
X.sup.2 represents zero, one, two, three or four substituents,
wherein each such substituent is independently selected from the
group consisting of alkyl, cycloalkyl, aryl, heterocyclyl,
heteroaryl, alkylcycloalkyl, alkylaryl, alkylheterocyclyl,
alkylheteroaryl, halogen, nitro, amide, ester, cyano, alkoxy,
alkylamino, arylamino, an inorganic support and a polymeric moiety,
and anion represents a group bearing a single negative charge; or a
borane derivative of said complex.
[0031] In one embodiment, X.sup.1 and X.sup.2 are each absent
(i.e., the bipyridine moiety is unsubstituted). In another
embodiment, L.sup.1 is phosphine (PR.sup.aR.sup.b). In another
embodiment, L.sup.1 is amine (NR.sup.aR.sup.b). In another
embodiment, L.sup.2 is CO. Each possibility represents a separate
embodiment of the present invention.
[0032] In some embodiments, the Ruthenium complex acts as a
catalyst (and is thus designated "Ruthenium catalyst").
[0033] In one embodiment, the Ruthenium complex is represented by
the structure of formula A1. In a particular embodiment of formula
A1, the Ruthenium complex is represented by the structure of
formula B1. In another particular embodiment of formula A1, the
Ruthenium complex is represented by the structure of formula C1. In
one embodiment, the Ruthenium complex is represented by the
structure of formula 3 (also shown in FIG. 1B).
[0034] In another embodiment of the present invention, the
Ruthenium complex is represented by the structure of formula A2. In
one embodiment of formula A2, the Ruthenium complex is represented
by the structure of formula B2. In another particular embodiment of
formula A2, the Ruthenium complex is represented by the structure
of formula C2.
[0035] In one embodiment, Y is halogen, such as chloro. For
example, the Ruthenium complex is represented by the structure of
formulae 4, 7 or 9.
[0036] In another embodiment of the present invention, the
Ruthenium complex is represented by the structure of formula
A3.
[0037] The structures of Ruthenium complexes of Formulae A1, B1,
C1, A2, B2, C2, A3, 3, 4, 7 and 9 are described in detail
hereinbelow.
[0038] In another embodiment, the present invention provides a
borane derivative of a Ruthenium complex, the borane derivative
represented by the structure of formula F:
##STR00006##
wherein [0039] each L.sup.1 is independently selected from the
group consisting of phosphine (PR.sup.aR.sup.b), phosphite
P(OR.sup.a)(OR.sup.b), phosphinite P(OR.sup.a)(R.sup.b), amine
(NR.sup.aR.sup.b), imine, oxazoline, sulfide (SR.sup.a), sulfoxide
(S(.dbd.O)R.sup.a), heteroaryl containing at least one heteroatom
selected from nitrogen and sulfur; arsine (AsR.sup.aR.sup.b),
stibine (SbR.sup.aR.sup.b) and a N-heterocyclic carbene represented
by the structures:
[0039] ##STR00007## [0040] L.sup.3 is absent or is a mono-dentate
two-electron donor selected from the group consisting of CO,
PR.sup.aR.sup.bR.sup.c, P(OR.sup.a)(OR.sup.b)(OR.sup.c), NO.sup.+,
AsR.sup.aR.sup.bR.sup.c, SbR.sup.aR.sup.bR.sup.c,
SR.sup.aR.sup.bR.sup.c, nitrile (RCN), isonitrile (RNC), N.sub.2,
PF.sub.3, CS, heteroaryl, tetrahydrothiophene, alkene and alkyne;
[0041] L.sup.4 is --CH.sub.2-L.sup.1- or a group of the
formula:
##STR00008##
[0041] R.sup.a, R.sup.b and R.sup.c are each independently alkyl,
cycloalkyl, aryl, heterocyclyl, heteroaryl, alkylcycloalkyl,
alkylaryl, alkylheterocyclyl or alkylheteroaryl; [0042] R, R.sup.1,
R.sup.2 and R.sup.3 are each independently H, alkyl, cycloalkyl,
aryl, heterocyclyl, heteroaryl, alkylcycloalkyl, alkylaryl,
alkylheterocyclyl or alkylheteroaryl; [0043] X.sup.1 represents
zero, one, two or three substituents and X.sup.2 represents zero,
one, two, three or four substituents, wherein each such substituent
is independently selected from the group consisting of alkyl,
cycloalkyl, aryl, heterocyclyl, heteroaryl, alkylcycloalkyl,
alkylaryl, alkylheterocyclyl, alkylheteroaryl, halogen, nitro,
amide, ester, cyano, alkoxy, alkylamino, arylamino, an inorganic
support and a polymeric moiety.
[0044] In some embodiments, the borane derivative is represented by
the structure of any of formulae D, E, G and H. It is noted that
compounds D and E are borane derivatives of the Ruthenium complex
of formula A1 as described hereinabove.
[0045] In other embodiments, the borane derivative is represented
by the structure of any of formulae 2', 4', 6' and 8'.
[0046] The structures of borohydride-Ruthenium complexes of D, E,
G, H, 2', 4', 6' and 8' are described in detail hereinbelow.
[0047] The present invention further provides various processes
which utilize the Ruthenium complexes of the present invention as
catalysts.
[0048] Thus, in some embodiments, the present invention provides a
process for hydrogenating amides (including polyamides and
polypeptides) by reacting the amide with molecular hydrogen
(H.sub.2) in the presence of the Ruthenium complexes of the present
invention to generate the corresponding alcohol and amine. As
contemplated herein, the inventors have discovered a novel process
for converting amides to alcohols and amines in high yields and
high turnover numbers. This reaction is catalyzed by a Ruthenium
complex, which is represented by anyone of formulae A1, A2, A3, B1,
B2, C1, C2, 3, 4, 7 and 9, or any other Ruthenium complex covered
by such formulae, optionally in the presence of a base. In
addition, this reaction is catalyzed by the Ruthenium complexes
described in US Patent publication US 2009/0112005, in particular
Ruthenium complexes of formula A1', A2' and A3' wherein L.sub.1 is
N(R).sub.2. The contents of US 2009/0112005 are incorporated by
reference herein and the structures of the Ruthenium complexes of
formula A1', A2' and A3' are provided hereinbelow. One embodiment
of such compounds is a pincer complex represented by the structure
of formula 1 (FIG. 1A). Each possibility represents a separate
embodiment of the present invention.
[0049] In a similar manner, lactams (cyclic amides) can be
hydrogenated to the corresponding amino alcohols. In addition,
polyamides and/or polypeptides can be hydrogenated to the
corresponding alcohols and amines.
[0050] Depending on the complex being used, the reaction permits
the optional use of one or more equivalents of a base.
[0051] Similar to the hydrogenation of amides, the novel Ruthenium
complexes of the present invention can also catalyze the
hydrogenation of esters and organic carbonates to alcohols, or the
hydrogenation of carbamates to the corresponding amines and
alcohols, or the hydrogenation of urea derivatives to the
corresponding amines and methanol. Thus, in other embodiments, the
present invention further provides a process for hydrogenating an
ester, organic carbonate, carbamate or urea derivative, with
molecular hydrogen (H.sub.2) in the presence of the Ruthenium
complex, as described herein. As contemplated herein, the inventors
have further discovered a novel process for converting esters
(e.g., formate esters), organic carbonates, carbamates or urea
derivatives to alcohols and/or amines in high yields and high
turnover numbers. Polyesters, polycarbonates, polycarbamates and/or
polyureas can be hydrogenated in a similar manner. These reactions
are catalyzed by a Ruthenium complex, which is represented by
anyone of formulae A1, A2, A3, B1, B2, C1, C2, 3, 4, 7 and 9 or any
other Ruthenium complex covered by such formulae. These reactions
are also catalyzed by the borohydride complexes described herein,
such as complexes D, E, F, G and H, and compounds 2', 4', 6' and
8'. Currently preferred catalysts (complexes) for hydrogenation of
organic carbonates, carbamates and urea derivatives are Ruthenium
complexes which are represented by anyone of formulae A1, A2, A3,
B1, B2, C1, C2, 3, 4, 7 and 9. In some preferred embodiments,
hydrogenation of esters is catalyzed by the borohydride complexes
described herein, such as complexes D, E, F, G and H, and compounds
2', 4', 6' and 8' Depending on the complex being used, the reaction
permits the optional use of one or more equivalents of a base.
[0052] In another embodiment, the hydrogenation of organic
carbonates, carbamates and urea derivatives to amines and alcohols
(including hydrogenation of polycarbonates, polycarbamates and
polyurea derivatives) can be catalyzed by any of the Ruthenium
complexes described in US Patent publication US 2009/0112005, in
particular Ruthenium complexes of formula A1', A2' and A3' wherein
L.sub.1 is N(R).sub.2. One embodiment of such compounds is a pincer
complex represented by the structure of formula 1 (FIG. 1A). Each
possibility represents a separate embodiment of the present
invention.
[0053] In a similar manner, lactones (e.g., cyclic esters) can be
hydrogenated to alcohols. For example, cyclic di-esters
(di-lactones) can be hydrogenated to the corresponding (vicinal)
diols. In one particular embodiment, the present invention is
directed to a process comprising hydrogenation of cyclic di-esters
(di-lactones), which may be biomass-derived, e.g., glycolide and
lactide to the corresponding 1,2-diols (vicinal diols). The process
of lactone hydrogenation can be catalyzed by the same complexes
described above with respect to hydrogenation of esters to
alcohols. In other embodiments, the present invention includes
process for hydrogenating polyesters to the corresponding alcohols.
Each possibility represents a separate embodiment of the present
invention.
[0054] The present invention further provides a process for
preparing amides (including polyamides and polypeptides), by
reacting an amine and an alcohol in the presence of a Ruthenium
complex, to generate the amide compound and molecular hydrogen
(H.sub.2). As contemplated herein, the inventors have further
discovered a novel process for preparing amides in which primary
and secondary amines are directly acylated by equimolar amounts of
alcohols to produce amides and molecular hydrogen in high yields
and high turnover numbers. This reaction is catalyzed by a
Ruthenium complex or a boronated complex thereof, which is
represented by anyone of formulae A1, A2, A3, B1, C1, B2, C2, D, E,
F (for complex F preferably L.sub.4 is CH.sub.2NR.sup.aR.sup.b), H,
3, 4, 7, 9, 4' and 8', or any other Ruthenium complex or their
boronated complexes covered by such formulae. Depending on the
complex being used, the reaction permits the optional use of one or
more equivalents of a base. Use of diamines or dialcohols in the
reaction leads to diamides, whereas when diamines and dialcohols
are used together, the process results in a polyamide. Similarly,
beta-amino alcohols can be dehydrogenated in the presence of the
Ruthenium complexes of the present invention to form polypeptides.
Also, the process of the invention covers inter or intramolecular
coupling of amino alcohols to form lactams, including cyclic
peptides (in the case of coupling of beta-amino alcohols).
[0055] The amidation or polyamidation reactions (including the
coupling of beta-amino alcohols to form polypeptides), can also be
catalyzed by the Ruthenium complexes described in US Patent
publication US 2009/0112005, in particular Ruthenium complexes in
which L.sub.1 is N(R).sub.2. One embodiment of such compounds is a
pincer complex represented by the structure of formula 1 (FIG. 1A).
Other compounds are represented by any of formulae A1', A2' or A3'
wherein L.sub.1 is N(R).sub.2 as described herein. Polypeptide (or
cyclic peptide) preparation from beta-amino alcohols, catalyzed by
the Ruthenium complexes described in US Patent publication US
2009/0112005, namely compounds A1', A2' or A3' wherein L.sub.1 is
N(R).sub.2 has not previously been described, and constitutes
another embodiment of the present invention.
[0056] In some embodiments, beta-amino alcohols can be
dehydrogenated in the presence of Ruthenium complexes to form
cyclic dipeptides. Such reactions are catalyzed by a Ruthenium
complex or a boronated complex thereof, which is represented by
anyone of formulae A1, A2, A3, B1, C1, B2, C2, D, E, F (for complex
F preferably L.sub.4 is CH.sub.2NR.sup.aR.sup.b), H, 3, 4, 7, 9, 4'
and 8', or any other Ruthenium complex or their boronated complexes
covered by such formulae. Alternatively, such reactions can also be
catalyzed by the Ruthenium complexes described in US Patent
publication US 2009/0112005, in particular Ruthenium complexes in
which L.sub.1 is N(R).sub.2.
[0057] In other embodiments, beta-amino alcohols can be
dehydrogenated in the presence of Ruthenium complexes to form
pyrazines. Ruthenium complexes which catalyze such reactions are
those which contain two phosphinine ligands or N-heterocyclic
carbene ligands. Examples of such complexes include borohydride
complexes represented by formula F (wherein each one of L.sup.1 and
L.sup.4 contain a phosphine and/or N-heterocyclic carbene), G, 2'
and 6'. Other Ruthenium complexes which catalyze such reactions are
described in US Patent publication US 2009/0112005, in particular
Ruthenium complexes of formula A1', A2' and A3' which contain two
phosphinine ligands or N-heterocyclic carbene ligands.
[0058] The present invention further provides a process for
preparing esters by coupling of alcohols in the presence of a
Ruthenium complex, to generate the ester compound and molecular
hydrogen. In one embodiment, the process involves coupling of
primary alcohols. In another embodiment, the process involves
coupling of a primary and secondary alcohol. These reactions are
catalyzed by a Ruthenium complex or a boronated complex thereof,
which is represented by anyone of formulae A1, A2, A3, B1, C1, B2,
C2, D, E, F, G, H, 3, 4, 7, 9, 2', 4', 6' and 8' or any other
Ruthenium complex or their boronated complexes covered by such
formulae. Depending on the complex being used, the reaction permits
the optional use of one or more equivalents of a base. Use of
dialcohols in the reaction leads to polyesters or to lactones.
[0059] The present invention further relates to a process for
preparing a ketone by dehydrogenation of a secondary alcohol, by
reacting the secondary alcohol in the presence of the Ruthenium
complex which is represented by anyone of formulae A1, A2, A3, B1,
C1, B2, C2, D, E, F, G, H, 3, 4, 7, 9, 2', 4', 6' and 8' or any
other Ruthenium complex or their boronated complexes covered by
such formulae, thereby generating the ester and molecular
hydrogen.
[0060] The present invention further relates to a process for the
coupling of alcohols with water and a base to form carboxylic acid
salts, by contacting the alcohol and a base with water in the
presence of the Ruthenium complex which is represented by anyone of
formulae A1, A2, A3, B1, C1, B2, C2, D, E, F, G, H, 3, 4, 7, 9, 2',
4', 6' and 8' or any other Ruthenium complex or their boronated
complexes covered by such formulae, thereby generating the
carboxylic acid salt and molecular hydrogen. Optionally, the salt
can be converted to the carboxylic acid upon reaction with an acid.
This reaction can also be catalyzed by the Ruthenium complexes
described in US Patent publication US 2009/0112005, such as, but
not limited to the compounds of formula A1', A2' and A3', and
Pincer complex of Formula 1.
[0061] The present invention further provides a process for
preparing amides, by reacting an amine and an ester in the presence
of a Ruthenium complex, to generate the amide compound and
molecular hydrogen (H.sub.2). As contemplated herein, the inventors
have further discovered a novel process for preparing amides in
which primary and secondary amines are directly reacted with esters
to produce amides and molecular hydrogen in high yields and high
turnover numbers. This reaction is catalyzed by a Ruthenium complex
or a boronated complex thereof, which is represented by anyone of
formulae A1, A2, A3, B1, C1, B2, C2, D, E, F (when complex F is
used and L.sup.4 is --CH.sub.2-L.sup.1, L.sup.1 is preferably
NR.sup.aR.sup.b), H, 3, 4, 7, 9, 4' and 8', or any other Ruthenium
complex or their boronated complexes covered by such formulae.
Depending on the complex being used, the reaction permits the
optional use of one or more equivalents of a base. Reactions of
esters with diamines leads to diamides.
[0062] The present invention further provides a process for
preparing esters by acylation of alcohols using esters in the
presence of a Ruthenium complex, to generate the ester compound and
molecular hydrogen. In one embodiment, the process involves
reaction of primary alcohols and esters. In another embodiment, the
process involves reaction of a secondary alcohols and esters. These
reactions are catalyzed by a Ruthenium complex or a boronated
complex thereof, which is represented by anyone of formulae A1, A2,
A3, B1, C1, B2, C2, D, E, F, G, H, 3, 4, 7, 9, 2', 4', 6' and 8' or
any other Ruthenium complex or their boronated complexes covered by
such formulae. Depending on the complex being used, the reaction
permits the optional use of one or more equivalents of a base.
[0063] In some embodiments, the process of any of the embodiments
of the present invention as described herein is conducted under
neat conditions in the absence of a solvent. In other embodiments,
however, the process is conducted in the presence of an organic
solvent such as, but not limited to benzene, toluene, o-, m- or
p-xylene, mesitylene (1,3,5-trimethyl benzene), dioxane, THF, DME,
anisole and cyclohexane.
[0064] In some embodiments the process is conducted under heat. In
other embodiments, the process is conducted under inert gas. In
other embodiments, the process is conducted under heat and under
inert gas. However, the reactions of the invention can, when
appropriate, also be conducted in the open air.
[0065] In one embodiment, the Ruthenium complex of the present
invention is represented by the structure of formula A1, and the
reactions described herein do not require the presence of a base.
In another embodiment, Ruthenium complex is represented by the
structure of formula A2. When Z is H and Y is other than H, the
process further comprises adding at least one equivalent of a base
relative to the Ruthenium complex. When Z and Y are other than H,
the process further comprises adding at least two equivalents of a
base relative to the Ruthenium complex. When Z and Y are both H,
the process is conducted in the absence of a base. In another
embodiment, Ruthenium complex is represented by the structure of
formula A3. When Z is H, the process further comprises adding at
least one equivalent of a base relative to the Ruthenium complex.
When Z is other than H, the process further comprises adding at
least two equivalents of a base relative to the Ruthenium
complex.
[0066] Also encompassed by the present invention are certain
intermediate compounds and their use in the preparation of the
Ruthenium complexes of the present invention. Thus, in one
embodiment, the present invention relates to a compound represented
by the structure of formula Z:
##STR00009##
[0067] wherein [0068] L.sup.1 is selected from the group consisting
of phosphine (PR.sup.aR.sup.b), phosphite P(OR.sup.a)(OR.sup.b),
phosphinite P(OR.sup.a)(R.sup.b), amine (NR.sup.aR.sup.b), imine,
oxazoline, sulfide (SR.sup.a), sulfoxide (S(.dbd.O)R.sup.a),
heteroaryl containing at least one heteroatom selected from
nitrogen and sulfur; arsine (AsR.sup.aR.sup.b), stibine
(SbR.sup.aR.sup.b) and a N-heterocyclic carbene represented by the
structures:
[0068] ##STR00010## [0069] X.sup.1 represents zero, one, two or
three substituents and X.sup.2 represents zero, one, two, three or
four substituents, wherein each such substituent is independently
selected from the group consisting of alkyl, cycloalkyl, aryl,
heterocyclyl, heteroaryl, alkylcycloalkyl, alkylaryl,
alkylheterocyclyl, alkylheteroaryl, halogen, nitro, amide, ester,
cyano, alkoxy, alkylamino, arylamino, an inorganic support and a
polymeric moiety; and [0070] R.sup.a and R.sup.b are each
independently alkyl, cycloalkyl, aryl, heterocyclyl, heteroaryl,
alkylcycloalkyl, alkylaryl, alkylheterocyclyl or
alkylheteroaryl.
[0071] In some embodiments, the compound selected from the group
consisting of
##STR00011##
BRIEF DESCRIPTION OF THE DRAWINGS
[0072] The present invention will be understood and appreciated
more fully from the following detailed description taken in
conjunction with the appended figures:
[0073] FIG. 1: shows the structure of dearomatized PNN pincer
complexes 1 and 2 (FIG. 1A) and complex 3 (FIG. 1B).
[0074] FIG. 2: shows the X-ray structure of Ruthenium complex 4
with the thermal ellipsoids at 50% probability level. All C--H
hydrogen atoms are omitted for clarity.
[0075] FIG. 3: shows the X-ray structure of Ruthenium borohyride
complex 2' with the thermal ellipsoids at 50% probability level.
All C--H hydrogen atoms are omitted for clarity.
[0076] FIG. 4: shows the variable-temperature (213K-373K) 1H NMR of
Ruthenium borohydride complex 4' in the region of Ru--H and
BH.sub.4.sup.- ligands (toluene-d.sub.8 as solvent).
[0077] FIG. 5: shows MALDI-TOF mass spectra of polyamides
synthesized by the processes of the present invention. FIG. 5A:
polyamide 3a in TFA using HBA matrix. FIG. 5B: polyamide 3c in TFA
using HBA matrix. FIG. 5C: polyamide 3d in 50% TFA/DCM using
HBA-NaI. FIG. 5D: polyamide 3e in TFA using HBA matrix. FIG. 5E:
polyamide 3h in TFA using HBA matrix.
[0078] FIG. 6: TGA of polyamides 3.
DETAILED DESCRIPTION OF THE PRESENT INVENTION
[0079] The present invention provides novel Ruthenium based
complexes and catalysts and borohydride complexes thereof, and the
use of such complexes for, inter alia, (1) hydrogenation of amides
(including polyamides) to alcohols and amines; (2) preparing amides
from alcohols with amines (including the preparation of polyamides
(e.g., polypeptides) by reacting dialcohols and diamines and/or by
polymerization of amino alcohols); (3) hydrogenation of esters to
alcohols(including hydrogenation of cyclic esters (lactones) or
cyclic di-esters (lactones) or polyesters); (4) hydrogenation of
organic carbonates (including polycarbonates) to alcohols and
hydrogenation of carbamates (including polycarbamates) or urea
derivatives to alcohols and amines; (5) dehydrogenative coupling of
alcohols to esters; (6) dehydrogenation of secondary alcohols to
ketones; (7) amidation of esters (i.e., synthesis of amides from
esters and amines); (8) acylation of alcohols using esters; (9)
coupling of alcohols with water to form carboxylic acids; and (10)
dehydrogenation of beta-amino alcohols to form pyrazines. The
present invention further relates to the novel uses of certain
pyridine Ruthenium complexes.
[0080] Ruthenium Complexes
[0081] In one embodiment, the Ruthenium complex is represented by
any one of formulae A1, A2 or A3:
##STR00012##
[0082] wherein [0083] L.sup.1 is selected from the group consisting
of phosphine (PR.sup.aR.sup.b), phosphite P(OR.sup.a)(OR.sup.b),
phosphinite P(OR.sup.a)(R.sup.b), amine (NR.sup.aR), imine,
oxazoline, sulfide (SR.sup.a), sulfoxide (S(.dbd.O)R.sup.a),
heteroaryl containing at least one heteroatom selected from
nitrogen and sulfur; arsine (AsR.sup.aR.sup.b), stibine
(SbR.sup.aR.sup.b) and a N-heterocyclic carbene represented by the
structures:
[0083] ##STR00013## [0084] L.sup.2 is a mono-dentate two-electron
donor selected from the group consisting of CO,
PR.sup.aR.sup.bR.sup.c, P(OR.sup.a)(OR.sup.b)(OR.sup.c), NO.sup.+,
AsR.sup.aR.sup.bR.sup.c, SbR.sup.aR.sup.bR.sup.c, SR.sup.aR.sup.b,
nitrile (RCN), isonitrile (RNC), N.sub.2, PF.sub.3, CS, heteroaryl,
tetrahydrothiophene, alkene and alkyne; [0085] L.sup.3 is absent or
is L.sup.2; [0086] Y and Z are each independently H or an anionic
ligand selected from the group consisting of H, halogen, OCOR,
OCOCF.sub.3, OSO.sub.2R, OSO.sub.2CF.sub.3, CN, OR, N(R).sub.2 and
RS; [0087] R.sup.a, R.sup.b and R.sup.c are each independently
alkyl, cycloalkyl, aryl, heterocyclyl, heteroaryl, alkylcycloalkyl,
alkylaryl, alkylheterocyclyl or alkylheteroaryl; [0088] R, R.sup.1,
R.sup.2 and R.sup.3 are each independently H, alkyl, cycloalkyl,
aryl, heterocyclyl, heteroaryl, alkylcycloalkyl, alkylaryl,
alkylheterocyclyl or alkylheteroaryl; [0089] X.sup.1 represents
zero, one, two or three substituents and X.sup.2 represents zero,
one, two, three or four substituents, wherein each such substituent
is independently selected from the group consisting of alkyl,
cycloalkyl, aryl, heterocyclyl, heteroaryl, alkylcycloalkyl,
alkylaryl, alkylheterocyclyl, alkylheteroaryl, halogen, nitro,
amide, ester, cyano, alkoxy, alkylamino, arylamino, an inorganic
support and a polymeric moiety, and anion represents a group
bearing a single negative charge; or a borane derivative of said
complex.
[0090] In one embodiment, X.sup.1 and X.sup.2 are absent (i.e. the
bipyridine moiety is unsubstituted).
[0091] In another embodiment, L.sup.1 is phosphine
(PR.sup.aR.sup.b). In another embodiment, L.sup.2 is CO.
[0092] In one embodiment, the Ruthenium complex is represented by
the structure of formula A1:
##STR00014##
[0093] In a particular embodiment of formula A1, the Ruthenium
complex is represented by the structure of formula B1. In another
particular embodiment of formula A1, the Ruthenium complex is
represented by the structure of formula C1.
##STR00015##
[0094] Each of L.sup.1, L.sup.2, X.sup.1, X.sup.2, R.sup.a and
R.sup.b in Formulae B1 and C1 are as defined for formula A1. Each
possibility represents a separate embodiment of the present
invention.
[0095] In one embodiment, each of R.sup.a and R.sup.b is
tert-butyl. In another currently, each of R.sup.c and R.sup.d are
isopropyl, Each possibility represents a separate embodiment of the
present invention.
[0096] In one embodiment, the Ruthenium complex is represented by
the structure of formula 3 (also shown in FIG. 1B).
##STR00016##
[0097] In another embodiment of the present invention, the
Ruthenium complex is represented by the structure of formula
A2:
##STR00017##
[0098] In one embodiment of Formula A2, Z and Y are either each H,
each a halogen (e.g., F, Cl, Br, I) or one of Z and Y is H and the
other a halogen. Each possibility represents a separate embodiment
of the present invention.
[0099] In one particular embodiment, Z is H and Y is other than H
in formula A2. When such a complex is used, the processes of the
invention as described hereinbelow are typically conducted in the
presence of at least one equivalent of a base relative to the
Ruthenium complex. In another particular embodiment, each of Z and
Y is other than H in formula A2. When such a complex is used, the
processes of the invention as described hereinbelow are typically
conducted in the presence of at least two equivalents of a base
relative to the Ruthenium complex. In another particular
embodiment, Z and Y are both H in formula A2. When such a complex
is used, no base is required for the processes of the
invention.
[0100] In one embodiment of formula A2, the Ruthenium complex is
represented by the structure of formula B2:
##STR00018##
[0101] In another particular embodiment of formula A2, the
Ruthenium complex is represented by the following structure of
formula C2:
##STR00019##
[0102] Each of L.sup.1, L.sup.2, X.sup.1, X.sup.2, Y, R.sup.a and
R.sup.b in formulae B2 and C2 are as defined in formula A2. Each
possibility represents a separate embodiment of the present
invention.
[0103] In one embodiment, Y is halogen, such as chloro. For
example, the Ruthenium complex may be represented by the structure
of any of formulae 4, 7 or 9:
##STR00020##
[0104] In another embodiment of the present invention, the
Ruthenium complex is represented by the structure of formula
A3:
##STR00021##
[0105] In one particular embodiment, Z is H in formula A3. When
such a complex is used, the processes of the invention as described
hereinbelow are typically conducted in the presence of at least one
equivalent of a base relative to the Ruthenium complex. In another
particular embodiment, Z is other than H in formula A3. When such a
complex is used, the processes of the invention as described
hereinbelow are typically conducted in the presence of at least two
equivalents of a base relative to the Ruthenium complex.
[0106] Compounds of formula A2 and formula A3 are precursors of
compounds of formula A1. Additionally some precursors of the
complexes of formula A1 include, but are not limited to, compounds
of general formulae (i), (ii) and (iii):
##STR00022##
[0107] It is understood that any one or more of the precursors can
themselves function as complexes in the process of the present
invention. For example, when structures (i) and (ii) and their
equivalents are used, at least one equivalent of base relative to
the Ruthenium complex can be used (e.g., alkoxide, hydroxide).
Alternatively, when structure (iii) or its equivalents are used, at
least two equivalents of base relative to the Ruthenium complex can
be used. Non-limiting examples of bases are alkoxide (e.g.,
t-butoxide, methoxide, ethoxide), or hydroxide.
Borohydride Complexes:
[0108] It has been unexpectedly discovered that certain reactions
such conversion of primary alcohols to esters, as well as the
dehydrogenation of secondary alcohols to ketones, as well as other
reactions contemplated herein, can be effectively accomplished with
stable, readily synthesized PNN- and PNP Ru borohydride complexes,
in the absence of a base, under mild and neutral conditions,
optionally in the absence of hydrogen acceptor.
[0109] Thus, in one embodiment, the present invention provides a
borane derivative of a Ruthenium complex, the borane derivative
represented by the structure of formula F:
##STR00023##
[0110] wherein [0111] each L.sup.1 is independently selected from
the group consisting of phosphine (PR.sup.aR.sup.b), phosphite
P(OR.sup.a)(OR.sup.b), phosphinite P(OR.sup.a)(R.sup.b), amine
(NR.sup.aR.sup.b), imine, oxazoline, sulfide (SR.sup.a), sulfoxide
(S(.dbd.O)R.sup.a), heteroaryl containing at least one heteroatom
selected from nitrogen and sulfur; arsine (AsR.sup.aR.sup.b),
stibine (SbR.sup.aR.sup.b) and a N-heterocyclic carbene represented
by the structures:
[0111] ##STR00024## [0112] L.sup.3 is absent or is a mono-dentate
two-electron donor selected from the group consisting of CO,
PR.sup.aR.sup.bR.sup.c, P(OR.sup.a)(OR.sup.b)(OR.sup.c), NO.sup.+,
AsR.sup.aR.sup.bR.sup.c, SbR.sup.aR.sup.bR.sup.c, SR.sup.aR.sup.b,
nitrile (RCN), isonitrile (RNC), N.sub.2, PF.sub.3, CS, heteroaryl
and tetrahydrothiophene; [0113] L.sup.4 is --CH.sub.2-L.sup.1- or a
group of the formula:
[0113] ##STR00025## [0114] R.sup.a, R.sup.b and R.sup.c are each
independently alkyl, cycloalkyl, aryl, heterocyclyl, heteroaryl,
alkylcycloalkyl, alkylaryl, alkylheterocyclyl or alkylheteroaryl;
[0115] R, R.sup.1, R.sup.2 and R.sup.3 are each independently H,
alkyl, cycloalkyl, aryl, heterocyclyl, heteroaryl, alkylcycloalkyl,
alkylaryl, alkylheterocyclyl or alkylheteroaryl; [0116] X.sup.1
represents zero, one, two or three substituents and X.sup.2
represents zero, one, two, three or four substituents, wherein each
such substituent is independently selected from the group
consisting of alkyl, cycloalkyl, aryl, heterocyclyl, heteroaryl,
alkylcycloalkyl, alkylaryl, alkylheterocyclyl, alkylheteroaryl,
halogen, nitro, amide, ester, cyano, alkoxy, alkylamino, arylamino,
an inorganic support and a polymeric moiety.
[0117] In some embodiments, the borane derivative is represented by
the structure of any of formulae D, E, G and H. Each possibility
represents a separate embodiment of the present invention. It is
noted that compounds D and E are borane derivatives of the
Ruthenium complex of formula A1 as described hereinabove.
##STR00026##
[0118] In some other embodiments, the borane derivative is
represented by the structure of any of formulae 2', 4', 6' and 8'.
Each possibility represents a separate embodiment of the present
invention.
##STR00027##
[0119] The present invention further provides processes for
preparing the novel boronated derivatives of Ruthenium based
catalytic complexes. Thus, in one embodiment, the present invention
provides a process for preparing a Ruthenium complex represented by
the structure of formula D
##STR00028##
by reacting sodium borohydride (NaBH.sub.4) with a precursor of
formula A2
##STR00029##
[0120] wherein [0121] L.sup.1 is selected from the group consisting
of phosphine (PR.sup.aR.sup.b), phosphite P(OR.sup.a)(OR.sup.b),
phosphinite P(OR.sup.a)(R.sup.b), amine (NR.sup.aR.sup.b), imine,
oxazoline, sulfide (SR.sup.a), sulfoxide (S(.dbd.O)R.sup.a),
heteroaryl containing at least one heteroatom selected from
nitrogen and sulfur; arsine (AsR.sup.aR.sup.b), stibine
(SbR.sup.aR.sup.b) and a N-heterocyclic carbene represented by the
structures:
[0121] ##STR00030## [0122] L.sup.2 is a mono-dentate two-electron
donor selected from the group consisting of CO,
PR.sup.aR.sup.bR.sup.c, P(OR.sup.a)(OR.sup.b)(OR.sup.c), NO.sup.+,
AsR.sup.aR.sup.bR.sup.c, SbR.sup.aR.sup.bR.sup.c, SR.sup.aR.sup.b,
nitrile (RCN), isonitrile (RNC), N.sub.2, PF.sub.3, CS, heteroaryl,
tetrahydrothiophene, alkene and alkyne; [0123] L.sup.3 is absent or
is L.sup.2; [0124] Y and Z are each independently halogen,
OCOCF.sub.3, OSO.sub.2R or OSO.sub.2CF.sub.3, [0125] R.sup.a,
R.sup.b and R.sup.c are each independently alkyl, cycloalkyl, aryl,
heterocyclyl, heteroaryl, alkylcycloalkyl, alkylaryl,
alkylheterocyclyl or alkylheteroaryl; [0126] R, R.sup.1, R.sup.2
and R.sup.3 are each independently H, alkyl, cycloalkyl, aryl,
heterocyclyl, heteroaryl, alkylcycloalkyl, alkylaryl,
alkylheterocyclyl or alkylheteroaryl; [0127] X.sup.1 represents
zero, one, two or three substituents and X.sup.2 represents zero,
one, two, three or four substituents, wherein each such substituent
is independently selected from the group consisting of alkyl,
cycloalkyl, aryl, heterocyclyl, heteroaryl, alkylcycloalkyl,
alkylaryl, alkylheterocyclyl, alkylheteroaryl, halogen, nitro,
amide, ester, cyano, alkoxy, alkylamino, arylamino, an inorganic
support and a polymeric moiety.
[0128] In another embodiment, the present invention provides a
process for preparing a borane derivative of a Ruthenium complex
represented by the structure of formula F
##STR00031##
the process comprising the step of reacting sodium borohydride
(NaBH.sub.4) with a precursor of formula
##STR00032##
[0129] wherein [0130] L.sup.1 is selected from the group consisting
of phosphine (PR.sup.aR.sup.b), phosphite P(OR.sup.a)(OR.sup.b),
phosphinite P(OR.sup.a)(R.sup.b), amine (NR.sup.aR.sup.b), imine,
oxazoline, sulfide (SR.sup.a), sulfoxide (S(.dbd.O)R.sup.a),
heteroaryl containing at least one heteroatom selected from
nitrogen and sulfur; arsine (AsR.sup.aR.sup.b), stibine
(SbR.sup.aR.sup.b) and a N-heterocyclic carbene represented by the
structures:
[0130] ##STR00033## [0131] L.sup.2 is a mono-dentate two-electron
donor selected from the group consisting of CO,
PR.sup.aR.sup.bR.sup.c, P(OR.sup.a)(OR.sup.b)(OR.sup.c), NO.sup.+,
AsR.sup.aR.sup.bR.sup.c, SbR.sup.aR.sup.bR.sup.c, SR.sup.aR.sup.b,
nitrile (RCN), isonitrile (RNC), N.sub.2, PF.sub.3, CS, heteroaryl,
tetrahydrothiophene, alkene and alkyne; [0132] L.sup.3 is absent or
is L.sup.2; [0133] L.sup.4 is --CH.sub.2-L.sup.1- or a group of the
formula:
[0133] ##STR00034## [0134] Y and Z are each independently halogen,
OCOCF.sub.3, OSO.sub.2R or OSO.sub.2CF.sub.3, R.sup.a, R.sup.b and
R.sup.c are each independently alkyl, cycloalkyl, aryl,
heterocyclyl, heteroaryl, alkylcycloalkyl, alkylaryl,
alkylheterocyclyl or alkylheteroaryl; [0135] R, R.sup.1, R.sup.2
and R.sup.3 are each independently H, alkyl, cycloalkyl, aryl,
heterocyclyl, heteroaryl, alkylcycloalkyl, alkylaryl,
alkylheterocyclyl or alkylheteroaryl; [0136] X.sup.1 represents
zero, one, two or three substituents and X.sup.2 represents zero,
one, two, three or four substituents, wherein each such substituent
is independently selected from the group consisting of alkyl,
cycloalkyl, aryl, heterocyclyl, heteroaryl, alkylcycloalkyl,
alkylaryl, alkylheterocyclyl, alkylheteroaryl, halogen, nitro,
amide, ester, cyano, alkoxy, alkylamino, arylamino, an inorganic
support and a polymeric moiety.
CHEMICAL DEFINITIONS
[0137] As used herein, the term alkyl, used alone or as part of
another group, refers, in one embodiment, to a "C.sub.1 to C.sub.12
alkyl" and denotes linear and branched, saturated or unsaturated
(e.g., alkenyl, alkynyl) groups, the latter only when the number of
carbon atoms in the alkyl chain is greater than or equal to two,
and can contain mixed structures. Non-limiting examples are alkyl
groups containing from 1 to 6 carbon atoms (C.sub.1 to C.sub.6
alkyls), or alkyl groups containing from 1 to 4 carbon atoms
(C.sub.1 to C.sub.4 alkyls). Examples of saturated alkyl groups
include, but are not limited to, methyl, ethyl, n-propyl,
isopropyl, n-butyl, iso-butyl, sec-butyl, tert-butyl, amyl,
tert-amyl, hexyl, Examples of alkenyl groups include, but are not
limited to, vinyl, allyl, butenyl and the like. Examples of alkynyl
groups include, but are not limited to, ethynyl, propynyl and the
like. Similarly, the term "C.sub.1 to C.sub.12 alkylene" denotes a
bivalent radical of 1 to 12 carbons.
[0138] The alkyl group can be unsubstituted, or substituted with
one or more substituents selected from the group consisting of
halogen, hydroxy, alkoxy, aryloxy, alkylaryloxy, heteroaryloxy,
oxo, cycloalkyl, phenyl, heteroaryls, heterocyclyl, naphthyl,
amino, alkylamino, arylamino, heteroarylamino, dialkylamino,
diarylamino, alkylarylamino, alkylheteroarylamino,
arylheteroarylamino, acyl, acyloxy, nitro, carboxy, carbamoyl,
carboxamide, cyano, sulfonyl, sulfonylamino, sulfinyl,
sulfinylamino, thiol, alkylthio, arylthio, or alkylsulfonyl groups.
Any substituents can be unsubstituted or further substituted with
any one of these aforementioned substituents. By way of
illustration, an "alkoxyalkyl" is an alkyl that is substituted with
an alkoxy group.
[0139] The term "cycloalkyl" used herein alone or as part of
another group, refers to a "C.sub.3 to C.sub.8 cycloalkyl" and
denotes any unsaturated or unsaturated (e.g., cycloalkenyl,
cycloalkynyl) monocyclic or polycyclic group. Nonlimiting examples
of cycloalkyl groups are cyclopropyl, cyclobutyl, cyclopentyl,
cyclohexyl or cycloheptyl, Examples or cycloalkenyl groups include
cyclopentenyl, cyclohexenyl and the like. The cycloalkyl group can
be unsubstituted or substituted with any one or more of the
substituents defined above for alkyl. Similarly, the term
"cycloalkylene" means a bivalent cycloalkyl, as defined above,
where the cycloalkyl radical is bonded at two positions connecting
together two separate additional groups.
[0140] The term "aryl" used herein alone or as part of another
group denotes an aromatic ring system containing from 6-14 ring
carbon atoms. The aryl ring can be a monocyclic, bicyclic,
tricyclic and the like. Non-limiting examples of aryl groups are
phenyl, naphthyl including 1-naphthyl and 2-naphthyl, and the like.
The aryl group can be unsubstituted or substituted through
available carbon atoms with one or more groups defined hereinabove
for alkyl. An alkylaryl group denotes an alkyl group bonded to an
aryl group (e.g., benzyl).
[0141] The term "heteroaryl" used herein alone or as part of
another group denotes a heteroaromatic system containing at least
one heteroatom ring atom selected from nitrogen, sulfur and oxygen.
The heteroaryl contains 5 or more ring atoms. The heteroaryl group
can be monocyclic, bicyclic, tricyclic and the like. Also included
in this expression are the benzoheterocyclic rings. If nitrogen is
a ring atom, the present invention also contemplates the N-oxides
of the nitrogen containing heteroaryls. Nonlimiting examples of
heteroaryls include thienyl, benzothienyl, 1-naphthothienyl,
thianthrenyl, furyl, benzofuryl, pyrrolyl, imidazolyl, pyrazolyl,
pyridyl, pyrazinyl, pyrimidinyl, pyridazinyl, indolyl, isoindolyl,
indazolyl, purinyl, isoquinolyl, quinolyl, naphthyridinyl,
quinoxalinyl, quinazolinyl, cinnolinyl, pteridinyl, carbolinyl,
thiazolyl, oxazolyl, isothiazolyl, isoxazolyl and the like. The
heteroaryl group can be unsubstituted or substituted through
available atoms with one or more groups defined hereinabove for
alkyl.
[0142] The term "heterocyclic ring" or "heterocyclyl" used herein
alone or as part of another group denotes a five-membered to
eight-membered rings that have 1 to 4 heteroatoms, such as oxygen,
sulfur and/or nitrogen. These five-membered to eight-membered rings
can be saturated, fully unsaturated or partially unsaturated.
Non-limiting examples of heterocyclic rings include piperidinyl,
piperidinyl, pyrrolidinyl pyrrolinyl, pyrazolinyl, pyrazolidinyl,
piperidinyl, morpholinyl, thiomorpholinyl, pyranyl, thiopyranyl,
piperazinyl, indolinyl, dihydrofuranyl, tetrahydrofuranyl,
dihydrothiophenyl, tetrahydrothiophenyl, dihydropyranyl,
tetrahydropyranyl, and the like. The heterocyclyl group can be
unsubstituted or substituted through available atoms with one or
more groups defined hereinabove for alkyl.
[0143] The inorganic support which is attached to the bipyridine
ring can be, for example, silica, silica gel, glass, glass fibers,
titania, zirconia, alumina and nickel oxide.
[0144] The polymer which is attached to the bipyridine pyridine
ring can be, for example, selected from polyolefins, polyamides,
polyethylene terephthalate, polyvinylchloride,
polyvinylidenechloride, polystyrene, polymethracrylate, natural
rubber, polyisoprene, butadiene-styrene random copolymers,
butadiene acrylonitrile copolymers, polycarbonate, polyacetal,
polyphenylenesulfide, cyclo-olefin copolymers,
styrene-acrylonitrile copolymers, ABS, styrene-maleic anhydride
copolymers, chloroprene polymers, isobutylene copolymers,
polystyrene, polyethylene, polypropylene, and the like.
[0145] The term "anion" as used herein refers to any moiety or
group bearing a negative charge. Examples of anionic moieties
include, but are not limited to halogen (e.g., F, Cl, Br, I),
OCOR', OCOCF.sub.3, OSO.sub.2R', OSO.sub.2CF.sub.3, BF.sub.4,
PF.sub.6, SbF.sub.6, BR.sub.4, ClO.sub.4, AlCl.sub.4, CN, OH, OR'
or NR'.sub.2 wherein R' is selected from alkyl, cycloalkyl, aryl,
alkylaryl, heterocyclyl and heteroaryl, wherein each of the alkyl,
cycloalkyl, aryl, alkylaryl, heterocyclyl and heteroaryl is as
defined above.
Novel Processes
[0146] The present invention further provides various processes
which utilize the Ruthenium complexes of the present invention as
catalysts.
[0147] In general, the processes of the present invention can be
conducted in the absence or in the presence of a solvent. When a
solvent is present, it can be an organic solvent, including but not
limited to benzene, toluene, o-, m- or p-xylene mesitylene
(1,3,5-trimethyl benzene), dioxane, THF, DME, anisole and
cyclohexane.
[0148] The stoichiometric ratios of reagents can vary, and depend
on the particular alcohol amine, amide, ester etc., being used, as
well as solvent used for the reaction. The reactions of the present
invention can be performed for as long as needed so as to effect
desired transformation, for example 1 hr to 24 hr or longer than 24
hr. The temperature range can vary from room temperature to heated
conditions, for example up to 200.degree. C.
[0149] 1. Hydrogenation of Amides to Alcohols and Amines
[0150] The present invention provides a process for hydrogenating
amides (including polyamides and polypeptides) by reacting the
amide with molecular hydrogen (H.sub.2) in the presence of the
Ruthenium complexes of the present invention to generate the
corresponding alcohol and amine. As contemplated herein, the
inventors have discovered a novel process for converting amides to
alcohols and amines in high yields and high turnover numbers. This
reaction is catalyzed by a Ruthenium complex, which is represented
by anyone of formulae A1, A2, A3, B1, B2, C1, C2, 3, 4, 7 and 9 or
any other Ruthenium complex covered by such formulae. In addition,
this reaction is catalyzed by any of the Ruthenium complexes
described in US Patent publication US 2009/0112005, the contents of
which are incorporated by reference herein. The compounds of US
2009/0112005 are pyridine based derivatives represented by the
structure of formula A1', A2' and A3'. Compounds which catalyze
hydrogenation of amides to alcohols and amines are those wherein
L.sub.1 is N(R).sub.2:
##STR00035##
[0151] wherein [0152] L.sub.1 is N(R).sub.2, [0153] L.sub.2 is
selected from the group consisting of nucleophilic carbene
(:C(R).sub.2), P(R).sub.2, P(OR).sub.2, N(R).sub.2, imine, SR, SH,
S(.dbd.O)R, heteroaryl wherein the heteroatom is selected from
nitrogen and sulfur, As(R).sub.2, Sb(R).sub.2 and an N-heretocyclic
carbene represented by the structure:
[0153] ##STR00036## [0154] each of R, R.sup.2 and R.sup.3 are
independently selected from the group consisting of alkyl,
cycloalkyl, aryl, alkylaryl, heterocyclyl and heteroaryl; [0155]
L.sub.3 is a mono-dentate two-electron donor selected from the
group consisting of CO, P(R).sub.3, P(OR).sub.3, NO.sup.+,
As(R).sub.3, Sb(R).sub.3, S(R).sub.2, nitrile (RCN) and isonitrile
(RNC) wherein R is as defined above; [0156] L.sub.4 is absent or is
L.sub.3; [0157] Y and Z are each independently H or an anionic
ligand selected from the group consisting of halogen, OCOR,
OCOCF.sub.3, OSO.sub.2R, OSO.sub.2CF.sub.3, CN, OH, OR, N(R).sub.2,
RS and SH; wherein R is as defined above; [0158] X represents zero,
one, two or three substituents selected from the group consisting
of alkyl, aryl, halogen, nitro, amide, ester, cyano, alkoxy,
cycloalkyl, alkylaryl, heterocyclyl, heteroaryl, an inorganic
support and a polymeric moiety; and [0159] anion represents a group
bearing a single negative charge.
[0160] One embodiment of such compounds is a pincer complex
represented by the structure of formula 1 (FIG. 1A).
[0161] Depending on the complex being used, the reaction permits
the optional use of one or more equivalents of a base.
[0162] The process of the invention, i.e., the direct catalytic
conversion of amides to alcohols and amides is illustrated in
Scheme 4. This novel, environmentally benign reaction can be used
to prepare alcohols and amines from any type of amide, with high
atom economy and in some embodiments no stoichiometric activating
agents, thus generating no waste. Thus, in one embodiment, the
present invention provides a process for hydrogenating an amide
represented by the formula R.sup.4C(.dbd.O)--N--R.sup.5R.sup.5' to
an alcohol of formula R.sup.4CH.sub.2OH and amine of formula
R.sup.5R.sup.5'NH:
##STR00037##
wherein R.sup.4, R.sup.5 and R.sup.5' are each independently
selected from the group consisting of H, an unsubstituted or
substituted alkyl, alkoxyalkyl, cycloalkyl, aryl, alkylaryl,
heterocyclyl and heteroaryl.
[0163] A variety of amides can be used in the process of the
invention. In some embodiments, the amide is selected from the
group consisting of N-benzyl-2-methoxyacetamide,
N-hexyl-2-methoxyacetamide, N-hexyl-3-methyloxetane-3-carboxamide,
N-hexyl-2-furanylcarboxamide, N-benzylbenzamide, N-ethylacetamide,
N-methylpropionamide, N-cyclohexyl-2-methoxyacetamide,
N-phenylacetamide, N-phenylhexylamide, 2-methoxy-N-phenylacetamide,
N-phenylbenzamide, Ethylenediamine-N,N'-(2-methoxyacetamide),
N-hexanoylmorpholine, N-butanoylmorpholine,
N-2-metoxyacetylpyrrolidine, N-formylmorpholine,
N,N-dimethylformamide, N,N-diethylbenzamide, benzamide,
4-methylbenzamide, cyclohexanecarboxamide, hexanamide, acetamide,
acrylamide and pivalamide. Each possibility represents a separate
embodiment of the present invention.
[0164] In a similar manner, cyclic amides (lactams) can be
hydrogenated to the corresponding amino alcohols. In one
embodiment, the lactam is a cyclic peptide, which can be
hydrogenated with the Ruthenium complex of the present invention to
the respective amino alcohol. In a similar manner, polyamides can
be hydrogenated to amines and alcohols, and polypeptides can be
hydrogenated to amino alcohols.
[0165] 2. Hydrogenation of Esters, Organic Carbonates, Carbamates
and Urea Derivatives
[0166] Similar to the hydrogenation of amides, the novel Ruthenium
complexes of the present invention can also catalyze the
hydrogenation of esters, hydrogenation of organic carbonates,
hydrogenation of carbamates, or hydrogenation of urea derivatives
to the corresponding amines and/or alcohols. Thus, in some
embodiments, the present invention further provides a process for
hydrogenating an ester, organic carbonate, carbamate or urea
derivative with molecular hydrogen (H.sub.2) in the presence of the
Ruthenium complex of the present invention. As contemplated herein,
the inventors have discovered a novel process for converting esters
(e.g., formate esters), organic carbonates, carbamates and/or urea
derivatives to alcohols and/or amines in high yields and high
turnover numbers. This reaction is catalyzed by a Ruthenium
complex, which is represented by anyone of formulae A1, A2, A3, B1,
B2, C1, C2, 3, 4, 7 and 9 or any other Ruthenium complex covered by
such formulae. These reactions are also catalyzed by the
borohydride complexes described herein, such as complexes D, E, F,
G and H, and compounds 2', 4', 6' and 8'. Currently preferred
complexes for hydrogenation of organic carbonates, carbamates and
urea derivatives are Ruthenium complexes which are represented by
anyone of formulae A1, A2, A3, B1, B2, C1, C2, 3, 4, 7 and 9. In
some preferred embodiments, hydrogenation of esters is catalyzed by
the borohydride complexes described herein, such as complexes D, E,
F, G and H, and compounds 2', 4', 6' and 8'. Again, depending on
the complex being used, the reaction permits the optional use of
one or more equivalents of a base.
[0167] In other embodiments, the hydrogenation of organic
carbonates, carbamates and urea derivatives can be catalyzed by any
of the Ruthenium complexes described in US Patent publication US
2009/0112005, the contents of which are incorporated by reference
herein. Examples of such compounds are compounds of formula A1',
A2' and A3' wherein L.sub.1 is N(R).sub.2, as described above with
respect to processes for hydrogenation of amides to amines and
alcohols.
[0168] One embodiment of such compounds is a pincer complex
represented by the structure of formula 1 (FIG. 1A).
[0169] One embodiment of the process of the invention. i.e., the
direct catalytic conversion of esters to alcohols, is illustrated
in Scheme 5A, whereby an ester represented by the formula
R.sup.6C(.dbd.O)--OR.sup.7 is hydrogenated to the corresponding
alcohol or alcohols:
##STR00038##
[0170] wherein R.sup.6 is selected from the group consisting of H,
an unsubstituted or substituted alkyl, alkoxyalkyl, cycloalkyl,
aryl, alkylaryl, heterocyclyl and heteroaryl; and R.sup.7 is
selected from the group consisting of an unsubstituted or
substituted alkyl, alkoxyalkyl, cycloalkyl, aryl, alkylaryl,
heterocyclyl and heteroaryl.
[0171] It is apparent to a person of skill in the art that when the
ester is symmetric (i.e., R.sup.6=R.sup.7), the reaction yields two
equivalents of the same alcohol. However, when the ester is
asymmetric (i.e., R.sup.6 is different from R.sup.7), the reaction
yields a mixture of two alcohols.
[0172] In one embodiment, R.sup.6 is H and the process comprises
hydrogenating a formate ester of formula H--C(.dbd.O)--OR.sup.7 to
methanol and an alcohol of formula R.sup.7--OH.
[0173] A variety of esters can be used in the process of the
invention. In some embodiments, the ester is selected from the
group consisting of hexyl hexanoate, butyl butyrate, methyl
formate, ethyl formate, propyl formate and butyl formate. In other
embodiments, the ester is a cyclic ester (a lactone). In yet other
embodiments, the ester is a cyclic di-ester (di-lactone). In yet
other embodiments, the ester is a biomass-derived cyclic di-ester
(di-lactone) such as, but not limited to glycolide or lactide. In
yet another embodiment, the ester is polyester. Each possibility
represents a separate embodiment of the present invention.
[0174] Catalytic homogeneous hydrogenation of cyclic di-esters
(di-lactone), specifically glycolide and lactide to the
corresponding 1,2-diols (vicinal diols) is of significant interest
conceptually and practically, since these compounds are produced
from biomass sources such as glycolic acid and lactic acid
respectively via self-esterification, and their efficient
hydrogenation can provide an alternative, mild approach to the
indirect transformation of biomass resources to important synthetic
building blocks. As contemplated herein, the unprecedented,
environmentally benign, atom-economical route for the synthesis of
propylene glycol and ethylene glycol are efficiently catalyzed by
bipyridine based PNN-Ru(II) dearomatized pincer complex of formula
(1), as well as other Ruthenium complexes as described herein.
These catalytic reactions proceed under neutral homogeneous
conditions, at mild temperatures and mild hydrogen pressures. The
optical purity of a chiral diol is unaffected during the
hydrogenation reactions.
[0175] The process of lactone or di-lactone hydrogenation can be
catalyzed by the same complexes described above with respect to
hydrogenation of esters to alcohols.
##STR00039##
[0176] wherein R.sup.6 is as described above.
[0177] A variety of cyclic di-esters (di-lactones) can be used in
the process of the invention. In some embodiments, the ester is a
biomass-derived cyclic di-ester (di-lactone) such as, but not
limited to glycolide or lactide. Each possibility represents a
separate embodiment of the present invention.
[0178] Another embodiment of the process of the invention, i.e.,
the direct catalytic hydrogenation of organic carbonates, is
illustrated in Scheme 6, whereby a carbonate represented by the
formula R.sup.8O--C(.dbd.O)--OR.sup.8' is hydrogenated to the
corresponding alcohols(s) and methanol:
##STR00040##
[0179] wherein R.sup.8 and R.sup.8' are the same or different and
are selected from the group consisting of an unsubstituted or
substituted alkyl, alkoxyalkyl, cycloalkyl, aryl, alkylaryl,
heterocyclyl and heteroaryl.
[0180] It is apparent to a person of skill in the art that when the
organic carbonate is symmetric (i.e., R.sup.8=R.sup.8') the
reaction yields two equivalents of the same alcohol, and one
equivalent of methanol. However, when the organic carbonate is
asymmetric (i.e., R.sup.8 is different from R.sup.8'), the reaction
yields a mixture of two alcohols, and methanol.
[0181] A variety of organic carbonates can be used in the process
of the invention. In some embodiments, the carbonate is dimethyl
carbonate, diethyl carbonate, dipropyl carbonate or dibutyl
carbonate. In another embodiment, the carbonate is a polycarbonate,
such as polyethylene carbonate or polypropylene carbonate. Each
possibility represents a separate embodiment of the present
invention.
[0182] Another embodiment of the process of the present invention,
i.e., the direct catalytic hydrogenation of carbamates, is
illustrated in Scheme 7A, whereby a carbamate represented by the
formula R.sup.9O--C(.dbd.O)--NHR.sup.10 is hydrogenated to the
corresponding amine, alcohol and methanol:
##STR00041##
[0183] wherein R.sup.9 is selected from the group consisting of an
unsubstituted or substituted alkyl, alkoxyalkyl, cycloalkyl, aryl,
alkylaryl, heterocyclyl and heteroaryl; and R.sup.10 is selected
from the group consisting of H or an unsubstituted or substituted
alkyl, alkoxyalkyl, cycloalkyl, aryl, alkylaryl, heterocyclyl and
heteroaryl.
[0184] A variety of organic carbamates can be used in the process
of the invention. In some embodiments, the carbamate is methyl
benzylcarbamate or methyl 4-methoxybenzylcarbamate. In another
embodiment, the carbamate is a polycarbamate. Each possibility
represents a separate embodiment of the present invention.
[0185] Another embodiment of the process of the present invention,
i.e., the direct catalytic hydrogenation of urea derivatives, is
illustrated in Scheme 7B, whereby a urea derivative is hydrogenated
to the corresponding amine(s) and methanol:
##STR00042##
[0186] wherein each of R.sup.9a and R.sup.10a, which may be the
same or different, is selected from the group consisting of an
unsubstituted or substituted alkyl, alkoxyalkyl, cycloalkyl, aryl,
alkylaryl, and heterocyclyl, and each of R.sup.9 and R.sup.10b,
which may be the same or different, is selected from the group
consisting of H, an unsubstituted or substituted alkyl,
alkoxyalkyl, cycloalkyl, aryl, alkylaryl, and heterocyclyl.
Alternatively, at least one of R.sup.9a and R.sup.10a, and/or
R.sup.9b and R.sup.10b together with the nitrogen to which they are
attached form a heterocyclic ring.
[0187] A variety of symmetrical (R.sup.9a=R.sup.10a,
R.sup.9b=R.sup.10b) and asymmetrical (R.sup.9a.noteq.R.sup.10a,
R.sup.9b.noteq.R.sup.10b) urea derivatives can be used in the
process of the invention, with each possibility representing a
separate embodiment of the present invention. In some embodiments,
the urea derivative is 1,3-dimethylurea, and the product of the
reaction is methanol and two molecules of methylamine. In another
embodiment, the urea derivative is selected from the group
consisting of 1,3-dipropylurea, 1,3-dihexylurea,
1,3-bis(2-methoxyethyl)urea, 1,3-dicyclohexylurea,
1,3-dibenzylurea, 1,3-bis(4-methylbenzyl)urea,
1,3-bis(4-methylbenzyl)urea, 1,3-diphenylurea,
1,3-bis(4-(tert-butyl)phenyl)urea, 1,1,3,3-tetramethylurea, and
di(piperidin-1-yl)methanone. Polyurea derivatives can also be
hydrogenated in a similar manner. Each possibility represents a
separate embodiment of the present invention.
[0188] 3. Dehydrogenative Coupling of Alcohols and Amines with
Liberation of H.sub.2 to Form Amides or of Beta-Amino Alcohols to
Form Pyrazines:
[0189] The present invention further provides a process for
preparing amides, by reacting an amine and an alcohol in the
presence of a Ruthenium complex, to generate the amide compound and
molecular hydrogen (H.sub.2). As contemplated herein, the inventors
have further discovered a novel process for preparing amides in
which primary and secondary amines are directly acylated by
equimolar amounts of alcohols to produce amides and molecular
hydrogen in high yields and high turnover numbers. This reaction is
catalyzed by a Ruthenium complex or a boronated complex thereof,
which is represented by anyone of formulae A1, A2, A3, B1, C1, B2,
C2, D, E, F (when complex F is used and L is --CH.sub.2-L.sup.1,
L.sup.1 is preferably NR.sup.aR.sup.b), H, 3, 4, 7, 9, 4' and 8',
or any other Ruthenium complex or their boronated complexes covered
by such formulae. Depending on the complex being used, the reaction
permits the optional use of one or more equivalents of a base.
[0190] Use of diamines or dialcohols in the reaction leads to
diamides, whereas when diamines and dialcohols are used together,
the process results in a polyamide. Furthermore, reactions of
amino-alcohols results in cyclic amides (lactams). For example,
reaction of H.sub.2N(CR.sup.1R.sup.2).sub.nCH.sub.2OH results in
lactams for n=4, 5 or 6, such as caprolactam for n=6 and
R.sup.1=R.sup.2=H. For n>6, the reaction typically results in
polymers. In another embodiment, when amino alcohols such as
R--CH(NH.sub.2)CH.sub.2OH are used, peptides or polypeptides are
formed (e.g., dehydrogenation of alaninol with the Ruthenium
complexes of the present invention results in polyalanine).
[0191] The process of the invention, i.e., the direct catalytic
conversion of alcohols and amines into amides and dihydrogen is
illustrated in Scheme 8A. In accordance with this process, an amine
represented by formula R.sup.11R.sup.11'NH is reacted with an
alcohol represented by the formula R.sup.12CH.sub.2OH to generate
an amide represented by the structure
R.sup.12--C(.dbd.O)--NR.sup.11R.sup.11'. This novel,
environmentally benign reaction can be used to produce various
amides from very simple substrates, with high atom economy and in
some embodiments no stoichiometric activating agents, thus
generating no waste.
##STR00043##
wherein R.sup.10, R.sup.11 and R.sup.12 are each independently
selected from the group consisting of H an unsubstituted or
substituted alkyl, alkoxyalkyl, cycloalkyl, aryl, alkylaryl,
heterocyclyl and heteroaryl, wherein R.sup.10, R.sup.11 and
R.sup.12 can be the same or different from each other.
[0192] A variety of alcohols can be used in the process of the
invention. In some embodiments, the alcohol is selected from the
group consisting of methanol, ethanol, propanol, butanol, pentanol,
hexanol, 2-methoxyethanol, and 2-methyl-1-butanol. Each possibility
represents a separate embodiment of the present invention.
[0193] A variety of primary and secondary amines (as well as
ammonia) may be used in the process of the invention. In some
embodiments, the amine is selected from the group consisting of
benzylamine, 1-hexylamine, 1-pentylamine, 1-(2-furyl)methylamine,
aniline, morpholine, pyrrolidine, 2-methylhexylamine, and
cyclohexylamine. Each possibility represents a separate embodiment
of the present invention.
[0194] In another embodiment, the process of the invention can also
be applied to bis-acylation reactions with diamines. Upon reacting
alcohols and diamines, the corresponding bis-amides are produced in
high yields. In some embodiments, the diamine is ethylenediamine,
diethylenetriamine or 1,6-diaminohexane.
[0195] Similarly, when diamines and dialcohols are used, polyamides
or peptides are obtained. The applicants have surprisingly
discovered that Ruthenium complexes catalyze the synthesis of
polyamides directly from diols and diamines. This polyamidation
reaction is general, environmentally benign and atom economical. It
proceeds under neutral reaction conditions without the use of
activators, condensing agents or other additives. A preferable
solvent for use in this reaction is 1,4-dioxane, however other
solvents can be used as apparent to a person of skill in the art.
Moreover, these methods produce H.sub.2 as the only byproduct
(Scheme 8B):
##STR00044##
[0196] A variety of dialcohols can be used for this reaction,
non-limiting examples of which include hexane-1,2-diol,
octane-1,8-diol, 1,3-phenylenedimethanol,
(5-methoxy-1,3-phenylene)dimethanol, 1,4-phenylenedimethanol,
pyridine-2,6-diyldimethanol, pentane-1,5-diol,
cyclohexane-1,4-diyldimethanol, and
(5-(hexyloxy)-1,3-phenylene)dimethanol.
[0197] A variety of diamines can be used for this reaction,
non-limiting examples of which include hexane-1,6-diamine,
ethane-1,2-diamine, 1,3-phenylenedimethanamine, and
1,4-phenylenedimethanamine. The reaction between the amine and
alcohol can be inter-molecular (i.e., the amine and the alcohol are
present in separate molecules). Alternatively, the reaction between
the amine and alcohol can be intra-molecular. i.e., the amine and
alcohol functionalities can be present in the same molecule,
resulting in intra-molecular cyclization to generate a lactam.
[0198] In addition, the aforementioned amidation and polyamidation
reactions are also catalyzed by the Ruthenium complexes described
in US Patent publication US 2009/0112005, in particular Ruthenium
complexes in which L.sub.1 is N(R).sub.2, as described above for
the reciprocal hydrogenation reactions of amides to alcohols and
amines. One embodiment of such compounds is a pincer complex
represented by the structure of formula 1 (FIG. 1A).
[0199] In some embodiments, beta-amino alcohols can be
dehydrogenated in the presence of Ruthenium complexes to form
cyclic dipeptides. Such reactions are catalyzed by a Ruthenium
complex or a boronated complex thereof, which is represented by
anyone of formulae A1, A2, A3, B1, C1, B2, C2, D, E, F (for complex
F preferably L.sub.4 is CH.sub.2NR.sup.aR.sup.b), H, 3, 4, 7, 9, 4'
and 8', or any other Ruthenium complex or their boronated complexes
covered by such formulae. Alternatively, such reactions can also be
catalyzed by the Ruthenium complexes described in US Patent
publication US 2009/0112005, in particular Ruthenium complexes in
which L.sub.1 is N(R).sub.2, as described above for the reciprocal
hydrogenation reactions of amides to alcohols and amines.
[0200] Preparation of polypeptides or cyclic peptides by
dehydrogenation of beta-amino alcohols, catalyzed by the Ruthenium
complexes described in US Patent publication US 2009/0112005,
namely compounds A1', A2' or A3' in which L, is N(R).sub.2, has not
previously been described, and constitutes another embodiment of
the present invention.
[0201] In another embodiment, beta-amino alcohols can be
dehydrogenated to form pyrazines in the presence of Ruthenium
complexes. Ruthenium complexes which catalyze the dehydrogenation
of beta-amino alcohols to pyrazines are those which contain two
phosphinine ligands or N-heterocyclic carbene ligands. Examples of
such complexes are described in US Patent publication US
2009/0112005, in particular Ruthenium complexes of Formulae A1',
A2' and A3', and any Ruthenium complexes covered by such Formulae,
wherein the Ruthenium complex comprises two phosphine (P(R).sub.2)
ligands or two N-heterocyclic carbene ligands:
##STR00045##
[0202] wherein [0203] L.sub.1 and L.sub.2 are each independently
selected from the group consisting of phosphine (P(R).sub.2), and
an N-heretocyclic carbene represented by the structure:
[0203] ##STR00046## [0204] wherein each of R, R.sup.2 and R.sup.3
are independently selected from the group consisting of alkyl,
cycloalkyl, aryl, alkylaryl, heterocyclyl and heteroaryl; [0205]
L.sub.3 is a mono-dentate two-electron donor selected from the
group consisting of CO, P(R).sub.3, P(OR).sub.3, NO.sup.+,
As(R).sub.3, Sb(R).sub.3, S(R).sub.2, nitrile (RCN) and isonitrile
(RNC) wherein R is as defined above; [0206] L.sub.4 is absent or is
L.sub.3; [0207] Y and Z are each independently H or an anionic
ligand selected from the group consisting of halogen, OCOR,
OCOCF.sub.3, OSO.sub.2R, OSO.sub.2CF.sub.3, CN, OH, OR, N(R).sub.2,
RS and SH; wherein R is as defined above; [0208] X represents zero,
one, two or three substituents selected from the group consisting
of alkyl, aryl, halogen, nitro, amide, ester, cyano, alkoxy,
cycloalkyl, alkylaryl, heterocyclyl, heteroaryl, an inorganic
support and a polymeric moiety; [0209] and anion represents a group
hearing a single negative charge.
[0210] Preferably the Ruthenium complex is represented by the
structure of formula 2.
[0211] Other examples of such complexes include borohydride
complexes represented by formula F (wherein each one of L.sup.1 and
L.sup.4 contain a phosphine (PR.sup.aR.sup.b), and/or
N-heterocyclic carbene), or complexes G, 2' and 6', with each
possibility representing a separate embodiment of the present
invention. A non-limiting example of a process for pyrazine
formation is illustrated in Scheme 46 hereinbelow.
[0212] 4. Dehydrogenative Coupling of Alcohols:
[0213] The present invention further provides a process for
preparing esters by coupling of alcohols in the presence of a
Ruthenium complex, to generate the ester compound and molecular
hydrogen. In one embodiment, the process involves coupling of
primary alcohols. In another embodiment, the process involves
coupling of a primary and secondary alcohol. These reactions are
catalyzed by a Ruthenium complex or a boronated complex thereof,
which is represented by anyone of formulae A1, A2, A3, B1, C1, B2,
C2, D, E, F, G, H, 3, 4, 7, 9, 2', 4', 6' and 8' or any other
Ruthenium complex or their boronated complexes covered by such
formulae. Depending on the complex being used, the reaction permits
the optional use of one or more equivalents of a base. Use of
dialcohols in the reaction leads to polyesters or to lactones.
[0214] In one embodiment, the process of the invention, i.e., the
direct catalytic coupling of primary alcohols into esters and
dihydrogen is illustrated in Scheme 9A. In accordance with this
process, two equivalents of a primary alcohol represented by
formula R.sup.13CH.sub.2OH are converted to an ester by the
structure R.sup.13--C(.dbd.O)--OCH.sub.2R.sup.13. This novel,
environmentally benign reaction, can be used to produce various
esters from very simple substrates, with high atom economy and in
some embodiments no stoichiometric activating agents, thus
generating no waste.
##STR00047##
[0215] In another embodiment, the process of the invention involves
the catalytic coupling of a primary alcohol and a secondary
alcohol, as illustrated in Scheme 9B.
##STR00048##
wherein R.sup.13, R.sup.13' and R.sup.13'' are each independently
selected from the group consisting of H, an unsubstituted or
substituted alkyl, alkoxyalkyl, cycloalkyl, aryl, alkylaryl,
heterocyclyl and heteroaryl.
[0216] When primary alcohols are used, the process of the invention
contemplates symmetric coupling of alcohols to yield symmetric
esters (i.e., 2 equivalents of the same alcohol are coupled).
However, the present invention further contemplates the generation
of asymmetric esters by coupling of different alcohols. In
accordance with this embodiment, a first primary alcohol
represented by formula R.sup.13CH.sub.2OH is reacted with a second
alcohol represented by formula R.sup.13'CH.sub.2OH so as to
generate an ester by the structure R.sup.13--C(.dbd.O)--O
CH.sub.2R.sup.13' or an ester of formula
R.sup.13'--C(.dbd.O)--OCH.sub.2R.sup.13, as illustrated in Scheme
10:
##STR00049##
wherein R.sup.13 and R.sup.13' are the same or different from each
other and are each independently selected is from the group
consisting of H, an unsubstituted or substituted alkyl,
alkoxyalkyl, cycloalkyl, aryl, alkylaryl, heterocyclyl and
heteroaryl.
[0217] A variety of alcohols can be used in the process of the
invention. In some embodiments, the alcohol is selected from the
group consisting of methanol, ethanol propanol, butanol, pentanol,
hexanol, 2-methoxyethanol, 2-methyl-1-butanol, benzyl alcohol,
1-phenylethanol and cyclohexane methanol. Each possibility
represents a separate embodiment of the present invention.
[0218] In another embodiment, the process of the invention can also
be applied to bis-acylation reactions with dialcohols to yield
polyesters.
[0219] The reaction between the alcohols can be inter-molecular
(i.e., the two alcohols are separate molecules). Alternatively, the
reaction between the alcohols can be intra-molecular, i.e., the
alcohol functionalities can be present in the same molecule,
resulting in intra-molecular cyclization to generate a lactone. In
some embodiments, the intra-molecular dehydrogenation of diols to
generate a lactone is catalyzed by borohydride Ruthenium complexes
as described herein, for example compounds D, E, F, G, H, 2', 4',
6' and 8'. In some embodiments, the complex is a Ruthenium complex
of formula 2'. In other embodiment, the complex is a Ruthenium
complex of formula 4'. Each possibility represents a separate
embodiment of the present invention.
[0220] 5. Dehydrogenation of Secondary Alcohols:
[0221] The present invention further relates to a process for
preparing a ketone by dehydrogenation of a secondary alcohol,
comprising the step of reacting the secondary alcohol in the
presence of the Ruthenium complex which is represented by anyone of
formulae A1, A2, A3, B1, C1, B2, C2, D, E, F, G, H, 3, 4, 7, 9, 2',
4', 6' and 8' or any other Ruthenium complex or their boronated
complexes covered by such formulae, thereby generating the ketone
and molecular hydrogen.
[0222] The process of the invention, i.e., the direct catalytic
conversion of secondary alcohols into ketones and dihydrogen is
illustrated in Scheme 11A. In accordance with this process, a
secondary alcohol represented by formula R.sup.14CH(OH)R.sup.14' is
converted to a ketone represented by the structure
R.sup.14--C(.dbd.O)--R.sup.14':
##STR00050##
[0223] A variety of alcohols can be used in the process of the
invention. In some embodiments, the alcohol is selected from the
group consisting of 1-phenyl-1-ethanol, 2-hexanol, cyclohexanol and
2-propanol. Each possibility represents a separate embodiment of
the present invention.
[0224] 6. Synthesis of Amides from Esters and Alcohols
[0225] The present invention further provides a process for
preparing amides, by reacting an amine and an ester in the presence
of a Ruthenium complex, to generate the amide compound and
molecular hydrogen (H.sub.2). As contemplated herein, the inventors
have further discovered a novel process for preparing amides in
which primary and secondary amines are directly reacted with esters
to produce amides and molecular hydrogen in high yields and high
turnover numbers. This reaction is catalyzed by a Ruthenium complex
or a boronated complex thereof, which is represented by anyone of
formulae A1, A2, A3, B1, C1, B2, C2, D, E, F (when complex F is
used and L.sup.4 is --CH.sub.2-L.sup.1, L.sup.1 is preferably
NR.sup.aR.sup.b), H, 3, 4, 7, 9, 4' and 8', or any other Ruthenium
complex or their boronated complexes covered by such formulae.
Depending on the complex being used, the reaction permits the
optional use of one or more equivalents of a base. Reactions of
esters with diamines leads to diamides.
[0226] The process of the invention, i.e., the direct catalytic
reaction of esters and amines into amides and dihydrogen is
illustrated in Scheme 11B. In accordance with this process, an
amine represented by formula R.sup.15R.sup.15'NH is reacted with an
ester represented by the formula
R.sup.16--C(.dbd.O)--OCH.sub.2R.sup.16' to generate an amide
represented by the structure
R.sup.16--C(.dbd.O)--NR.sup.15R.sup.15'. This novel,
environmentally benign reaction can be used to produce various
amides from very simple substrates, with high atom economy and in
some embodiments no stoichiometric activating agents, thus
generating no waste.
##STR00051##
wherein R.sup.15, R.sup.15', R.sup.16 and R.sup.16' are each
independently selected from the group consisting of H, an
unsubstituted or substituted alkyl, alkoxyalkyl, cycloalkyl, aryl,
alkylaryl, heterocyclyl and heteroaryl, wherein R.sup.15, R.sup.15'
and R.sup.16 can be the same or different from each other.
[0227] A variety of esters can be used in the process of the
invention. In some embodiments, the ester is selected from the
group consisting of ethyl acetate, butyl butyrate, pentyl
pentanoate and hexyl hexanoate. Each possibility represents a
separate embodiment of the present invention.
[0228] A variety of primary and secondary amines (as well as
ammonia) may be used in the process of the invention. In some
embodiments, the amine is selected from the group consisting of
pyrrolidine, morpholine, 1-methyl piperazine, piperidine,
piperazine, 1-hexylamine and p-tolylmethanamine.
[0229] In another embodiment, the process of the invention can also
be applied to bis-acylation reactions with diamines. Upon reacting
alcohols and diamines, the corresponding bis-amides are produced in
high yields.
[0230] 7. Acylation of Alcohols Using Esters with Liberation of
H.sub.2
[0231] The present invention further provides a process for
preparing esters by acylation of alcohols using esters in the
presence of a Ruthenium complex, to generate the ester compound and
molecular hydrogen. In one embodiment, the process involves
reaction of primary alcohols and esters. In another embodiment, the
process involves reaction of a secondary alcohols and esters. These
reactions are catalyzed by a Ruthenium complex or a boronated
complex thereof, which is represented by anyone of formulae A1, A2,
A3, B1, C1, B2, C2, D, E, F, G, H, 3, 4, 7, 9, 2', 4', 6' and 8' or
any other Ruthenium complex or their boronated complexes covered by
such formulae. Depending on the complex being used, the reaction
permits the optional use of one or more equivalents of a base.
[0232] In one embodiment, the process of the invention, i.e., the
direct catalytic acylation of alcohols using esters to yield an
ester and dihydrogen is illustrated in Scheme 12A. In accordance
with this process, two equivalents of a primary or secondary
alcohol represented by formula R.sup.17R.sup.17'CHOH reacts with
one equivalent an ester by the structure
R.sup.18--C(.dbd.O)--OCH.sub.2R.sup.18' as shown in Scheme 12A.
This novel, environmentally benign reaction, can be used to produce
various esters from very simple substrates, with high atom economy
and in some embodiments no stoichiometric activating agents, thus
generating no waste.
##STR00052##
wherein R.sup.17, R.sup.17', R.sup.18 and R.sup.18' are each
independently selected from the group consisting of H, an
unsubstituted or substituted alkyl, alkoxyalkyl, cycloalkyl, aryl,
alkylaryl, heterocyclyl and heteroaryl.
[0233] A variety of alcohols can be used in the process of the
invention. In some embodiments, the alcohol is selected from the
group consisting of cyclohexanol, cyclopentanol, 1-phenylethanol,
isopropanol and 3-pentanol. Each possibility represents a separate
embodiment of the present invention.
[0234] A variety of esters can be used as the starting materials.
In some embodiments, the ester is selected from the group
consisting of ethyl acetate, hexyl hexanoate, pentyl pentanoate,
butyl butyrate, ethyl butyrate and methyl hexanoate.
[0235] 8. Coupling of Alcohols with Water to Form Carboxylic Acid
with Liberation of H.sub.2
[0236] The present invention further provides a process for
preparing carboxylic acids by contacting primary alcohols with
water in the presence of a Ruthenium complex and a base, to
generate the carboxylic acid salt and molecular hydrogen and, if
desired, followed by conversion of the carboxylic acid salt to the
corresponding carboxylic acid. These reactions are catalyzed by a
Ruthenium complex or a boronated complex thereof, which is
represented by anyone of formulae A1, A2, A3, B1, C1, B2, C2, D, E,
F, G, H, 3, 4, 7, 9, 2', 4', 6' and 8' or any other Ruthenium
complex or their boronated complexes covered by such formulae.
Depending on the complex being used, the reaction permits the
optional use of one or more equivalents of a base. This reaction
can also be catalyzed by the Ruthenium complexes described in US
Patent publication US 2009/0112005, such as, but not limited to
compounds of formulae A1', A2' and A3':
##STR00053##
[0237] wherein [0238] L.sub.1 and L.sub.2 are each independently
selected from the group consisting of nucleophilic carbene
(:C(R).sub.2), P(R).sub.2, P(OR).sub.2, N(R).sub.2, imine, SR, SH,
S(.dbd.O)R, heteroaryl wherein the heteroatom is selected from
nitrogen and sulfur. As(R).sub.2, Sb(R).sub.2 and an N-heretocyclic
carbene represented by the structure:
[0238] ##STR00054## [0239] each of R, R.sup.2 and R.sup.3 are
independently selected from the group consisting of alkyl,
cycloalkyl, aryl, alkylaryl, heterocyclyl and heteroaryl; [0240]
L.sub.3 is a mono-dentate two-electron donor selected from the
group consisting of CO, P(R).sub.3, P(OR).sub.3, NO.sup.+,
As(R).sub.3, Sb(R).sub.3, S(R).sub.2, nitrile (RCN) and isonitrile
(RNC) wherein R is as defined above; [0241] L.sub.4 is absent or is
L.sub.3; [0242] Y and Z are each independently H or an anionic
ligand selected from the group consisting of halogen, OCOR,
OCOCF.sub.3, OSO.sub.2R, OSO.sub.2CF.sub.3, CN, OH, OR, N(R).sub.2,
RS and SH; wherein R is as defined above; [0243] X represents zero,
one, two or three substituents selected from the group consisting
of alkyl, aryl, halogen, nitro, amide, ester, cyano, alkoxy,
cycloalkyl, alkylaryl, heterocyclyl, heteroaryl, an inorganic
support and a polymeric moiety; and [0244] anion represents a group
bearing a single negative charge.
[0245] Preferred complexes for this reaction are Pincer complexes
represented by the structure of Formula 1.
[0246] In one embodiment, the process of the invention, i.e., the
direct catalytic conversion of primary alcohols to carboxylic acids
and dihydrogen is illustrated in Scheme 12B. In accordance with
this process, a primary alcohol represented by formula
R.sup.17CH.sub.2OH is contacted with water and a base (e.g., NaOH)
as shown in Scheme 12B. This novel environmentally benign reaction,
can be used to produce various carboxylic acids and their salts
from very simple substrates, with high atom economy and in some
embodiments no stoichiometric activating agents, thus generating no
waste. If desired, the salt is neutralized with the appropriate
acid to provide the corresponding carboxylic acid.
##STR00055##
wherein R.sup.17 is selected from the group consisting of H, an
unsubstituted or substituted alkyl, alkoxyalkyl, cycloalkyl, aryl,
alkylaryl, heterocyclyl and heteroaryl.
[0247] A variety of bases can be used for this reaction,
non-limiting examples of which include an inorganic or organic base
selected from sodium carbonate, potassium carbonate, sodium
hydroxide, potassium hydroxide, sodium ethoxide, potassium
tert-butoxide, sodium methoxide. The acid used to neutralize the
salt can be, e.g. a mineral acid such as hydrochloric acid,
hydrobromic acid, and the like. Each possibility represents a
separate embodiment of the invention.
[0248] A variety of alcohols can be used in the process of the
invention. In some embodiments, the alcohol is selected from the
group consisting of butanol, pentanol, decanol 2-methoxyethanol,
2-phenylethanol, cyclohexylmethanol, 3-phenylbutan-1-ol,
but-3-en-1-ol, (4-methoxyphenyl)methanol, and
(2,4-dimethoxyphenyl)methanol. Each possibility represents a
separate embodiment of the present invention.
[0249] The disclosures of all cited references are incorporated by
reference as if fully set forth herein.
[0250] The principles of the present invention are demonstrated by
means of the following non-limiting processes.
Examples
Example 1: Hydrogenation of Amides to the Corresponding Alcohols
and Amines
[0251] Examples of processes involving the hydrogenation of amides
to alcohol and amines are shown in Scheme 13:
##STR00056##
(a) Using catalyst 3: A 100 mL Fischer-Porter tube was charged
under nitrogen with the catalyst 3 (0.01 mmol), an amide (1.0
mmol), and THF (2 mL). The nitrogen present in the Fischer-Porter
(100 mL) was replaced by H.sub.2 (twice with 30 psi) at room
temperature, then it was filled with H.sub.2 (10 atm). The solution
was heated at 110.degree. C. (bath temperature) with stirring for
48 hrs. After cooling to room temperature, the H.sub.2 was vented
carefully and the products were determined by GC with m-xylene as
internal standard, using a Carboxen 1000 column on a HP 690 series
GC system. (b) Using complex 4+Base (generation of catalyst 3 in
situ): In an open air, a solution of amide (1.0 mmol) in THF (1.0
mL) was transferred via syringe into a Fischer-Porter tube (100 mL)
contains 0.01 mmol of catalyst 4. Then, KO.sup.tBu (0.01 mmol) in
THF (1.0 mL) was added and the air present in the Fischer-Porter
tube was flushed with hydrogen (thrice with 30 psi) and filled with
H.sub.2 (10 atm). The solution was heated at 110.degree. C. (bath
temperature) with stirring for 48 hrs. After cooling to room
temperature, the H.sub.2 was vented carefully and the products were
determined by GC with m-xylene as internal standard, using a
Carboxen 1000 column on a HP 690 series GC system. Results of some
typical processes are shown in Tables 1A, 1B and 2.
A. Selective Hydrogenation of Amides to Alcohols and Amines Using
H.sub.2 Catalyzed by BPy-PNN-Ru(II) Pincer Complexes 1, 4 and 7
TABLE-US-00001 [0252] TABLE 1A Hydrogenation of amides catalyzed by
complex 1, 4 and 7 Reaction condition.sup.a ##STR00057## Yield
(%).sup.b Entry Catalyst Alcohol Amine 1 1 62.7 62.0.sup. 2 1 66.3
66.8.sup.c 3 4 -- -- 4 4 + 80.2 81.8.sup.d KO.sup.tBu 5 7 + 76.8
78.0.sup.d KO.sup.tBu .sup.aComplex 1, 4 and 7 (0.01 mol), amide (1
mmol), H.sub.2 (10 atm), and dry THF (2 ml) were heated in a
Fischer-Porter tube at 110.degree. C. (bath temperature) for 48 h.
.sup.bYields of products were analyzed by GC (m-xylene as internal
standard). .sup.c1,4-dioxane (2 mL) at 140.degree. C. after 48 h.
.sup.done equivalent (relative to Ru) of base was used.
TABLE-US-00002 TABLE 1B Hydrogenation of amides to alcohols and
amines selectively catalyzed by pincer complex 3.sup.a Products
(yield [%]).sup.b Entry Amide Alcohol Amine 1 ##STR00058##
##STR00059## ##STR00060## 2 ##STR00061## ##STR00062## ##STR00063##
3 ##STR00064## ##STR00065## ##STR00066## 4 ##STR00067##
##STR00068## ##STR00069## 5 ##STR00070## ##STR00071## ##STR00072##
6 ##STR00073## EtOH (71.0) EtNH.sub.2.sup.c 7 ##STR00074##
##STR00075## MeNH.sub.2.sup.c 8 ##STR00076## ##STR00077##
##STR00078## 9 ##STR00079## EtOH (94.1) ##STR00080## 10
##STR00081## ##STR00082## ##STR00083## 11 ##STR00084## ##STR00085##
##STR00086## 12 ##STR00087## ##STR00088## ##STR00089## 13
##STR00090## ##STR00091## ##STR00092## 14 ##STR00093## EtOH (97.1)
##STR00094## 15 ##STR00095## ##STR00096## ##STR00097## 16
##STR00098## ##STR00099## ##STR00100## 17 ##STR00101## MeOH (97.1)
##STR00102## 18 ##STR00103## MeOH (96.3) (32.1).sup.g Me.sub.2NH 19
##STR00104## ##STR00105## EtNH.sub.2.sup.c .sup.aComplex 3 (0.01
mol), amide (1 mmol), H.sub.2 (10 atm), and dry THF (2 ml) were
heated in a Fischer-Porter tube at 110.degree. C. (bath
temperature) for 48 h. .sup.bYields of products were analyzed by GC
(m-xylene as internal standard). .sup.cThe amines (EtNH.sub.2
(entry 6 and 18) and MeNH.sub.2 (entry 7)) were analyzed in the gas
phase by GC-MS. .sup.dIn the reactions involving anilide
derivatives (entries 9-12), trace amounts of the corresponding
secondary amines were detected by GC-MS. .sup.e0.5 mmol of
bis-amide was used. .sup.fYield after 32 h. .sup.gComplex 1 was
used.
B. Selective Hydrogenation of Primary Amides to Alcohols and
Ammonia Using H.sub.2 Catalyzed by Ruthenium Pincer Complex 3
##STR00106##
TABLE-US-00003 [0253] TABLE 2 Hydrogenation of primary amides to
alcohols and ammonia selectively catalyzed by complex 3 Yield Entry
Amides Alcohols (%).sup.b 1 ##STR00107## ##STR00108## 86.8 .sup.
(63.7).sup.c,d 2 ##STR00109## ##STR00110## .sup. 88.1.sup.d 3
##STR00111## ##STR00112## .sup. 90.7.sup.d 4 ##STR00113##
##STR00114## 89.1 .sup. (91.7).sup.d,e 5 ##STR00115## ##STR00116##
.sup. 92.5.sup.d 6 ##STR00117## ##STR00118## 95.7 7 ##STR00119##
##STR00120## 42.4 .sup.aComplex 3 (0.01 mol), amide (1 mmol),
H.sub.2 (10 atm), and dry THF (2 ml) were heated in a
Fischer-Porter tube at 110.degree. C. (bath temperature) for 72 h.
.sup.bYields of products were analyzed by GC (m-xylene as internal
standard) and ammonia was analyzed in the gas phase by GC-MS.
.sup.cYield in the parenthesis after 48 h. .sup.dTraces of
corresponding esters were also observed in GC. .sup.e1,4-dioxane (2
mL) at 140.degree. C. after 60 h.
DISCUSSION
[0254] The applicants have previously reported the dehydrogenative
coupling of alcohols with amines to form amides, catalyzed by
complex 1, with liberation of hydrogen gas (Gunanathan 2007). To
explore whether it might be possible to reverse this reaction by
the application of hydrogen pressure, complexes 1-4 were tested as
catalysts for the hydrogenation of amides. Thus, upon treatment of
N-benzyl-2-methoxyacetamide with dihydrogen (10 atm) at 110.degree.
C. (bath temperature) in dry THF for 48 h with a catalytic amount
of 1 (1 mol %), 62.7% of 2-methoxyethanol and 62.0% of benzyl amine
were obtained. Performing the reaction at 140.degree. C. using
1,4-dioxane as solvent did not significantly improve the yield
(alcohol yield 66.3%). It was significant that the reaction was
selective and the corresponding secondary amine was not observed.
Under the same conditions complex 2 was inactive. Remarkably,
employing complex 3 (1 mol %) as catalyst, hydrogenation of
N-benzyl-2-methoxyacetamide under identical conditions (THF,
110.degree. C.) resulted in the selective formation of 89.2%
2-methoxyethanol and 89.6% benzyl amine (Table 1B, entry 1). Thus,
the normally observed C--O hydrogenolysis did not take place at
all. Of practical significance, the air-stable complex 4 (which is
stable in air for at least two days in solution) in the presence of
one equivalent (relative to Ru) of base also efficiently catalyzes
the hydrogenation of amides to alcohols and amines, by generation
of the catalyst 3 in situ. Thus, upon heating a THF solution of 4
(1 mol %) with KO.sup.tBu (1 mol %) and N-benzyl-2-methoxyacetamide
(1 mmol) at 110.degree. C. under H.sub.2 (10 atm) for 48 h, 80.2%
of alcohol and 81.8% of amine were formed. No reaction took place
in the absence of base. Hydrogenation of N-hexyl-2-methoxyacetamide
catalyzed by 3 yielded 2-methoxy ethanol and hexyl amine in 90.7%
and 90.3% yields, respectively (Table 1B, entry 2),
N-hexyl-3-methyloxetane-3-carboxamide undergoes hydrogenation to
the alcohol and amine without hydrogenolysis of the strained
oxetane ring (Table 1B, entry 3). The heterocyclic amide,
N-hexylfuran-2-carboxamide was hydrogenated to yield 68.8% of
furfuryl alcohol and 68.1% of hexylamine (Table 1B, entry 4). The
aromatic non-activated amide, N-benzylbenzamide is also
hydrogenated to benzyl alcohol and benzyl amine (Table 1B, entry
5), but the yield is lower, probably because of steric reasons.
Significantly, the aliphatic non-activated amides, N-ethylacetamide
and N-methylpropionamide also underwent hydrogenation to yield the
corresponding alcohols and amines (71% of ethanol and ethylamine
for entry 6 and 68.4% of n-propanol and methylamine for entry 7).
The product gaseous amines were analyzed by GC-MS spectrometry of
the gas phase and not quantified. As expected, the activated
amides, anilide derivatives, were converted into their
corresponding alcohols and aniline in excellent yields (91-95%;
Table 1B, entries 9-12) along with trace amounts of the secondary
amines (detected by GC-MS) under similar conditions. The reaction
is also effective for bis-amides. Thus,
N,N'-(ethane-1,2-diyl)bis(2-methoxyacetamide) (0.5 mmol) was also
hydrogenated using catalyst 3 under mild conditions (Table 1B,
entry 13), Noteworthy, tert-amides also underwent hydrogenation
almost quantitatively to yield alcohols and secondary amines in
equivalent amounts (Table 1B, entries 14-16). Gratifyingly, heating
a solution of N-formymorpholine (1 mmol) and complex 3 in THF at
110.degree. C. yielded after 32 h 97.1% of methanol and 98.3% of
morpholine; no decarbonylation of the formyl group took place
(Table 1B, entry 17). These results highlight the substantial scope
of the unprecedented, selective hydrogenation of amides catalyzed
by 3, or by the air-stable 4 with an equivalent of base (which
generates 3 in situ).
[0255] In conclusion, amides can be selectively hydrogenated to
alcohols and amines for the first time. The reaction proceeds under
mild pressure, neutral, homogeneous conditions using Ruthenium
complexes as catalysts according to the invention and dihydrogen by
metal-ligand cooperation. This new catalytic protocol exhibits a
broad substrate scope providing a variety of amines and alcohols in
good to excellent yield.
C. Hydrogenation of Cyclic Di-Peptides
[0256] The process of the present invention can also be used for
catalytic hydrogenation of di-peptides. For example, cyclic
di-peptides can be hydrogenated to amino alcohols. In a general
procedure, a 100 mL Fischer-Porter tube was charged with the
catalyst 1 (0.02 mmol), the cyclic di-peptides (1.0 mmol) and THF
(2 mL) under an atmosphere of purified nitrogen in a Vacuum
Atmospheres glove box. The pressure tube was taken out of the glove
box, and subjected to three successive cycles of
pressurization/venting with H.sub.2 (3 atm), then pressurized with
H.sub.2 (12 atm) and closed. The tube was placed behind a
protective shield and the reaction mixture was heated in an oil
bath at 110.degree. C. with constant stirring for 60 h. After
cooling to room temperature, excess H.sub.2 was vented off
carefully and the product was determined by GC and GC-MS. Some
representative results are presented in Table 3 hereinbelow.
TABLE-US-00004 TABLE 3 Hydrogenation of cyclic di-peptides to amino
alcohols selectively catalyzed by complex 1 Amino alcohols Entry
Cyclic di-peptides Conditions (Yield (%)) 1 ##STR00121## Solvent =
THF (2 mL) PH.sub.2 = 10 atm Temperature = 110.degree. C. (bath)
Time = 60 h ##STR00122## 2 ##STR00123## ##STR00124##
Example 2: Hydrogenation of Formate Esters to Methanol and
Alcohols: Dimethyl Carbonate to Methanol: Esters and Lactones to
Alcohols, and Hydrogenation of Polycarbonates
A. Hydrogenation of Formates/Carbonate:
[0257] A 100 mL Fischer-Porter tube was charged under nitrogen with
catalyst 3 (0.01 mmol), formate ester (15.0 mmol) or dimethyl
carbonate (10.0 mmol) and THF (2 mL). After the nitrogen present in
the Fischer-Porter tube was replaced by H.sub.2 (twice with 30 psi)
at room temperature, the tube was filled with H.sub.2 (10 atm). The
solution was heated at 110.degree. C. (bath temperature) with
stirring for 36 hrs. After cooling to room temperature, excess
H.sub.2 was vented carefully and the products were analyzed by GC
with m-xylene as internal standard, using a Carboxen 1000 column on
a HP 690 series GC system.
B. Hydrogenation of Methyl Formate and Dimethyl Carbonate Under 50
Atmospheres and Very Low Catalyst Loading (Entries 6 and 10,
Respectively, Table 4):
[0258] A 30 mL Teflon coated Iron-Fischer-Porter (Autoclave) was
charged under nitrogen with catalyst 3 (0.005 mmol), Methyl Formate
(25.0 mmol) and THF (5 mL). After the nitrogen present in the
autoclave was replaced by H.sub.2 (twice with 50 psi) at room
temperature, it was filled with H.sub.2 (40 atm). The solution was
heated at 110.degree. C. (bath temperature) with stirring for 14
hrs. After cooling to room temperature, the H.sub.2 was vented
carefully at 0.degree. C. and the products were determined by GC
with m-xylene as internal standard, using a Carboxen 1000 column on
a HP 690 series GC system. The same procedure was used for
hydrogenation of dimethyl carbonate.
##STR00125##
TABLE-US-00005 TABLE 4 Hydrogenation of Formates.sup.a and Dimethyl
Carbonate.sup.b Entry Catalyst Substrate Conv. (%) Products
(%).sup.c TON 1 1 HCOOMe 71.7 71.0.sup.d 710 (MF) 2 1 HCOOMe >99
~99.sup.e 990 3 1 HCOOMe 78.3 2 MeOH (77.0).sup.a 1155 4 3 HCOOMe
96.0 2 MeOH (95.8) 1440 5 7 + HCOOMe 92.8 2 MeOH (91.2).sup.f 1370
KO.sup.tBu 6 3 HCOOMe 94.0 2 MeOH (93.7).sup.g 4685 7 3 HCOOEt 92.0
MeOH (92.0) 1380 and EtOH (91.7) 8 3 HCOO.sup.nBu 86.3 MeOH (86.3)
1295 and n-BuOH (86.0) 9 3 DMC 96.2 3 MeOH (96.2) 962 10 3 DMC 89.0
3 MeOH (87.6).sup.g 4380 .sup.aComplex 1 or 3 (0.01 mmol), formate
(15 mmol), H.sub.2 (10 atm), and dry THF (2 ml) were heated in a
Fischer-Porter tube at 110.degree. C. (bath temperature) for 48 h.
.sup.b10 mmol of DMC was used. .sup.cYields of products and
conversion of starting material were analyzed by GC (m-xylene as
internal standard). .sup.d100 psi H.sub.2, 1,4-dioxane (2 mL) at
145.degree. C. after 30 h. .sup.e130 psi H.sub.2, 1,4-dioxane (2
mL) at 145.degree. C. after 36 h. .sup.fone equivalent (relative to
Ru) of base was used. .sup.gComplex 3 (0.005 mmol), MF/DMC (25
mmol), H.sub.2 (50 atm), and dry THF (5 ml) were heated in a
autoclave at 110.degree. C. (bath temperature) for 14 h.
C. Hydrogenation of Methyl Formate and Dimethyl Carbonate Under
Neat Conditions
[0259] A 100 mL Fischer-Porter tube was charged under nitrogen with
catalyst 3 (0.01 mmol), and methyl formate or dimethyl carbonate
(10.0 mmol). After the nitrogen in the Fischer-Porter tube was
replaced by H.sub.2 (twice with 30 psi) at 0.degree. C., the tube
was filled with H.sub.2 (10 atm). The solution was heated at
80.degree. C. (for MF) and 100.degree. C. (for DMC) (bath
temperature) with stirring for 8 hrs. After cooling to room
temperature, excess H.sub.2 was vented carefully and the products
were analyzed by GC with m-xylene as internal standard, using a
Carboxen 1000 column on a HP 690 series GC system.
##STR00126##
TABLE-US-00006 TABLE 5 Hydrogenation of methyl formate and dimethyl
carbonate Entry Catalyst Substrate Conv. (%) Products (%).sup.a 1 1
HCOOMe 15.6 2 MeOH (15.2).sup.b 2 3 HCOOMe >99 2 MeOH
(>99).sup.c 3 3 DMC >99 3 MeOH (>99).sup.d (89.1).sup.e
.sup.aYields of product and conversion of starting material were
analyzed by GC (m-xylene as internal standard). .sup.bComplex 3 or
1 (0.01 mol), formate (10 mmol), and H.sub.2 (10 atm) were heated
in a Fischer-Porter tube at 80.degree. C. (bath temperature) for 18
h. .sup.c10 mmol of DMC was used. .sup.cYields after 8 h. .sup.dat
100.degree. C. after 8 h. .sup.eat 100.degree. C. after 2 h.
D. Hydrogenation of Carbamates:.sup.a
TABLE-US-00007 [0260] TABLE 6 hydrogenation of carbamates to amines
and alcohols Entry Carbamate Alcohol Amine Yield.sup.b 1
##STR00127## 2 MeOH ##STR00128## 97.8 2 ##STR00129## 2 MeOH
##STR00130## 98.0 .sup.aComplex 3 (0.01 mol), carbamate (1 mmol),
and H.sub.2 (10 atm) were heated in a Fischer-Porter tube at
110.degree. C. (bath temperature) for 48 h. .sup.bYields of product
(based on MeOH) were analyzed by GC (m-xylene as internal
standard).
E. Hydrogenation of Unactivated Esters (Hexyl Hexanoate):
[0261] A 30 mL Teflon coated Iron-Fischer-Porter (Autoclave) was
charged under nitrogen with catalyst 3 (0.01 mmol for entry 1 and
0.005 mmol for entry 2 respectively), hexyl hexanoate (20.0 mmol)
and THF (5 mL). After the nitrogen present in the autoclave was
replaced by H.sub.2 (twice with 50 psi) at room temperature, it was
filled with H.sub.2 (50 atm). The solution was heated at
110.degree. C. (bath temperature) with stirring for 16 hrs. After
cooling to room temperature, the H.sub.2 was vented carefully and
the yields of product and conversion of starting material were
analyzed by GC (m-xylene as internal standard, using a Carboxen
1000 column on a HP 690 series GC system. Very high turnover
numbers (TON) were obtained.
##STR00131##
TABLE-US-00008 TABLE 7 Hydrogenation of esters to alcohols Alcohol
Yield Entry Cat. Ester (20 mmol) (%) TON 1 3 (0.01 mmol) Hexyl
hexanoate 1-Hexanol >99 2000 2 3 (0.005 mmol) Hexyl hexanoate
1-Hexanol 82.1 3284
F. Hydrogenation of Biomass-Derived Cyclic Di-Esters to
1,2-Diols
[0262] The cyclic di-ester of glycolic acid (derived from sugar
cane), glycolide was chosen as a model substrate for catalytic
hydrogenation by Ruthenium complex 3. A 1,4-dioxane solution
containing glycolide (1 mmol) and 1 mol % of complex 3 was heated
under hydrogen pressure (6 atm) at 135.degree. C. for 36 h using a
pressure vessel. The reaction mixture was cooled and excess H.sub.2
was vented carefully and the products were determined by GC and
GC-MS showing formation of ethylene glycol (EG) as the only product
in 61% yield (Table 8, entry 1) with 67% conversion of the
glycolide. After removal of the solvent, the obtained crude viscous
liquid was further analyzed by ESI, illustrating that there was no
formation of polymeric material.
[0263] Performing the same reaction under similar conditions using
10 atm of H.sub.2 resulted in 88% of ethylene glycol after 36 h
(Table 8, entry 2). Optimization studies revealed that the reaction
could be performed at lower temperature using THF as solvent. Thus,
heating complex 3 (0.01 mmol) with glycolide (1 mmol) and
dihydrogen (10 atm) at 110.degree. C. in 3 mL of dry THF for 48 h
using a Fisher-Porter tube, yielded 93% of ethylene glycol (Table
8, entry 3). A high turnover number (425) was achieved at higher
pressure. Thus, heating a THF solution of glycolide (10 mmol) and a
catalytic amount of complex 3 (0.02 mmol) at 110.degree. C. under
H.sub.2 (50 atm) using a high pressure reactor resulted in 85%
yield of ethylene glycol selectively after 12 h (Table 8, entry
4).
##STR00132##
TABLE-US-00009 TABLE 8 Catalytic hydrogenation of glycolide to
ethylene glycol ##STR00133## temp. P(H.sub.2) time yield entry
solvent (.degree. C.) (atm) (h) (%).sup.b 1 1,4-dioxane 135 6 36 61
2 1,4-dioxane 135 10 36 88 3 THF 110 10 48 93 .sup. 4.sup.c THF 110
50 12 85 .sup.aComplex 3 (0.01 mmol), glycolide (1 mmol), H.sub.2,
and dry solvent (3 mL) were heated in a Fischer-Porter tube at the
specified (oil bath) temperature. .sup.bYields of ethylene glycol
were analyzed by GC using m-xylene as an internal standard.
.sup.cComplex 3 (0.02 mmol), glycolide (10 mmol), and THF (5 mL)
were heated under H.sub.2 pressure in a high-pressure reactor.
[0264] To expand the scope of this efficient hydrogenation
reaction, optimized catalytic conditions were further tested with
lactide, which is derived from the glucose fermentation product
lactic acid. Thus, meso-lactide was heated with H.sub.2 (10 atm) at
110.degree. C. in THF for 48 h with a catalytic amount of 3 (1 mol
%), 87% of 1,2-propanediol was obtained selectively (Table 9, entry
1). Remarkably, the hydrogenation of chiral lactide, L-lactide
catalyzed by complex 3 under the optimized conditions yielded
optically pure (S)-(+)-1,2-propanediol as sole product without
racemization even under high pressure. Hence, upon treatment of
L-lactide (10 mmol) with dihydrogen (50 atm) at 135.degree. C. for
12 h with a catalytic amount of 3 (0.02 mmol) using 5 mL of THF as
a solvent, selectively yielded 91% to propylene glycol (Table 9,
entry 3). After careful removal of the solvent under reduced
pressure, the reaction mixture was passed through short silica gel
bed and the diol was eluted with CH.sub.2Cl.sub.2: MeOH (10:1) and
concentrated under vacuum to yield 73% of the optically pure
1,2-prpanediol. The optical rotation of the pure product was
essentially the same as reported in the literature. Thus, under
these experimental condition, no racemization took place.
##STR00134##
TABLE-US-00010 TABLE 9 Catalytic hydrogenation of lactide to
propylene glycol di-ester temp P(H.sub.2) time yield Entry
(lactide) solvent (.degree. C.) (atm) (h) (%).sup.b 1 meso THF 110
10 48 87 2 chiral (S,S) THF 110 10 48 82 3.sup.c chiral (S,S) THF
110 50 12 91 (73).sup.d .sup.aComplex 3 (0.01 mmol), meso or chiral
lactide (1 mmol), H.sub.2, and dry THF (3 mL) were heated in a
Fischer-Porter tube at 110.degree. C. (oil bath) temperature.
.sup.bYields of propylene glycol were analyzed by GC using m-xylene
as an internal standard. .sup.cComplex 3 (0.02 mmol), L-lactide (10
mmol), and THF (5 mL) were heated under H.sub.2 pressure in a
high-pressure reactor. .sup.dIsolated yield.
[0265] In conclusion, cyclic di-esters such as glycolide and
lactide are selectively hydrogenated to the corresponding 1,2-diols
for the first time. This offers an environmentally benign, atom
economic and an alternative approach to the indirect transformation
of biomass to important synthetic building blocks, propylene and
ethylene glycol. The reactions proceed under mild, neutral and
homogeneous conditions with minimal pressure of molecular hydrogen.
Importantly, the chirality is unaffected during the
hydrogenation.
GENERAL EXPERIMENTAL
[0266] All experiments with metal complexes and phosphine ligands
were carried out under an atmosphere of purified nitrogen in a
Vacuum Atmospheres glove box equipped with a MO 40-2 inert gas
purifier or using standard Schlenk techniques. All solvents were
reagent grade or better. All non-deuterated solvents were refluxed
over sodium/benzophenone ketyl and distilled under argon
atmosphere. Deuterated solvents were used as received. All solvents
were degassed with argon and kept in the glove box over 4 .ANG.
molecular sieves. Most of the chemicals used in the catalytic
reactions (cyclic di-esters) are commercially available and were
used as received.
[0267] Thin layer chromatography (TLC) was performed using Merck
1.05554 aluminum sheets precoated with silica gel 60 F254 and the
spots were visualized with UV light at 254 nm or under iodine
vapor. Column chromatography purifications were performed by flash
chromatography using Merck silica gel 60 (0.063-0.200 mm).
[0268] 1H, 13C and 31P NMR spectra were recorded using a Bruker
AMX-300 NMR spectrometer. NMR chemical shifts are reported in ppm
downfield from tetramethylsilane (for CDCl3), 1H NMR chemical shift
is referenced to the residual hydrogen signal of the deuterated
solvent (7.15 ppm for benzene). 31P NMR chemical shift is reported
in ppm downfield from H.sub.3PO.sub.4 and referenced to an external
85% solution of phosphoric acid in D2O. Abbreviations used in the
NMR follow-up experiments: br, broad; s, singlet; d, doublet; t,
triplet; q, quartet; m, multiplet. IR spectra were recorded on a
Nicolet FT-IR spectrophotometer. Mass spectra were recorded on
Micromass Platform LCZ 4000, using Electro Spray Ionization (ESI)
mode. GC-MS was carried out on HP 6890 (flame ionization detector
and thermal conductivity detector) and HP 5973 (MS detector)
instruments equipped with a 30 m column (Restek 5MS, 0.32 mm
internal diameter) with a 5% phenylmethylsilicone coating (0.25 mm)
and helium as carrier gas. GC analysis were carried out using a
Carboxen 1000 column on a HP 690 series GC system or HP-5 cross
linked 5% phenylmethylsilicone column (30 m.times.0.32
mm.times.0.25 .mu.m film thickness, FID) on a HP 6890 series GC
system using m-xylene (1 mmol) as an internal standard.
[0269] General Procedure for Catalytic Hydrogenation:
[0270] (a) Catalytic Hydrogenation of Glycolide to Ethylene
Glycol:
##STR00135##
[0271] (i.) Substrate/catalyst 100/1: A solution of catalyst 3 (4.5
mg, 0.01 mmol) in THF or 1,4-dioxane (1.0 mL) was transferred into
a 100 mL Fischer-Porter tube followed by addition of the glycolide
(116 mg, 1.0 mmol) in THF or 1,4-dioxane (2.0 mL) under an
atmosphere of purified nitrogen in a Vacuum Atmospheres glove box.
The pressure tube was taken out of the glove box, followed by three
successive cycles of pressurization/venting with H.sub.2 (2 atm),
then pressurized with H.sub.2 (10 atm) and well-closed. The tube
was covered by a protective shield and the reaction mixture was
heated in an oil bath at 110.degree. C. with constant stirring for
48 h. After cooling to room temperature, excess H.sub.2 gas was
vented carefully and the products were determined by GC with
m-xylene (1.0 mmol) as an internal standard, using a HP-5 cross
linked 5% phenylmethylsilicone column (30 m.times.0.32
mm.times.0.25 .mu.m film thickness) on a HP 6890 series GC
system.
[0272] (ii) Substrate/catalyst 500/1: in a nitrogen glove box, a
solution of catalyst 3 (9 mg, 0.02 mmol) in THF (5 mL) was added to
a stainless-steel high pressure reactor (30 mL) equipped with a
magnetic stirring bar containing 10.0 mmol (1.16 g) of the solid
glycolide. The high pressure reactor was taken out of the glove box
and the nitrogen present in the pressure reactor was flushed with
hydrogen by two successive cycles of pressurization/venting with
H.sub.2 (5 atm), then pressurized with H.sub.2 (50 atm) and
well-closed. The tube was covered by a protective shield and the
reaction mixture was heated in an oil bath at 110.degree. C. with
constant stirring for 12 h. After cooling to room temperature,
excess H.sub.2 gas was vented carefully and the products were
determined by GC with m-xylene (1.0 mmol) as an internal standard.
(After 3 hrs. the conversion of the glycolide was only 39%).
[0273] (Note: Complex 3 also catalyzed the dehydrogenation of
ethylene glycol to glycolide and other polymeric material (poly
glycolide) with liberation of H.sub.2 after 24 hrs in 1,4-dioxane
(conversion of ethylene glycol 16%) or under solvent free (neat)
condition with less conversion (21%)).
[0274] (b) Catalytic Hydrogenation of Meso-Lactide to Propylene
Glycol:
##STR00136##
[0275] A solution of catalyst 3 (4.5 mg, 0.01 mmol) in THF (1.0 mL)
was transferred into a 100 mL Fischer-Porter tube followed by
addition of the meso-lactide (144 mg, 1.0 mmol) in THF (2.0 mL)
under an atmosphere of purified nitrogen in a Vacuum Atmospheres
glove box. The pressure tube was taken out of the glove box,
followed by three successive cycles of pressurization/venting with
H.sub.2 (2 atm), then pressurized with H.sub.2 (10 atm) and
well-closed.
[0276] The tube was covered by a protective shield and the reaction
mixture was heated in an oil bath at 110.degree. C. with constant
stirring for 48 h. After cooling to room temperature, excess
H.sub.2 gas was vented carefully and the products were determined
by GC with m-xylene (1.0 mmol) as an internal standard.
[0277] (c) Catalytic Hydrogenation of L-lactide to
S-(+)-1,2-propanediol:
##STR00137##
[0278] (i) Substrate/catalyst 100/1: A solution of catalyst 3 (4.5
mg, 0.01 mmol) in THF (1.0 mL) was transferred into a 100 mL
Fischer-Porter tube followed by addition of L-lactide (144 mg, 1.0
mmol) in THF (2.0 mL) under an atmosphere of purified nitrogen in a
glove box. The pressure tube was taken out of the glove box,
followed by three successive cycles of pressurization/venting with
H.sub.2 (2 atm), then pressurized with H.sub.2 (10 atm) and closed.
The tube was covered by a protective shield and the reaction
mixture was heated in an oil bath at 110.degree. C. with constant
stirring for 48 h. After cooling to .about.5.degree. C. (with a
cold water bath), excess H.sub.2 gas was vented carefully and the
products were determined by GC with m-xylene (1.0 mmol) as an
internal standard. After careful removal of the solvent under
reduced pressure, the reaction mixture was passed through short
silica gel bed and the diol was eluted with CH.sub.2Cl.sub.2: MeOH
(10:1) and concentrated under vacuum to yield 67% of the optically
pure 1,2-propanediol. The optical rotation of the pure product was
essentially the same as reported in the literature.
[0279] (ii) Substrate/catalyst 500/1: in a nitrogen glove box, a
solution of catalyst 3 (9 mg, 0.02 mmol) in THF (5 mL) was added to
a stainless-steel high pressure reactor (30 mL) equipped with a
magnetic stirring bar containing 10.0 mmol (1.44 g) of the
L-lactide. The high pressure reactor was taken out of the glove box
and the nitrogen present in the pressure reactor was flushed with
hydrogen by two successive cycles of pressurization/venting with
H.sub.2 (5 atm), then pressurized with H.sub.2 (50 atm) and
well-closed. The tube was covered by a protective shield and the
reaction mixture was heated in an oil bath at 110.degree. C. with
constant stirring for 12 h. After cooling to .about.5.degree. C.
(with a cold water bath), excess H.sub.2 gas was vented carefully
and the products were determined by GC with m-xylene as an internal
standard. After careful removal of the solvent under reduced
pressure, the reaction mixture was passed through short silica gel
bed and the diol was eluted with CH.sub.2Cl.sub.2: MeOH (10:1) and
concentrated under vacuum to yield 67% of the optically pure
1,2-propanediol. The optical rotation of the pure product was
essentially the same as reported in the literature.
Hydrogenation of L-lactide to S-(+)-1,2-propanediol Catalyzed by
NHC--Ru(H) Catalyst
##STR00138##
[0280] The NHC Ru(II) pincer catalyst was prepared according to: E.
Fogler, E. Balaraman, Y. Ben-David, G. Leitus, L. J. W. Shimon and
D. Milstein, Organometallics, 2011, 30, 3826 A 100 mL
Fischer-Porter tube was charged under nitrogen with the catalyst
(4.5 mg, 0.01 mmol), L-lactide (144 mg, 1.0 mmol) and THF (3 mL).
The Fischer-Porter tube was purged by three successive cycles of
pressurization/venting with H.sub.2 (2 atm), then pressurized with
H.sub.2 (10 atm). The solution was heated at 110.degree. C. (bath
temperature) with stirring for 48 h. After cooling to
.about.5.degree. C. excess H.sub.2 gas was vented and the products
were determined by GC. The solvent was removed under reduced
pressure and the reaction mixture was passed through short silica
gel bed. The 1,2-diol was eluted with CH.sub.2Cl.sub.2:MeOH (10:1)
and concentrated under vacuum to yield 57% of the optically pure
(S)-(+)-1,2-propanediol ([.alpha.].sub.D.sup.22=+27.degree. (c=1,
CHCl.sub.3)
G. Hydrogenation of Urea Derivatives to Amines and Methanol
##STR00139##
[0282] 1,3-Dimethylurea was selected as a benchmark substrate for
the unprecedented hydrogenation of urea derivatives catalyzed by
complex 3. Upon treatment of 1,3-dimethylurea (1 mmol) and a
catalytic amount of complex 3 (1 mol %) with H.sub.2 (10 atm) at
110.degree. C. (bath temperature) in dry THF resulted in 41%
conversion of dimethylurea to methanol and methylamine after 48 h
(Table 10, entry 1). The formed methanol was quantified as 35% by
GC and the gaseous amine was characterized by GC-MS of the gas
phase of the reaction mixture and not quantified. The yield of
methanol increased at longer reaction time (Table 10, entry 2).
Performing the same reaction under using 13.6 atm of H.sub.2 and 2
mol % of catalyst resulted in 93% of methanol after 72 h (Table 10,
entry 3).
TABLE-US-00011 TABLE 10 Novel hydrogenation of 1,3-dimethylurea to
methanol and methylamine catalyzed by 3 ##STR00140## 2
H.sub.3C--NH.sub.2 Reaction conditions.sup.[a] Cat. 3 PH.sub.2 hrs
Conv. Yield of MeOH Entry (mol %) (atm) (atm) (%).sup.[b]
(%).sup.[b],[c] 1 1 10 48 41 35 2 1 10 60 53 52 3 2 13.6 72 96 93
.sup.[a]Complex 3, 1,3-dimethylurea (1 mmol), H.sub.2, and dry THF
(2 mL) were heated in a Fischer-Porter tube (100 mL) at 110.degree.
C. (bath temperature) for specifed time. .sup.[b]Conversion of
dimethylurea and yields of methanol were analyzed by GC using
m-xylene as an internal standard. .sup.[c]The MeNH.sub.2 was
analyzed in the gas phase (as well as in liquid phase) by GC-MS and
not quantified.
[0283] Various urea derivatives were subjected to hydrogenation
(Table 11). Hydrogenation of 1,3-dihexylurea under the same
conditions (cat/urea derivative=2:100 (mmol), 13.6 atm of H.sub.2,
2 mL of dry THF, at 110.degree. C.) yielded methanol and
1-hexylamine in 83% and 87% respectively after 72 h (Table 11,
entry 2). As expected, the activated urea derivative,
1,3-bis(2-methoxyethyl)urea gave almost quantitative conversion to
methanol and 2-methoxyethylamine upon hydrogenation (Table 11,
entry 3). Aromatic and substituted aromatic urea derivatives also
underwent hydrogenation very efficiently in moderate yields (Table
11, entries 5-7) along with trace amounts of the corresponding
formamides (detected by GC-MS). The hydrogenation of diphenylurea
derivatives proceeds very smoothly to yield methanol and anilines.
Thus, upon heating a THF solution of 3 (0.02 mmol) and
1,3-diphenylurea (1 mmol) at 110.degree. C. under H.sub.2 (12 atm),
complete conversion to selectively form 90% of methanol and 95% of
aniline took place (Table 11, entry 8). Remarkably,
tetra-substituted urea derivatives were also selectively
hydrogenated to yield methanol and the corresponding amines, with
cleavage of the C--N bond. Thus, heating a THF solution containing
1,1',3,3'-tetramethylurea (1 mmol) and a catalytic amount of the
complex 3 (2 mol %) under hydrogen pressure (13.6 atm) using
pressure vessel at 110.degree. C. for 72 h resulted in 53%
conversion of tetramethylurea (TMU) to methanol (51%) and
N,N'-dimethylamine (Table 11, entry 11).
TABLE-US-00012 TABLE 11 Hydrogenation of urea derivatives to amines
and methanol catalyzed by BPy--PNN--Ru(II) pincer complex
3..sup.[a] ##STR00141## Products (yield {%}).sup.[b] Entry Amide
MeOH Amine .sup. 1.sup.[c] ##STR00142## 89 ##STR00143## 2
##STR00144## 83 ##STR00145## 3 ##STR00146## 94 ##STR00147## 4
##STR00148## 73 ##STR00149## .sup. 5.sup.[c] ##STR00150## 61
##STR00151## .sup. 6.sup.[c] ##STR00152## 67 ##STR00153## 7
##STR00154## 58 ##STR00155## 8 ##STR00156## 90 ##STR00157## 9
##STR00158## 93 ##STR00159## 10.sup.[c],[d] ##STR00160## 51
(CH.sub.3).sub.2NH 11.sup.[c] ##STR00161## 63 ##STR00162##
.sup.[a]Compex 3 (0.02 mmol), urea derivative (1 mmol), H.sub.2
(13.6 atm), and dry THF (2 mL) were heated in a Fischer-Porter tube
(100 mL) at 110.degree. C. (bath temperature) for 72 hrs (most of
the reactions were repeated twice). .sup.[b]Yields of products were
analyzed by GC (1 mmol of m-xylene as an internal standard).
.sup.[c]The amines n-propylamine and Me.sub.2NH for (entries 1 and
10 respectively) were analyzed in the gas phase (as well as in
liquid phase) by GC-MS and not quantified. .sup.[d]The
corresponding formamides (entries 5-6 and 10-11) were observed on
GC-MS and not quantified.
[0284] General Procedure for the Catalytic Hydrogenation of Urea
Derivatives:
[0285] A 100 mL Fischer-Porter tube was charged with catalyst 3
(0.02 mmol), urea derivative (1.0 mmol) and THF (2 mL) under an
atmosphere of purified nitrogen in a Vacuum Atmospheres glove box.
The pressure tube was taken out of the glove box, followed by three
successive cycles of pressurization/venting with H.sub.2 (3 atm),
then pressurized with H.sub.2 (10 atm) and well-closed. The tube
was covered by a protective shield and the reaction mixture was
heated in an oil bath at 110.degree. C. with constant stirring for
48 h. After cooling to room temperature, excess H.sub.2 gas was
vented carefully and the products were determined by gas
chromatography (GC).
[0286] G. Hydrogenation of Polypropylene Carbonate
##STR00163##
(1) A 100 mL Fischer-Porter tube was charged under nitrogen with
catalyst 3 (9 mg, 0.02 mmol), polypropylene carbonate
(M.sub.n=50,000 by GPC; 0.255 g) and THE (2 mL). The Fischer-Porter
tube was purged by three successive cycles of pressurizing/venting
with H.sub.2 (3 atm) and pressurized with 10 atm of H.sub.2. The
solution was heated at 110.degree. C. (bath temperature) with
stirring for 8 h. After cooling (.about.5.degree. C.; ice/water),
excess H.sub.2 was vented carefully and the products were analyzed
by GC-MS. The solvent was removed under vacuum to give pure
1,2-propanediol (isolated yield=0.180 g corresponds to 94.8%) and
methanol (97% yield).
(2) Hydrogenation Under Solvent-Free (Neat) Conditions:
[0287] A 100 mL Fischer-Porter tube was charged with catalyst 3
(0.01 mmol) and polypropylene carbonate (M.sub.n=50,000 by GPC;
0.510 g) under an atmosphere of purified nitrogen in a glovebox.
The pressure tube was taken out of the glove box and purged by
three successive cycles of pressurization/venting with H.sub.2 (2
atm), then pressurized with H.sub.2 (12.2 atm). The tube was placed
behind a protective shield and heated in an oil bath at 130.degree.
C. with constant stirring for 14 h. After cooling to
.about.5.degree. C., excess H.sub.2 gas was vented carefully and
the products (methanol and 1,2-propanediol) were analyzed by gas
chromatography (GC and GC-MS) and quantified by .sup.1H NMR using
toluene as internal standard. Quantitative conversion of the
polymer took place, to yield 4.96 mmol of 1,2-propanediol and
methanol. Isolated yield of 1,2-propanediol was 0.368 g (4.83
mmol).
Example 3: Dehydrogenative Coupling of Primary Alcohols to
Esters
[0288] Some processes involving the coupling of alcohols to esters
are shown in Scheme 21:
##STR00164##
A. Typical Procedures for the Catalytic Dehydrogenative Coupling of
Primary Alcohols (Table 12)
[0289] (a) Complex 3 (0.01 mmol), an alcohol (10 mmol), and toluene
(2 mL) were taken in a Schlenk flask under an atmosphere of
purified nitrogen in a glove box. The flask was equipped with a
condenser and the solution was refluxed with stirring in an open
system under argon for 24 hrs. After cooling to room temperature,
the consumption of starting material and the formation of ester
were determined by GC with m-xylene as an internal standard using a
Carboxen 1000 column on a HP 690 series GC system. (b) Complex 4
(0.01 mmol), an alcohol (10 mmol), KO.sup.tBu (0.01 mmol) and
toluene (2 mL) were taken in a Schlenk flask under an atmosphere of
purified nitrogen in a glove box. The flask was equipped with a
condenser and the solution was refluxed with stirring in an open
system under argon for 18 hrs. After cooling to room temperature,
the consumption of starting material and the formation of ester
were determined by GC with m-xylene as an internal standard using a
Carboxen 1000 column on a HP 690 series GC system.
TABLE-US-00013 TABLE 12 Coupling of primary alcohols to form esters
Conv. Entry Cat. Alcohol Ester (%) Yield (%) 1 4 1-Hexanol Hexyl
hexanoate -- -- 2 4 + 1-Hexanol Hexyl hexanoate 95.3 95.0 + traces
t-BuOK of aldehyde 3 7 + 1-Hexanol Hexyl hexanoate 90.0 89.3 +
traces t-BuOK of aldehyde 4 3 1-Hexanol Hexyl hexanoate 98.6 98.2 5
3 1-Pentanol Pentyl pentanoate 98.3 98.0 6 3 Benzyl Benzyl benzoate
94.1 92.9 + 0.9% alcohol aldehyde 7 3 1-Butanol Butyl butyrate 90.1
89.7 + 0.3% aldehyde 8 3 Cyclohexane Cyclohexyl- 98 96.2 + 1.6%
methanol methyl aldehyde cyclohexane carboxylate
B. Catalytic Dehydrogenation of Primary Alcohols Under Neat
Condition (Absence of Solvent) (Table 13):
[0290] Complex 3 (0.01 mmol) was heated under an argon flow in
different alcohols (10 mmol) at the specified temperatures and
times (Table 13). After cooling to room temperature, the
consumption of starting material and the formation of ester were
determined by GC with m-xylene as an internal standard using a
Carboxen 1000 column on a HP 690 series GC.
TABLE-US-00014 [0290] TABLE 13 Coupling of primary alcohols to form
esters under neat conditions Temp. Time Conv. Yield Entry Cat.
Alcohol (.degree. C.) (hrs) Ester (%) (%) 1 3 1-Pentanol 138 12
Pentyl 97.7 97.5 + pentanoate traces of alde- hyde 2 3 1-Butanol
117 12 Butyl 89.0 87.7 + butyrate 1.2% alde- hyde 3 3 Ethanol 79 72
Ethyl 52.0 51.7 (20 mmol) acetate
C. Catalytic Dehydrogenative Coupling of Alcohols Under Open Air
(Table 14):
[0291] To an oven dried Schlenk flask cooled to room temperature
under open air were added complex 4 (0.01 mmol), an alcohol (5
mmol) in toluene (2 mL), followed by KO.sup.tBu (0.01 mmol) in
toluene (1 mL) and the flask was equipped with a condenser and the
solution was refluxed with stirring in an open system under air for
18 hrs. After cooling to room temperature, the consumption of
starting materials was determined by GC with m-xylene as an
internal standard, using a Carboxen 1000 column on a HP 690 series
GC system.
TABLE-US-00015 TABLE 14 Coupling of primary alcohols to form esters
under open air Entry Alcohol Ester Conv. (%) Yield (%) 1 1-Hexanol
Hexyl hexanoate 89.8 86.3 + 2.8% aldehyde 2 Benzyl Benzyl benzoate
90.4 84.8 + 5.3% alcohol aldehyde
Example 4: Dehydrogenative Coupling of Alcohols and Amines with
Liberation of H.sub.2 to Form Amides
[0292] Some processes involving the coupling of alcohols and amines
to generate amides are shown in Scheme 22:
##STR00165##
A. Typical Procedure for the Catalytic Dehydrogenative
Mono-Acylation of Amines with Alcohols (Table 15): (a) Complex 3
(0.01 mmol), an alcohol (10 mmol), an amine (10 mmol), and benzene
(3 mL) were taken in a Schlenk flask under an atmosphere of
purified nitrogen in a Vacuum Atmospheres glove box. The flask was
equipped with a condenser and the solution was refluxed with
stirring in an open system under argon for 20 hrs. After cooling to
room temperature, the consumption of starting materials was checked
by GC using a Carboxen 1000 column on a HP 690 series GC system.
(b) Complex 4 (0.01 mmol), an alcohol (10 mmol), an amine (10
mmol), KO.sup.tBu (0.01 mmol), and benzene (3 mL) were taken in a
Schlenk flask under an atmosphere of purified nitrogen in a Vacuum
Atmospheres glove box. The flask was equipped with a condenser and
the solution was refluxed with stirring in an open system under
argon for 20 hrs. After cooling to room temperature, the
consumption of starting materials was checked by GC using a
Carboxen 1000 column on a HP 690 series GC system.
TABLE-US-00016 TABLE 15 Coupling of amines and alcohols to generate
amides Yield Entry Alcohol Amine Amide (isolated) 1 ##STR00166##
##STR00167## ##STR00168## 95.0 2 ##STR00169## ##STR00170##
##STR00171## 96.3 3 ##STR00172## ##STR00173## ##STR00174## 97.8
.sup. (94.0).sup.a 4 ##STR00175## ##STR00176## ##STR00177## 93.0 5
##STR00178## ##STR00179## ##STR00180## 85.8 6 ##STR00181##
##STR00182## ##STR00183## 86.7 7 ##STR00184## ##STR00185##
##STR00186## 62.0 8 ##STR00187## ##STR00188## ##STR00189## 56.0 9
##STR00190## ##STR00191## ##STR00192## 72.2 10 ##STR00193##
##STR00194## ##STR00195## 96.1 11 ##STR00196## ##STR00197##
##STR00198## 84.3 12 ##STR00199## ##STR00200## ##STR00201## 87.0 13
##STR00202## ##STR00203## ##STR00204## 90.0 14 ##STR00205##
##STR00206## ##STR00207## 68.sup.b 15 ##STR00208## ##STR00209##
##STR00210## 88.4 .sup.aComplex 3 (0.0033 mmol), an alcohol (5.0
mmol), an amine (5.0 mmol), and benzene (3 mL) were refluxed for
about 38 hrs (maximum turnover number = 1500). .sup.bNo
racemisation was observed.
B. Catalytic Dehydrogenative Bis-Acylation of Diamines with
Alcohols (Table 15; Entries 13 and 15):
[0293] Complex 3 (0.01 mmol), an alcohol (10.5 mmol), a diamine (5
mmol), and benzene (5 mL) were placed in a Schlenk flask under an
atmosphere of purified nitrogen in a Vacuum Atmospheres glove box.
The flask was equipped with a condenser and the solution was
refluxed with stirring in an open system under argon flow. The
reaction mixture was cooled to room temperature and the consumption
of starting materials was checked by GC using a Carboxen 1000
column on a HP 690 series GC system.
C. Amidation Reaction Under Open Air (Table 16):
[0294] To an oven dried Schlenk flask cooled to room temperature
under open air were added complex 4 (0.01 mmol), an alcohol (5
mmol), an amine (5 mmol) in benzene (2 mL), followed by KO.sup.tBu
(0.01 mmol) in benzene (1 mL) and the flask was equipped with a
condenser and the solution was refluxed with stirring in an open
system under air for 24 hrs. After cooling to room temperature, the
consumption of starting materials was determined by GC with
m-xylene as an internal standard, using a Carboxen 1000 column on a
HP 690 series GC system.
##STR00211##
TABLE-US-00017 TABLE 16 Coupling of amines and alcohols to generate
amides under open air Conv. of alcohol Yield Entry Alcohol Amine
Amide (%) (isolated) 1 ##STR00212## ##STR00213## ##STR00214## 77 71
2 ##STR00215## ##STR00216## ##STR00217## 88 80 3 ##STR00218##
##STR00219## ##STR00220## 81 74 4 ##STR00221## ##STR00222##
##STR00223## 66 61
D. Amidation Reaction Under Neat Condition (Table 17):
[0295] Complex 3 (0.01 mmol), an alcohol (5 mmol), an amine (5
mmol) were taken in a Schlenk flask under an atmosphere of purified
nitrogen in a Vacuum Atmospheres glove box. The flask was equipped
with a condenser and the solution was heated at 130.degree. C.
(bath temperature) with stirring in an open system under argon for
24 hrs. After cooling to room temperature, the consumption of
starting materials was determined by GC with m-xylene as an
internal standard, using a Carboxen 1000 column on a HP 690 series
GC system.
##STR00224##
TABLE-US-00018 TABLE 17 Coupling of amines and alcohols to generate
amides under neat conditions Conv. of alcohol Yield Entry Alcohol
Amine Amide (%) (isolated) 1 ##STR00225## ##STR00226## ##STR00227##
97 87.6 2 ##STR00228## ##STR00229## ##STR00230## 85.2 76.0 3
##STR00231## ##STR00232## ##STR00233## 92.3 82.0 4 ##STR00234##
##STR00235## ##STR00236## 87.0 79.6 5 ##STR00237## ##STR00238##
##STR00239## 82.7 73.0
E. Amidation Reaction by In-Situ Generation of the Catalyst from
the Precursor Ligand (Table 18):
[0296] To a Schlenk flask cooled under argon were added ligand.
BPy-.sup.tPNN (5) (0.01 mmol) and Ru-Precursor
RuHCl(CO)(PPh.sub.3).sub.3 (0.01 mmol), followed by benzene (1 mL)
and the solution was heated (.about.80.degree. C.) with stirring
for about 1 hr. After cooling to room temperature, were added an
alcohol (5 mmol), an amine (5 mmol), and t-BuOK (0.01 mmol) in
benzene (2 mL) and the solution was refluxed with stirring in an
open system under air for 24 hrs. After cooling to room
temperature, the consumption of starting materials was determined
by GC with m-xylene as an internal standard, using a Carboxen 1000
column on a HP 690 series GC system.
##STR00240##
TABLE-US-00019 TABLE 18 Coupling of amines and alcohols to generate
amides with in-situ generation of catalyst Yield Entry Alcohol
Amine Amide (isolated) 1 ##STR00241## ##STR00242## ##STR00243##
72.0 2 ##STR00244## ##STR00245## ##STR00246## 67.6
Purification of Amides:
[0297] After completion of the reaction, the solvent was removed
(Table 15-16, and 18) under vacuum and the resulting residue was
purified by the column chromatography on silica gel using
EtOAc/n-hexane.
Example 5: Polyamides Synthesis from Diols and Diamines
[0298] The applicants have unexpectedly discovered that the
catalysts of the present invention also catalyze the synthesis of
polyamides directly from diols and diamines. In some preferred
embodiments, 1,4-dioxane is used as a solvent. This polyamidation
reaction is general, environmentally benign and atom economical. It
proceeds under neutral reaction conditions without the use of
activators, condensing agents or other additives. Moreover, these
methods produce H.sub.2 as the only byproduct (Scheme 26).
##STR00247##
[0299] Upon refluxing a 1,4-dioxane solution containing equimolar
amounts of 1,6-hexanediol and 1,6-hexanediamine in the presence of
1 mol % of complex 1 under an argon atmosphere for 3 days, a white
solid separated out in the reaction mixture. The solid was filtered
off and successively washed with THF:EtOAc (1:1), dichloromethane
and 20% methanol in water. The resultant white solid was dried
under high vacuum at 80.degree. C. for 12 hrs to afford polymer 3a
in 82% yield (Table 19, entry 1). The solid was insoluble in MeOH,
THF, 1,4-dioxane and chlorinated solvents, partially soluble in
dimethylsulfoxide and dimethylformamide upon warming. The polyamide
obtained was dissolved in deuterated trifluoroacetic acid (TFA) or
trifluoroethanol (TFE) and characterized by NMR. The presence of
CH.sub.2 attached to the carbonyl group was confirmed by .sup.1H
NMR, showing a broad singlet at 2.39 ppm for the four hydrogen
atoms. A peak at 180.4 ppm in the .sup.13C{.sup.1H} NMR spectrum
and an IR band at 1633 cm.sup.-1 confirm the presence of the amide
C.dbd.O group. The average molecular weight M.sub.n of the
polyamide 3a was 16.6 kDa as measured by .sup.1H NMR using
trifluoroethanol (TFE) as a solvent. The obtained solid was
dissolved in TFA:CH.sub.3CN (1:1) and MALDI-TOF mass spectrum was
recorded using DHB (2,5-dihydroxybenzoic acid) as the matrix (FIG.
5A). The polyamide has three possible types of end groups
(amine-amine, amine-alcohol or alcohol-alcohol, compounds 3aa, 3ab
and 3ac, respectively) and it also might result in a cyclic form.
The spectrum revealed the highest molecular weight of 4195 Da,
which corresponds to a polyamide having 18 monomers with OH/OH end
groups. Due to insolubility of the polymer in DMF, GPC (gel
permeation chromatography) was not performed.
Different Types of End Groups in Polyamide 3a:
##STR00248##
[0301] The same reaction was performed using the bipyridine based
complex 3 as catalyst. After 3 days in refluxing dioxane polymer 3a
was formed as a white solid and isolated after work-up in 78%
yield. Analysis of the obtained solid exhibited a similar MALDI-TOF
pattern and .sup.1HNMR spectrum as observed with catalyst 1. Thus,
under these conditions complexes 1 and 3 exhibit similar catalytic
activity in the polyamidation reaction. However, using complex 3 it
is possible to perform the polyamidation reaction in the absence of
solvent, and using a lower catalyst loading. Thus, heating
equivalent amounts of 1,6-hexanediol and 1,6-hexanediamine with the
thermally stable complex 3 (0.2 mol %) in the absence of solvent at
130.degree. C. for 14 hrs, followed by heating to 190.degree. C.
for an hour under Argon flow and cooling to room temperature
resulted in a solid (Table 19, entry 16). The solid was washed with
THF, water, ethanol and hexane and dried under vacuum for 12 hrs
and isolated in 84% yield. The MALDI-TOF mass spectrum of this
solid exhibited a highest molecular weight of 4951 Da. The higher
molecular weight obtained under these conditions is likely due to
the higher temperatures employed and absence of solvent, allowing
polymerization in the melt.
[0302] Refluxing of 1,10-decanediol and 1,6-hexanediamine in
1,4-dioxane in the presence of 1 mol % of complex 1 resulted in 88%
yield of the polyamide 3b (Table 19, entry 2). The presence of the
amide functional group of 3b was confirmed by IR, showing an
absorption frequency at 1637 cm.sup.-1 and a signal at 181.6 ppm in
the .sup.13C{.sup.1H} NMR spectrum. The number average molecular
weight of 3b was found to be 10.3 kDa based on .sup.1H NMR spectra
using trifluoroethanol (TFE) as a solvent. A MALDI-TOF mass
spectrum indicated a molecular weight up to 4965 Da, which
corresponds to a polyamide comprised of 18 monomers. Due to
insolubility in DMF, GPC was not performed.
[0303] To further investigate the polyamidation reaction, various
combinations of diols and diamines were studied. Thus,
polyamidation reaction of 1,3-phenylenedimethanol and
1,6-hexanediamine with 1 mol % of complex 1 under argon atmosphere
for 3 days resulted in a solid which was isolated by filtration.
The solid was washed successively with THF: EtOAC (1:1),
dichloromethane and 20% MeOH in water, and finally dried under high
vacuum at 80.degree. C. to afford 82% of compound 3c (Table 19,
entry 3). The IR spectrum of the polyamide 3c showed the presence
of the NH group as broad peak at 3297 cm.sup.-1 and the amide
C.dbd.O peak at 1631 cm.sup.-1. The .sup.13C{.sup.1H} NMR spectrum
exhibited the C.dbd.O carbon at 165.8 ppm. Polyamide 3c was further
analyzed by MALDI-TOF by dissolving it in 80% TFA in acetonitrile
using DHB as matrix (FIG. 5B). It gave a series of peaks in the
range of 700-5932 Da. In an attempt to get a higher molecular
weight, polyamide 3c was refluxed with- or without
1,3-phenylenedimethanol in the presence of the complex 1. However,
a higher molecular weight was not observed. This might be due to
the insolubility of 3c in 1,4-dioxane. Due to insolubility in DMF,
GPC analysis was not performed.)
##STR00249##
[0304] In order to increase the solubility of the polyamides, ether
substituted aromatic diols were employed for the polymerization
reactions. Thus, the reaction of
(5-methoxy-1,3-phenylene)dimethanol and 1,6-hexanediamine gave 86%
of compound 3d (Table 19, entry 4) as a gummy solid and exhibited a
mass peak at 7199 Da in the MALDI-TOF spectrum using HBA+NaI as a
matrix and a solution of the polyamide 3d in TFA:dichloromethane
1:1 (FIG. 5C). The polyamide 3d was dissolved completely in warm
DMF and the molecular weight was measured using gel-permeation
chromatography (GPC) using DMF with 0.1% LiBr (wt/v) as the eluent
at a flow rate of 1.0 mL/min with column temperature at 50.degree.
C. yielding Mn=18.7 kDa with PDI of 2.08. The significantly lower
molecular weight in MALDI-TOF when compared with GPC is likely to
be a result of the high PDI. As previously reported, in case of
polydispersities higher than PDI=1.2, MALDI-TOF leads to
under-represented high-mass components with respect to the lower
mass components, resulting in significantly lower average molecular
weight values.
[0305] Exploring the scope of the polyamidation reaction,
equivalent amounts of 1,4-phenylenedimethanol and 1,6-hexanediamine
were refluxed with 1 mol % of complex 1 for 3 days, leading to 88%
yield of the crude compound 3e (Table 19, entry 6). Successive
washings with THF:EtOAC (1:1), dichloromethane, and 20% MeOH in
water resulted in 80% yield of the solid after drying under vacuum.
IR (peak at 1626 cm.sup.-1) and NMR spectra confirm the presence of
amide functionality. MALDI-TOF spectrum of the compound 3e in
TFA:CH.sub.3CN (1:1) revealed only oligomeric mixtures in the range
of 700-2500 Da (FIG. 5D). The mass unit of 2322 Da corresponds to
only 9 monomer units. Reaction of the shorter diamine
1,2-ethylenediamine with 1,4-phenylenedimethanol did not result in
significant progress of the polyamidation reaction, giving the
polyamide 3f in 63% yield (Table 19, entry 6), comprised of low
molecular weight oligomeric mixtures in the range of 600-1900.
[0306] Next, the polyamidation reaction was examined using
heteroaromatic diols. Thus, reaction of equivalent amounts of
pyridine-2,6-diyldimethanol and 1,6-hexanediamine catalyzed by 1
mol % 1, furnished after 3 days of reflux in 1,4-dioxane the
polyamide 3g (Table 19, entry 7) as a gummy insoluble solid which
separated out from the reaction mixture and after work up gave a
yield of 74%. The NMR and IR spectra confirm the presence of the
amide carbonyl group. GPC analysis was performed for polyamide 3g
using DMF as a solvent upon heating at 80.degree. C. The Mn
calculated from the GPC was 26.9 kDa with PDI of 1.98. The
polyamide 3g was also analyzed by MALDI-TOF. The MALDI-TOF mass
spectrum shows a series of peaks in the range of 600-4700 Da and
the highest mass peak at 4583 appeared with low intensity and
corresponds to 18 monomer units.
[0307] Next, aromatic diamines were studied for polyamidation
reactions. Upon refluxing 1,4-phenylenedimethanol and
1,3-phenylenedimethanamine, a white solid was obtained after 3 days
and was filtered off and dried under vacuum to provide 86% of
polyamide 3h (Table 19, entry 8). The NMR and MALDI-TOF of 3h (FIG.
5E) reveal high molecular weight oligomeric mixtures. The highest
mass unit obtained for the polyamide 3h was 3861 Da, having amine
end groups and corresponding to 14 monomer units in the chain. The
other oligomer peaks appear at 3594, 3328, 3062, 2796, 2530, 2264,
1732, 1466, 1200, 668 mass units. Further, heating the compound 3h
in refluxing 1,4-dioxane in the presence of 1 mol % of the catalyst
1 did not result in progress of the polymer chain (due to
insolubility in DMF, GPC analysis was not performed).
##STR00250##
[0308] The polyamidation reaction of 1,4-phenylenedimethanol and
1,4-phenylenedimethanamine afforded a mixture of oligomers 3i in
84% isolated yield (Table 19, entry 9). The MALDI-TOF spectrum
showed the highest mass unit of 3747 Da, indicating the presence of
14 monomer units. The reaction of 1,3-phenylenedimethanol and
1,3-phenylenedimethanamine led to 3j (Table 19, entry 10) in 78%
yield after workup, with a maximum mass unit of 1467, corresponding
to 5.5 monomer units. The reaction of 1,5-pentanediol and
1,4-phenylenedimethanamine gave 80% of compound 3k (Table 19, entry
11). Interestingly, 3k showed a series of mass peaks in the range
of 500-5200 Da corresponding to 22 monomer units. Reaction of
cyclohexane-1,4-diyldimethanol and 1,4-phenylenedimethanamine gave
66% of compound 3l (Table 15, entry 12), with peaks at 1912 Da
corresponding to only 7 monomeric units in MALDI-TOF spectrum. (Due
to insolubility in DMF, GPC analysis was not performed.)
[0309] Polyamidation of (5-methoxy-1,3-phenylene)dimethanol,
1,4-phenylenedimethanamine using 1 mol % catalyst 1 afforded
compound 3m (Table 19, entry 13) in 76% yield, with the mass
obtained at 4450 Da by MALDI-TOF, corresponding to 15 monomer
units. The GPC analysis of 3m showed a molecular weight Mn=5.3 kDa.
Similarly, the reaction of (5-(hexyloxy)-1,3-phenylene)dimethanol
and 1,3-phenylenedimethanamine gave 88% of the polyamide 3n (Table
19, entry 14). The number average molecular weight Mn of 3n was
11.3 kDa based on GPC analysis. Reaction of
(5-(hexyloxy)-1,3-phenylene)dimethanol and
1,4-phenylenedimethanamine gave 77% of the polyamide 3o (Table 15,
entry 15) with a mass of 3052 Da corresponding to 8 monomers based
on the MALDI-TOF spectrum.
[0310] Thus, a variety of polyamides have been synthesized having
different spacers in good yield. The synthesis of polyamides using
non-activated/non-ether linked substrates was demonstrated. The
synthesized polyamides were characterized by spectroscopic
techniques. The molecular weight was determined by .sup.1H NMR and
GPC analysis. The heteroaromatic polyamide 3g gave the highest
number average molecular weight compared to the corresponding
aliphatic and aromatic derived polyamides (3a and 3d respectively).
MALDI-TOF spectra of insoluble polyamides was also obtained. The
results are summarized in Table 19.
TABLE-US-00020 TABLE 19 Catalytic polyamidation using diols and
diamines..sup.[a] Highest molecular weight by Isolated MALDI- Entry
Diols Diamines Polyamides Yield (%) TOF (Da) Mn (10.sup.3) PDI 1
##STR00251## ##STR00252## ##STR00253## 82 4195 16.6.sup.[b] -- 2
##STR00254## ##STR00255## ##STR00256## 88 5000 10.3.sup.[b] -- 3
##STR00257## ##STR00258## ##STR00259## 82 5932 -- -- 4 ##STR00260##
##STR00261## ##STR00262## 86 7199 18.7.sup.[c] 2.08 5 ##STR00263##
##STR00264## ##STR00265## 80 2322 -- -- 6 ##STR00266## ##STR00267##
##STR00268## 63 1849 -- -- 7 ##STR00269## ##STR00270## ##STR00271##
74 4583 26.9.sup.[c] 1.98 8 ##STR00272## ##STR00273## ##STR00274##
86 3861 -- -- 9 ##STR00275## ##STR00276## ##STR00277## 84 3734 --
-- 10 ##STR00278## ##STR00279## ##STR00280## 78 1467 -- -- 11
##STR00281## ##STR00282## ##STR00283## 80 5200 -- -- 12
##STR00284## ##STR00285## ##STR00286## 66 1912 -- -- 13
##STR00287## ##STR00288## ##STR00289## 76 4450 5.3.sup.[c] 3.20 14
##STR00290## ##STR00291## ##STR00292## 88 -- 11.3.sup.[c] 2.18 15
##STR00293## ##STR00294## ##STR00295## 77 3052 5.4.sup.[c] 2.51
16.sup.[d] ##STR00296## ##STR00297## ##STR00298## 84 4951 -- --
.sup.[a]Complex 1 (0.01 mmol), diol (1 mmol), diamine (1 mmol) and
1,4-dioxane (2 mL) were refluxed at an oil bath temperature of
135.degree. C. in a Schlenk tube under Argon for 3 days. .sup.[b]Mn
was calculated from .sup.1H NMR .sup.[c]Mn was obtained from GPC
analysis .sup.[d]No solvent was used. Catalyzed by complex 3.
[0311] Thermogravimetric analyses (TGA) of the synthesized
polyamides were performed. Weight losses of 30% and 50% occurred at
similar temperatures and were not significantly dependent on
polymer structure (FIG. 6, Table 20). However, the aliphatic
polyamide 3a was less thermally stable and exhibited 83% weight
loss at 495.degree. C., while the arene-based polyamides 3d,m,n
(except 3g) exhibited 62-70% weight loss at 680.degree. C. (Table
20). The pyridine-based polyamide 3g was less stable, and exhibited
92% weight loss at 520.degree. C.
TABLE-US-00021 TABLE 20 Thermal studies of polyamides 3 at various
temperatures by TGA. T (.degree. C. at T (.degree. C. at 5% 10% T
(.degree. C. at T (.degree. C. at 50 T (.degree. C. at Mn weight
weight 30% % weight 70% weight Polyamides (10.sup.3) loss) loss)
weight loss) loss) loss) ##STR00299## 16.6 360 395 425 437 451
(70%) 495 (83%) ##STR00300## 18.7 120 170 430 458 680 (62%)
##STR00301## 26.9 100 380 458 470 478 (70%) 520 (92%) ##STR00302##
5.3 180 350 402 430 680 (64%) ##STR00303## 11.3 140 170 400 420 680
(64%)
Polymerization with Catalyst 3:
Synthesis of Nylon-6,6 by Catalytic Method Under Neat
Condition:
[0312] Complex 3 (0.01 mmol), 1,6-hexanediol (5 mmol), and
1,6-hexanediamine (5 mmol) were taken in a Schlenk flask under an
atmosphere of purified nitrogen in a glove box. The flask was
equipped with a condenser and gradually heated up to 135.degree. C.
(bath temperature) and continued the heating at the same
temperature with stirring in an open system under argon for 14 hrs.
During the heating effervescence was observed and the viscous
liquid became solid. After cooling to room temperature, the solid
thus obtained (low molecular weight oligomer; m.p=215.9.degree. C.
(by TGA)) was again heated up to 190.degree. C. using sand bath for
about an hour in an open system under argon. The resulting solid
was washed with THF, water, ethanol and finally with hexane (in
order to remove other impurities) and dried under vacuum for
overnight.
##STR00304##
DSC:
TABLE-US-00022 [0313] Temperature (.degree. C.) Weight loss (in %)
100 2.70 200 3.5 300 5.7 350 8.47 400 22.2 450 62.2 500 64.7 550
65.5 600 66.0 TGA: m.p 251.9.degree. C. (regenerated with the same
melting point after 4 cycles with freezing point of 216.1.degree.
C.). MOLDI-TOF: (matrix = DHB (2,5-dihydroxybenzoicacid), solvent =
trifluroethanol:CH.sub.2Cl.sub.2) up to 4800 Da.
[0314] In conclusion, polyamidation based on coupling of
non-activated diols and diamines, with extrusion of H.sub.2,
catalyzed by complexes 1 and 3 was developed. Guan et al have also
reported the utilization of the amidation reaction catalyzed by
complex 1 for the preparation of other polyamides, bearing
ether-functionalized spacers. The polyamidation reaction proceeds
under neutral conditions, with liberation of molecular hydrogen and
with no preactivation of the substrate being required. The reaction
can be applied to a variety of diols and diamines for the synthesis
of functional polyamides. The number average molecular weight of
the polymers obtained in our work was measured by .sup.1H NMR,
MALDI-TOF and, in case of the DMF-soluble polymers, by GPC
analysis. Mean molecular weights up to 26.9 kDa were obtained, with
polydispersities in the range of PDI=1.98-3.2. The variation in
chain lengths for different substrate combinations is probably
influenced by the different solubilities of the polymers. The
insoluble polyamides were characterised spectrosepoically and by
MALDI-TOF. It was observed that molecular weights determined by GPC
were significantly higher than those obtained by MALDI-TOF. This is
another example of the MALDI-TOF method favoring lower molecular
weights in case of PDI>1.2 The thermal properties of the
polyamides with different spacers were studied and it was found
that aliphatic/pyridinic spacer-based polyamides are less stable at
high temperature as compared with aromatic derived polyamides.
Polyamidation in absence of solvent was also demonstrated. This
simple, environmentally benign and general polymerization reaction
provides a new approach to the important area of polyamide
synthesis.
General Procedure for the Catalytic Direct Polyamidation of Diols
with Diamines Catalyzed by Complex 1:
[0315] Complex 1 (0.01 mmol), diol (1 mmol), amine (1 mmol), and
1,4-dioxane (2 mL) were added to schlenk flask under an atmosphere
of purified nitrogen in a glove box. The flask was equipped with a
condenser and the solution was refluxed with stirring in an open
system under argon flow for 3 days. During the course of the
reaction, a white colored solid separated out for 24 hrs. The
reflux was continued for 3 days. After cooling to room temperature,
the solid obtained was filtered and washed successively with
methanol and dichloromethane, or with THF:ethylacetate (1:1),
dichloromethane and 20% methanol in water to give the product
polyamide. T. The solid obtained was dried under vacuum at
80.degree. C. for 8-12 hrs. The products were analyzed by NMR. IR
and MALDI TOF.
Spectral Data for Polyamides:
Polyamide 3a:
##STR00305##
[0317] IR (KBr pellet): 3304, 2935, 2859, 1633, 1536, 1474, 1276
cm.sup.-1; .sup.1H NMR (TFA-d): 1.08 (broad s, 4H), 1.34 (broad s,
4H), 1.52 (broad s, 4H), 2.39 (broad s, 4H), 3.17 (broad s, 4H);
.sup.--C{.sup.1H}NMR (TFA-d): 26.8, 27.8, 29.5, 35.0, 44.5,
180.4.
[0318] MALDI-TOF (matrix: HBA (2,5-dihydroxybenzoic acid), solvent
acetonitrile:TFA): m/z=569 to 4195 Da. The spectrum of polyamide 3a
shows a series of peaks at 569 (3aa+H.sup.+(n=2)), 795
(3aa+H.sup.+(n=3)), 909 (3ab+H.sup.+(n=3)), 1022 (3c(n=4)), 1135
(3ab+H.sup.+(n=4)), 1247 (3aa+H.sup.+(n=5)), 1361
(3ab+H.sup.+(n=5)), 1474 (3ac(n=6)), 1588 (3ab+2H.sup.+(n=6)), 1700
(3ac (n=7)), 1814 (3ab+2H.sup.+(n=7)), 1926 (3ac (n=8)), 2041
(3ab+3H.sup.+(n=8)), 2153 (3ac+H.sup.+(n=9)), 2266
(3ab+2H.sup.+(n=9)), 2379 (3ac+H.sup.+(n=10)), 2494
(3ab+4H.sup.+(n=10)), 2606 (3ac+2H.sup.+(n=11)), 2720
(3ab+4H.sup.+(n=11)), 2832 (3ac+2H.sup.+(n=12)), 2947
(3ab+5H.sup.+(n=12)), 3058 (3ac+2H.sup.+(n=13)), 3170
(3ab+H.sup.+(n=13)), 3288 (3ac+6H.sup.+(n=14)), 3402
(3ab+8H.sup.+(n=14)), 3515 (3ac+7H.sup.+(n=15)), 3625, 3739
(3ac+5H.sup.+(n=16)), 3840, 3853, 3966 (3ac+5H.sup.+(n=17)), 4079
(3ab+6H.sup.+(n=13)), 4195 (3ac+9H.sup.+(n=18)).
Polyamide 3b:
##STR00306##
[0320] IR (KBr pellet): 3306, 2933, 2854, 1637, 1540, 1437, 1383,
1239 cm.sup.-1; .sup.1H NMR (TFA-d): 1.28 (broad s, 12H), 1.63
(broad s, 8H), 2.61 (broad s, 4H), 3.46 (broad s, 4H);
.sup.13C{.sup.1H}NMR (TFA-d): 27.6, 29.3, 30.4, 35.5, 44.7, 181.6.
MALDI-TOF (matrix: HBA (2,5-dihydroxybenzoic acid)+NaI, solvent
dichloromethane: TFA): m/z=1258 to 4965 Da.
Polyamide 3c:
##STR00307##
[0322] IR (KBr pellet): 3297, 2935, 2857, 1631, 1532, 1274
cm.sup.-1; .sup.1H NMR (DMSO-d): 1.32 (broad s, 4H, CH.sub.2), 1.51
(broad s, 4H, CH.sub.2), 3.23-3.32 (m, 4H, NCH.sub.2), 7.50 (t, 1H,
.dbd.CH), 7.91 (d, 2H, .dbd.CH), 8.26 (s, 1H, .dbd.CH), 8.54 (broad
s, 2H, NH). .sup.13C{.sup.1H}NMR (DMSO-d.sub.6): 26.2, 29.1, 39.2,
126.1, 128.2, 129.5, 134.9, 165.8, MALDI-TOF (matrix:
2,5-dihydroxybenzoic acid, solvent acetonitrile:TFA): m/z=700 to
5932 Da. The following peaks were observed: 5932 (3c (n=23)+24),
5918 (3c (n=23)+10), 5685 (3c (n=22)+23), 5671 (3c (n=22)+9), 5439
(3c (n=21)+23), 5425 (3c (n=21)+9), 5192 (3c (n=20)+22), 5178 (3c
(n=20)+8), 4946 (3c (n=19)+22), 4932 (3c (n=19)+8), 4699 (3c
(n=18)+21), 4685 (3c (n=18)+7), 4453 (3c (n=17)+21), 4439 (3c
(n=17)+7), 4207 (3c (n=16)+21), 4193 (3c (n=16)+7), 3961 (3c
(n=15)+21), 3947 (3c (n=15)+7), 3714 (3c (n=14)+20), 3700 (3c
(n=14)+6), 3468 (3c (n=13)+20), 3454 (3c (n=13)+6), 3219 (3c
(n=12)+17), 3205 (3c (n=12)+3), 2973 (3c (n=11)+17), 2959 (3c
(n=11)+3), 2727 (3c (n=10)+17), 2713 (3c (n=10)+3), 2481 (3c
(n=9)+17), 2467 (3c (n=9)+3), 2234 (3c (n=8)+16), 2220 (3c
(n=8)+2), 1988 (3c (n=7)+16), 1974 (3c (n=7)+2), 1742 (3c
(n=6)+16), 1728 (3c (n=6)+2), 1496 (3c (n=5)+16), 1482 (3c
(n=5)+2). The excess mass units are due to the protonation of the
amine functionality in TFA.
##STR00308##
Polyamide 3d:
[0323] .sup.1H NMR (DMSO-d.sub.6): 1.32 (broad s, 4H, CH.sub.2),
1.51 (broad s, 4H, CH.sub.2), 3.15 (s, 2H, NCH.sub.2), 3.38 (broad
s, 2H, NCH.sub.2), 3.82 (s, 3H, OCH.sub.3), 7.48 (s, 2H, .dbd.CH),
7.88 (s, 1H, .dbd.CH), 8.53 (broad s, 2H, NH); .sup.13C{.sup.1H}NMR
(DMSO-d.sub.6): 26.3, 29.1, 48.6, 55.6, 66.4, 115.0, 119.1, 136.3,
159.1, 165.6;
[0324] GPC (0.1% LiBr in DMF): Mn=18.7.times.10.sup.3 g/mol,
Mw=39.1.times.10.sup.3 g/mol
[0325] MALDI-TOF (matrix: 2,5-dihydroxybenzoic acid+NaI, solvent
dichloromethane:TFA): m/z=1116 to 7199 Da. The MALDI-TOF exhibited
a series of oligomeric peaks at 1116 (3d (n=4)+8H.sup.+,
NH.sub.2/OH), 1386 (3d (n=5)+2H.sup.+, NH.sub.2/OH), 1661 (3d
(n=6)+H.sup.+, NH.sub.2/OH), 1935 (3c(n=7)+3H.sup.+, cyclic), 2210
(3d (n=8)+2H.sup.+, cyclic), 2484 (3d (n=9), cyclic), 2762 (3d
(n=10)+2H.sup.+, cyclic), 3034, 3309, 3582, 3861, 4144 (3d (n=15),
NH.sub.2/OH), 4410, 4682, 4974 (3d (n=18)+2H.sup.+, NH.sub.2/OH),
5254 (3d (n=19)+6H.sup.+, NH.sub.2/OH), 5526 (3d (n=20)+2H.sup.+,
NH.sub.2/OH), 6102 (3d (n=22)+Na+3H.sup.+, NH.sub.2/OH), 6351 (3d
(n=23)+3, cyclic), 6641 (3d (n=24)+13, NH.sub.2/OH), 6904 (3d
(n=25), NH.sub.2/OH) and 7199 (3d (n=26)+23, cyclic).
Polyamide 3e:
##STR00309##
[0327] IR (KBr pellet): 3312, 2936, 2857, 1626, 1540, 1498, 1287
cm.sup.-1. .sup.1H NMR (DMSO-d.sub.6): 1.29-1.51 (m, 8H), 3.23
(broad s, 4H), 4.52 (s), 5.32 (broad s), 7.36 (d), 7.78 (d), 7.87
(s), 8.38 (t), 8.54 (broad s).
[0328] MALDI-TOF (matrix=DHB, solvent acetonitrile:TFA): m/z=743 to
2322 Da. The oligomeric peaks are 743 (3e (n=3)+H.sup.+), 989 (3e
(n=4)+H.sup.+), 1235 (3e (n=5)+H.sup.+), 1482 (3e (n=6)+2H.sup.+),
1728 (3e (n=7)+H.sup.+), 1973 (3e (n=8)+H.sup.+), 2221 (3e
(n=9)+3H.sup.+), 2464 (3e (n=10)+3H.sup.+).
Polyamide 3f:
##STR00310##
[0330] .sup.1H NMR (DMSO-d.sub.6): 2.67 (t), 3.44 (broad s), 4.53
(s), 7.37 (d), 7.80 (d), 7.90 (s), 8.56 (broad s), 8.71 (broad s).
MALDI-TOF (matrix: 2,5-dihydroxybenzoic acid, solvent:
acetonitrile:TFA): m/z=765 to 1835 Da. Oligomeric peaks were
observed at 765 (3f (n=4)+H.sup.+), 955 (3f (n=5)+H.sup.+), 1145
(3f (n=6)+H.sup.+), 1335 (3f (n=7)+H.sup.+), 1525 (3f
(n=8)+H.sup.+), 1715 (3f (n=9)+H.sup.+), 1849 (3f (n=9)+H.sup.+,
ending with OH/OH groups).
[0331] Polyamide 3g:
##STR00311##
[0332] IR (KBr pellet): 3325, 2932, 2859, 1662, 1538, 1445, 1243
cm.sup.-1; .sup.1H NMR (DMSO-d.sub.6): 1.27 (broad m, 4H,
CH.sub.2), 1.50 (broad m, 4H, CH.sub.2), 3.29 (broad s, 4H,
NCH.sub.2), 8.13 (m, 3H, .dbd.CH), 9.28 (broad s); .sup.3C NMR
(DMSO-d.sub.6): 13.9, 22.1, 26.1, 29.4, 30.9, 40.1, 124.1, 139.3,
148.8, 163;
[0333] GPC (0.1% LiBr in DMF): Mn=26.9.times.10.sup.3 g/mol,
Mw=53.3.times.10.sup.3 g/mol
[0334] MALDI-TOF (matrix: 2,5-dihydroxybenzoic acid, solvent
acetonitrile:TFA): m/z=610 to 4583 Da. The spectrum exhibits a
series of oligomeric peaks at 610 (3g (n=2), NH.sub.2/NH.sub.2),
742 (3g (n=3)+H.sup.+, cyclic), 907 (3g (n=3)+Na.sup.++3H.sup.+,
OH/OH), 989 (3g (n=4)+H.sup.+, cyclic), 1203, 1236 (3g
(n=5)+H.sup.+, cyclic), 1484 (3g (n=6)+2H.sup.+, cyclic), 1500,
1732 (3g (n=7)+3H.sup.+, cyclic), 1781, 1796, 1914, 1978 (3g
(n=8)+2H.sup.+, cyclic), 2063, 2079, 2092, 2210, 2226 (3g
(n=9)+3H.sup.+, cyclic), 2242, 2360, 2374, 2389, 2473 (3g
(n=10)+3H.sup.+, cyclic), 2492, 2507, 2657, 2671, 2685, 2789, 2803,
2836, 2953, 2968, 2981, 3085, 3100, 3132, 3250, 3264, 3278, 3396
(3g (n=13)+3Na.sup.+, NH.sub.2/NH.sub.2), 3427 (3g (n=13) +KK,
OK/OH), 3561, 3576 (3g (n=14)+2H.sup.+, NH.sub.2/NH.sub.2), 3679,
3709 (3g (n=15)+3H.sup.+, cyclic), 3726, 3844 (3g (n=15)+Na.sup.+,
NH.sub.2/NH.sub.2), 3975 (3g (n=16)+Na.sup.+, cyclic), 4449 (3g
(n=18) +3H.sup.+, cyclic), 4569 (3g (n=18)+7H.sup.+,
NH.sub.2/NH.sub.2).
Polyamide 3h:
##STR00312##
[0336] IR (KBr pellet): 3285, 2921, 1638, 1540, 1439, 1318
cm.sup.-1. .sup.1H NMR (DMSO-d.sub.6): 3.68 (s), 4.47 (broad s),
7.21-7.37 (broad m), 7.92-7.94 (m), 9.15 (broad s);
.sup.13C{.sup.1H}NMR (DMSO-d.sub.6): 42.7, 45.5, 62.6, 125.2,
125.8, 126.1, 127.2, 136.6, 139.6, 165.6; MALDI-TOF (matrix:
2,5-dihydroxybenzoic acid, solvent acetonitrile:TFA): m/z=668 to
3861 Da.
Polyamide 3i:
##STR00313##
[0338] IR (KBr pellet): 3346, 3056, 2923, 1640, 1540, 1496, 1317
cm.sup.-1; .sup.1H NMR (DMSO-d.sub.6): 3.59 (s), 4.43 (broad m),
7.23-7.27 (broad m), 7.37 (d), 7.83 (d), 7.94 (m), 9.13 (broad s);
.sup.13C{.sup.1H}NMR (DMSO-d.sub.6): 42.4, 45.1, 62.4, 126.0,
127.1, 132.7, 137.5, 137.9, 138.0, 138.3, 142.1, 145.9, 165.5,
166.1; MALDI-TOF (matrix: 2,5-dihydroxybenzoic acid, solvent
ACETONITRILE: TFA): m/z=400 to 3734 Da
Polyamide 3j:
##STR00314##
[0340] IR (KBr pellet): 3290, 3061, 2920, 1640, 1533, 1478, 1272
cm.sup.-1: .sup.1H NMR (DMSO-d.sub.6): 4.45-4.47 (m, 4H), 7.17-7.28
(m, 4H), 7.50 (t, 1H), 7.97 (d, 2H), 8.36 (s, 1H), 9.13 (broad m,
2H); .sup.13C{.sup.1H}NMR (DMSO-d.sub.6): 42.8, 66.4, 125.6, 126.5,
126.7, 128.5, 128.7, 129.9, 134.6, 139.7, 165.9.
[0341] GPC (0.1% LiBr in DMF): Mn=1.4.times.10.sup.3 g/mol,
Mw=5.01.times.10.sup.3 g/mol
[0342] MALDI-TOF (matrix: 2,5-dihydroxybenzoic acid, solvent
acetonitrile:TFA): m/z=500 to 1467 Da
Polyamide 3k:
##STR00315##
[0344] IR (KBr pellet): 3245, 3069, 2964, 2944, 1629, 1556, 1424,
1262 cm.sup.-1; .sup.1H NMR (DMSO-d.sub.6): 1.35-1.79 (m, 2H),
2.07-2.15 (m, 4H), 4.19-4.21 (broad m, 4H), 7.16 (broad s, 4H),
8.27 (broad m); .sup.13C{.sup.1H}NMR (DMSO-d.sub.6): 21.3, 21.9,
32.9, 35.0, 41.7, 46.8, 61.1, 127.0, 127.3, 138.1, 171.6. MALDI-TOF
(matrix=DHB, solvent acetonitrile:TFA): m/z=500 to 5200 Da
Polyamide 3l:
##STR00316##
[0346] IR (KBr pellet): 3282, 3060, 2934, 2860, 1633, 1551, 1443,
1386 cm.sup.-1; .sup.1H NMR (TFA-d): 7.26 (d), 7.19 (d), 7.11
(broad s), 4.44 (broad s), 4.18 (s), 3.83 (s), 2.56 (broad s), 2.00
(broad s), 0.92-1.82 (m); .sup.13C{.sup.1H}NMR (TFA-d): 29.3, 45.2,
46.9, 130.6, 131.0, 131.9, 139.2, 182.7. MALDI-TOF (matrix=DHB,
solvent acetonitrile:TFA): m/z=400 to 1912 Da
Polyamide 3m:
##STR00317##
[0348] IR (KBr pellet): 3294, 3063, 2935, 1642, 1593, 1536, 1423,
1283, 1061 cm.sup.-1. .sup.1H NMR (DMSO-d.sub.6): 3.56 (s), 3.81
(s), 4.42 (broad s), 7.24 (broad s), 7.54 (s), 7.96 (s), 9.11
(broad s); .sup.13C{.sup.1H}NMR (DMSO-d.sub.6): 42.5, 55.6, 66.3,
115.3, 118.7, 127.3, 135.9, 138.0, 159.1, 165.5, 165.8;
[0349] GPC (0.1% LiBr in DMF): Mn=5.39.times.10.sup.3 g/mol
Mw=17.3737.times.10.sup.3 g/mol
[0350] MALDI-TOF (matrix: 2,5-dihydroxybenzoic acid, solvent
acetonitrile:TFA): m/z=600 to 4450 Da
Polyamide 3n:
##STR00318##
[0352] .sup.1H NMR (TFA-D): 3.74 (s, 2H, NCH.sub.2), 3.88 (s, 2H,
NCH.sub.2), 4.60 (s, 3H, OCH.sub.3), 7.19-7.23 (m, 4H, Arom-H),
7.44 (s, 2H, Arom-H), 7.77 (s, 1H, Arom-H); .sup.13C{.sup.1H}NMR
(TFA-D): 47.2, 57.6, 68.7, 119.7, 121.1, 129.0, 129.8, 131.9,
136.3, 138.5, 162.3, 173.0; GPC (0.1% LiBr in DMF):
Mn=11.3.times.10.sup.3 g/mol. Mw=24.71.times.10.sup.3 g/mol
Polyamide 3o:
##STR00319##
[0354] IR (KBr pellet): 3325, 3079, 2929, 2869, 1644, 1592, 1532,
1434, 1333, 1062 cm.sup.-1; .sup.1H NMR (TFA-d): 7.78 (s, 1H), 7.46
(s, 2H), 7.21 (s, 4H), 4.56 (broad s, 4H), 3.94 (broad s, 2H), 1.65
(broad s, 2H), 1.26 (broad s, 2H), 1.15 (broad s, 4H), 0.70 (broad
s, 3H); .sup.13C{.sup.1H}NMR (TFA-d): 14.5, 24.1, 27.1, 30.5, 33.2,
47.0, 72.1, 120.4, 121.0, 130.5, 136.0, 137.8, 162.1, 173.0.
[0355] GPC (0.1% LiBr in DMF): Mn=5.4.times.10.sup.3 g/mol,
Mw=13.76.times.10.sup.3 g/mol
[0356] MALDI-TOF (matrix=DHB, solvent acetonitrile:TFA): up to
m/z=3052 Da
Example 6: Dehydrogenation of L-alaninol to Form Poly(Alanine)
Catalyzed by Ruthenium Complexes 1 or 3
##STR00320##
[0358] Complex 3 (0.01 mmol), L-alaninol (1 mmol), and 1,4-dioxane
(2 mL) were taken in a Schlenk flask under an atmosphere of
purified nitrogen in a glove box. The flask was taken out the glove
box, and equipped with a condenser. The solution was refluxed with
stirring in an open system under argon for 48 h. After cooling to
room temperature, the solvent was concentrated (.about.0.5 mL)
under reduced vacuum followed by addition of CH.sub.2Cl.sub.2 (in
order to remove the unreacted starting material). The white solid
precipitated out from the solution at .about.5.degree. C. (after 30
min) and was collected by simple filtration and washed with toluene
and dried under vacuum at 80.degree. C. for about 14 h to yield 77%
of polypeptide.
[0359] Using Complex 1 under the same procedure, 72% yield was
obtained.
Poly(alanine):
[0360] mp: 190-194.degree. C. (decompose) .sup.1H NMR (400 MHz,
DMSO-d.sub.6): 0.93 (broad s, 3H, CH.sub.3), 4.22-4.26 (m, 1H,
NCH), 8.00 (1H, CONH). .sup.13C{.sup.1H}NMR (300 MHz, TFA-d.sub.4):
20.0 (CH.sub.3), 21.7 (CH.sub.3), 53.1 (NCH), 53.4 (NCH), 174.9
(C.dbd.O).
[0361] MS (ES.sup.+): 165.3 (100%, cycloala-ala+Na, .sup.+), 240
(18%, M (n=1)+Na), 311 (65%. M (n=2)+Na), 382 (32%, M (n=3)+Na)),
453 (10%, M (n=4)+Na)), 524 (6%, M (n=5)+Na)). Maldi-Tof: 754 ((M
(n=8)+K+H)), 903 ((M (n=10)+2Na+H)), 1001 ((M (n=12)+3H)), 1150 ((M
(n=14)+10H)), 1248, 1396 ((M (n=17)+K+3H)), 1494 ((M (cyclic,
n=21)+3H), 1644 ((M (n=23)+7H)). [.alpha.]=-105.degree. (50 mg/5
mL, Acetic Acid)
Example 7: Coupling of Alcohols with Water to Form Acids with
Liberation of H.sub.2
##STR00321##
TABLE-US-00023 [0362] TABLE 21 Direct Transformation of Alcohols to
Acids Using Water Yield (%) Entry Alcohols Acids isolated 1
##STR00322## ##STR00323## 84 2 ##STR00324## ##STR00325## 88 3
##STR00326## ##STR00327## 78 4 ##STR00328## ##STR00329## 73 5
##STR00330## ##STR00331## 78 6 ##STR00332## ##STR00333## 80 7
##STR00334## ##STR00335## 74 8 ##STR00336## ##STR00337## 63 9
##STR00338## ##STR00339## 91 10 ##STR00340## ##STR00341## 89 11
##STR00342## ##STR00343## 83
General Procedure for the Dehydrogenation of Alcohols to Acids
Catalyzed by 3:
[0363] A mixture of an alcohol (10 mmol), degassed double distilled
water (2 mL) and sodium hydroxide (11 mmol) were combined in a
Schlenk-flask under argon atmosphere. The biphasic mixture was
degassed by purging with argon for 10 min. Complex 3 (0.02 mmol)
was added and the reaction mixture was refluxed under a stream of
argon. After 18 h water was added (10 mL), and the mixture was
extracted with diethyl ether (2.times.10 mL). The aqueous phase was
acidified with 5N HCl and extracted with ethyl acetate (5.times.20
mL). The combined extracts were washed with brine (25 mL), dried
over Na.sub.2SO.sub.4, and evaporated under reduced pressure,
affording the pure acid.
Example 8--General Experimental (Ruthenium Complex)
[0364] All experiments with metal complexes and phosphine ligands
were carried out under an atmosphere of purified nitrogen in a
Vacuum Atmospheres glove box equipped with a MO 40-2 inert gas
purifier or using standard Schlenk techniques. All solvents were
reagent grade or better. All non-deuterated solvents were refluxed
over sodium/benzophenone ketyl and distilled under argon
atmosphere. Deuterated solvents were used as received. All solvents
were degassed with argon and kept in the glove box over 4 .ANG.
molecular sieves. Most of the chemicals used in catalysis reactions
were purified according to standard procedure (or by vacuum
distillation/sublimation). The 6-methyl-2,2'-bipyridine (BPy-Me)
and 6-chloromethyl-2,2'-bipyridine (BPy-CH.sub.2Cl) precursors
(Schubert et al.; Smith et al.), and RuHCl(PPh.sub.3).sub.3(CO)
(Ahmad et al.) were prepared according to literature
procedures.
[0365] Thin layer chromatography (TLC) was performed on Merck
1.05554 aluminum sheets precoated with silica gel 60 F254 and the
spots visualized with UV light at 254 nm or under iodine. Column
chromatography purifications were performed by flash chromatography
using Merck silica gel 60 (0.063-0.200 mm). .sup.1H. .sup.13C and
.sup.31P NMR spectra were recorded at 300, 75, and 122 MHz,
respectively, using Bruker AMX-300 NMR spectrometers. .sup.1H and
.sup.13C{.sup.1H} NMR chemical shifts are reported in ppm downfield
from tetramethylsilane. .sup.31P NMR chemical shifts are reported
in parts per million downfield from H.sub.3PO.sub.4 and referenced
to an external 85% solution of phosphoric acid in D.sub.2O.
Abbreviations used in the NMR follow-up experiments: br, broad; s,
singlet; d, doublet: t, triplet; q, quartet; m, multiplet. IR
spectra were recorded on a Nicolet FT-IR spectrophotometer. Mass
spectra were recorded on Micromass Platform LCZ 4000, using Electro
Spray Ionization (ESI) mode. Elemental analysis were performed on
Thermo Finnigan Italia S.p.A-FlashEA 1112 CHN Elemental Analyzer
(manufactured by Thermo Finnigam Italia S.p.A).
Synthesis of Ligand 5:
6-methyl-2,2'-bipyridine (BPy-Me)
##STR00344##
[0367] Prepared according to procedure 5 described in Org. Lett.
2000, 3373 (Schubert et al.). .sup.1H NMR (CDCl.sub.3): 2.61 (s,
3H, CH.sub.3), 7.13 (d, 1H, J.sub.HH=7.80 Hz, H-5), 7.26-7.27 (m,
1H, H-5'), 7.57 (t, 1H, J.sub.HH=7.80 Hz, H-4), 7.74-7.79 (m, 1H,
H-4'), 8.17 (d, 1H, J.sub.HH=7.50 Hz, H-3), 8.40 (d, 1H,
J.sub.HH=8.10 Hz, H-3'), 8.64-8.67 (m, 1H, H-6').
6-chloromethyl-2,2'-bipyridine (BPy-CH.sub.2Cl)
##STR00345##
[0369] Prepared according to procedure described in Org. Synth.
2002, 78, 82 (Smith et al.). .sup.1H NMR (CDCl.sub.3): 4.75 (s, 2H,
CH.sub.2), 7.27-7.32 (m, 1H), 7.49 (d, 1H, J.sub.HH=7.50 Hz),
7.77-7.86 (m, 2H), 8.33 (d, 1H, J.sub.HH=7.80 Hz), 8.43 (d, 1H,
J.sub.HH=8.10 Hz), 8.66-8.68 (m, 1H).
6-di-tert-butylphosphinomethyl-2,2'-bipyridine (BPy-.sup.tPNN)
5
##STR00346##
[0371] To an oven dried 50 mL pressure vessel equipped with
magnetic stirring bar was added 6-chloromethyl-2,2'-bipyridine
(BPy-CH.sub.2Cl) (2.05 g, 10.00 mmol), di-tert-butyl phosphine
(1.75g, 12.00 mmol), and 30 mL MeOH in a nitrogen glove box. The
flask was sealed and heated at 50.degree. C. for 48 hrs with
stirring outside the glove box. After cooling, it was reintroduced
to the glove box, triethylamine (1.82g, 18.00 mmol) was added and
the reaction mixture was stirred at room temperature for 1 hr. The
solvents were removed under reduced pressure to obtain a white
solid. The residue was washed with ether (3.times.20 mL) and the
ether filtered and was removed under reduced pressure to yield a
white solid. It was recrystallized from MeOH at ca. -30.degree. C.
to yield 2.67 g (85%) of
6-di-tert-butylphosphinomethyl-2,2'-bipyridine (BPy-.sup.tPNN).
[0372] Alternative Method for the Preparation of BPy-.sup.tPNN
(5):
[0373] An oven-dried 500 mL three-necked round bottom flask
equipped with an argon inlet, a stirring bar, dropping funnel and
one rubber septum was cooled under a stream of argon. The flask was
then charged with 6-methyl-2,2'-bipyridine (3.40 g, 20 mmol) in 80
mL dry ether. The solution was cooled to 0.degree. C. and 13.4 mL
of a 1.8 M solution of commercial lithium diisopropylamide (LDA) in
heptane/THF/ethylbenzene (24 mmol) was added dropwise via syringe
during 15 minutes. The resulting brown colored mixture was stirred
for 1 hr at 0.degree. C. and then cooled to -78.degree. C. and a
solution of di-tert-butylchlorophosphine (4.34 g, 24 mmol) in 30 mL
dry ether was added dropwise (.about.30 min) to it. The stirring
was continued for a further 1 hr at -78.degree. C. and the mixture
was allowed to slowly warm up to room temperature and stirred
overnight. To this reaction mixture was added 40 mL of degassed
water and the ether phase was separated under N.sub.2 atmosphere.
The aqueous phase was extracted with ether (2.times.50 mL). The
combined ether solutions were dried over anhydrous
Na.sub.2SO.sub.4, filtered under N.sub.2 pressure, and the solvent
was removed under vacuum to get brownish-white solid. This was
purified by column chromatography in the nitrogen glove box (basic
alumina:hexane:ether (10:1) as eluent) to yield 4.46 g (71%) of
6-di-tert-butylphosphinomethyl-2,2'-bipyridine (BPy-.sup.tPNN) as a
white solid.
[0374] .sup.31P{.sup.1H}NMR (CD.sub.2Cl.sub.2): 37.57 (s). .sup.1H
NMR (CD.sub.2Cl.sub.2): 1.17 (d, J.sub.PH=11.0 Hz, 18H,
P(C(CH.sub.3).sub.3).sub.2), 3.12 (d, J.sub.PH=3.3 Hz, 2H,
P--CH.sub.2), 7.24 (ddd, J.sub.HH=7.5 Hz, J.sub.HH=4.8H,
J.sub.PH=1.2 Hz, 1H, H-5'), 7.40 (td, J.sub.HH=7.8 Hz,
J.sub.PH=1.0H, 1H, H-5), 7.67 (t, J.sub.HH=7.8 Hz, 1H, H-4), 7.76
(dt, J.sub.HH=7.8 Hz, J.sub.HH=1.8H, 1H, H-4'), 8.14 (br d,
J.sub.HH=7.8 Hz, 1H, H-3), 8.40 (td, J.sub.HH=8.0 Hz, J.sub.HH=1.0
Hz, 1H, H-3'), 8.62-8.64 (m, 1H, H-6'). .sup.13C{.sup.1H}NMR
(CDCl.sub.3): 29.61 (s, P(C(C.sub.aH.sub.3).sub.3), 29.74 (s,
P(C(C.sub.bH.sub.3).sub.3), 31.77 (d, J.sub.PC=24.0 Hz, PCH.sub.2),
31.93 (d, J.sub.PC=21.8, P(C(CH.sub.3).sub.3).sub.2), 117.72 (s,
C-3), 121.04 (s, C-3'), 123.38 (s, C-5), 123.85 (d, J.sub.PC=8.4
Hz, C-5), 136.75, (s, C-4'), 136.91 (s, C-4), 148.98 (s, C-6'),
154.97 (s, C-2), 156.49 (s, C-2'), 161.43 (d, J.sub.PC=13.8, C-6).
Assignment of signals was confirmed by DEPT 135, COSY, and HSQC.
Anal. Calcd. for C.sub.19H.sub.27N.sub.2P: C, 72.58; H, 8.66.
Found: C, 72.75, H, 8.83.
Synthesis of Complexes 4 and 3:
##STR00347##
[0375] Synthesis of RuHCl(CO)(BPy-.sup.tPNN) 4
##STR00348##
[0377] To an oven dried 25 mL pressure vessel equipped with
magnetic stirring bar was added ligand, BPy-.sup.tPNN (5) (157 mg,
0.52 mmol), RuHCl(COXPPh.sub.3).sub.3 (476 mg, 0.5 mmol), and 12 mL
dry THF in a nitrogen glove box. The flask was sealed and heated at
65.degree. C. for 8 hrs with stirring outside the glove box, then
cooled to room temperature to lead to reddish-brown solid. It was
reintroduced to the glove box, and the solvent was decanted and the
solid thus obtained was washed with ether (3.times.3 mL), then
dried under vacuum to give pure complex 4 (212 mg, 88%).
[0378] .sup.31P{.sup.1H}NMR (CD.sub.2Cl.sub.2): 107.01 (s). .sup.1H
NMR (CD.sub.2Cl.sub.2): -15.26 (d, .sup.2J.sub.PH=24.6 Hz, 1H,
Ru--H), 1.27 (d, J.sub.PH=13.2 Hz, 9H, P(C(CH.sub.a3).sub.3), 1.49
(d, J.sub.PH=13.8 Hz, 9H, P(C(CH.sub.b3).sub.3). AB system centered
at 3.06 and 3.75 (ABq, J.sub.HH=16.8 Hz and J.sub.PH=10.2 Hz, 2H,
PCH.sub.aH.sub.b), 7.44-7.46 (m, 1H, H-5'), 7.57 (d, J.sub.HH=7.8
Hz, 1H, H-5), 7.83-7.90 (m, 2H, H-4 and H-4'), 7.97 (d,
J.sub.HH=8.1 Hz, 1H, H-3), 8.05 (d, J.sub.HH=7.8 Hz, 1H, H-3),
9.12-9.15 (br m, 1H, H-6'). .sup.13C{.sup.1H}NMR
(CD.sub.2Cl.sub.2): 28.63 (d, J.sub.PC=3.8 Hz,
P(C(C.sub.aH.sub.3).sub.3), 29.79 (d, J.sub.PC=4.5 Hz,
P(C(C.sub.bH.sub.3).sub.3), 36.20 (d, J.sub.PC=24.0 Hz, PCH.sub.2),
37.21 (d, J.sub.PC=15.0 Hz, P(C.sub.a(CH.sub.3).sub.3), 37.27 (d,
J.sub.PC=15.8 Hz, P(C.sub.b(CH.sub.3).sub.3), 119.39 (s, C-3),
121.31 (s, C-3'), 122.82 (d, J.sub.PC=9.0 Hz, C-5), 126.11 (s,
C-5), 136.30, (s, C-4'), 137.26 (s, C-4), 153.19 (s, C-6), 154.80
(s, C-2), 155.89 (s, C-2'), 161.72 (br d, J.sub.PH=14 Hz, C-6),
207.37 (d, J.sub.PC=15.0 Hz, Ru--CO). IR (KBr, pellet): 1990
(vRu--H), 1906 (vCO) cm.sup.-1. Anal. Calcd. for
C.sub.20H.sub.28N.sub.2OPClRu: C, 50.05; H, 5.88. Found: C, 50.28,
H, 6.01. MS (ESI, MeOH): 446 (100%, (M-Cl).sup.+). The crystal
suitable for a single-crystal X-ray diffraction was obtained from
CD.sub.2Cl.sub.2 (20 mg in 0.3 mL) at -32.degree. C. after several
days.
X-Ray Crystal Structure Determination of 4:
[0379] A crystal was mounted in a MiTeGen loop and flash frozen in
a nitrogen stream at 120K. Data were collected on a Nonius Kappa
CCD diffractometer mounted on a FR590 generator equipped with a
sealed tube with MoK.alpha. radiation (.lamda.=0.71073 .ANG.) and a
graphite monochromator. The structure was solved using direct
methods with SHELXS-97 based on F.sup.2.
Complex 4:
[0380] C.sub.20H.sub.28N.sub.2OPClRu, Orange, prism,
0.16.times.0.16.times.0.12 mm.sup.3, monoclinic, P2.sub.1/c,
.alpha.=8.1380(2) .ANG., b=14.3161(2) .ANG., c=17.5802(3) .ANG.,
.beta.=92.253(1) deg., V=2046.59(7) .ANG..sup.3. Z=4, fw=479.93,
D.sub.c=1.558 Mg/m.sup.3, .mu.=0.986 mm.sup.-1. Full matrix
least-squares of refinement based on F.sup.2 gave an agreement
factor R=0.0326 for data with I>2.sigma.(I) and R=0.0435 for all
data (4691 reflections) with a goodness-of-fit of 0.994. Idealized
hydrogen atoms were placed and refined in the riding mode, with the
exception of the hydride ligand H1-Ru, which was located in the
difference map and refined independently.
Synthesis of [RuH(CO)(BPy-.sup.tPNN*)] 3
##STR00349##
[0382] (a) To a suspension of complex 4 (48 mg, 0.1 mmol) in dry
THF (5 ml) in a nitrogen glove box was added KO.sup.tBu (11.2 mg,
0.1 mmol) at ca. -32.degree. C. and the mixture was stirred at
-32.degree. C. for 3 hrs and the solvent was removed under vacuum.
The product was extracted using a benzene: pentane (3:7) mixture
(3.times.5 mL) and passed through celite. The resulting solution
was concentrated under vacuum to ca. 0.5 mL and 5 mL pentane was
added to cause precipitation of a greenish-block solid, which was
filtered and washed with pentane (3.times.2 mL), then dried under
vacuum (42 mg, 94%).
[0383] (b) 9.6 mg, of RuHCl(CO)(BPy-.sup.tPNN) 4 (0.02 mmol) were
placed in to a J. Young NMR tube, dissolved in .about.0.4 mL of
C.sub.6D.sub.6 and 1 eq. of potassium bis(trimethylsilyl)amide
(KHMDS, 4.0 mg) was added to generate dark-green/black complex 3.
The resulting complex 3 exhibits a broad singlet at 92.70 in
.sup.31P{.sup.1H}NMR, and the hydride ligand appears as broad
doublet at -25.73 ppm (.sup.2J.sub.PH=23 Hz) in the .sup.1HNMR
spectrum.
[0384] .sup.31P{.sup.1H}NMR (THF-d; 202 MHz): 95.64 (s). .sup.1H
NMR (THF-d; 500 MHz): -20.93 (d, .sup.2J.sub.PH=25.0 Hz, 1H,
Ru--H), 1.25 (d, J.sub.PH=13.0 Hz, 9H, P(C(CH.sub.a3).sub.3), 1.28
(d, J.sub.PH=12.5 Hz, 9H, P(C(CH.sub.b3).sub.3), 3.36 (s, 1H,
.dbd.CHP), 6.00 (d, 1H, H-3), 6.12 (d, J.sub.HH=9.0 Hz, 1H, H-5),
6.37 (d, J.sub.HH=8.0 Hz, 1H, H-4), 7.19 (t, J.sub.HH=6.0 Hz, 1H,
H-5'), 7.65-7.71 (m, 2H, H-3' and H-4'), 8.89-8.90 (br m, 1H,
H-6'). .sup.13C{.sup.1H}NMR (THF-d; 125 MHz): 30.09 (d,
J.sub.PC=5.0 Hz, P(C(C.sub.aH.sub.3).sub.3), 30.19 (d, J.sub.PC=3.8
Hz, P(C(CH.sub.3).sub.3), 36.20 (d, J.sub.PC=22.5 Hz,
P(C.sub.a(CH.sub.3).sub.3), 37.45 (d, J.sub.PC=27.5 Hz,
P(C.sub.b(CH.sub.3).sub.3), 66.56 (d, J.sub.PC=48.8 Hz, .dbd.CHP),
99.87 (s, C-3), 117.64 (d, J.sub.PC=17.5 Hz, C-5), 121.47 (s,
C-3'), 124.60, (s, C-5'), 131.81 (s, C-4), 136.92 (s, C-4'), 153.21
(s, C-6'), 155.06 (s, C-2), 161.55 (s, C-2'), 168.97 (d,
J.sub.PC=16.3 Hz, C-6), 208.1 (d, J.sub.PC=13.8 Hz, Ru--CO).
Assignment of signals was confirmed by DEPT 135, COSY, and HSQC. IR
(KBr, pellet): 2017 (vRu--H), 1907 (vCO) cm.sup.-1. Anal. Calcd.
for C.sub.20H.sub.27N.sub.2OPRu: C, 54.17; H, 6.14. Found: C,
54.32, H, 6.37. MS (ESI, CH.sub.3CN): 445 (100%, (M+1).sup.+).
Synthesis of 6-di-iso-propylphosphinomethyl-2,2'-bipyridine
(BPy-.sup.iso(Pr)PNN) 6
##STR00350##
[0386] To an oven dried 50 mL pressure vessel equipped with
magnetic stirring bar was added 6-chloromethyl-2,2'-bipyridine
(BPy-CH.sub.2C1) (1.03 g, 5.00 mmol), di-iso-propyl phosphine (710
mg, 6.00 mmol), and 15 mL MeOH in nitrogen glove box. The flask was
sealed and heated at 50.degree. C. for 48 hrs with stirring outside
the glove box. After cooling, it was reintroduced to the glove box,
triethylamine (910 mg, 9.00 mmol) was added and the reaction
mixture was stirred at room temperature for 1 hr. The solvents were
removed under reduced pressure to obtain a white solid. The residue
was washed with ether (2.times.10 mL), filtered and was removed
under reduced pressure to yield a pale yellow liquid. It was
further purified by basic alumina chromatography under the glove
box using hexane as an eluent to yield pure 6.
[0387] Yield=874 mg (61%). .sup.31P{.sup.1H}NMR (CD.sub.2Cl.sub.2):
15.84 (s). .sup.1H NMR (CD.sub.2Cl.sub.2): 1.11 (dd, J.sub.PH=13.8
Hz, J.sub.HH=7.2 Hz, 6H, P(CH(CH.sub.a3).sub.2), 1.17 (dd,
J.sub.PH=14.4 Hz, J.sub.HH=7.2 Hz, 6H, P(CH(CH.sub.b3).sub.2), 1.89
(sep d, J.sub.HH=7.2 Hz, J.sub.PH=2.1 Hz, 2H,
P(CH(CH.sub.a/b3).sub.2), 3.12 (d, J.sub.PH=1.8 Hz, 2H,
P--CH.sub.2), 7.28-7.34 (m, 1H, H-5'), 7.33 (d merged with m, 1H,
J.sub.HH=7.8 Hz, H-5), 7.73 (t, J.sub.HH=7.8 Hz, 1H, H-4), 7.82
(dt, J.sub.HH=7.8 Hz, J.sub.HH=1.8H, 1H, H-4'), 8.21 (d,
J.sub.Hn=7.8 Hz, 1H, H-3), 8.46 (br d, J.sub.HH=8.1 Hz, 1H, H-3'),
8.67-8.69 (m, 1H, H-6'). .sup.13C{.sup.1H}NMR (CD.sub.2Cl.sub.2):
18.89 (d, J.sub.PC=10.5 Hz, P(C(C.sub.aH.sub.3).sub.2), 19.62 (d,
J.sub.PC=15.0 Hz, P(C(C.sub.bH.sub.3).sub.2), 23.62 (d,
J.sub.PC=15.0 Hz, PCH.sub.2), 32.45 (d, J.sub.PC=22.5,
P(C(C.sub.a/bH.sub.3).sub.2), 117.63 (s, C-3), 120.77 (s, C-3'),
123.50 (s, C-5'), 123.60 (s, C-5), 136.68, (s, C-4'), 136.90 (s,
C-4), 149.06 (s, C-6'), 155.18 (s, C-2), 156.38 (s, C-2'), 161.34
(d, J.sub.PC=9.0, C-6). Assignment of signals was confirmed by DEPT
135. Anal. Calcd. for C.sub.17H.sub.23N.sub.2P: C, 71.30; H, 8.10.
Found: C, 71.52, H, 8.34.
Synthesis of RuHCl(CO)(BPy-.sup.iso(Pr)PNN) 7
##STR00351##
[0389] To a suspension of RuHCl(CO)(PPh.sub.3).sub.3 (476 mg, 0.5
mmol) in dry THF (12 ml) in a nitrogen glove box was added ligand,
BPy-.sup.iso(Pr)PNN (6) (143 mg, 0.5 mmol), and the mixture was
stirred for overnight at room temperature to obtain reddish-brown
solid. The solvent was decanted and the solid thus obtained was
washed with pentane (3.times.5 mL), then dried under vacuum to give
pure complex 7 (206 mg, 91%).
[0390] .sup.31P{.sup.1H} NMR (see below) of complex shows a singlet
at 95.38 ppm. The .sup.1H NMR spectrum of the complex exhibits a
doublet resonance at -15.26 ppm (.sup.2J.sub.PH=24.6 Hz) for Ru--H.
The "arm" methylene protons give rise ABq system centered at 3.65
and 3.77 ppm with J.sub.HH=17.4 Hz and J.sub.PH=10.2 Hz. The
BPy-C6'H appears as multiplet at 9.18-9.26 ppm, representing an
upfield shift of ca. 0.53 ppm relative to the corresponding proton
of the ligand (8.67-8.69 ppm), upon complexation with
ruthenium.
[0391] .sup.31P{.sup.1H}NMR (CD.sub.2Cl.sub.2): 95.38 (s). .sup.1H
NMR (CD.sub.2Cl.sub.2): -14.75 (d, J.sub.PH=23.7 Hz, 1H, Ru--H),
0.95 (dd, J.sub.PH=15.3 Hz, J.sub.HH=6.9 Hz, 3H,
P(CH(CH.sub.a3).sub.2), 1.12 (dd, J.sub.PH=17.1 Hz, J.sub.HH=6.9
Hz, 3H, P(CH(CH.sub.3).sub.2), 1.38 (dd, J.sub.PH=13.2 Hz,
J.sub.HH=7.2 Hz, 3H, P(CH(CH.sub.b3).sub.2), 1.49 (dd.
J.sub.PH=16.8 Hz, J.sub.HH=7.2 Hz, 3H, P(CH(CH.sub.b3).sub.2),
2.16-2.33 (m, 1H, P(CH(CH.sub.a,a'3) 2), 2.66-2.82 (m, 1H,
P(CH(CH.sub.b,b'3).sub.2), AB system centered at 3.65 and 3.77
(ABq, J.sub.HH=17.4 Hz and J.sub.PH=10.2 Hz, 2H, PCH.sub.aH.sub.b),
7.44-7.48 (m, 1H, H-5), 7.53 (d, J.sub.HH=7.8 Hz, 1H, H-5),
7.83-7.94 (m, 2H, H-4 and H-4'), 7.97 (d merged with m,
J.sub.HH=8.1 Hz, 1H, H-3), 8.06 (d, J.sub.HH=8.1 Hz, 1H, H-3'),
9.18-9.26 (br m, 1H, H-6'). .sup.13C{.sup.1H}NMR
(CD.sub.2Cl.sub.2): 17.35 (d, J.sub.PC=4.5 Hz,
P(C(C.sub.aH.sub.3).sub.2), 18.21 (s, P(C(C.sub.a'H.sub.3).sub.2),
19.24 (d, J.sub.PC=5.3 Hz, P(C(C.sub.bH).sub.2), 20.15 (d,
J.sub.PC=4.5 Hz, P(C(C.sub.b'H.sub.3).sub.2), 24.58 (d,
J.sub.PC=29.3 Hz, P(C.sub.a(CH.sub.3).sub.2), 28.12 (d,
J.sub.PC=24.0 Hz, P(C.sub.b(CH.sub.3).sub.2), 40.94 (d,
J.sub.PC=21.8 Hz, PCH.sub.2), 119.63 (s, C-3), 122.59 (s, C-3'),
122.80 (d, J.sub.PC=9.8 Hz, C-5), 126.00 (s, C-5'), 136.25, (s,
C-4'), 137.02 (s, C-4), 153.06 (s, C-6'), 154.47 (s, C-2), 155.99
(s, C-2'), 161.11 (d, J.sub.PC=4.5, C-6), 207.31 (d, J.sub.PC=15.0
Hz, Ru--CO). IR (KBr, pellet): 1962 (vRu--H), 1915 (vCO) cm.sup.-1.
Anal. Calcd. for C.sub.18H.sub.24N.sub.2OPClRu: C, 47.84; H, 5.35.
Found: C, 48.01, H, 5.54.
Synthesis of 6-(N,N-diethyl)aminomethyl-2,2'-bipyridine (BPy-NNN)
8
##STR00352##
[0393] A solution of 6-chloromethyl-2,2'-bipyridine
(BPy-CH.sub.2C1) in 20 mL of dry THF was cooled to 0.degree. C. and
a solution diethylamine (5 mL) in THF (10 mL) was added to it
dropwise over 10 min. The mixture was allowed to slowly warm up to
room temperature and refluxed under N.sub.2 for 6 hrs. The solvent
was removed under vacuum and the residue was dissolved in 50 mL of
diethyl ether and washed with 2.times.10 mL of a 10% aqueous KOH
solution. The organic phase was separated and dried over
Na.sub.2SO.sub.4 and the ether was removed under vacuum. The
residue was purified by flash chromatography (silica gel; EtOAc:
Hexane as eluent), yielding (78% yield)
6-(N,N-diethyl)aminomethyl-2,2'-bipyridine (BPy-NNN) 8 as a
yellow-brown oil.
[0394] .sup.1H NMR (CDCl.sub.3): 1.15 (t, J.sub.HH=7.2 Hz, 6H,
N(CH.sub.2CH.sub.3).sub.2), 2.70 (q, J.sub.HH=7.2 Hz, 4H,
N(CH.sub.2CH.sub.3).sub.2), 7.28-7.32 (m, 1H, H-5'), 7.54 (d,
J.sub.HH=7.8 Hz, 1H, H-5), 7.77-7.84 (m, 2H, H-4 and H-4'), 8.26
(d, J.sub.HH=8.1 HZ, 1H, H-3), 8.41 (br d, J.sub.HH=8.1 Hz, 1H,
H-3'), 8.67-8.69 (m, 1H, H-6'). .sup.13C{.sup.1H}NMR (CDCl.sub.3):
11.69 (s, N(CH.sub.2CH.sub.3).sub.2), 47.36 (s,
N(CH.sub.2CH.sub.3).sub.2), 58.81 (s, Arm-CH.sub.2), 119.33 (s,
C-3), 121.17 (s, C-3), 123.26 (s, C-5'), 123.58 (s, C-5), 136.87,
(s, C-4'), 137.33 (s, C-4), 149.14 (s, C-6'), 155.34 (s, C-2),
156.33 (s, C-2'), 158.68 (br s, C-6). Assignment of signals was
confirmed by DEPT 135. Anal. Calcd. for C.sub.15H.sub.19N.sub.3: C,
74.65; H, 7.94. Found: C, 74.81, H, 8.08.
Example 9--Borohydride Complexes
[0395] As contemplated herein, certain reactions described herein,
such as novel ester synthesis, novel amide synthesis, as well as
the dehydrogenation of secondary alcohols to ketones, and
hydrogenation of esters to alcohols, can be effectively
accomplished also with stable, readily synthesized PNN- and PNP Ru
borohydride complexes, in absence of base, under neutral
conditions, and in absence of hydrogen acceptor.
##STR00353##
Synthesis and Characterization of
[RuH(.eta..sup.2-BH.sub.4)(.sup.tBu-PNP]2'
[0396] The N.sub.2-bridged binuclear Ru(II) complex
[(.sup.tBu-PNP)RuCl.sub.2].sub.2(.mu.-N.sub.2) 1' was prepared by
the reaction of RuCl.sub.2(PPh.sub.3).sub.3 with one equivalent of
.sup.tBu-PNP (Zhang et al. 2004). Treatment of 1' with an excess (5
equiv) of NaBH.sub.4 in 2-propanol for 12 hrs resulted in formation
of the Ru(II) hydrido borohydride complex 2' in almost quantitative
yield (by NMR) (Scheme 25). The .sup.31{.sup.1H} NMR spectrum of 2'
exhibits a singlet peak at 86.3 ppm, representing a downfield shift
of 21 ppm relative to 1' (65.0 ppm). In the .sup.1H NMR spectrum,
the hydride ligand gives rise to a triplet peak at -16.09 ppm with
J.sub.PH=18.0 Hz. In addition, two broad signals are observed for
the two bridging hydrides at -16.01 and -4.48 ppm and another broad
feature at 5.49 ppm belonging to the terminal boron hydrides. The
IR spectrum of 2' indicates two strong bands in the terminal B--H
region at 2395 and 2327 cm.sup.-1 and two bands in the bridging
M-H--B region at 2104 and 2024 cm,.sup.-1 consistent with the
bidentate .eta..sup.2-BH.sub.4 binding mode (Marks et al.).
##STR00354##
[0397] Single crystals suitable for an X-ray diffraction study were
obtained by slow evaporation of a pentane solution of 2' at
-32'.degree. C. The crystal structure of 2' (FIG. 3) displays a
distorted octahedral geometry around the ruthenium center,
including the .sup.tBu-PNP, hydride and BH.sub.4 units. The hydride
ligand is bound to the Ru center cis to the pyridine nitrogen
(N1-Ru1-Hru, 81 (2).degree.), while the BH.sub.4 unit is
coordinated to Ru(II) center in a .eta..sup.2' mode. The two Ru--H
bonds to the chelating BH.sub.4 unit are not equal (1.67(5) and
1.85(6) .ANG., respectively), while the corresponding Ru--H bonds
in the structure of RuH(BH.sub.4)(PMe.sub.3).sub.3 (Statler et al.)
are of equal length. The difference in the case of 2' is a result
of the larger trans effect of hydride relative to that of the
pyridinic nitrogen atom. Because of the meridional coordination
geometry of the .sup.tBu-PNP framework and lack of a plane of
symmetry involving the P, N, P atoms, the protons of the four
tert-butyl and two methylene groups are magnetically
inequivalent.
TABLE-US-00024 TABLE 22 Selected Bond Distances (.ANG.) and Angles
(deg) of Complex 2' Ru1-N1 2.123 (3) Ru1-P1 2.311 (1) Ru1-P2 2.322
(1) Ru1-HRu 1.57 (5) Ru1-HB2 1.67 (5) Ru1-HB4 1.85 (6) N1-Ru1-HRu
81 (2) HRu-Ru1-HB4 166 (2) P1-Ru1-P2 159.6 (1) HB2-Ru1-N1 177 (2)
N1-Ru1-P2 83.0 (1) P1-Ru1-N1 82.5 (1) P2-Ru1-HRU 79 (2) HRU-Ru1-P1
85 (2) HB2-Ru1-HB4 70 (2) HB3-B1-HB1 113 (3) HB2-B1-HB4 104 (3)
Synthesis and Characterization of [RuH(.eta..sup.2-BH.sub.4)(PNN)]
4'
[0398] The N.sub.2-bridged binuclear Ru(II) complex
[(RuCl.sub.2(PNN)).sub.2](.mu.-N.sub.2) 3' was prepared by the
reaction of RuCl.sub.2(PPh.sub.3).sub.3 with one equivalent of PNN,
employing a similar method to the one used for the preparation of
1. Treatment of 3' with an excess (5 equiv) of NaBH.sub.4 in
2-propanol for 12 hrs resulted in the formation of the
ruthenium(II) hydrido borohydride complex 4' in excellent yield as
indicated by .sup.31P{.sup.1H} NMR spectroscopy (Scheme 26). The
.sup.31P{.sup.1H} NMR spectrum of 4' shows a singlet peak at 116.7
ppm, representing a downfield shift of 29 ppm relative to 3'. The
hydride ligand gives rise to a doublet at -16.24 ppm with
J.sub.PH=28.0 Hz in the .sup.1H NMR spectrum. The IR spectrum of 4'
exhibits two strong bands in the terminal B--H region at 2378 and
2311 cm.sup.-1 and two bands in the bridging M-H--B region at 2096
and 1956 cm,.sup.-1 similar to the IR spectrum of complex 2',
consistent with the bidentate .eta..sup.2-BH.sub.4 binding mode
(Marks et al.).
##STR00355##
[0399] At room temperature, one broad singlet peak at -13.01 ppm is
observed in the .sup.1H NMR spectrum of 4' for one proton of
BH.sub.4. A variable-temperature .sup.1H NMR study of 4' in
toluene-d.sub.8 is shown in FIG. 2, revealing interesting fluxional
behavior of the BH.sub.4.sup.- ligand. At 213K, two singlets are
observed at -13.21 and -4.33 ppm for the bridging hydrides and two
broad singlets at 4.70 and 5.13 ppm for the two terminal hydrides
of the BH.sub.4.sup.- ligand, respectively. Upon raising the
temperature to 248K, the signals for the two terminal hydrides
coalesce while the signal at -4.33 ppm collapses. At 263K, the
signals (.about.5 ppm) for the two terminal hydrides and the signal
at -4.33 ppm for one bridging hydride disappear in the baseline and
the signal (-13.21 ppm) of another bridging hydride also collapses.
Upon temperature increase to 323K, the resonance at -13.21 ppm also
disappears into the baseline. Upon raising the temperature to 353K,
a very broad singlet peak appears at -2 ppm, indicating that the
four hydrides of BH.sub.4.sup.- start to coalesce. The signal of
the terminal Ru--H ligand appears as a doublet peak throughout the
213-373K temperature range, indicating that it does not participate
in the fluxional process of the BH.sub.4.sup.- ligand. These
variable-temperature .sup.1H NMR spectra of complex 4' are similar
to those reported for the complexes RuH(BH.sub.4)(PMe).sub.3
(Statler et al.) and RuH(BH.sub.4)(ttp)
(ttp=PhP(CH.sub.2CH.sub.2CH.sub.2PPh.sub.2).sub.2) (Letts et al.).
The bridging hydride (-4.33 ppm) trans to the terminal Ru--H
exchanges positions with the two terminal hydrides on the boron at
263K. These hydrogen atoms further exchange with the bridging
hydride (-13.21 ppm) trans to pyridinic nitrogen above 323K and the
calculated coalescence frequency at -2.0 ppm was observed at
353K.
Synthesis and Characterization of
[RuCl.sub.2(PPh.sub.3)(.sup.iPr-PNP)] 5 and
[RuH(.eta..sup.1-BH.sub.4)(PPh.sub.3)(.sup.iPr-PNP)]6'
[0400] Heating of RuCl.sub.2(PPh.sub.3).sub.3 with one equivalent
of .sub.iPr-PNP
(.sup.iPr-PNP=2,6-bis(di-iso-propylphosphinomethyl)pyridine) in THF
at 65.degree. C. for 6 hrs resulted in formation of the PPh.sub.3
complex 5' in 75% yield (Scheme 27). The .sup.31P{.sup.1H} NMR
spectrum of 5' exhibits one doublet at 46.4 ppm and one triplet
peak at 43.2 ppm, indicating that triphenylphosphine is coordinated
to the Ru(II) center, as observed also with the reported
Ph-PNP-Ru(II) dichloride complex
(Ph-PNP=2,6-bis(diphenylphosphinomethyl)pyridine) (Jia et al.). In
contrast, the .sup.tBu complexes 1' and 3' do not contain
coordinated PPh.sub.3, under similar preparation conditions,
probably because of the steric bulk of the tert-butyl group of
.sup.tBu-PNP and PNN ligands. The two methylene groups of
.sup.iPr-PNP give rise to one triplet peak at 3.92 ppm with
J.sub.PH=4.0 Hz, indicating the existence of a symmetric plane
involving the P, N, P atoms. The PPh.sub.3 ligand is coordinated to
the Ru(II) center trans to the nitrogen atom of .sup.iPr-PNP and
the chloride ligands are coordinated to metal center trans to each
other.
[0401] In analogy to the preparation of complexes 2' and 4',
treatment of complex 5' with excess (2.5 equiv) of NaBH.sub.4 in
isopropanol at room temperature resulted in precipitation of the
Ru(II) hydrido borohydride complex 6' as a yellow solid in 85%
yield (Scheme 27). The .sup.31P{.sup.1H} NMR spectrum of 6'
exhibits a doublet signal at 61.6 ppm and a triplet signal at 67.9
ppm, corresponding to the two phosphorus atoms of .sup.iPr-PNP and
one phosphorus atom of PPh.sub.3, respectively. It is noted that
the signal of the PPh.sub.3 ligand of 6' is downfield shifted
relative to that of .sup.iPr-PNP, unlike the corresponding signals
of complex 5. The Ru--H gives rise in the .sup.1H NMR of 6' to a
quartet signal at -14.00 ppm with J.sub.PH=J.sub.P'H=28.0 Hz. A
broad peak at -0.84 ppm is assigned to the four protons of the
BH.sub.4 ligand, which is probably coordinated to the Ru(II) center
in a .eta..sup.1 mode, similar to the reported bonding of ruthenium
borohydride complexes by Ohkuma et al. and Guo et al. The IR
spectrum of 6' exhibits strong absorptions at 2361, 2292 and a
strong broad peak at 1884 cm,.sup.-1 consistent with the
monodentate .eta..sup.1-BH.sub.4 bonding mode (Marks et al.).
##STR00356##
Synthesis of Borohydride Complex 8'
##STR00357##
[0403] RuHCl(CO)(BPy-.sup.tPNN) complex 4 (82 mg, 0.17 mmol) and
NaBH.sub.4 (32 mg, 0.85 mmol) were placed in a 20 mL Schlenk flask
equipped with a Teflon-coated magnetic stirring bar. A 1:1 mixture
of toluene and ethanol (4 mL) was added to the flask. It was then
stirred at 65.degree. C. for 5 min (to get homogeneous solution)
then at room temperature for 2 hr to give a reddish yellow
solution. The solvent was removed in vacuo. The resulting residue
was dissolved in CH.sub.2Cl.sub.2 (6 mL) and the remaining
insoluble materials were removed by filtration through a Celite pad
(0.5 g). The filtrate was concentrated to ca. 0.5 mL and 5 mL of
pentane was added to cause precipitation of a orange-yellow solid,
which was filtered and dried under vacuum to give 72 mg (92%) of
analytically pure RuH(CO)(.eta..sup.1BH4)BPy-.sup.tPNN) complex 8'.
.sup.31P{.sup.1H}NMR (202 MHz, CD.sub.2Cl.sub.2): 110.67 (s).
.sup.1H NMR (500 MHz, CD.sub.2Cl.sub.2): -12.27 (d,
.sup.2J.sub.PH=21.5 Hz, 1H, Ru--H), -2.34--1.90 (br d, 4H,
Ru--HBH.sub.3), 1.31 (d, J.sub.PH=13.0 Hz, 9H,
P(C(CH.sub.a3).sub.3), 1.43 (d, J.sub.PH=13.5 Hz, 9H,
P(C(CH.sub.b3).sub.3), ABX system centred at 3.62 and 3.69 (2H,
PCH.sub.aH.sub.b), 7.41-7.43 (m, 1H, H-5'), 7.56 (d, J.sub.HH=8.0
Hz, 1H, H-5), 7.85-7.89 (m, 2H, H-4 and H-4'), 7.96 (d,
J.sub.HH=7.5 Hz, 1H, H-3), 8.04 (d, J.sub.HH=8.0 Hz, 1H, H-3'),
9.12-9.13 (br m, 1H, H-6'). .sup.13C{.sup.1H}NMR (125 MHz,
CD.sub.2Cl.sub.2): 28.43 (d, J.sub.PC=3.8 Hz,
P(C(C.sub.aH.sub.3).sub.3), 29.63 (d, J.sub.PC=3.8 Hz,
P(C(C.sub.bH.sub.3).sub.3), 35.87 (d, J.sub.PC=16.3 Hz,
P(C.sub.a/b(CH.sub.3).sub.3), 37.34 (d, J.sub.PC=16.3 Hz,
PCH.sub.2), 119.26 (s, C-3), 121.16 (s, C-3'), 122.53 (d,
J.sub.PC=8.8 Hz, C-5), 125.71 (s, C-5), 135.97, (s, C-4'), 137.07
(s, C-4), 153.69 (s, C-6'), 154.79 (br s, C-2), 155.91 (s, C-2'),
163.95 (d, J.sub.PC=3.78 Hz, C-6), 206.90 (br d, J.sub.PC=15 Hz,
Ru--CO). IR (KBr disc, CH.sub.2Cl.sub.2): 2313 (B--H stretching),
1988 (Ru--H stretching), 1046 (BH.sub.3 deformation), 1019
(BH.sub.3 deformation). Assignment of signals was confirmed by DEPT
135, COSY, and HSQC.
Dehydrogenation of Alcohols Using Complexes 2', 4', 6' and 8' as
Catalysts.
[0404] As some of the inventors of the present invention have
demonstrated (Zhang 2004, Zhang 2005), PNP and PNN Ru(II) complexes
catalyze the dehydrogenation of secondary alcohols to ketones and
primary alcohols to esters. It has now been discovered that the
ruthenium hydrido borohydride complexes of 2', 4', and 6' and 8'
catalyze the dehydrogenation of alcohols under base-free conditions
and in absence of hydrogen acceptors. Indeed, when complex 2' was
heated with 1000 equivalents of 1-phenyl-1-ethanol in toluene for
24 hrs, 28.6% of the alcohol were converted to acetophenone,
accompanied by the evolution of hydrogen gas (Table 23, entry 1).
Similarly, upon heating of 1-phenyl-1-ethanol with 0.1% 4' or 6' in
toluene for 24 hrs, acetophenone was formed in 86.5% and 76.5%
yield, respectively (Table 23, entry 2 and 3), indicating that the
catalytic activity of 4' was significantly higher than that of
complexes 2' and 6', probably as a result of the potentially
"hemilabile" amine arm of 4', which can play an important role in
the catalytic cycle (Zhang 2005). A longer reaction time resulted
in a higher yield of the ketone (Table 23, entry 4). Other
secondary alcohols can also be dehydrogenated to the corresponding
ketones using 4' as catalyst in good yields (Table 23, entries
5-8). The catalysis by 4' was quite sensitive to the reaction
temperature, and when 2-propanol was heated at 83.degree. C. with
0.1% 4', acetone was formed in only 12.6% yield after 48 hrs
(TON=126), while when heated in toluene at 105.degree. C., 89.9% of
acetone were formed during the same reaction period (TON=899).
TABLE-US-00025 TABLE 23 Dehydrogenation of secondary alcohols to
the corresponding ketones with complexes 2', 4', 6' as catalysts
Conver- Yield of Temp. Time sion ketone entry Cat. Alcohol
(.degree. C.) (h) (%) (%).sup.a 1 2' 1-phenyl-1-ethanol 115 24 28.6
28.6 2 4' 1-phenyl-1-ethanol 115 24 86.5 86.5 3 6'
1-phenyl-1-ethanol 115 24 77 76.5 4 4' 1-phenyl-1-ethanol 115 48 93
93 5 4' 2-hexanol 115 48 83.2 83 6 4' 2-butanol 110 48 88.8 88.7 7
4' cyclohexanol 115 48 56.5 56.5 8 4' 2-propanol 105 48 90 89.9 9
4' 2-propanol .sup. 83.sup.b 48 12.6 12.6 .sup.areaction
conditions: catalyst 0.01 mmol, alcohol 10 mmol, toluene 2 mL,
reflux under argon flow .sup.breflux in neat 2-propanol under
argon.
[0405] In comparison to the dehydrogenation of secondary alcohols
to the corresponding ketones, homogeneous systems capable of
dehydrogenation of primary alcohols to the corresponding aldehydes
or esters are very rare (Zhang 2005, Murahashi et al., Blum et al.,
Lin et al. and Zhao et al), probably because of decarbonylation of
the product (or intermediate) aldehyde to form an inactive carbonyl
complex.
[0406] When a toluene solution of benzyl alcohol and 0.1% complex
2' was refluxed for 24 hrs in an open system, benzyl benzoate was
formed in 70% yield, accompanied by a small amount of benzaldehyde
(4%) (Table 24, entry 1). Refluxing 1-hexanol with 0.1% 2 in
toluene (115.degree. C.) or neat (157.degree. C.) for 24 hrs
resulted in formation of 60-70% of hexyl hexanoate, accompanied by
2.5-10% hexanal (Table 24, entries 2 and 3). Complex 6' was
slightly less catalytically active than 2 (Table 24, entry 7). The
PNN complex 4' exhibited significantly higher catalytic activity
than that of the PNP complexes 2' and 6'; benzyl alcohol, 1-hexanol
and 1-butanol were dehydrogenated to the corresponding esters in
over 90% yield after heating with 0.1% 4' in toluene (Table 24,
entry 4-6).
TABLE-US-00026 TABLE 24 Dehydrogenation of primary alcohols to
esters and aldehydes with complexes 2', 4', 6' as catalysts Yield
of Yield Temp. Conversion Aldehyde of ester entry Cat. Alcohol
(.degree. C.) (%) (%) (%).sup.a 1 2' benzyl 115 75 4 70 alcohol 2
2' 1-hexanol 115 72 2.5 69 3 2' 1-hexanol 157.sup.a 70 10 59.4 4 4'
benzyl 115 99 0 99 alcohol 5 4' 1-hexanol 115 94 0 94 6 4'
1-butanol 110 96 0.2 95.5 7 6' benzyl 115 62 3.4 58.6 alcohol 8 6'
1-hexanol 157.sup.b 57.5 9.5 47.4 .sup.areaction conditions:
catalyst 0.01 mmol, alcohol 10 mmol and toluene 2 mL heated under
reflux for 24 hrs under argon flow .sup.breflux in neat 1-hexanol
under argon flow
##STR00358##
TABLE-US-00027 TABLE 25 Dehydrogenation of alcohols to esters using
complex 8' as catalyst Entry Alcohols Esters Conv. (%) Yield
(%).sup.a 1 1-Hexanol Hexyl hexanoate 99.8 99.0 2 Benzyl alcohol
Benzyl benzoate ~100 99.3 .sup.aComplete conversion of alcohol was
observed and no formation of aldehyde (by GC).
Amidation Using Complex 4' as a Catalyst
##STR00359##
[0408] Complex 4' (4.4 mg, 0.01 mmol), 1-hexanol (1.02 g, 10 mmol),
benzyl amine (1.07 g, 10 mmol) and toluene (3 mL) were taken in a
Schlenk flask under an atmosphere of purified nitrogen in a glove
box. The flask was equipped with a condenser and the solution was
refluxed with stirring in an open system under argon for 18 h.
After cooling to room temperature, the consumption of starting
materials was checked by GC using a Carboxen 1000 column on a HP
690 series GC system and shows that 100% conversion of the
1-hexanol. To the reaction mixture, hexane (30 mL) was added to
precipitate out the N-benzylhexanamide as white coloured solid and
filtered off the solid to get the pure product in 98% yield.
Amidation Using Complex 8' as Catalyst
##STR00360##
TABLE-US-00028 [0409] TABLE 26 Amidation using complex 8' as a
catalyst Yield Entry Alcohols Amines Amides (isolated) 1
##STR00361## ##STR00362## ##STR00363## 59.sup.a 3 ##STR00364##
##STR00365## ##STR00366## 71.sup.b .sup.aConversion of alcohol is
87.8%. Other products are Ester (5.2%) and Imine (17%) also formed
(by GC). .sup.bConversion of alcohol is 91.1%. Other products are
Ester (3.5%) and Imine (12%) also formed (by GC).
##STR00367##
TABLE-US-00029 TABLE 27 Ester hydrogenation Yield Entry Cat. Esters
Alcohols Conv. (%) (%) 1 8' Hexyl hexanoate 1-Hexanol 99.8 98.9 (2
mmol) 2 8' Methyl formate MeOH 96.5 94.7 (15 mmol) 3 4' Hexyl
hexanoate 1-Hexanol ~100 99.4 (2 mmol) 4 4' Butyl butyrate
1-Butanol ~100 98.0 (2 mmol) 5 6' Butyl butyrate 1-Butanol 9.8 9.0
(2 mmol)
Dehydrogenation of Diols to the Corresponding Lactones Catalyzed by
Complexes 2' and 4'.sup.a
TABLE-US-00030 [0410] TABLE 28 Dehydrogenation of esters to
lactones Lactone yield entry cat. diol (%).sup.b 1 2' ##STR00368##
##STR00369## 2 4' ##STR00370## ##STR00371## 3 4' ##STR00372##
##STR00373## 4 4' ##STR00374## ##STR00375## 5 4' ##STR00376##
##STR00377## .sup.aReaction conditions: catalyst (0.01 mmol), diol
(3 mmol) and 2 mL of toluene were refluxed in an open system under
argon for 48 hrs. .sup.bYields of the lactones were analyzed by
.sup.1H NMR of the reaction mixture. .sup.cIsolated yield.
[0411] General procedure for the catalytic dehydrogenation of diols
to lactones. Complexes 2' or 4' (0.01 mmol), diol (3 mmol), and
toluene (2 mL) were taken in a Schlenk flask under an atmosphere of
purified nitrogen in a Vacuum Atmospheres glove box. The flask was
equipped with a condenser and the solution was refluxed with
stirring in an open system under argon for 48 hrs. After cooling to
room temperature, the yield of the lactones was determined by
.sup.1H NMR spectroscopy from the reaction mixture. The resulting
mixture was concentrated in vacuo for about 3-4 h. The purification
was performed on silica gel column using hexane-ethylacetate
mixture as eluent. The products were analyzed by .sup.1H NMR and
the spectra were identical with the authentic samples.
Example 10: Experimental Section--Borohydride Complexes
General Procedures
[0412] All experiments with metal complexes and phosphine ligands
were carried out under an atmosphere of purified nitrogen in a
Vacuum Atmospheres glove box equipped with a MO 40-2 inert gas
purifier or using standard Schlenk techniques. All solvents were
reagent grade or better. All non-deuterated solvents were refluxed
over sodium/benzophenone ketyl and distilled under argon
atmosphere. Deuterated solvents were used as received. All solvents
were degassed with argon and kept in the glove box over 4 .ANG.
molecular sieves. Complexes 1' and 3' were prepared as reported
previously (Zhang 2004, Milstein). .sup.iPr-PNP
(2,-6-bis-(di-iso-propylphosphinomethyl)pyridine) (Jansen et al.),
RuCl.sub.2(PPh.sub.3).sub.3, (Holm et al.) were prepared according
to literature procedures.
[0413] .sup.1H, .sup.13C and .sup.31P NMR spectra were recorded at
400 or 500, 100 or 126, and 162 or 202 MHz, respectively, using a
Bruker AMX-400 and AMX-500 NMR spectrometers. .sup.1H and
.sup.13C{.sup.1H} NMR chemical shifts are reported in ppm downfield
from tetramethylsilane. .sup.31P NMR chemical shifts are reported
in parts per million downfield from H.sub.3PO.sub.4 and referenced
to an external 85% solution of phosphoric acid in D.sub.2O.
Abbreviations used in the NMR follow-up experiments: b, broad; s,
singlet; d, doublet; t, triplet; q, quartet; m, multiplet, v,
virtual. Elemental analyses were performed at Kolbe Laboratorium,
Mulheim, Germany.
Synthesis of [RuH(BH.sub.4)(.sup.tBu-PNP)]2'
[0414] To a suspension of complex 1' (58 mg, 0.05 mmol) in
2-propanol (10 ml) was added a very fine powder of NaBH.sub.4 (9.5
mg, 0.25 mmol), and the mixture was stirred at room temperature for
12 hrs. The mixture was filtered and the orange filtrate was taken
to dryness under vacuum. The residue was extracted with diethyl
ether (3.times.5 mL). The ether solution was evaporated under
vacuum to yield complex 2' as an orange solid. The complex was
dried under vacuum overnight. Yield: 50 mg (98%).
[0415] .sup.31P{.sup.1H} NMR (C.sub.6D.sub.6): 86.3 (s); .sup.1H
NMR (C.sub.6D.sub.6): -16.09 (t, 1H, J.sub.PH=18.0 Hz, Ru--H),
-16.01 (br s, 1H, BH.sub.4), -4.48 (br s, 1H, BH.sub.4), 1.45 (t,
18H, J.sub.PH=6.0 Hz, P(C(CH.sub.3).sub.3)), 1.56 (t, 18H,
J.sub.PH=6.0 Hz, P(C(CH.sub.3).sub.3).sub.2), 3.08 (dt, 2H,
J.sub.HH=16.0 Hz, J.sub.PH=4.0 Hz, --CHHP), 3.19 (dt, 2H,
J.sub.HH=16.0 Hz, J.sub.PH=4.0 Hz, --CHHP), 5.49 (br s, 2H,
BH.sub.4), 6.52 (d, 2H, J.sub.HH=8.0 Hz, pyridine-H3, H5), 6.76 (t,
1H, J.sub.HH=8.0 Hz, pyridine-H4). .sup.13C{.sup.1H} NMR
(C.sub.6D.sub.6): 29.7 (s, P(CH(CH.sub.3).sub.2).sub.2), 30.2 (s,
P(C(CH.sub.3).sub.3).sub.2), 35.0 (t, J.sub.PC=6.5 Hz,
P(C(CH.sub.3).sub.3).sub.2), 35.6 (t, J.sub.PC=5.0 Hz,
P(C(CH.sub.3).sub.3).sub.2), 39.0 (t, J.sub.PC=7.0 Hz, CH.sub.2P),
118.2 (t, J.sub.PC=4.0 Hz, pyridine-C3, C5), 131.0 (s,
Pyridine-C4), 165.1 (t, J.sub.PC=4.5 Hz, Pyridine-C2, C6).
[0416] IR (KBr pellets): 2395, 2327, 2104, 2024, 1461, 1184
cm.sup.-1.
[0417] Anal. Calcd. for C.sub.23H.sub.48BNP.sub.2Ru: C, 53.90; H,
9.45. Found: C, 53.86, H, 9.49.
Synthesis of [RuH(BH.sub.4)(PNN)] 4'
[0418] To a suspension of complex 3' (51 mg, 0.05 mmol) in
2-propanol (10 ml) was added a very fine powder of NaBH.sub.4 (9.5
mg, 0.25 mmol), and the mixture was stirred at room temperature for
12 hrs. The mixture was filtered and the orange filtrate was taken
to dryness under vacuum. The orange solid residue was extracted
with diethyl ether (3.times.5 mL). The ether solution was
evaporated under vacuum yielding complex 4' as a red-orange solid,
which was dried under vacuum overnight. Yield: 40 mg (91%).
[0419] .sup.31P{.sup.1H} NMR (C.sub.6D.sub.6): 116.7 (s); .sup.1H
NMR (C.sub.6D.sub.6, 298 K): -16.24 (t, 1H, J.sub.PH=28.0 Hz,
Ru--H), -13.10 (Br s, 1H, BH.sub.4), 0.84 (t, 3H, J.sub.HH=6.0 Hz,
N(CH.sub.2CH.sub.3).sub.2), 0.99 (t, 3H, J.sub.HH=6.0 Hz,
N(CH.sub.2CH.sub.3).sub.2), 1.28 (d, 9H, J.sub.PH=12.0 Hz,
P(C(CH.sub.3).sub.3)), 1.43 (d, 9H, J.sub.PH=12.0 Hz,
P(C(CH.sub.3).sub.3).sub.2), 2.31 (m, 1H,
N(CH.sub.2CH.sub.3).sub.2), 2.49 (m, 1H,
N(CH.sub.2CH.sub.3).sub.2), 2.71 (dd, 1H, J.sub.HH=16.0 Hz,
J.sub.PH=8.0 Hz, --CHHP), 2.98 (dd, 1H, J.sub.HH=16.0 Hz,
J.sub.PH=12.0 Hz, --CHHP), 3.05 (m, 1H, N(CH.sub.2CH.sub.3).sub.2),
3.41 (d, 1H, J.sub.HH=14.0 Hz, NCHH-py), 3.54 (d, 1H, J.sub.HH=14.0
Hz, NCHH-py), 3.73 (m, 1H, N(CH.sub.2CH.sub.3).sub.2), 6.30 (d, 1H,
J.sub.HH=8.0 Hz, pyridine-H5), 6.51 (d, 1H, J.sub.HH=8.0 Hz,
pyridine-H3), 6.71 (t, 1H, J.sub.HH=8.0 Hz, pyridine-H4). .sup.1H
NMR (Toluene-d.sub.8, 243 K): -16.30 (t, 1H, J.sub.PH=28.0 Hz,
Ru--H), -13.21 (Br s, 1H, BH.sub.4), -4.33 (br s, 1H, BH.sub.4),
0.71 (br s, 3H, N(CH.sub.2CH.sub.3).sub.2), 0.92 (br s, 3H,
N(CH.sub.2CH.sub.3).sub.2), 1.18 (d, 9H, J.sub.PH=12.0 Hz,
P(C(CH.sub.3).sub.3)), 1.35 (d, 9H, J.sub.PH=12.0 Hz,
P(C(CH.sub.3).sub.3).sub.2), 2.10 (m, 1H,
N(CH.sub.2CH.sub.3).sub.2), 2.31 (m, 1H,
N(CH.sub.2CH.sub.3).sub.2), 2.53 (dd, 1H, J.sub.HH=16.0 Hz,
J.sub.PH=8.0 Hz, --CHHP), 2.82 (dd, 1H, J.sub.HH=16.0 Hz,
J.sub.PH=8.0 Hz, --CHHP), 2.93 (br m, 1H,
N(CH.sub.2CH.sub.3).sub.2), 3.15 (d, 1H, J.sub.HH=16.0 Hz,
NCHH-py), 3.33 (d, 1H, J.sub.HH=16.0 Hz, NCHH-py), 3.37 (m, 1H,
N(CH.sub.2CH.sub.3).sub.2), 4.69 (br s, 1H, BH.sub.4), 5.00 (br s,
1H, BH.sub.4), 6.16 (d, 1H, J.sub.HH=8.0 Hz, pyridine-H5), 6.38 (d,
1H, J.sub.HH=8.0 Hz, pyridine-H3), 6.62 (t, 1H, J.sub.HH=8.0 Hz,
pyridine-H4). .sup.13C{.sup.1H} NMR (C.sub.6D.sub.6): 8.8 (s,
N(CH.sub.2CH.sub.3).sub.2), 11.0 (s, N(CH.sub.2CH.sub.3).sub.2),
29.0 (d, J.sub.PC=4.0 Hz, P(C(CH.sub.3).sub.3).sub.2), 34.2 (d,
J.sub.PC=15.1 Hz, P(C(CH.sub.3).sub.3).sub.2), 37.0 (d,
J.sub.PC=10.0 Hz, P(C(CH.sub.3).sub.3).sub.2), 38.9 (d,
J.sub.PC=19.1 Hz, PCH.sub.2--), 51.1 (s, N(CH.sub.2Me).sub.2), 51.2
(s, N(CH.sub.2Me).sub.2), 63.7 (s, py-CH.sub.2N), 117.5 (s, Py-C3),
118.5 (s, Py-C5), 128.8 (s, Py-C4), 159.9 (s, Py-C6), 163.7 (d,
J.sub.PC=4.0 Hz, py-C2).
[0420] IR (KBr pellets): 2378, 2311, 2096, 1956, 1469, 1177
cm.sup.-1.
[0421] Anal. Calcd. for C.sub.19H.sub.40BN.sub.2PRu: C, 51.93; H,
9.18. Found: C, 51.86, H, 9.24.
Synthesis of [RuCl.sub.2(PPh.sub.3)(.sup.1Pr-PNP)] 5'
[0422] To a suspension of Ru(PPh.sub.3).sub.3Cl.sub.2 (480 mg, 0.5
mmol) in dry THF (20 ml) was added .sup.iPr-PNP (170 mg, 0.5 mmol)
and the mixture was stirred and heated at 65.degree. C. for 6 hrs.
The yellow solution was concentrated to 4 mL under vacuum and 20 mL
of pentane were added to precipitate a yellow solid. The solid was
isolated by filtration, washed with pentane (3.times.2 mL) and
dried under vacuum to give 290 mg (75% yield) of 5 as a yellow
solid.
[0423] .sup.31P{.sup.1H} NMR (CD.sub.2Cl.sub.2): 46.4 (d,
J.sub.PP=27.5 Hz), 43.2 (t, J.sub.PP=27.5 Hz). .sup.1H NMR
(CD.sub.2Cl.sub.2): 0.87 (q, 12H, J.sub.PH=J.sub.HH=8.0 Hz,
P(CH(CH.sub.3).sub.2).sub.2), 1.13 (q, 12H, J.sub.PH=J.sub.HH=8.0
Hz, P(CH(CH.sub.3).sub.2).sub.2), 2.43 (m, 4H,
P(CH(CH.sub.3).sub.2).sub.2), 3.92 (t, 4H, J.sub.PH=4.0 Hz,
--CH.sub.2P), 7.26 (m, 9H, P(C.sub.6H.sub.5).sub.3), 7.30 (d, 2H,
J.sub.HH=8.0 Hz, pyridine-H3, 5), 7.53 (t, 1H, J.sub.HH=8.0 Hz,
pyridine-H4), 7.91 (m, 6H, P(C.sub.6H.sub.5).sub.3).
.sup.13C{.sup.1H} NMR (CD.sub.2Cl.sub.2): 19.6 (s,
P(CH(CH.sub.3).sub.2).sub.2), 20.7 (s,
P(CH(CH.sub.3).sub.2).sub.2), 25.1 (t, J.sub.PC=8.0 Hz,
P(CH(CH.sub.3).sub.2).sub.2), 38.9 (t, J.sub.PC=10.1 Hz,
CH.sub.2P), 119.9 (s, Py-C3,5), 127.2 (d, J.sub.PC=9.0 Hz,
m-C.sub.6H.sub.5-P), 128.8 (s, p-C.sub.6H.sub.5-P), 135.0 (d,
J.sub.PC=9.0 Hz, o-C.sub.6H.sub.5-P), 136.7 (s, Py-C4), 140.4 (d,
J.sub.PC=36.2 Hz, ipso-C.sub.6H.sub.5-P), 164.8 (t, J.sub.PC=4.0
Hz, py-C2,6).
[0424] Anal. Calcd. for C.sub.37H.sub.50NP.sub.3Cl.sub.2Ru: C,
57.44; H, 6.52. Found: C, 57.28; H, 6.53.
Synthesis of [RuH(BH.sub.4)(PPh.sub.3)(.sup.iPr-PNP)] 6'
[0425] To a suspension of complex 5 (77 mg, 0.1 mmol) in 2-propanol
(10 ml) was added a fine powder of NaBH.sub.4 (9.5 mg, 0.25 mmol).
The mixture was stirred at room temperature for 12 hrs and then
filtered. The resulting yellow solid was washed with 2-propanol
(3.times.1.5 mL) and then dissolved in benzene (10 mL) and the
solution was filtered. The yellow filtrate was evaporated to
dryness under vacuum, yielding complex 6' as a yellow solid which
was dried under vacuum overnight to give 61 mg (85% yield).
.sup.31P{.sup.1H} NMR (C.sub.6D.sub.6): 61.6 (d, J.sub.PP=29.2 Hz),
67.9 (t, J.sub.PP=29.2 Hz). .sup.1H NMR (C.sub.6D.sub.6): -14.0 (q,
1H, J.sub.PH=28.0 Hz, Ru--H), -0.84 (br s, 4H, BH.sub.4), 0.91 (q,
6H, J.sub.PH=J.sub.HH=8.0 Hz, P(CH(CH.sub.3).sub.2).sub.2), 0.87
(m, 12H, J.sub.PH=J.sub.HH=8.0 Hz, P(CH(CH.sub.3).sub.2).sub.2),
1.18 (q, J.sub.PH=J.sub.HH=8.0 Hz, 6H,
P(CH(CH.sub.3).sub.2).sub.2), 1.44 (m, 2H,
P(CH(CH.sub.3).sub.2).sub.2), 1.77 (m, 2H,
P(CH(CH.sub.3).sub.2).sub.2), 2.85 (dt, 2H, J.sub.HH=16.0 Hz,
J.sub.PH=4.0 Hz, -CHHP), 3.92 (dt, 2H, J.sub.HH=16.0 Hz,
J.sub.PH=4.0 Hz, --CHHP), 6.56 (d, 2H, J.sub.HH=8.0 Hz,
pyridine-H3, 5), 6.79 (t, 1H, J.sub.HH=8.0 Hz, pyridine-H4), 7.01
(d, 3H, J.sub.HH=8.0 Hz, P(C.sub.6H.sub.5).sub.3), 7.12 (t, 6H,
J.sub.HH=8.0 Hz, P(C.sub.6H.sub.5).sub.3), 8.18 (t, 6H,
J.sub.HH=8.0 Hz, P(C.sub.6H.sub.5).sub.3). .sup.13C{.sup.1H} NMR
(C.sub.6D.sub.6): 18.0 (s, P(CH(CH.sub.3).sub.2).sub.2) 18.5 (s,
P(CH(CH.sub.3).sub.2).sub.2), 19.6 (s, P(CH(CH.sub.3).sub.2).sub.2)
20.8 (s, P(CH(CH.sub.3).sub.2).sub.2), 25.6 (t, J.sub.PC=8.0 Hz,
P(CH(CH.sub.3).sub.2).sub.2), 26.4 (t, J.sub.PC=11.6 Hz,
CH.sub.2P), 39.2 (t, J.sub.PC=6.0 Hz, P(CH(CH.sub.3).sub.2).sub.2),
118.4 (t, J.sub.PC=2.5 Hz, Py-C3,5), 127.1 (d, J.sub.PC=9.0 Hz,
m-C.sub.6H.sub.5-P), 128.8 (s, p-C.sub.6H.sub.5-P), 134.2 (s,
Py-C4), 135.7 (d, J.sub.PC=10.1 Hz, o-C.sub.6H.sub.5-P), 142.0 (d,
J.sub.PC=36.2 Hz, ipso-C.sub.6H.sub.5-P), 163.7 (t, J.sub.PC=4.5
Hz, py-C2,6).
[0426] IR (KBr pellet): 2361, 2293, 2246, 1884, 1458, 1060
cm.sup.-1.
[0427] Anal. Calcd. for C.sub.37H.sub.55BNP.sub.3Ru: C, 61.84; H,
7.72. Found: C, 61.98; H, 7.66.
Typical Procedures for the Catalytic Dehydrogenation of
Alcohols
[0428] (a) Complexes 2' (0.01 mmol), 4' (0.01 mmol) or 6' (0.01
mmol) were dissolved in the neat primary or secondary alcohol (10
mmol). The flask was equipped with a condenser and the solution was
heated with stirring in an open system under argon at the specified
temperature and time (Tables 18 and 19). After cooling to room
temperature, the product aldehydes, esters or ketones were
determined by GC, using mesitylene or (in the case of 1-butanol)
benzene as internal standards, employing a Carboxen 1000 column on
a HP 690 series GC system.
[0429] (b) A solution containing the catalyst (0.01 mmol)
(complexes 2', 4' or 6') and the alcohol (10 mmol) in toluene (2
mL) was heated in a flask equipped with a reflux condenser under
argon in an open system at the specified temperatures and times
(Tables 2 and 3). After cooling to room temperature, the products
were determined by GC using mesitylene or benzene (for 1-butanol)
as internal standards, employing a Carboxen 1000 column on a HP 690
series GC system.
X-Ray Crystal Structure Determination of 2'.
[0430] The crystal was mounted on a nylon loop and flash frozen in
a nitrogen stream at 120 K. Data were collected on a Nonius Kappa
CCD diffractometer mounted on a FR590 generator equipped with a
sealed tube with Mo K.alpha. radiation (.lamda.=0.71073 .ANG.) and
a graphite monochromator. The four structures were solved using
direct methods with SHELXS-97 based on F.sup.2.
[0431] Complex 2': C.sub.23H.sub.48BNP.sub.2Ru, yellow plate,
0.40.times.0.40.times.0.30 mm.sup.3, monoclinic, P2.sub.1 (No. 4),
a=12.541 (3) .ANG., b=15.314 (3) .ANG., c=15.131 (3) .ANG.,
.beta.=111.85 (3).degree., V=2697.3 (9) .ANG..sup.3, Z=4, fw=512.4,
F(000)=1088, D.sub.c=1.262 Mg/m.sup.3, .mu.=0.709 mm.sup.-1. The
final cycle of refinement based on F.sup.2 gave an agreement factor
R=0.027 for data with I>2.sigma.(I) and R=0.030 for all data
(6375 reflections) with a goodness-of-fit of 1.080. Idealized
hydrogen atoms were placed and refined in the riding mode, with the
exception of Hru and Hb1-Hb4 which were located in the difference
map and refined independently.
Example 11--Synthesis of Complex 9 and Catalysis by it
##STR00378##
[0433] (a) Synthesis of the Ligand BPy-(pH)PNN (10)
[0434] An oven-dried 250 mL three-necked round bottom flask
equipped with an argon inlet, a stirring bar, dropping funnel and
one rubber septum was cooled under a stream of argon. The flask was
then charged with chlorodiphenylphosphine (1.08 g, 6 mmol) in 30 mL
dry ether. The solution was cooled to 0.degree. C. and a THF
solution (5 mL) of potassium tert-butoxide (74 mg, 6.6 mmol) was
added dropwise via syringe during 10 min. The resulting brown
coloured mixture was stirred for 1 hr at 0.degree. C. and then a
solution of 6-chlorometyl-2,2'-bipyridine (1.02 g, 5 mmol) in 20 mL
dry ether was added dropwise (.about.15 min) to it. The stirring
was continued for a further 1 hr at the same temperature and the
mixture was allowed to slowly warm up to room temperature and
stirred overnight. To this reaction mixture was added 20 mL of
degassed water and the ether phase was separated under N.sub.2
atmosphere. The aqueous phase was extracted with ether (2.times.20
mL). The combined ether solutions were dried over anhydrous
Na.sub.2SO.sub.4, filtered under N.sub.2 pressure, and the solvent
was removed under vacuum to get brownish-white solid. This was
purified by column chromatography in the nitrogen glove box (basic
alumina; hexane:ether (10:1) as eluent) to yield 1.08 g (61%) of
6-di-phenyphosphinomethyl-2,2'-bipyridine (BPy-(Ph)PNN) as a white
crystalline solid.
[0435] .sup.31P{.sup.1H}NMR (122 MHz, CD.sub.2Cl.sub.2): -8.28 (s).
.sup.1H NMR (300 MHz, CD.sub.2Cl.sub.2): 3.81 (s, 2H, P--CH2), 7.13
(d, JHH=7.5 Hz, 1H, H-5), 7.32 (ddd, JHH=7.5 Hz, JHH=4.8H, JPH=1.2
Hz, 1H, H-5'), 7.40-7.45 (m, 6H, Ph-H), 7.58-7.63 (m, 4H, Ph-H),
7.69 (t, JHH=7.8 Hz, 1H, H-4), 7.80 (dt, JHH=7.8 Hz, JHH=2.1 Hz,
1H, H-4'), 8.28 (br d, JHH=8 Hz, 2H, H-3 and H-3'), 8.68-8.70 (m,
1H, H-6'). .sup.13C{.sup.1H}NMR (125 MHz, CD2Cl2): 38.35 (d,
JPC=16.3 Hz, P--CH2), 118.07 (s, C-3), 121.02 (s, C-3'), 123.55 (s,
C-5'), 123.61 (d, JPC=8.4 Hz, C-5), 128.34 (s, Ph-C), 128.40
(Ph-C), 128.65 (s, Ph-C), 132.90 (s, Ph-C), 133.05 (s, Ph-C),
136.61, (s, C-4'), 136.97 (s, C-4), 138.72 (d, JPC=15.0 Hz, Ph-C
(quar)), 149.02 (s, C-6'), 155.49 (s, C-2), 156.22 (s, C-2'),
157.64 (d, JPC=7.5, C-6). Anal. Calcd. for C23H19N2P: C, 77.95; H,
5.40. Found: C, 78.13. H, 5.61. MS (ESI, MeOH): 355 (100%, M+1)+).
Assignment of signals was confirmed by DEPT 135, COSY, and
HSQC.
[0436] (b) Synthesis of Complex 9
[0437] To an oven dried 25 mL pressure vessel equipped with
magnetic stirring bar was added ligand. BPy-(Ph)PNN (10) (148 mg,
0.42 mmol), RuHCl(CO)(PPh.sub.3).sub.3(382 mg, 0.4 mmol), and 8 mL
dry THF in a nitrogen glove box. The flask was sealed and heated at
65.degree. C. for 12 hr with stirring outside the glove box, then
cooled to room temperature to lead to reddish-brown solid. It was
reintroduced to the glove box, and the solvent was decanted and the
solid thus obtained was washed with ether (3.times.5 mL), then
dried under vacuum to give analytically pure complex
RuHCl(CO)(BPy-(Ph)PNN) (184 mg, 84%). .sup.31P{1H}NMR (202 MHz,
CD.sub.2Cl.sub.2): 69.44 (s). .sup.1H NMR (500 MHz,
CD.sub.2Cl.sub.2): -14.09 (d, JPH=25.5 Hz, 1H, Ru--H), 4.38-4.50
(m, 2H, P--CH2), 7.39-7.40 (m, 3H, Ph-H), 7.46-7.51 (m, 4H, Ph-H),
7.60-7.64 (m, 3H, Ph-H), 7.87-7.90 (m, 2H, H-5 and H-5'), 7.57 (d,
JHH=7.8 Hz, 1H, H-5), 7.93-7.97 (m, 2H, H-4 and H-4'), 8.04 (d,
JHH=8.0 Hz, 1H, H-3), 8.10 (d, JHH=8.0 Hz, 1H, H-3'), 9.22 (br s,
1H, H-6). .sup.13C{1H}NMR (125 MHz, CD2Cl2): 45.52 (d, JPC=26.3 Hz,
P--CH2), 120.04 (s, C-3), 122.65 (s, C-3'), 123.09 (d, JPC=11.3,
C-5), 126.21 (s, C-5'), 128.16 (s, Ph-C), 128.24 (s, Ph-C), 128.28
(s, Ph-C), 128.37 (s, Ph-C), 129.82 (s, Ph-C), 130.37 (s, Ph-C),
131.60 (d, JPC=11.3 Hz, Ph-Ca (ortho)), 133.46 (d, JPC=11.3 Hz,
Ph-Cb (ortho)), 133.78 (d, JPC=43.8 Hz, Ph-Cb (quar)), (136.64, (s,
C-4'), 137.39 (s, C-4), 139.86 (d, JPC=50.0 Hz, Ph-Ca (quar)),
153.39 (s, C-6'), 154.67 (s, C-2), 156.05 (s, C-2'), 160.04 (d,
JPC=6.3, C-6), 206.53 (d, JPC=7.5 Hz, Ru--CO). IR (KBr, pellet):
1915 (vCO) cm-1. MS (ESI, CH3CN): 519 (100%, (M-1)+) and MS (ESI,
CH3OH): 485 (100%, (M-Cl)+).
Some Examples of Reactions Catalyzed by Complex 9:
##STR00379##
##STR00380##
##STR00381##
[0438] Example 12: Direct Synthesis of Amides from Esters Using
Ruthenium-Pincer Catalyst with Liberation of H.sub.2 Under Neutral
Conditions
[0439] PNN-type pincer ruthenium complexes used for catalytic
conversion of esters and amines into amides:
##STR00382##
[0440] The applicants of the present invention have discovered that
amide synthesis from esters and amines can be achieved using the
ruthenium PNN catalyst 1. The reaction is general, efficient,
environmentally benign and atom economical. It proceeds under
neutral conditions without acid/base/activators/promoters. Notably,
this reaction affords with amide in high TON (1000) and H.sub.2 as
the only byproduct (Scheme 43).
[0441] When a benzene solution containing 10 mmol of pyrrolidine,
10 mmol of ethyl acetate and 0.01 mmol of complex 1 was refluxed
under Argon atmosphere, quantitative conversion of pyrrolidine was
observed by GC after 28 hrs, to yield 98% of N-acetyl pyrrolidine
after column purification (Table 29, entry 1). The N-acetyl
pyrrolidine was characterized by NMR and GC-MS. Similar results
were obtained in toluene. Reaction of ethyl acetate with morpholine
in benzene under reflux resulted after 36 hrs in 79% conversion
with the isolation of the corresponding amide in 77% yield (Table
29, entry 2). Refluxing of 1-methyl piperazine, ethyl acetate and
benzene in the presence of complex 1 provides the corresponding
amide in 56% yield with the conversion of the ester being 59%
(Table 29, entry 3).
[0442] Various esters and amines reacted similarly. Refluxing a
toluene solution containing butyl butyrate (5 mmol), piperidine (10
mmol) and 0.1 mol % of the PNN complex 1 under argon atmosphere for
19 hrs resulted in 100% conversion of piperidine as observed by GC
analysis, with the exclusive formation of the
1-(piperidin-1-yl)butan-1-one in 94% yield after isolation from
alumina column chromatography (Table 29, entry 4). The product was
completely characterized by NMR spectroscopy. Unlike the
traditional methods, this reaction does not form any alcohol as
by-product, resulting in the irreversible, unique incorporation of
both the acyl and alkoxo parts of the starting ester into the
product amide. Significantly the TON of ester-amide exchange
reaction was high (1000). Similarly, refluxing the toluene solution
containing butyl butyrate, morpholine or N-methyl piperazine in the
presence of complex 1 resulted in 100% conversion of the amine with
the isolation of the amides in 95 and 94% yields, respectively.
Refluxing of excess of butyl butyrate and piperazine in toluene led
to bis-acylation of the piperazine, providing the corresponding
amide in 61% yield.
[0443] To explore the synthetic utility of this reaction, pentyl
pentanoate was reacted with various amines. The reaction of pentyl
pentanoate with piperidine gave 100% conversion with the isolation
of the amide in 96% yield. Morpholine and N-methyl piperazine
furnished the respective amide in 96 and 94% isolated yield.
[0444] Next, reactions were studied with primary amines. The
reaction of ethyl butyrate and hexyl amine in the presence of 0.1
mol % of 1 in refluxing toluene led to 100% conversion of the hexyl
amine with the isolation of 97% of the corresponding amide as the
only product Similarly, reaction of pentyl pentanoate and
4-methylbenzyl amine in refluxing toluene resulted in 100%
conversion with isolation of corresponding amide in 98% yield.
These reactions did not lead any alcohol as waste product.
[0445] The reactions were also studied in absence of solvent. Thus,
heating pentylpentanoate, piperidine and complex 1 at 135.degree.
C. resulted in 52% conversion.
TABLE-US-00031 TABLE 29 Amination of esters catalyzed by the
ruthenium complex 1.sup.[a] Conv. En- Time of try Ester Amine (hrs)
amine Isolated Yield (%) 1 ##STR00383## ##STR00384## 26 100
##STR00385## 2 ##STR00386## ##STR00387## 36 79 ##STR00388## 3
##STR00389## ##STR00390## 24 59 ##STR00391## 4 ##STR00392##
##STR00393## 19 100 ##STR00394## 5 ##STR00395## ##STR00396## 21 100
##STR00397## 6 ##STR00398## ##STR00399## 24 100 ##STR00400## 6
##STR00401## ##STR00402## 36 100 ##STR00403## 7 ##STR00404##
##STR00405## 19 100 ##STR00406## 8 ##STR00407## ##STR00408## 26 100
##STR00409## 9 ##STR00410## ##STR00411## 24 100 ##STR00412## 10
##STR00413## ##STR00414## 18 100 ##STR00415## 11 ##STR00416##
##STR00417## 26 100 ##STR00418## 12 ##STR00419## ##STR00420## 18
100 ##STR00421## 13 ##STR00422## ##STR00423## 24 100 ##STR00424##
14 ##STR00425## ##STR00426## 18 100 ##STR00427## .sup.[a]Complex 1
(0.01 mmol), ester (5 mmol), amine (10 mmol) and toluene/benzene (3
ml) were reluxed at an oil bath temperature of 135.degree. C. in a
Schlenk tube. Conversion of amine was analyzed by GC using m-xylene
as internal standard.
In summary, acylation of amines using esters as the acylating
partner is efficiently catalyzed by complex 1 under neutral
conditions. The use of symmetrical esters results in the
incorporation of both the acyl and alkoxo parts of the substrate
ester into the product amide with liberation of H.sub.2. This
offers an environmentally benign, atom economical method for amide
synthesis from esters without any waste generation. This catalytic
cycle produces a high turnover number (1000) and both primary and
secondary amines can be used.
Example 13: Ruthenium-Pincer Catalyzed Acylation of Alcohols Using
Esters with Liberation of H.sub.2 Under Neutral Conditions
[0446] The acylation of esters with secondary alcohols can be
carried out selectively to give the mixed ester using the PNN
catalyst 1. The reaction is general, efficient, and environmentally
benign. It proceeds under neutral conditions without acids or
bases, activators, or molecular sieves. Uniquely, when a
symmetrical ester (such as ethyl acetate) is reacted with a
secondary alcohol, the only co-product is molecular hydrogen,
unlike the generally employed transesterification reaction which
gives an alcohol co-product (or its derivative) (Scheme 44).
##STR00428##
[0447] When a benzene solution containing 15 mmols of cyclohexanol,
5 mmols of ethyl acetate and 0.05 mmols of complex 1 was refluxed
under argon atmosphere, GC analysis after 28 hrs showed that all of
the ethyl acetate disappeared and cyclohexyl acetate was formed as
a single product (Table 30, entry 1). .sup.1H NMR and GC-MS of the
isolated product were identical to cyclohexyl acetate prepared by
refluxing neat acetic anhydride with cyclohexanol.
[0448] Likewise, refluxing a toluene solution containing one
equivalent of hexyl hexanoate, 2 equivalents of cyclohexanol and 1
mol % of the PNN complex 1 under argon atmosphere for 20 h resulted
in 84% conversion of hexyl hexanoate as determined by GC analysis,
with the exclusive formation of the ester cyclohexyl hexanoate in
83% yield (Table 30, entry 2). Notably, unlike the traditional
transesterification methods, this reaction does not form an alcohol
product; rather, an irreversible incorporation of both the acyl and
alkoxo parts of the starting ester into the product ester takes
place. While 2 equivalents of the alcohol with respect to the ester
are sufficient, somewhat higher yields are obtained when 3
equivalents of alcohol were used. Thus, reaction of 3 equivalents
of cyclohexanol with hexyl hexanoate resulted after 26 h in 96%
conversion with 95% yield of cyclohexyl hexanoate, as observed by
GC, and confirmed by GC-MS by comparison with an authentic sample
(Table 30, entry 3). The pure product was isolated by evaporation
of the solvent followed by passing through a basic alumina plug and
analysis by NMR and GC-MS. Use of the PNP complexes 2 or 3 resulted
after 20 h in 58% or 17% yield of cyclohexyl hexanoate,
respectively. Studying the scope of this new reaction with regard
to the secondary alcohol, reaction of hexyl hexanoate with
cyclopentanol in the presence of 1 mol % 1 was carried out. After
26 h reflux in toluene, cyclopentyl hexanoate (70% yield) was
formed, with 71% conversion of hexyl hexanoate (Table 30, entry 4).
Similarly, upon reaction of hexyl hexanoate with excess of
1-phenylethanol, 50% conversion of hexyl hexanoate with the
formation of 49% of the acylated product was observed (Table 30,
entry 5). The lower conversion of the ester is a result of facile
dehydrogenation of 1-phenylethanol to acetophenone (49%). Because
of the expected easy dehydrogenation of the isopropyl alcohol to
acetone, transesterification with this alcohol was performed in a
closed vessel, to retard this dehydrogenation process. Thus,
heating hexyl hexanoate with excess of isopropyl alcohol resulted
after 19 h in 83% conversion of hexyl hexanoate with the formation
of isopropyl hexanoate in 67% yield (entry 6). The reaction of
hexyl hexanoate and 3-pentanol led to 91% conversion of the ester
with formation of 3-pentyl hexanoate in 90% yield after 26 h reflux
(entry 7).
[0449] Exploring further the scope with regard to the ester
substrate, pentyl pentanoate was reacted with cyclohexanol,
resulting in 93% conversion with the formation of 93% cyclohexyl
pentanoate (entry 8). Like in the case of hexyl hexanoate, the
presumably formed pentanol intermediate is converted into pentyl
pentanoate with the liberation of H.sub.2. Similarly, treatment of
pentyl pentanoate with cyclopentanol, 1-phenylethanol and
3-pentanol, furnished 87, 51, 91% conversion of pentyl pentanoate,
respectively, with the predominant formation of the corresponding
cross-ester as the product in 85, 49, 90% yields, respectively
(entries 9-11).
[0450] Next we studied the reaction of butyl butyrate with various
secondary alcohols. Reaction of 5 mmol of butyl butyrate with 15
mmol of cyclohexanol led to 93% conversion of the ester with the
formation of 92% of cyclohexyl butyrate after 34 h (entry 12). Upon
refluxing of butyl butyrate with cyclopentanol, after 28 hrs 75%
conversion of the ester, with formation of 74% cyclopentyl butyrate
were observed (entry 13). In a similar reaction with
1-phenylethanol or 3-pentanol, 41 and 77% conversion, respectively,
into the product was noted by GC analysis after 36 h (entries 14
and 15).
[0451] These reactions were also studied with unsymmetrical esters.
The reaction of ethyl butyrate with 3-pentanol in the presence of 1
mol % of 1 under refluxing toluene led to 75% conversion of ethyl
butyrate with the formation of 73% of 3-pentyl butyrate as the
exclusive product (entry 16). Traces of 3-pentyl acetate, resulting
from reaction with the formed ethanol, were also observed. The
remaining ethanol probably evaporated from the reaction mixture
under the reflux conditions. Similarly, the reaction of methyl
hexanoate with cyclohexanol results in 42% conversion after 17 h
with the formation of 42% of cyclohexyl hexanoate (entry 17).
[0452] Since the dehydrogenation of the secondary alcohol to ketone
is slower than the dehydrogenative coupling of the primary alcohol
to ester, most of the secondary alcohol reacts with the ester,
although some ketone resulting from excess alcohol was observed.
The slow reaction of the secondary alcohol with PNN complex may be
due to the steric hindrance.
TABLE-US-00032 TABLE 30 Acylation of alcohols catalyzed by the
ruthenium complex 1.sup.a) Conv. of En- Time ester Yield try Ester
alcohol (hrs) % % 1.sup.b) ##STR00429## ##STR00430## 28 100
##STR00431## 2.sup.c) ##STR00432## ##STR00433## 20 84 ##STR00434##
3 ##STR00435## ##STR00436## 26 96 (cat 1) 58 (cat. 2) 17 (cat. 3)
##STR00437## 4 ##STR00438## ##STR00439## 26 71 ##STR00440## 5
##STR00441## ##STR00442## 36 50 ##STR00443## 6.sup.d) ##STR00444##
##STR00445## 19 83 ##STR00446## 7 ##STR00447## ##STR00448## 26 91
##STR00449## 8 ##STR00450## ##STR00451## 36 93 ##STR00452## 9
##STR00453## ##STR00454## 36 87 ##STR00455## 10 ##STR00456##
##STR00457## 18 51 ##STR00458## 11 ##STR00459## ##STR00460## 26 91
##STR00461## 12 ##STR00462## ##STR00463## 34 93 ##STR00464## 13
##STR00465## ##STR00466## 28 75 ##STR00467## 14 ##STR00468##
##STR00469## 36 41 ##STR00470## 15 ##STR00471## ##STR00472## 18 77
##STR00473## 16.sup.e) ##STR00474## ##STR00475## 20 75 ##STR00476##
17 ##STR00477## ##STR00478## 17 42 ##STR00479## .sup.a)Complex 1
(0.05 mmol), ester (5 mmol), alcohol (15 mmol) and toluene (3 ml)
were refluxed/heated at an oil bath temperature of 135.degree. C.
under argon. Conversion of ester and yield of product were analyzed
by GC using m-xylene or benzene as internal standards. A small
amount of the secondary alcohol was converted into the
corresponding ketone. .sup.b)Benzene was used as solvent. Efficient
cooling of the reflux condenser is required to avoid losses of
ethyl formate. .sup.c)1 (0.05 mmol), hexyl hexanoate (5 mmol),
cyclohexanol (10 mmol) and toluene (3 ml) were used. .sup.d)a
closed system and 3 ml of 2-propanol were used. An equivalent
amount of 1-hexanol (67%) was also detected. .sup.e)m-xylene was
used as solvent and benzene as internal standard.
EXPERIMENTAL SECTION
[0453] General Procedure for the Catalytic Acylation of
Alcohols:
[0454] Complex 1 (0.05 mmol), ester (5 mmol), alcohol (15 mmol) and
toluene (3 mL) were added to Schlenk flask under an atmosphere of
nitrogen in a glove box. The flask was equipped with a condenser
and the solution was refluxed with stirring in an open system under
argon for the specified time (Table 30). In the case of
isopropanol, the reactions were performed in a closed system at
135.degree. C. The reaction products were analyzed by GC-MS. After
cooling to room temperature, m-xylene (1 mmol) or benzene (1 mmol)
were added as internal standards to the reaction mixture and the
products were quantitatively analyzed by GC using a Carboxen 1000
column on a HP 690 series GC system or HP-5 cross linked 5% PH ME
Siloxane column (30m.times.0.32 mm.times.0.25 .mu.m film thickness)
on a HP 6890 series GC system. In the reaction of cyclohexanol and
esters, evaporation of the solvent, followed by purification over
basic alumina column chromatography afforded the pure transesters.
.sup.1H NMR of the products isolated from the catalysis was
identical with the literature.
Example 14: Synthesis of Cyclic Dipeptides and Pyrazines from
.beta.-Aminoalcohols
A. Formation of Cyclic Dipeptides
[0455] Dehydrogenative coupling of .beta.-aminoalcohols can lead to
cyclic dipeptide formation (Scheme 45), except in case of R=H, Me
(in which case linear polypeptides are the main products; in case
of R=Me, a small amount of cyclic dipeptide is also formed).
##STR00480##
[0456] Refluxing a dioxane solution of
(S)-2-amino-4-methylpentan-1-ol with complex 1 (1 mol %) led to 64%
isolated yield of the cyclic dipeptide,
3,6-diisobutylpiperazine-2,5-dione 7b after workup (Table 31, entry
1). The product structure was confirmed by MS, NMR
spectroscopies.
[0457] Upon refluxing a dioxane solution containing 2 mmol of
(2S,3S)-2-amino-3-methylpentan-1-ol and 0.02 mmol of catalyst 1 for
19 hrs and cooling the reaction mixture, the solid product
precipitated and was filtered off and dried under vacuum to give
pure 3-(sec-butyl)-6-(sec-butyl)piperazine-2,5-dione 7c in 72%
yield (Table 31, entry 2). The structure was confirmed by NMR and
MS spectroscopies. Under the same conditions, cyclic peptidation of
(S)-2-amino-3-methylbutan-1-ol led to
3,6-diisopropylpiperazine-2,5-dione 7d as an insoluble solid which
separated from the reaction mixture and was isolated by filtration
and dried under vacuum to give 78% of
(3S,6S)-3,6-diisopropylpiperazine-2,5-dione 7d (Table 31, entry 3).
The optical rotation of the pure product (-52.degree.) was
essentially the same as reported in the literature (-54.degree.).
Thus, under these experimental condition, no racemization took
place.
[0458] The reaction of (S)-2-amino-3-phenylpropan-1-ol and 1 in
refluxing dioxane led to 90% conversion with the isolation of the
corresponding 3,6-dibenzylpiperazine-2,5-dione 7e in 72% yield
(Table 31, entry 4). Reaction of 2-amino-2-methylpropan-1-ol under
the same conditions yielded 100% conversion with isolation of the
corresponding cyclic dipeptide
3,3,6,6-tetramethylpiperazine-2,5-dione 7f in 92% yield (Table 31,
entry 5).
[0459] Tricyclic ring systems represent an important structural
motif in many naturally existing alkaloids. Refluxing a dioxane
solution of (S)-pyrrolidin-2-yl-methanol in the presence of
catalyst 1 followed by solvent evaporation, hexane addition to the
crude solid, and its isolation by filtration and washing with
hexane led to octahydrodipyrrolo[1,2-a:1',2'-d]pyrazine-5,10-dione
7g in 99% isolated yield (Table 31, entry 6).
TABLE-US-00033 TABLE 31 Synthesis of cyclic dipeptides from
.beta.-aminoalcohols catalyzed by complex 1. Iso- lated En- Cata-
Yields try lyst Aminoalcohol cyclic dipeptide (%) 1 1 ##STR00481##
##STR00482## 64 2 1 ##STR00483## ##STR00484## 72 3 3 ##STR00485##
##STR00486## 87 4 3 ##STR00487## ##STR00488## 82 5 1 ##STR00489##
##STR00490## 92 6 1 ##STR00491## ##STR00492## 99 .sup.[a]Complex 1
or 3 (0.02 mmol), aminoalcohol (2 mmol) and dioxane (2 ml) were
refluxed under argon (oil bath temperature of 135.degree. C.) for
19 h.
B. Formation of Pyrazines
[0460] Pyrazines are biologically important organic compounds and
their synthesis is of industrial significance. When the RuPNP
complex 2 was used as catalyst, pyrazine derivatives were obtained
from .beta.-amino alcohols (Scheme 46). Thus, a toluene solution of
isoleucinol with complex 2 (1 mol %) was vigorously refluxed under
argon for 24 hrs resulting in complete conversion of isoleucinol.
The solvent was evaporated under vacuum and the residue was
subjected to silica-gel column chromatography to afford
2,6-diiso-butyl pyrazine 8a in 53% yield (Table 32, Entry 1).
.sup.1H NMR exhibits the characteristic aromatic CH at 8.27 ppm and
GC-MS confirms the respective molecular weight. The same reaction
was also conducted by reflux under air using complex 2, resulting
in 48% isolated yield of 8a. The similarity in yields of 8a under
argon and under air indicates that air does not play a role as
oxidant in the dehydrogenation of the presumed intermediate
1,4-dihydropyrazine to form the pyrazine. Significantly, no cyclic
dipeptide was obtained under these conditions. Similar results were
obtained with other aminoalcohols. Thus, toluene solutions of
(S)-2-amino-3-methylbutan-1-ol, (S)-2-amino-4-methylpentan-1-ol,
and (S)-2-amino-2-phenylethanol, were vigorously refluxed (bath
temperature 165.degree. C.) for 24 hrs while monitoring reaction
progress by GC-MS. After complete disappearance of the amino
alcohol, the crude product was purified by column chromatography to
get the corresponding pyrazine products 8b-d (Table 32).
##STR00493##
TABLE-US-00034 TABLE 32 Synthesis of pyrazines from
.beta.-aminoalcohols catalyzed by the ruthenium PNP complex 2.(a)
Isolated Yields Entry .beta.-Aminoalcohol Pyrazine (%) 1
##STR00494## ##STR00495## 53 2 ##STR00496## ##STR00497## 35
3.sup.(b) ##STR00498## ##STR00499## 38 4 ##STR00500## ##STR00501##
45 5.sup.(c) ##STR00502## ##STR00503## 48 .sup.(a)Complex 2 (0.02
mmol), aminoalcohol (2 mmol) and toluene (2 ml) were vigorously
refluxed (oil bath temperature at 165.degree. C. for 24 h).
.sup.(b)Heated in absence of solvent (oil bath temperature at
165.degree. C.). .sup.(c)Reaction performed under air.
General Procedure for the Synthesis of Cyclic Dipeptides from
.beta.-Aminoalcohols:
[0461] Complex 1 (0.02 mmol), aminoalcohol (2 mmol) and dioxane (2
mL) were added to Schlenk flask under an atmosphere of nitrogen in
a glovebox. The flask was equipped with a condenser and the
solution was refluxed with stirring in an open system under argon
for 19 hrs. The reaction products were analyzed by GC-MS on Agilent
7820A GC coupled with 5975 MSD system. The reaction mixture was
cooled; the solid obtained was filtered off, washed with hexane and
dried to give the pure cyclic dipeptide.
General Procedure for the Synthesis of Pyrazines from
.beta.-Aminoalcohols:
[0462] Complex 2 (0.02 mmol), aminoalcohol (2 mmol) and toluene (2
mL) were added to Schlenk flask under an atmosphere of nitrogen in
a glovebox. The flask was equipped with a condenser and the
solution was refluxed with stirring under argon in an open system
for the 24 hrs. The reaction products were analyzed by GC-MS on
Agilent 7820A GC coupled with 5975 MSD system. The solvent was
evaporated from the reaction mixture and the crude product was
subjected to silica-gel column chromatography using EtOAc:hexane to
afford the pyrazine derivatives.
Characterization Data of Cyclic Dipeptides
(3S,6S)-3,6-diisobutylpiperazine-2,5-dione
##STR00504##
[0464] mp: 270-272.degree. C.
[0465] .sup.1H NMR (300 MHz, CD.sub.3COOD): 0.84 (broad s, 12H,
CH.sub.3), 1.7 (broad s, 6H, CH.sub.2, CH), 4.23 (broad s, 2H,
NCH).
[0466] .sup.13C{.sup.1H}NMR (300 MHz, CDCl.sub.3): 21.3 (CH.sub.3),
21.6 (CH.sub.3), 23.7 (CH.sub.3), 23.8 (CH.sub.3), 26.0 (CH), 26.2
(CH), 43.7 (CH.sub.2), 46.4 (CH.sub.2), 55.4 (NCH), 55.8 (NCH),
174.9 (C.dbd.O), 175.0 (C.dbd.O).
[0467] MS (ES.sup.+, CH.sub.2Cl.sub.2+TFA): 227 (60%, M+H.sup.+),
249 (100%, M+Na), 475 (70%, 2M+Na).
3-((R)-sec-butyl)-6-((S)-sec-butyl)piperazine-2,5-dione
##STR00505##
[0469] mp: 276-280.degree. C. (decompose)
[0470] .sup.1H NMR (300 MHz, CDCl.sub.3): 0.86-1.02 (m, 12H,
CH.sub.3), 1.19-1.47 (m, 4H, CH.sub.2), 2.10-2.26 (m, 2H,
CH.sub.2), 3.91-4.07 (m, 2H, NCH), 6.11-6.31 (m, 2H, NH).
[0471] MS (ES.sup.+, CH.sub.2Cl.sub.2+TFA): 227 (40%, M+H), 244
(100%), 249 (40%, M+Na), 467 (80%), 475 (5%, 2M+Na).
(3S,6S)-3,6-diisopropylpiperazine-2,5-dione
##STR00506##
[0473] mp: 290-294.degree. C. (decompose)
[0474] .sup.1H NMR (300 MHz, CDCl.sub.3 and CD.sub.3COOD): 0.91 (d,
J=6.6 Hz, 6H, CH.sub.3), 1.01 (d, J=6.6 Hz, 6H, CH.sub.3),
2.44-2.53 (m, 2H, CH), 4.11 (m, 2H, NCH).
[0475] .sup.13C{.sup.1H}NMR (300 MHz, CDCl.sub.3): 15.7 (CH.sub.3),
18.2 (CH.sub.3), 32.3 (CH), 59.8 (NCH), 171.2 (C.dbd.O).
[0476] MS (ES.sup.+, CH.sub.2Cl.sub.2+TFA): 199 (100%, M+H.sup.+),
221 (60%, M+Na), 419 (15%, 2M+Na).
[0477] [.alpha.]=-52.degree. (c=0.01, AcOH)
(3S,6S)-3,6-dibenzylpiperazine-2,5-dione
##STR00507##
[0479] mp: 299-302.degree. C. (decompose)
[0480] .sup.1H NMR (300 MHz, CDCl.sub.3 and CD.sub.3COOD):
2.15-2.22 (m, 2H, CH.sub.2), 2.95-3.01 (m, 2H, CH.sub.2), 4.39-4.43
(m, 2H, NCH), 7.03 (d, J=6.9 Hz, 4H, .dbd.CH), 7.31-7.39 (m, 6H,
.dbd.CH). .sup.13C{.sup.1H}NMR (300 MHz, CD.sub.3COOD): 39.6
(CH.sub.2), 56.2 (NCH), 128.4 (.dbd.CH), 129.4 (.dbd.CH), 129.9
(.dbd.CH), 133.5 (quat-C), 169.9, 173.0 (C.dbd.O).
[0481] MS (ES.sup.+, CH.sub.2Cl.sub.2+TFA): 295 (80%, M+H), 317
(100%, M+Na), 611 (60%, 2M+Na).
3,3,6,6-tetramethylpiperazine-2,5-dione
##STR00508##
[0483] .sup.1H NMR (300 MHz, DMSO-d.sub.6): 1.30 (s, 12H, CH %),
8.09 (s, 2H, NH).
[0484] .sup.13C{.sup.1H}NMR (300 MHz, DMSO-d.sub.6): 28.6
(CH.sub.3), 55.7 (quat-C), 170.2 (C.dbd.O).
[0485] MS (ES.sup.+): 170 (100%, M.sup.+), 192(30%), 200(25%).
(5aS,10aS)-octahydrodipyrrolo[1,2-a:1',2'-d]pyrazine-5,10-dione
##STR00509##
[0487] mp: 146-148.degree. C.
[0488] .sup.1H NMR (300 MHz, CDCl.sub.3): 1.88-2.33 (m, 8H,
CH.sub.2), 3.49-3.54 (m, 4H, NCH.sub.2), 4.16 (t, 2H, NCH).
[0489] .sup.13C{.sup.1H}NMR (300 MHz, CDCl.sub.3): 23.3 (CH.sub.2),
27.6 (CH.sub.2), 45.1 (NCH.sub.2), 60.5 (NCH), 166.3 (C.dbd.O).
[0490] MS (ES.sup.+): 194 (70%, M.sup.+), 216 (100%, M+Na-1), 217
(10%, M+Na).
Characterization Data of Pyrazines
2,5-di-sec-butylpyrazine
##STR00510##
[0492] .sup.1H NMR (300 MHz, CDCl.sub.3): 0.77 (t, 6H, CH.sub.3,
J=7.2 Hz), 1.22 (d, 6H, CH.sub.3, J=6.9 Hz), 1.52-1.74 (m, 4H,
CH.sub.2), 2.68-2.76 (m, 2H, CH), 8.27 (s, 2H, .dbd.CH).
[0493] .sup.13C{.sup.1H}NMR (300 MHz, CDCl.sub.3): 11.6 (CH.sub.3),
19.6 (CH.sub.3), 29.3 (CH.sub.2), 40.2 (CH), 142.4 (.dbd.CH), 158.1
(quat-C).
2,5-diisopropylpyrazine
##STR00511##
[0495] .sup.1H NMR (300 MHz, CDCl.sub.3): 1.23 (d, 12H, CH.sub.3,
J=7.2 Hz), 2.95-3.04 (m, 2H, CH), 8.30 (s, 2H, .dbd.CH).
[0496] .sup.13C{.sup.1H}NMR (300 MHz, CDCl.sub.3): 21.8 (CH.sub.3),
33.1 (CH), 141.4 (.dbd.CH), 158.9 (quat-C).
2,5-diisobutylpyrazine
##STR00512##
[0498] .sup.1H NMR (300 MHz, CDCl.sub.3): 0.94 (d, 12H, CH.sub.3,
J=6.6 Hz), 2.04-2.13 (m, 2H, CH), 2.63 (d, 4H, CH.sub.2, J=7.2 Hz),
8.32 (s, J=6.9 Hz, 2H, .dbd.CH).
[0499] .sup.13C{.sup.1H}NMR (300 MHz, CDCl.sub.3): 21.9 (CH.sub.3),
28.6 (CH), 43.6 (CH.sub.2), 143.5 (.dbd.CH), 153.4 (quat-C).
2,5-diphenylpyrazine
##STR00513##
[0501] .sup.1H NMR (300 MHz, CDCl.sub.3): 7.48-7.57 (m, 6H,
.dbd.CH.sub.3), 8.07-8.10 (m, 4H, .dbd.CH), 9.09 (s, 2H,
.dbd.CH).
[0502] .sup.13C{.sup.1H}NMR (300 MHz, CDCl.sub.3): 126.8 (.dbd.CH),
129.1 (.dbd.CH), 129.7 (.dbd.CH), 136.3 (quat-C), 141.2 (.dbd.CH),
150.6 (quat-C).
[0503] While certain embodiments of the invention have been
illustrated and described, it will be clear that the invention is
not limited to the embodiments described herein. Numerous
modifications, changes, variations, substitutions and equivalents
will be apparent to those skilled in the art without departing from
the spirit and scope of the present invention as described by the
claims, which follow.
REFERENCES AND NOTES
(A) References Related to Ruthenium Complexes:
[0504] (1) Seyden-Penne, J. Reductions by the Alumino and
Borohydrides in Organic Synthesis; 2nd ed.; Wiley-VCH: New York,
1997. [0505] (2) (a) Rylander, P. M. Hydrogenation Methods;
Academic Press: London, 1985. (b) Hartwig, J. Organotransition
Metal Chemistry; University Science Books: Sausalito, C A, 2010; pp
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G. R.; Cole-Hamilton. D. J. Chem. Commun. 2007, 3154. (c) Beamson,
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Synth. Catal. 2010, 352, 869. (d) Beamson, G.; Papworth, A. J.;
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[0507] (4) (a) Fernandes. A. C.; Romao, C. C. J. Mol. Catal. A.,
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W.; Himizu, A.; Kobayashi, C.; Sakaguchi, A.; Ikariya, T. Angew.
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Amines: Synthesis, Properties and Applications; Cambridge
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[0510] (8) (a) Zhang, J.; Gandelman, M.; Shimon. L. J. W.;
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