U.S. patent application number 12/103543 was filed with the patent office on 2008-08-14 for catalysts for nucleophilic substitution, synthesis thereof, composition containing them and use thereof.
This patent application is currently assigned to RHODIA CHIMIE. Invention is credited to Henri-Jean Cristau, Vincent Schanen, Marc Taillefer.
Application Number | 20080194886 12/103543 |
Document ID | / |
Family ID | 26212973 |
Filed Date | 2008-08-14 |
United States Patent
Application |
20080194886 |
Kind Code |
A1 |
Schanen; Vincent ; et
al. |
August 14, 2008 |
CATALYSTS FOR NUCLEOPHILIC SUBSTITUTION, SYNTHESIS THEREOF,
COMPOSITION CONTAINING THEM AND USE THEREOF
Abstract
The invention concerns novel catalysts for aromatic nucleophilic
substitution. Said catalysts are compounds of the general formula
(I), wherein: R.sub.1, R.sub.2, R.sub.3, R.sub.4, R.sub.5, and
R.sub.6, identical or different, are selected among hydrocarbon
radicals; the Pn's, advantageously the same, are selected among
metalloid elements of column V of a period higher than nitrogen; Z
is a metalloid element of column V, advantageously distinct from
Pn; preferably a nitrogen (N, P, As, Sb). The invention is
applicable to organic synthesis.
Inventors: |
Schanen; Vincent; (Lyon,
FR) ; Cristau; Henri-Jean; (Sait-Aunes, FR) ;
Taillefer; Marc; (Vailhauques, FR) |
Correspondence
Address: |
BUCHANAN, INGERSOLL & ROONEY PC
POST OFFICE BOX 1404
ALEXANDRIA
VA
22313-1404
US
|
Assignee: |
RHODIA CHIMIE
AUBERVILLIERS
FR
|
Family ID: |
26212973 |
Appl. No.: |
12/103543 |
Filed: |
April 15, 2008 |
Related U.S. Patent Documents
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Application
Number |
Filing Date |
Patent Number |
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11784472 |
Apr 6, 2007 |
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12103543 |
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10472912 |
Mar 1, 2004 |
7217842 |
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PCT/FR02/01286 |
Apr 12, 2002 |
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11784472 |
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Current U.S.
Class: |
568/938 ;
568/937; 570/147 |
Current CPC
Class: |
B01J 2231/40 20130101;
C07F 9/5355 20130101; C07B 39/00 20130101; C07F 9/065 20130101;
B01J 31/0268 20130101; B01J 31/0234 20130101; C07C 17/208 20130101;
C07C 25/13 20130101; C07C 205/12 20130101; C07C 17/208 20130101;
B01J 31/0239 20130101; B01J 31/0271 20130101; C07C 201/12 20130101;
C07C 201/12 20130101 |
Class at
Publication: |
568/938 ;
570/147; 568/937 |
International
Class: |
C07C 205/06 20060101
C07C205/06; C07C 25/13 20060101 C07C025/13 |
Foreign Application Data
Date |
Code |
Application Number |
Apr 12, 2001 |
FR |
01/05034 |
Apr 10, 2002 |
FR |
02/04522 |
Claims
1.-21. (canceled)
22. A process for the preparation of a fluoroaromatic compound
according to an aromatic substitution process comprising the steps
of: a) reacting a fluoride as nucleophilic agent and an aromatic
substrate of general formula (III): Ar-.XI. (III) wherein Ar is an
aromatic radical wherein the nucleus bearing .XI. is electron-poor
either because it comprises at least one hetero atom in its ring,
or because the sum of the up of its substituents, besides the .XI.,
is at least equal to 0.2, optionally 0.5; and is a leaving group,
optionally in the form of an anion .XI., in a polar aprotic
solvent, in the presence of a catalyst which is a compound of
general formula (I): ##STR00029## wherein: R.sub.1, R.sub.2,
R.sub.3, R.sub.4, R.sub.5 and R.sub.6, which are identical or
different, are hydrocarbon-based radicals; the Pn are phosphorus,
and Z is nitrogen.
23. The process as claimed in claim 22, wherein the compounds of
formula (I) are neutral.
24. The process as claimed in claim 22, wherein the compounds of
formula (I) are cationic compounds and are optionally introduced in
the form of a salt of formula (II): ##STR00030## wherein X.sup.- is
a counterion which is an anion or a mixtures of anion, optionally a
monovalent anion.
25. The process as claimed in claim 22, wherein said
hydrocarbon-based radicals R.sub.1, R.sub.2, R.sub.3, R.sub.4,
R.sub.5 and R.sub.6 are: alkyls, optionally substituted aryls,
amino and imino groups, optionally in which the nitrogen linked to
a Pn does not bear hydrogen, hydrocarbyloxy groups, or a polymer
arm.
26. The process as claimed in claim 22, wherein each of the
radicals R.sub.1, R.sub.2, R.sub.3, R.sub.4, R.sub.5 and R.sub.6
contains not more than 20 carbon atoms.
27. The process as claimed in claim 22, wherein the compound of
formula (I) or (II) contains in total not more than 100 carbon
atoms, optionally not more than 60 carbon atoms.
28. The process as claimed in claim 22, wherein R.sub.1, R.sub.2,
and R.sub.3 are identical.
29. The process as claimed in claim 22, wherein R.sub.4, R.sub.5
and R.sub.6 are identical.
30. The process as claimed in claim 22, wherein R.sub.1, R.sub.2,
R.sub.3, R.sub.4, R.sub.5 and R.sub.6 are identical.
31. The process as claimed in claim 22, wherein R.sub.1, R.sub.2,
R.sub.3, R.sub.4, R.sub.5 and R.sub.6 are phenyl groups.
32. The process as claimed in claim 22, wherein at least 3,
optionally all of the radicals R.sub.1, R.sub.2, R.sub.3, R.sub.4,
R.sub.5 and R.sub.6 are linked to the Pn via aromatic carbon atoms
and/or a nitrogen atom of a peralkylated amine or imine
function.
33. The process as claimed in claim 22, wherein not more than two
of the radicals R.sub.1 to R.sub.3 and/or not more than two of the
radical R.sub.4 to R.sub.6 are alkyls and in that it contains more
than 12 carbon atoms.
34. The process as claimed in claim 33, wherein the counterions
X.sup.- are anions or mixtures of anions which are sparingly
nucleophilic.
35. The process as claimed in claim 34, wherein the counterions
X.sup.- are Cl.sup.- or Br.sup.-
36. The process as claimed in claim 22, wherein the molar ratio
between the catalyst and the nucleophilic agent being not less than
0.1%.
37. The process as claimed in claim 36, wherein said molar ratio is
not less than 0.5%.
38. The process as claimed in claim 22, wherein the nucleophilic
agent is alkali metal or alkaline-earth metal fluoride.
39. The process as claimed in claim 38 wherein said nucleophilic
agent is sodium or potassium fluoride.
40. The process as claimed in claim 22 wherein Ar bears at least 1
leaving group other than .XI..
41. The process as claimed in claim 22 wherein .XI. represents an
iodine, chlorine or bromine atom or a pseudohalogen.
42. The process as claimed in claim 41 wherein .XI. represents a
chlorine or bromine atom.
43. The process as claimed in claim 22 wherein Ar bears at least a
non-leaving withdrawing substituent.
44. The process as claimed in claim 43 wherein the withdrawing
substituent is: an halogen atom NO.sub.2 SO.sub.2Alk SO.sub.3Alk Rf
CF.sub.3 CN CHO COAlk CO.XI.', wherein .XI.' is as above defined
COOAlk Phosphone, or phosphonate with the symbol Alk representing a
hydrogen, a linear or branched, optionally C.sub.1 to C.sub.4 alkyl
group.
45. The process as claimed in claim 44 wherein said substituents
are halogen atoms or nitro group.
46. The process as claimed in claim 44 wherein the electron
withdrawing substituent(s) is (are) located in an ortho and/or para
position relative to the leaving group (s) .XI..
47. The process as claimed in claim 22 wherein the aromatic
substrate is: para-chloronitrobenzene, 2,4-dichloronitrobenzene,
1,3,5-trichlorobenzene.
48. The process as claimed in claim 22 wherein the ratio between
said nucleophilic agent and said aromatic substrate is between 1
and 1.5.
49. The process as claimed in claim 48 wherein the said ratio is
in
50. The process as claimed in claim 22 wherein the solvent has a
dielectric constant epsilon at least equal to about 10 and less
than or equal to 100.
51. The process as claimed in claim 50 wherein the solvent has a
dielectric constant epsilon greater than or equal to 25.
52. The process a claimed in claim 51 wherein the solvent has a
donor index between 10 and 50.
53. The process as claimed in claim 52 wherein the solvent is DMSO
or sulfolane.
54. The process as claimed in claim 22 wherein the reaction is
performed at a temperature ranging from about 150.degree. C. to
about 250.degree. C.
Description
[0001] The present invention relates to a novel method for
performing nucleophilic substitutions, especially of SN.sub.Ar
type, and is more particularly directed toward novel catalysts.
Although the effect is less pronounced, it is also directed toward
the use of these catalysts for SN.sub.2 reactions.
[0002] The invention is more particularly of interest to aromatic
nucleophilic substitution reactions involving the following
reaction scheme: [0003] attack of a nucleophilic agent on an
aromatic substrate with creation of a bond between said
nucleophilic agent and said substrate, on a carbon bearing a
leaving group, so as to form an intermediate compound known as a
Meisenheimer intermediate (when the nucleophile is an anion) or
equivalent, and then [0004] loss of said leaving group.
##STR00001##
[0004] Example of a Meisenheimer intermediate with optional radical
R n the number of substituents EWG Electron-Withdrawing Group Nu
anionic nucleophile
##STR00002##
Example of an intermediate equivalent to the Meisenheimer
intermediate with optional radical R EWG Electron-Withdrawing Group
Nu neutral nucleophile
[0005] Examples of SN.sub.Ar intermediates will be given below:
[0006] Reactions of this type are particularly advantageous for
obtaining halogenated aromatic derivatives and are especially used
to perform exchanges between fluorine, on the one hand, and
halogen(s) of a higher row or pseudohalogen on an aromatic
substrate.
[0007] The leaving group may thus be a nitro group, advantageously
a pseudohalogen, or, preferably, a halogen atom, especially having
an atomic number higher than that of fluorine.
[0008] The term "pseudohalogen" is intended to denote a group
which, on leaving, leads to an oxygenated anion, the anionic charge
being borne by the chalcogen atom and the acidity of which is at
least equal to that of acetic acid, advantageously to the second
acidity of sulfuric acid, and preferably to that of trifluoroacetic
acid. In order to determine the position on the acidity scale,
reference should be made to the pKa values for the average to
strong acidities from carboxylic acids up to acetic acid and to
determine the position on the scale of Hammett constants (see FIG.
1) starting from trifluoroacetic acid.
[0009] As illustrations of pseudohalogens of this type, mention may
be made in particular of sulfinic and sulfonic acids, which are
perhalogenated on the carbon bearing sulfur, and also carboxylic
acids perfluorinated .alpha. to the carboxylic function.
[0010] When the leaving group is a nitro group, this group is
generally replaced with a chlorine or fluorine atom. However, most
of these reagents make it necessary to work at very high
temperatures and the mechanism is not always found to be a
nucleophilic substitution. Moreover, loss of the nitro group leads
to the formation of oxygenated and halogenated nitrogen derivatives
that are particularly aggressive with regard to the substrate, or
even explosive.
[0011] As regards the variant involving the substitution of a
halogen atom present on an aromatic nucleus with another halogen
atom, this generally requires at least a partial deactivation of
said nucleus. To this end, the aryl radical to be converted is
preferably electron-poor and has an electron density at most equal
to that of benzene, and at most in the region of that of a
chlorobenzene, preferably a dichlorobenzene.
[0012] This depletion may be due to the presence in the aromatic
ring (six-membered) of a hetero atom, for instance in pyridine or
quinoline (the depletion in this case involves a six-membered
ring). In this particular case, the depletion is large enough for
the substitution reaction to take place very easily and does not
require any particular associated activation. The electron-poor
state may also be induced with electron-withdrawing substituents
present on this aromatic ring. These substituents are preferably
chosen from groups that withdraw via an inductive effect or via a
mesomeric effect as defined in the reference organic chemistry book
"Advanced Organic Chemistry" by J. March, 3rd edition, published by
Willey, 1985 (cf. especially pages 17 and 238). As illustrations of
these electron-withdrawing groups, mention may be made especially
of NO.sub.2, quaternary ammonium, Rf and especially CF.sub.3, CHO,
CN and COY groups with Y possibly being a chlorine, bromine or
fluorine atom or an alkyloxy group.
[0013] The halogen-halogen exchange reactions mentioned above in
fact constitute the main synthetic route for gaining access to
fluorinated aromatic derivatives.
[0014] Thus, one of the techniques most widely used for
manufacturing a fluorinated derivative consists in reacting a
halogenated, generally a chlorinated, aromatic derivative, to
exchange the halogen(s) with one or more fluorine(s) of mineral
origin. An alkali metal fluoride is generally used, usually one of
high atomic weight, for instance sodium fluoride and especially
potassium, cesium and/or rubidium fluoride.
[0015] In general, the fluoride used is potassium fluoride, which
constitutes a satisfactory economic compromise.
[0016] Under these conditions, many processes, for instance those
described in the French certificate of addition No. 2 353 516 and
in the article Chem. Ind. (1978)-56 have been proposed and used
industrially to obtain aryl fluorides, on which aryls are grafted
electron-withdrawing groups, or alternatively aryls that are
naturally electron-poor, for instance pyridine nuclei.
[0017] However, except in the case where the substrate is
particularly adapted to this type of synthesis, this technique has
drawbacks, the main of which are those that will be analyzed
hereinbelow.
[0018] The reaction is slow and, on account of a long residence
time, requires large investments. This technique, as has already
been mentioned, is generally used at high temperatures that may be
up to about 250.degree. C., or even 300.degree. C. in the case of
electron-poor nuclei, ie in the zone in which the stablest organic
solvents begin to decompose.
[0019] The yields remain relatively mediocre unless particularly
expensive reagents are used, for instance fluorides of an alkali
metal with an atomic mass higher than that of potassium.
[0020] Finally, given the price of these alkali metals, their
industrial use is justifiable only for products of high added value
and when the improvement in the yield and the kinetics justify it,
which is rarely the case.
[0021] To solve or overcome these difficulties, many improvements
have been proposed. Thus, novel catalysts are proposed, and mention
may be made especially of tetradialkylaminophosphoniums and
especially those described in the patent applications filed in the
name of the German company Hoechst and its subsidiary companies
Clariant and Aventis (for example U.S. Pat. No. 6,114,589; U.S.
Pat. No. 6,103,659; etc.) and in the patent applications filed in
the name of the company Albemarle.
[0022] These novel catalysts do, admittedly, present a number of
advantages over common catalysts, but afford no advantage in terms
of their price and their complexity.
[0023] Consequently, one of the aims of the present invention is to
provide nucleophilic substitution catalysts that especially allow a
catalysis of SN.sub.2 and above all SN.sub.Ar reactions.
[0024] Another aim of the present invention is to provide
nucleophilic substitution catalysts that especially allow a
catalysis of SN.sub.Ar reactions, even when the nucleus that is the
site of said SN.sub.Ar is only weakly electron-poor.
[0025] Another aim of the present invention is to provide
nucleophilic substitution catalysts that are also phase-transfer
agents.
[0026] Another aim of the present invention is to provide
nucleophilic substitution catalysts that have a relatively high
decomposition temperature, for example at least equal to
200.degree. C., advantageously 250.degree. C. and even 300.degree.
C.
[0027] These aims, and others which will emerge hereinbelow, are
achieved by means of use, as a catalyst for nucleophilic
substitution, of a compound of general formula (I):
##STR00003##
in which: [0028] R.sub.1, R.sub.2, R.sub.3, R.sub.4, R.sub.5 and
R.sub.6, which may be identical or different, are chosen from
hydrocarbon-based radicals, one of the radicals R.sub.1 to R.sub.6
possibly being a hydrogen when the other radicals R.sub.1 to
R.sub.6 are such that the molecule contains more than one and
preferably more than two sequence(s) Pn=Z=Pn (in this case, one, or
more, Pn may be common to several sequences and Pn is
advantageously P and Z is advantageously N); [0029] the Pn, which
are advantageously the same, are chosen from the metalloid elements
of column V from a period higher than that of nitrogen; [0030] Z is
a metalloid element from column V, which is advantageously
different than Pn, preferably a nitrogen (N, P, As or Sb).
[0031] The fact that one of the radicals R.sub.1 to R.sub.6 is
hydrogen is not preferred.
[0032] The compounds of formula (I) may be neutral, and in this
case they are amphoteric, in other words they bear within the same
molecule the cationic function shown in formula (I) and the anionic
function that ensures electrical neutrality; however, the compounds
of formula (I) that are the easiest to use are cationic compounds
and are advantageously introduced in the form of a salt of formula
(II):
##STR00004##
in which: [0033] X.sup.- is a counterion chosen from anions and
mixtures of anions, which anions and mixtures of anions are
advantageously chosen from monovalent anions; [0034] said
hydrocarbon-based radicals R.sub.1, R.sub.2, R.sub.3, R.sub.4,
R.sub.5 and R.sub.6 are generally chosen from: [0035] alkyls;
[0036] optionally substituted aryls; [0037] amino and imino groups,
advantageously in which the nitrogen linked to a Pn does not bear
hydrogen; among the amino groups, N,N-dialkylamino, N,N-diarylamino
and N-aryl-N-alkylamino groups are preferably chosen; among the
imino groups that are particularly suitable are mono- and
diarylketimino, phosphinimino, and especially trialkyl-,
dialkylaryl-, diarylalkyl- and triarylphosphinimino, derivatives of
amidine type [of formula >N--C(-).dbd.N-- in which (--)
represents an open bond] including cyclic forms and including
guanidines [(>N--).sub.2C.dbd.N--)] may be attached to the Pn
via their amine function or via their imine function; [0038]
phosphino groups, such as dialkylphosphino, alkylarylphosphino and
especially diarylphosphino; however, especially when Pn is
phosphorus, it is preferable for there to be not more than two and
advantageously not more than one such group per Pn atom; [0039]
hydrocarbyloxy groups; [0040] a polymer arm.
[0041] As will be seen later, the compounds in which the radicals
R.sub.4, R.sub.5 or even R.sub.6 are phosphinimino are easy to
synthesize. Among these phosphinimino groups, mention may be made
of those in which the phosphorus bears aryl, alkyl or dialkylamino
groups.
[0042] The aryl groups forming part of the above compound are
advantageously homocyclic, taken in the sense antonymous to
heterocyclic.
[0043] The term "alkyl" is taken in its etymological sense as an
alcohol residue from which the OH function has been removed. Thus,
it essentially comprises radicals in which the free bond is borne
by a carbon atom sp.sup.3 hybridization, this carbon atom being
linked only to carbons or hydrogens. In the context of the present
invention, among the alkyls that may also be mentioned are the
compounds of formula C.sub.nH.sub.2n+1, alkyls which are
substituted with atoms and/or functions (depending on the
application, it is preferable, in order to avoid side reactions, to
select functions that are inert under the working conditions of the
invention) and especially those bearing ether function(s) and in
particular the mono-, oligo- or polyethoxylated chains derived from
epoxides, especially of ethylene and/or of a peralkylated amine
function, those which are substituted with halogens, and those
bearing one or more aromatic nuclei.
[0044] Said alkyls may also bear quaternary ammonium or phosphonium
functions.
[0045] Except when they represent an arm, the radicals R.sub.1,
R.sub.2, R.sub.3, R.sub.4, R.sub.5 and R.sub.6 advantageously
contain not more than 20 carbon atoms, and, unless it is linked to
a polymer, the molecule comprises in total not more than 100 carbon
atoms and preferably not more than 60 carbon atoms.
[0046] It is preferable for not more than 2 of the radicals
R.sub.1, R.sub.2, R.sub.3, R.sub.4, R.sub.5 and R.sub.6 to
represent a polymer arm; this arm is linked to the corresponding Pn
atom via a bond with a carbon atom of aliphatic or aromatic nature
or via a bond with an imino or amino group.
[0047] However, it is more practical to use molecules that are not
linked to a polymer.
[0048] For reasons of ease of synthesis, it is preferable for
R.sub.1, R.sub.2 and R.sub.3 to be identical. This is likewise the
case for R.sub.4, R.sub.5 and R.sub.6.
[0049] The radicals R.sub.1, R.sub.2, R.sub.3, R.sub.4, R.sub.5 and
R.sub.6 may be linked together and may form rings.
[0050] In particular: [0051] R.sub.1, R.sub.2 and R.sub.3 may be
linked together and may form rings, and [0052] R.sub.4, R.sub.5 and
R.sub.6 may be linked together and may form rings.
[0053] When the Pn are the same, the synthesis of the catalysts in
which the radicals R.sub.1, R.sub.2, R.sub.3, R.sub.4, R.sub.5 and
R.sub.6 are the same is easier and therefore less expensive. They
are therefore preferred in this respect. However, the activity of
the compounds not comprising this symmetry around Z is very
frequently excellent.
[0054] As has been mentioned above, when said hydrocarbon-based
radicals R.sub.1, R.sub.2, R.sub.3, R.sub.4, R.sub.5 and R.sub.6
are linked via a carbon to the atoms Pn, this carbon atom may be of
sp.sup.3 aliphatic hybridization, or of sp.sup.2 hybridization, ie
especially of aromatic nature on account of the instability of the
vinyl groups. Links with atoms of aromatic nature are preferred.
Another kind of link is preferred, which is the link via the
nitrogen atom of an amine function or of an imine function.
[0055] Thus, it is desirable for at least 3, advantageously at
least 4, preferably at least 5 and more preferably all of the
radicals R.sub.1, R.sub.2, R.sub.3, R.sub.4, R.sub.5 and R.sub.6 to
be linked to the Pn via an aromatic carbon atom and/or a nitrogen
atom of a peralkylated amine or imine function.
[0056] When the peralkylated imines are phosphonimines, this
results in several sequences of the type Pn=N=Pn with one common
atom Pn; in this case, to ensure solubility in solvents when the
molecule is symmetrical of order 4 (four identical substituents)
around a phosphorus, it is preferable for there to be a number of
carbon atoms greater by at least a third and advantageously by at
least a half of the sum of the nitrogen and phosphorus atoms.
[0057] The counterions are advantageously chosen from sparingly
nucleophilic anions and mixtures of anions X.sup.-, ie, when they
are single, they are such that XH has a pKa of not more than 3,
advantageously 2, preferably 1 and more preferably zero, and when
they consist of a mixture of anions, at least one of the anions is
sparingly nucleophilic.
[0058] It should be mentioned, however, that the counterions
corresponding to the superacids weaken the catalytic effect; thus,
bromide is more effective than BF.sub.4.sup.-. Thus, wherever it is
possible and when the catalysis needs to be strong, it is
preferable to avoid counteranions that correspond to a high Hammett
constant and thus to select anions corresponding to acids with a
Hammett constant of not more than 12 and preferably 10.
[0059] According to one of the preferred embodiments of the
invention, this use is implemented in a process that is useful for
performing a nucleophilic substitution of SN.sub.Ar type on an
aromatic substrate, characterized in that an aromatic substrate of
general formula (III):
Ar-(.XI.) [0060] in which Ar is an aromatic radical in which the
nucleus bearing .XI. is electron-poor either because it comprises
at least one hetero atom in its ring, or because the sum of the
.sigma..sub.p of its substituents, besides the .XI., is at least
equal to 2, advantageously 0.4 and preferably 0.5; the substituents
possibly being leaving groups capable of giving rise to a new
substitution and thus of being noted .XI., in a subsequent
SN.sub.Ar; [0061] in which .XI. is a leaving group, advantageously
in the form of an anion .XI..sup.-; is subjected to the action of a
nucleophilic agent capable of exchanging with the or at least one
of the substituents .XI. in the presence of a catalyst of formula
(I).
[0062] It is desirable for the molar ratio between the catalyst and
the nucleophilic agent used in the reaction to be at least equal to
0.1.Salinity., advantageously 0.5.Salinity., preferably 1.Salinity.
and more preferably 0.5%.
[0063] It is also desirable for the molar ratio between the
catalyst and the substrate used in the reaction to be at least
equal to 0.1.Salinity., advantageously 0.5.Salinity., preferably
1.Salinity. and more preferably 0.5%.
[0064] Strictly speaking, there is no upper limit, but, unless the
compound of formula II is used as the reagent that is the vector of
X.sup.-, which is then the nucleophile, it is more economical for
the molar ratio between the catalyst and the nucleophilic agent
used in the reaction to be not more than 1/3, advantageously 1/5
and preferably 10%.
[0065] Advantageously, .XI..sup.- is less nucleophilic than the
nucleophilic agent with which it exchanges; since the
nucleophilicity scales are difficult to use, a person skilled in
the art may use the empirical rule that .XI.H is advantageously
more acidic than the nucleophile in protonated form. .XI. may be a
nitro or quaternary ammonium group, but it is preferable for it to
be a pseudohalogen group or, preferably, a halogen atom chosen from
chlorine, bromine and iodine.
[0066] The term "pseudohalogen" is intended to denote a group whose
loss leads to an oxygenated anion, the anionic charge being borne
by the chalcogen atom, and whose acidity, expressed by the Hammett
constant, is at least equal to that of acetic acid, advantageously
to the second acidity of sulfuric acid and preferably to that of
trifluoroacetic acid.
[0067] Illustrations of pseudohalogens of this type that may be
mentioned in particular include the anions corresponding to
sulfinic acid and sulfonic acid, which are advantageously
perhalogenated on the sulfur-bearing carbon, and also carboxylic
acids that are perfluorinated a to the carboxylic function.
[0068] Since the nucleophilic substitution reaction is relatively
facilitated when .XI. represents an iodine atom, the process
claimed is more particularly advantageous when .XI. symbolizes a
chlorine or bromine atom or a pseudohalogen.
[0069] As regards the substituent(s) of Ar, occasionally referred
to as "groups R", they are present on the aromatic nucleus, and are
selected such that they induce an overall depletion of electrons on
the nucleus that is sufficient to allow the activation of the
substrate and the stabilization of the Meisenheimer complex (cf.
indication given above)
[0070] The aromatic substrate thus substituted has an electron
density at most equal to that of phenyl, advantageously at most in
the region of that of a chlorophenyl and preferably of a
difluorophenyl.
[0071] This depletion may also be due to the presence in the
aromatic ring of a hetero atom such as, for example, in pyridine or
quinoline. It is important to point out that this type of depletion
is observed only when Ar symbolizes a compound with a 6-membered
ring and the hetero atom belongs to column V (essentially nitrogen
or phosphorus) as defined in the Periodic Table of the Elements
published in the supplement to the Bulletin de la Societe Chimique
de France in January 1966.
[0072] Preferably, the group or at least one of the groups R is a
non-leaving electron-withdrawing substituent and more preferably is
other than a carbon-based substituent.
[0073] The substituent(s) R when they are withdrawing may be chosen
from halogen atoms and the following groups: [0074] NO.sub.2 [0075]
SO.sub.2Alk and SO.sub.3Alk [0076] Rf and preferably CF.sub.3
[0077] CN [0078] CHO [0079] COAlk [0080] CO.XI.', in which .XI.' is
chosen from the same values as .XI., with the same preferences
[0081] --COOAlk [0082] phosphone and phosphonate
[0083] with the symbol Alk representing a hydrogen or,
advantageously, a linear or branched, preferably C.sub.1 to C.sub.4
alkyl group.
[0084] Examples of preferred groups R that may be mentioned more
particularly include halogen atoms and the nitro group.
[0085] The electron-withdrawing substituent(s) R is(are) more
preferably located in an ortho and/or para position relative to the
leaving group(s) .XI..
[0086] As regards the nucleophilic agent intended to replace the
leaving group(s) X on the aromatic substrate, it may be generated
in situ during the irradiation reaction.
[0087] As nucleophilic agents that may be used according to the
invention, mention may be made especially of: [0088] phosphine,
arsine and ammonia, [0089] phosphines, arsines and amines, and
anions thereof, [0090] water and its anion, [0091] alcohols and
alkoxides, [0092] hydrazines and semicarbazides, [0093] salts of
weak acids such as carboxylates, thiolates, thiols and carbonates,
[0094] cyanide and its salts, [0095] malonic derivatives, and
[0096] imines.
[0097] The nitrogenous nucleophilic derivatives are of most
particular advantage in the context of the claimed process.
[0098] Nucleophilic agents whose nucleophilic function is an anion
give good results.
[0099] Another aim of the present invention is to provide a process
that is especially useful for performing exchange reactions between
fluorine and halogens with a higher atomic number present on the
aromatic substrate, and especially exchange reactions between
fluorine and chlorine.
[0100] Reverse exchange reactions, ie the replacement of one
halogen with a halogen of a higher row, are also possible. However,
this type of reaction is less advantageous and is also more
difficult to perform. Nevertheless, it is within the capability of
a person skilled in the art to exploit the teaching of the present
process to perform other exchange reactions, and especially these
reverse exchange reactions.
[0101] In the case of exchange reactions between fluorine and
halogens with a higher atomic number, the use of a fluoride as
nucleophilic agent is preferred.
[0102] Advantageously, the fluoride is a fluoride of an alkali
metal with an atomic number at least equal to that of sodium, and
is preferably a potassium fluoride.
[0103] The alkali metal or alkaline-earth metal fluoride is at
least partially present in the form of a solid phase.
[0104] In general, the reaction is performed at a temperature below
that selected for a reaction performed with a common catalyst (the
ultimate example of which is tetramethylammonium).
[0105] The reaction is generally performed in a solvent and, in
this case, it is preferable to perform the reaction at a
temperature at least 10.degree. C., advantageously 20.degree. C.
and preferably 40.degree. C. below the limit temperature usually
accepted for said solvent used.
[0106] A continuous recovery of the most volatile compounds may
also be performed gradually as they are formed. This recovery may
be performed, for example, by distillation.
[0107] According to one of the possible embodiments, the heating is
performed partially or totally by microwaves of the present
invention; in this case, it is preferable for the microwaves to be
emitted over short periods (from 10 seconds to 15 minutes)
alternating with phases of cooling. The respective durations of the
microwave emission periods and of the cooling periods are chosen
such that the temperature at the end of each microwave emission
period remains below an initial set temperature, which is generally
less than the resistance temperature of the ingredients of the
reaction mixture.
[0108] It is also possible to perform such a heating according to a
procedure in which the reaction mixture is simultaneously subjected
to microwaves and to cooling. According to this variant, the power
released by the microwaves is then chosen such that, for an initial
set temperature which is generally the working temperature, it is
equivalent to the energy removed by the cooling system, plus or
minus the heat evolved or absorbed by the reaction.
[0109] Such an actinic heating process moreover has the advantage
of being compatible with a continuous functioning mode. This mode
of use advantageously makes it possible to surmount the heat
exchange problems that may arise during the operations of opening
and closing of the reactor in which the microwaves are emitted.
[0110] According to this mode of functioning, the materials to be
activated are introduced continuously via an inlet orifice into the
reactor, where they undergo an activation by microwaves and the
activated products are removed continuously from said reactor via
an outlet orifice.
[0111] In the case of actinic heating by microwave, it is
recommended to use a power evolved by the microwaves of between 1
and 50 watts per milliequivalent of aromatic substrate. It is also
desirable to accept the constraint according to which the power
evolved by the microwaves is between 2 and 100 watts per gram of
reaction mixture.
[0112] The catalyst according to the invention may be used
concomitantly with a catalyst acknowledged as being a
phase-transfer catalyst, especially when this catalyst is a
catalyst of cationic nature.
[0113] Such a concomitant use is all the more appropriate since the
mechanism of action appears to be different.
[0114] The best phase-transfer catalysts that may be used are
generally oniums, ie they are organic cations whose charge is borne
by a metalloid. Among the oniums that may be mentioned are
ammoniums, phosphoniums and sulfoniums. However, other
phase-transfer catalysts may also be used provided that the
phase-transfer catalysts are positively charged. They may also be
cryptand cations, for example alkali-metal-cryptand crown
ethers.
[0115] These phase-transfer catalysts may be used in the presence
or absence, preferably in the presence, of an alkali metal cation
that is particularly heavy and thus from a high atomic row, such as
cesium and rubidium.
[0116] When the present invention is used to carry out a
chlorine/fluorine exchange reaction, a dipolar aprotic solvent, a
solid phase consisting at least partially of alkali metal fluorides
and a reaction-promoting cation are generally used, said cation
being a heavy alkali metal or an organic phase-transfer agent, this
agent being of cationic nature.
[0117] The content of alkali metal cation, when it is used as
promoter, is advantageously between 1 mol % and 5 mol % and
preferably between 2 mol % and 3 mol % of the nucleophilic agent
used. These ranges are closed ranges, ie they include their
limits.
[0118] The reagent may comprise, as promoter, phase-transfer agents
that are oniums (organic cations whose name ends with onium). The
oniums in general represent 1 mol % to 10 mol % and preferably from
2 mol % to 5 mol % of the aromatic substrate, and the counterion
may be of any nature but is usually halogenated.
[0119] Among the oniums, the preferred reagents are
tetraalkylammoniums of 4 to 28 carbon atoms and preferably from 4
to 16 carbon atoms. The tetraalkylammonium is generally
tetramethylammonium.
[0120] Phosphoniums and especially phenylphosphoniums should also
be mentioned, which have the advantage of being stable and
relatively sparingly hygroscopic; however, these reagents are
relatively expensive.
[0121] The aprotic solvent of halex type advantageously has a
significant dipolar moment. Thus, its relative dielectric constant
epsilon is advantageously at least equal to about 10; preferably,
the epsilon is less than or equal to 100 and greater than or equal
to 25.
[0122] It has been possible to show that the best results were
obtained when dipolar aprotic solvents with a donor index of
between 1.0 and 50 were used, said donor index being the .DELTA.H
(enthalpy variation) expressed in kilocalories of the combination
of said dipolar aprotic solvent with antimony pentachloride.
[0123] The oniums are chosen from the group of cations formed by
columns VB and VIB as defined in the Periodic Table of the Elements
published in the supplement to the Bulletin de la Societe Chimique
de France in January 1966, with four or three hydrocarbon-based
chains, respectively.
[0124] In general, it is known that a fine particle size has an
influence on the kinetics. Thus, it is desirable for said solid in
suspension to have a particle size such that its d.sub.90 (defined
as the mesh that allows 90% by mass of the solid to pass through)
is not more than 100 .mu.m, advantageously not more than 50 .mu.m
and preferably not more than 200 .mu.m. The lower limit is
advantageously characterized in that the d.sub.10 of said solid in
suspension is not less than 0.1 .mu.m and preferably not less than
1 .mu.m.
[0125] In general, the ratio between said nucleophilic agent,
preferably the alkali metal fluoride, and said substrate is between
1 and 1.5 and preferably in the region of 5/4 relative to the
exchange stoichiometry.
[0126] The mass content of solids present in the reaction medium is
advantageously not less than 1/5, advantageously 1/4 and preferably
1/3.
[0127] The stirring is advantageously performed such that at least
80% and preferably at least 90% of the solids are maintained in
suspension by the stirring.
[0128] According to the present invention, the reaction is
advantageously performed at a temperature ranging from about 150 to
about 250.degree. C. In the present description, the term "about"
is used to illustrate the fact that the values that follow it
correspond to mathematic round-ups and especially that, in the
absence of a decimal point, when the figure(s) the furthest to the
right in a number are zeros, these zeros are positional zeros
rather than significant figures, except, of course, if otherwise
specified.
[0129] However, it should be pointed out that when the temperature
increases, the kinetics increase but the selectivity decreases.
[0130] Another aim of the present invention is to provide a
composition capable of serving as a reagent for nucleophilic
substitution, especially aromatic nucleophilic substitution.
[0131] This aim is achieved by means of a composition comprising:
[0132] a polar aprotic solvent; [0133] a nucleophile; [0134] a
compound of formula (I).
[0135] It should be noted that the compounds of formulae (I) and
(II) are particularly suitable for the usual recycling
techniques.
[0136] Another aim of the invention is to provide, besides that of
having provided a novel family of novel compounds that is useful as
nucleophilic substitution catalysts having a pronounced catalytic
nature.
[0137] Another aim of the present invention is to provide a process
for synthesizing compounds that are used or that may be used as
catalysts for second order nucleophilic substitution and especially
for SN.sub.Ar nucleophilic substitution.
[0138] These aims have been achieved with compounds of formula (I)
in which the number of alkyl substituents is not more than 2 and in
which the total number of carbons is not less than 14 and
preferably 16 per positive charge borne by the molecule. It should
also be pointed out that it is particularly advantageous to have
molecules that are not completely symmetrical around one of the
atoms Z, but also around one of the atoms Pn.
[0139] Thus, it may be indicated that the sum of the carbons in the
radicals R.sub.1, R.sub.2, R.sub.3, R.sub.4, R.sub.5 and R.sub.6 is
greater than 12, preferably not less than 14 and advantageously not
less than 16.
[0140] The condition regarding the alkyls may also be expressed by
indicating that not more than 2 and preferably not more than one of
the radicals R.sub.1, R.sub.2 and R.sub.3, on the one hand, and/or
R.sub.4, R.sub.5 and R.sub.6, on the other hand, represent an alkyl
group.
[0141] Finally, when symmetry is not desired, the absence of
symmetry relative to Z may be expressed by indicating that the
combination consisting of R.sub.1, R.sub.2 and R.sub.3 must be
different, for at least one of these components, than the
combination R.sub.4, R.sub.5 and R.sub.6. As regards the
non-symmetry around one of the Pn when it is desired, this absence
of symmetry may be expressed in the following manner: at least one
of the radicals R.sub.4, R.sub.5 and R.sub.6 must be different than
the radical consisting of (R.sub.1) (R.sub.2)
(R.sub.3)P.sub.n.dbd.N--.
[0142] The limitation regarding the number of alkyl derivatives is
linked to the fact that, according to the present invention, it has
been shown that it was desirable for the substituents R.sub.1 to
R.sub.6 especially to have a donor nature via a mesomeric effect,
so as to delocalize the positive charge better. However, alkyl
chains with a carbon number of greater than 5 may be advantageous
for the compatibility of the catalyst with solvents of sparingly
polar nature, ie solvents that are not miscible in all proportions
with water.
[0143] According to the present invention, the targeted compounds
may be synthesized by the action of an iminoid of formula (R.sub.1)
(R.sub.2) (R.sub.3) P.sub.n=ZH or derivatives thereof on suitable
substrates, namely trivalent Pn compounds.
[0144] According to one of the modes of preparation, the iminoid in
hydrogenated form or in the form of a salt, advantageously an
alkali metal salt, is reacted with a trivalent Pn derivative
[halogen >Pn-X in which X represents a leaving group] bearing a
leaving group, advantageously halogen (preferably bromine or
chlorine) the iminoid anion replaces the leaving group giving a
sequence Pn=Z-Pn<. The final product may be obtained by
quaternizing the Pn that has remained trivalent using a compound
chosen from R.sub.4--X', R.sub.5--X' and R.sub.6--X', in which X'
is a leaving group, advantageously a halogen, preferably from a row
at least equal to that of chlorine; and especially bromine and
iodine.
[0145] The reaction may be written in the manner below:
##STR00005##
[0146] The quaternization reaction takes place at the end, and
reactions to introduce the radicals R.sub.4 and R.sub.5 may take
place in between.
[0147] For example, several iminoid groups may be grafted:
##STR00006##
[0148] Usually, in this route, the iminoid is condensed with a
phosphine already bearing two final substituents, in this case
R.sub.4 and R.sub.5.
##STR00007##
In this case also, one of the Pn, preferably both of them, is(are)
advantageously P. Z is advantageously nitrogen.
[0149] According to another mode of action, the anion of the
iminoid is converted into a cation by oxidation, advantageously
using a positive halogen (commonly written in the case of bromine
as Br.sup.+) or a molecular halogen, usually bromine, and is placed
in contact with a trisubstituted Pn (R.sub.4) (R.sub.5)
(R.sub.6)Pn; thus directly giving a compound according to the
present invention. This technique is developed further:
##STR00008##
In this case also, one of the Pn, and preferably both of them,
is(are) advantageously P. Z is advantageously nitrogen.
[0150] The reactivity and the polyvalency of (R.sub.1) (R.sub.2)
(R.sub.3)P.sub.n=ZH, and of the alkali metal salts thereof (where
appropriate in the presence of molecular halogen, usually bromine)
and especially those of (R.sub.1) (R.sub.2) (R.sub.3) P.dbd.NLi
makes it possible to perform many catalyst syntheses, whether or
not the molecules are already known. Its use constitutes an
advantageous route of access for the compounds used as catalyst in
the present invention. The reactions in the examples below are
typical examples thereof.
[0151] According to another embodiment of the present invention,
the synthesis may be performed by reacting a trisubstituted
phosphinimine compound with a halophosphonium halide, which
phosphonium bears three hydrocarbon-based substituents. The
halophosphonium halide:
##STR00009##
may be produced in situ by the action of a halide on a phosphine.
The reaction may be written as below, in which the condensation
example taken is the condensation of a phosphinimine with a
triphenylphosphine in the presence of bromine.
[0152] In this case, the synthesis of the phosphiniminophosphonium
bromide may be performed by reacting phosphinimines with
dibromophosphoranes corresponding to the desired salt. The
phosphinimines are obtained by deprotonating the corresponding
aminophosphonium salt in the presence of a strong base such as
sodium amide.
The reaction may be written as below:
##STR00010##
[0153] In this equation, the radicals R' may correspond, for
example, to R.sub.1, R.sub.2 and R.sub.3, and the radicals R may
correspond to R.sub.4, R.sub.5 and R.sub.6, or vice versa.
[0154] As regards the procedure, two options are possible, one
reacting the phosphinimine with the preformed dibromophosphorane,
another reacting this same phosphinimine with bromine and then with
the appropriate phosphine.
[0155] Needless to say, the technique is performed under an
atmosphere of dry inert gas. The starting phosphonimines are
generally obtained by the action of one equivalent of
N-butyllithium as base on an aminophosphonium halide, generally the
bromide. Certain phosphinimines are commercially available.
Dibromophosphorane is prepared beforehand by simple addition of a
stoichiometric amount of dibromine to the appropriate phosphine. As
indicated in the typical equation below:
##STR00011##
[0156] In this equation, the radicals R' may correspond, for
example, to R.sub.1, R.sub.2 and R.sub.3, and the radicals R may
correspond to R.sub.4, R.sub.5 and R.sub.6, or vice versa.
[0157] According to one variant already mentioned above of the
present invention, the synthesis of these symmetrical or
dyssymmetrical compounds is performed using an intermediate known
as a phosphonium azayldiide. This reaction may be represented
schematically as below, it being understood, of course, that, in
this example, the phenyls may be replaced with R.sub.1, R.sub.2,
R.sub.3 and Ar.sub.3 may be replaced with R.sub.4, R.sub.5 and
R.sub.6.
Equation No. 3
##STR00012##
[0159] The method described [lacuna] to gain access to tribromo
derivatives. By using only one equivalent of bromine (instead of
2), the monobromo salts are synthesized directly.
##STR00013##
[0160] In this equation, the radicals R' may correspond, for
example, to R.sub.1, R.sub.2 and R.sub.3, and the radicals R may
correspond to R.sub.4, R.sub.5 and R.sub.6, or vice versa.
[0161] This simple method makes it possible to obtain, in the same
reaction medium (R.sub.3PNLi is prepared in situ by the action of 2
equivalents of BuLi on the corresponding aminophosphonium salt) the
desired phosphiniminophosphonium salts under very mild conditions
and very quickly.
[0162] Needless to say, salts other than the lithium salts may be
used, but the lithium salt is the easiest to manufacture using
butyllithium. The reactions are performed in common solvents,
generally in optionally cyclic ethers, for instance THF, or
chlorinated derivatives, for instance dichloromethane, the
temperature usually used being between -30.degree. C. and room
temperature, more generally between -20.degree. C. and room
temperature.
[0163] The examples that follow are given as non-limiting
illustrations of the invention:
EXAMPLE 1
Preparation of 4-fluoronitrobenzene: Comparison with "Already-Known
Catalysts"
Procedure
[0164] The following are introduced into a 60 ml tube: [0165]
para-chloronitrobenzene [0166] DMSO [0167] the catalyst [0168]
KF.
[0169] The tubes are closed with a septum and a screw stopper, and
then heated with stirring for 4 hours at 150.degree. C. After
cooling to room temperature, about 10 g of water are added,
followed by 5 g of dichloromethane, and, after settling of the
phases and separation of the organic and aqueous phases, the
aqueous phase is back-extracted twice with 5 g of dichloromethane.
The various organic phases are combined and analyzed by GC.
TABLE-US-00001 Charge table PCNB KF DMSO Catalyst mass KF mass
equivalent/ mass Catalyst mass Catalysts Test (g) (g) pCNB (g)
nature (g) equivalent/pCNB A 5.0087 2.03 1.10 5 0 0 B 5.0062 2.03
1.10 5 TMAC 0.1086 0.031 C 5.0048 2.03 1.10 5 Bu.sub.4PBr 0.3237
0.030 D 5.0049 2.04 1.11 5 Tetrakis 0.381 0.030 E 5.0089 2.03 1.10
5 Ph.sub.4PBr 0.4002 0.030 F 5.004 2.03 1.10 5 PPNCl 0.548 0.030
TMAC = tetramethylammonium chloride Bu.sub.4PBr =
tetrabutylphosphonium bromide tetrakis =
tetrakis(diethylamino)phosphonium bromide Ph.sub.4PBr =
tetraphenylphosphonium bromide PPNCl =
bis(triphenylphosphoranylidene)ammonium chloride of formula:
##STR00014##
TABLE-US-00002 Results Degree of Catalyst conversion of Test nature
the pCNB Yield of PFNB A 7 4 B TMAC 46 46 C Bu.sub.4PBr 15 15 D
Tetrakis 17 17 E Ph.sub.4PBr 11 6 F (according to PPNCl 62 62 the
invention)
[0170] It is noted that the catalyst according to the invention is
by far the best catalyst, as regards both the reaction selectivity
and the degree of conversion.
EXAMPLE 2
Preparation of 2,4-difluoronitrobenzene: Comparison with
"Already-Known Catalysts"
##STR00015##
[0171] Procedure
[0172] The following are introduced into a 60 ml tube: [0173]
2,4-dichloronitrobenzene [0174] sulfolane [0175] the catalyst
[0176] KF.
[0177] The tubes are closed with a septum and screw stopper, and
are then heated with stirring for 4 hours at 170.degree. C. After
cooling to room temperature, about 10 g of water are added,
followed by 5 g of dichloromethane, and, after settling of the
phases and separation of the organic and aqueous phases, the
aqueous phase is back-extracted twice with 5 g of dichloromethane.
The various organic phases are combined and analyzed by GC.
TABLE-US-00003 Charge table DCNB KF Sulfolane Catalyst Catalysts
mass KF mass equivalent/ mass Catalyst mass equivalent/ Test (g)
(g) DCNB (g) nature (g) DCNB A 5.0062 3.33 2.2 6.3 0 0 B 5.0026
3.34 2.2 6.3 TMAC 0.0868 0.031 C 5.0084 3.33 2.2 6.3 Bu.sub.4PBr
0.266 0.030 D 5.0149 3.34 2.2 6.3 Tetrakis 0.312 0.030 E 5.0066
3.34 2.2 6.3 Ph.sub.4PBr 0.358 0.030 F 5.0092 3.34 2.2 6.3 PPNCl
0.449 0.030 TMAC = tetramethylammonium chloride Bu.sub.4PBr =
tetrabutylphosphonium bromide tetrakis =
tetrakis(diethylamino)phosphonium bromide Ph.sub.4PBr =
tetraphenylphosphonium bromide PPNCl =
bis(triphenylphosphoranylidene)ammonium chloride.
TABLE-US-00004 Results Degree of Catalyst conversion of Yield of
Yield of Test nature the DCNB CFNB DFNB A 25 20 2 B TMAC 97 29 68 C
Bu.sub.4PBr 95 27 67 D Tetrakis 96 24 69 E Ph.sub.4PBr 92 31 60 F
PPNCl 98 16 77.5
[0178] The catalyst according to the invention [lacuna] which gives
both the best degree of conversion, but also the one which gives
the best yield of difluoro product.
EXAMPLE 3
Preparation of 1-fluoro-3,5-dichlorobenzene and
1,3-difluoro-5-chlorobenzene: Examples for Comparison with
"Already-Known Catalysts"
##STR00016##
[0179] Procedure
[0180] The following are introduced into a 60 ml tube: [0181]
1,3,5-trichlorobenzene [0182] sulfolane [0183] the catalyst [0184]
KF.
[0185] The tubes are closed with a septum and screw stopper, and
are then heated with stirring at 210.degree. C. for the time
indicated in the table. After cooling to room temperature, about 10
g of water are added, followed by 5 g of dichloromethane, and,
after settling of the phases and separation of the organic and
aqueous phases, the aqueous phase is back-extracted twice with 5 g
of dichloromethane. The various organic phases are combined and
analyzed by GC.
TABLE-US-00005 Charge table TCB KF KF Sulfolane Catalyst Catalysts
mass mass equivalent/ mass Catalyst mass equivalent/ Test T (h) (g)
(g) TCB (g) nature (g) TCB A 3 1.508 0.96 2 2 Bu.sub.4PBr 0.055
0.02 B 3 1.506 0.97 2 2 Bu.sub.4PBr 0.143 0.05 C 2 1.503 0.97 2 2
Tetrakis 0.099 0.03 D 2 1.505 0.97 2 2 PPNCl 0.143 0.03
TABLE-US-00006 Results Degree of conversion Catalyst of the TCB
Yield of Yield of Test nature (%) FDCB CDFB A Bu.sub.4PBr 3 2.5 0 B
Bu.sub.4PBr 3 2.7 0 C Tetrakis 3 2.9 0 D PPNCl 23 21 0.7
[0186] The catalyst according to the invention is on the one hand
the one that gave the highest degree of conversion, but on the
other hand the only one that gave a small amount of
difluorination.
EXAMPLE 4
Preparation of 4-fluoronitrobenzene
##STR00017##
[0187] Procedure
[0188] The following are introduced in order into a 30 ml Schott
tube: [0189] 4-chloronitrobenzene [0190] the catalyst [0191] KF
[0192] DMSO.
[0193] The tubes are closed with a septum and screw stopper, and
are then heated with stirring for 3 hours at 150.degree. C. After
cooling to room temperature, about 10 g of water are added,
followed by 5 g of dichloromethane, then 5 g of dichloromethane
again, and, after settling of the phases and separation of the
organic and aqueous phases, the aqueous phase is back-extracted
twice with 5 g of dichloromethane. The various organic phases are
combined and analyzed by HPLC.
TABLE-US-00007 Charge table eq Kf eq DMSO mass Mass to to catalyst
in g eq cat. to Test PNCB g PNCB PNCB nature catalyst PNCB 1 2.0092
1.11 3.00 Nothing 0 0 2 2.0493 1.10 3.00
[(CH.sub.3).sub.2N].sub.3PNP[N(CH.sub.3).sub.2].sub.3, 0.2261 0.041
BF.sub.4- 3 2.1034 1.10 3.03 [(CH.sub.3).sub.2N].sub.3PNPBu.sub.3,
0.2495 0.041 Br.sup.- 4 2.0962 1.10 3.00 Ph.sub.3PNPBu.sub.3,
Br.sup.- 0.2982 0.040 5 2.0111 1.13 3.01
[(CH.sub.3).sub.2N].sub.3PNP[N(CH.sub.3).sub.2].sub.3, 0.2186 0.041
Br.sup.- 6 1.5620 1.09 3.23 Ph.sub.3PNP[N(CH.sub.3).sub.2].sub.3,
0.1871 0.043 Br.sup.- 7 1.5136 1.11 3.22
Ph.sub.3PNP((o)-MeOPh).sub.3, 0.2731 0.040 Br-- 8 1.5069 1.13 3.24
Bu3PNPBu.sub.3, Br-- 0.1992 0.042 Ph.sub.3PNP(Co)-MeOPh).sub.3,
Br-- =
##STR00018##
TABLE-US-00008 Results Test Catalysts Yield of PNFB 1 Nothing 5.87%
2 [(CH.sub.3).sub.2N].sub.3PNP[N(CH.sub.3).sub.2].sub.3,BF.sub.4-
10.60% 3 [(CH.sub.3).sub.2N].sub.3PNPBu.sub.3,Br- 15.77% 4
Ph.sub.3PNPBu.sub.3,Br- 28.00% 5
[(CH.sub.3).sub.2N].sub.3PNP[N(CH.sub.3).sub.2].sub.3,Br- 20.04% 6
Ph.sub.3PNP[N(CH.sub.3).sub.2].sub.3,Br- 45.50% 7
Ph.sub.3PNP((o)-MeOPh).sub.3,Br- 37.82% 8 Bu.sub.3PNPBu.sub.3,Br-
41.83%
EXAMPLE 5
Preparation of 1,3,5-trifluorobenzene
##STR00019##
[0194] Procedure
[0195] The following are introduced in order into a 30 ml Schott
tube: [0196] 1,3,5-trichlorobenzene [0197] the catalyst [0198] KF
[0199] sulfolane.
[0200] The tubes are closed with a septum and screw stopper, and
are then heated with stirring for 3 hours at 210.degree. C. After
cooling to room temperature, about 10 g of water are added,
followed by 5 g of dichloromethane, then 5 g of dichloromethane
again, and, after settling of the phases and separation of the
organic and aqueous phases, the aqueous phase is back-extracted
twice with 5 g of dichloromethane. The various organic phases are
combined and analyzed by GC.
TABLE-US-00009 Charge table eq eq Kf sulfolane Mass in g Mass to to
Catalyst of eq cat. to Test TCB g TCB TCB nature catalyst TCB 1
1.541 2.07 2.25 Nothing 0 0 2 1.5030 2.08 2.02
[(CH.sub.3).sub.2N].sub.3PNPBu.sub.3, 0.1579 0.041 Br.sup.- 3
1.5076 2.01 2.03 Ph.sub.3PNPBu.sub.3, Br-- 0.1860 0.040 4 1.5095
1.99 2.02 [(CH.sub.3).sub.2N].sub.3PNP[N(CH.sub.3).sub.2].sub.3,
0.1408 0.040 Br-- 5 1.4929 1.99 2.09
Ph.sub.3PNP[N(CH.sub.3).sub.2].sub.3, 0.1767 0.049 Br-- 6 1.0082
2.08 2.29 Bu.sub.3PNPBu.sub.3, Br-- 0.1616 0.058
TABLE-US-00010 Results Test Catalysts RY DCFB RY DFCB 1 Nothing
<0.5% <0.5% 2 [(CH.sub.3).sub.2N].sub.3PNPBu.sub.3,Br 25.39%
1.04% 3 Ph.sub.3PNPBu.sub.3,Br-- 15.70% 0.24% 4
[(CH.sub.3).sub.2N].sub.3PNP[N(CH.sub.3).sub.2].sub.3,Br-- 38.95%
2.73% 5 Ph.sub.3PNP[N(CH.sub.3).sub.2].sub.3,Br-- 25.24% 1.48% 6
Bu.sub.3PNPBu.sub.3,Br-- 11.55% 1.28%
Synthesis of Catalysts
[0201] The reactivity and polyvalency of (R.sub.1) (R.sub.2)
(R.sub.3) Pn=ZH, and of the alkali metal salts thereof (where
appropriate in the presence of molecular halogen, usually bromine)
and especially those of (R.sub.1) (R.sub.2) (R.sub.3) P.dbd.NLi,
makes it possible to perform numerous syntheses of catalysts,
whether or not the molecules are already known. Its use constitutes
an advantageous route of access for the compounds used as catalyst
in the present invention. The reactions below are examples
thereof.
EXAMPLE 6
Synthesis of Catalysts
[0202] The reaction of Ph.sub.3P.dbd.NLi with PCl.sub.3 leads
quantitatively to the synthesis of the protonated triphosphinimine
3. The synthesis of this compound is performed by passing via the
corresponding triphosphinimine (Ph.sub.3P.dbd.N).sub.3P; this
compound has a lone pair on the phosphorus atom, the electron
density of which is considerably increased by the triple donor
effect of the three Ph.sub.3P.dbd.N-- groups. This triphosphinimine
then becomes basic enough to become protonated within a few minutes
at 20.degree. C., probably by attacking the protons of THF, and
precipitating in this solvent in the form of the phosphonium salt
[(Ph.sub.3P.dbd.N)P--H].sup.+Cl.sup.-.
[0203] This availability of the lone pair makes this compound an
advantageous intermediate for subsequent quaternization and to form
a compound according to the invention.
Procedure
[0204] Trichlorophosphine (1.4 mmol, 1 equivalent) is added by
syringe in a single portion to a solution of Ph.sub.3P.dbd.NLi (4.2
mmol, 3 equivalents) in 50 ml of THF at 20.degree. C. The mixture
is stirred at this temperature for 30 minutes; a white precipitate
of N,N',N''-(phosphinio)tris-triphenylphosphinimine then forms in
the medium. This precipitate is filtered off, rinsed with THF and
obtained in pure form in a yield of 95%.
##STR00020##
[0205] (Ph.sub.3P.dbd.N).sub.3P is observed by .sup.31P NMR after
the action of nbutyllithium on a solution of the isolated salt 3 in
dimethyl sulfoxide at 20.degree. C. The triphosphinimine, which is
very sensitive to moisture and to oxygen, could not be isolated.
After deprotonation followed by addition of elemental sulfur, a
mixture of the starting phosphonium salt (12%) and of oxidized
triphosphinimine (Ph.sub.3P.dbd.N).sub.3P.dbd.O (52%) and
sulfurized triphosphinimine (Ph.sub.3P.dbd.N).sub.3P.dbd.S (24%) is
recovered.
[0206] The pKa of the
[(Ph.sub.3P.dbd.N).sub.3P--H].sup.+/(Ph.sub.3P.dbd.N).sub.3P couple
is between that of Ph.sub.3=P.dbd.NH/Ph.sub.3P.dbd.NLi and that of
the n-butane/n-butyllithium couple, ie between 28 and 43.
EXAMPLE 7
[0207] Addition of one equivalent of chlorodiphenylphosphine to
N-diphenylphosphinotriphenylphosphinimine 1, to give a
phosphinimine containing a P.dbd.N--P--P sequence 2.
##STR00021##
[0208] Ph.sub.2PCl (4 mmol) is added dropwise at 20.degree. C. to a
solution of N-diphenylphosphinotriphenylphosphinimine (4 mmol) in
THF. The solution is stirred for 12 hours at this temperature.
Compound 2 precipitates over time. The solution is then filtered,
the white solid collected is then recrystallized from acetonitrile
and is obtained in a yield of 73%. Its structure is confirmed by
melting point, mass spectrometry, .sup.31P NMR and IR.
[0209] This compound has been described once in 1969 by Madersteig
(Mardersteig, H. G.; Meinel, L.; Noth, H. Z. Anorg. Allg. Chem.
1969, 368, 254-261 or Z. Anorg. Allg. Chem. 1970, 375, 272-280)
starting with Ph.sub.3P.dbd.NSiMe.sub.3 and two equivalents of
Ph.sub.2PCl.
EXAMPLE 8
Synthesis of [Ph.sub.3P.dbd.N=PBu.sub.3].sup.+Br.sup.-
[0210] 28 mmol of n-BuLi (as a commercial hexane solution: Aldrich)
are added dropwise over about 15 minutes to a solution of 14 mmol
of aminotriphenylphosphonium bromide in 125 ml of anhydrous THF,
cooled to -15.degree. C. The mixture is stirred constantly at this
temperature for one hour (the diylide thus generated may be
analyzed by phosphorus NMR, taking the precaution of performing the
withdrawal under nitrogen). Under these conditions, 14 mmol (1
equivalent) of bromine predried by means of an acidic wash (36%
H.sub.2SO.sub.4) are added. The reaction mixture is then stirred
for 2 hours at a temperature of 0 to 5.degree. C. 14 mmol of
tributylphosphine are finally added to this solution. The mixture
obtained is stirred constantly for about 12 hours (overnight).
[0211] The solution obtained is filtered and the filtrate is
concentrated to dryness under reduced pressure. The .sup.31P NMR
analysis shows the majority presence of the expected product. The
residue thus recovered is taken up in dichloromethane and washed
with distilled water solution. The organic phase is dried over
MgSO.sub.4 and then concentrated to dryness. The product is
redissolved in a minimum amount of dichloromethane and purified by
adding a large volume of ether. The recovered product is subjected
to ion exchange using a sodium iodide NaI solution in order to
facilitate its purification.sup.a). After this treatment, the
residue is taken up in 20 ml of ether and left under cold
conditions (4.degree. C.) for 3 hours. The iodinated product
precipitates and is recovered in pure form by simple
filtration.
[0212] The product in its brominated form will be obtained by
simple ion exchange first using an AgNO.sub.3 solution and then
with an NaBr solution.sup.b). The oil obtained is left in the open
air for several days in order to obtain a crystalline solid.
a) General Procedure for Purification by Exchanging Br.sup.- or
Br.sub.3.sup.- with I.sup.-
[0213] The impure bromo residue recovered is taken up in
dichloromethane and washed successively with 3 aqueous NaI
solutions of concentration: (2.5 eq; 1.5 eq; 0.5 eq). The organic
phase is then dried over MgSO.sub.4 and concentrated to dryness in
view of the various treatments.
b) General procedure for changing from I.sup.- to Br.sup.-
[0214] The pure iodide obtained is redissolved in dichloromethane
and washed with aqueous silver nitrate solution (2 eq). The organic
phase is then washed with distilled water solution to remove the
silver iodide residues in suspension. The organic phase then
undergoes 3 washes with an aqueous NaBr solution (2.5 eq; 1.5 eq;
0.5 eq). The organic solution is finally dried over MgSO.sub.4 and
then concentrated to dryness under reduced pressure, thus allowing
the pure bromo compound to be isolated.
##STR00022##
C.sub.30H.sub.42BrNP.sub.2
[0215] 558.520 gmol.sup.-1 Pale yellow solid 55% yield
[0216] .sup.31P NMR (ppm) (CDCl.sub.3) 41.14 (s, .sup.(a)P; 17.28
(s, .sup.(b)P)
[0217] .sup.1H NMR (ppm) (CDCl.sub.3): 7.7-7.58 (m, 15H, aromatic);
1.98 (m, 6H, .sup.1CH.sub.2); 1.31 (m, 12H,
.sup.2CH.sub.2.sup.-3CH.sub.2--); 0.79 (t, 9H, CH.sub.3)
[0218] .sup.13C NMR (ppm) (CDCl.sub.3): 133.18 (d,
J.sup.4.sub.PC=2.83 Hz, C.sub.6H.sub.5 p-C); 131.31 (d,
J.sup.3.sub.PC=11.16 Hz, C.sub.6H.sub.5 m-C); 128.14 (d,
J.sup.2.sub.PC=13.01 Hz, C.sub.6H.sub.5 o-C); 128.14 (d,
J.sup.2.sub.PC=13.01 Hz, C.sub.6H.sub.5 o-C); 127.69 (dd,
J.sup.1.sub.PC=107.3 Hz, J.sup.3.sub.PaC=1.54 Hz, C.sub.6H.sub.5
ipso-C); 26.30 (d, J.sup.1.sub.PC=63.47 Hz, CH.sub.2); 23.09 (d,
J.sup.2.sub.PC=15.88 Hz, CH.sub.2); 23.11 (d, J.sup.3.sub.PC=4.57
Hz, CH.sub.2); 12.99 (s, CH.sub.3)
[0219] Mass: FAB.sup.+ M-Br.sup.-; 478 [NBA matrix]
[0220] Microanalysis EXP.: C, 65.05%; H, 7.70%; P, 10.50% THEO.: C,
64.45%; H, 7.51%; P: 11.10%; BR, 14.31%
EXAMPLE 9
Synthesis of
[Ph.sub.3P.dbd.N=P(o-C.sub.6H.sub.4OMe).sub.3].sup.+Br.sup.-
a) Synthesis of
[Ph.sub.3P.dbd.N=P(o-C.sub.6H.sub.4OMe).sub.3].sup.+Br.sub.2.sup.-
[0221] 28 mmol of n-BuLi (as a commercial hexane solution: Aldrich)
are added dropwise over about 15 minutes to a solution of 14 mmol
of aminotriphenylphosphonium bromide in 125 ml of anhydrous THF,
cooled to -15.degree. C. The mixture is left under constant
stirring at this temperature for one hour (the diylide thus
generated may be analyzed by phosphorus NMR, taking the precaution
to perform the withdrawal under nitrogen). Under these conditions,
35 mmol (2.5 equiv.) of a bromine solution predried by means of an
acidic wash (36% H.sub.2SO.sub.4) are added. The reaction mixture
is then stirred for 2 hours at a temperature of 0 to 5.degree. C.
14 mmol of tri-o-anisylphosphine are finally added to this
solution. The mixture obtained is left under constant stirring for
about 12 hours (overnight).
[0222] The solution obtained is filtered and the precipitate is
purified by simple washing, first with a solution of 30 ml of
ethanol and then with a solution of 50 ml of ether. The tribromo
salt of the expected product was obtained.
##STR00023##
C.sub.39H.sub.36Br.sub.3NO.sub.3P.sub.2
[0223] 868.569 gmol.sup.-1 White solid 65% yield
[0224] .sup.31P NMR (ppm) (CH.sub.2Cl.sub.2): 19.62 (d, .sup.(a)P,
J.sup.2.sub.PP=16.04 Hz); 15.06 (s, .sup.(b)P),
J.sup.2.sub.P-P=16.04 Hz)
[0225] .sup.1H NMR (ppm) (CDCl.sub.3): 7.66-6.74 (m, 27H,
aromatic); 3.16 (m, 9H, OCH.sub.3)
[0226] .sup.13C NMR (ppm) (CDCl.sub.3): 160.90 (d,
J.sup.2.sub.PC=2.98 Hz, C.sub.6H.sub.4 o-C-OMe); 135.39 (d, Ar),
134.12 (d, Ani); 133.19 (d, Ani); 132.03 (d, Ar); 128.93 (d);
128.03 (dd, J.sup.1.sub.PC=111.27 Hz, J.sup.3.sub.PC=2.05 Hz,
ipso-C--Ar); 121.13 (d, J.sup.3.sub.PC=13.77 Hz, Ani); 115.12 (dd,
J.sup.1.sub.PC=116.50 Hz, J.sup.3.sub.PC=2.05 Hz, ipso-C-Anisyl);
111.97 (d, J.sup.3.sub.PC=7.07 Hz, Ani); 55.25 (s, OMe).
[0227] Mass: FAB.sup.+ M-Br.sup.-; 628 [NBA matrix]
[0228] Microanalysis EXP.: C, 53.19%; H, 4.13%; N, 1.72% THEO.: C,
53.88%; H, 4.14%; N, 1.61%
b) Reduction of the Br.sub.3.sup.- to Br.sup.-
[0229] The tribromo salts obtained are taken up in a
dichloromethane solution and washed with aqueous sodium sulfite
solution (2 eq). Decolorization of the organic phase is then
rapidly observed, which is the characteristic sign of reduction of
the trihalides. The organic phase is dried over MgSO.sub.4 and then
concentrated to dryness under reduced pressure. The phosphorus,
proton and carbon spectra are good, but the microanalysis does not
correspond either to the monobromo product or to the tribromo
product.
c) Synthesis of
[Ph.sub.3P.dbd.N=P(o-C.sub.6H.sub.4OMe).sub.3].sup.+Br.sup.-
[0230] 28 mmol of n-BuLi (as a commercial hexane solution: Aldrich)
are added dropwise over about 15 minutes to a solution of 14 mmol
of aminotriphenylphosphonium bromide in 125 ml of anhydrous THF,
cooled to -15.degree. C. The mixture is left under constant
stirring at this temperature for one hour (the diylide thus
generated may be analyzed by phosphorus NMR, taking care to perform
the withdrawal under nitrogen). Under these conditions, 14 mmol (1
equivalent) of bromine predried by means of an acidic wash (36%
H.sub.2SO.sub.4) are added. The reaction mixture is then stirred
for 2 hours at a temperature of 0 to 5.degree. C. 14 mmol of
tri-o-anisylphosphine are finally added to this solution. The
mixture obtained is left under constant stirring for about 12 hours
(overnight). The solution obtained is filtered and the filtrate is
concentrated to dryness under reduced pressure. The .sup.3P NMR
analysis shows the majority presence of the expected product. The
residue thus recovered is taken up in dichloromethane and washed
with distilled water solution. The organic phase is dried over
MgSO.sub.4 and then concentrated to dryness. The product is
redissolved in a minimum amount of dichloromethane and purified by
adding a large volume of ether, from which it precipitates.
##STR00024##
C.sub.39H.sub.36BrNO.sub.3P.sub.2
[0231] 708.569 gmol.sup.-1 White solid 55% yield
[0232] .sup.31P NMR (ppm) (CH.sub.2Cl.sub.2): 20.17 (d, .sup.(a)P,
J.sup.2.sub.PP=16.15 Hz); 15.54 (s, (b) p), J.sup.2.sub.P-P=16.15
Hz)
[0233] .sup.1H NMR (ppm) (CDCl.sub.3): 7.67-6.75 (m, 27H,
aromatic); 3.19 (m, 9H, OCH.sub.3) (ppm) (CDCl.sub.3): .delta.4.9
ppm (s, OCH.sub.3 Ani); 111.6 ppm (d, .sup.3J.sub.P-C=6.7 Hz, CH
Ani); 114.8 ppm (d, .sup.1J.sub.P-C=112.1 Hz, C.sub.IV Ani); 120.8
ppm (d, .sup.3J.sub.PC=13.8 Hz, CH Ani); 127.1 ppm (d,
.sup.1J.sub.PC=115.9 Hz, C.sub.IV Ph); 128.9 ppm (d,
.sup.3J.sub.PC=13.4
[0234] .sup.13C NMR Hz, CH Ph); 131.8 ppm (d, .sup.2J.sub.PC=11.5
Hz, CH Ph); 133.2 ppm (d, .sup.4J.sub.PC=2.06 Hz, CH Ph); 133.9 ppm
(d, .sup.2J.sub.PC=10.05 Hz, CH Ani); 135.4 ppm (apparent s,
.sup.4J.sub.PC.apprxeq.0 Hz; CH Ani); 161.2 ppm (s, C-OMe Ani)
[0235] Mass: FAB.sup.+ M-Br.sup.-; 628 [NBA matrix]
[0236] Microanalysis EXP.: AWAITING THEO.: C, 66.11%; H, 5.12%; BR:
11.28%
EXAMPLE 10
Synthesis of
[(Me.sub.2N).sub.3--P.dbd.N=P--(NMe.sub.2).sub.3].sup.+Br.sup.-
[0237] Comment: In this case, we used iminotris(dimethylamino)
phosphorane [(CH.sub.3).sub.2N].sub.3P.dbd.NH as starting
substrate. Consequently, only one equivalent of n-BuLi is added to
generate the corresponding azayldiide.
[0238] 14 mmol of n-BuLi (as a commercial hexane solution: Aldrich)
are added dropwise over about 15 minutes to a solution of 14 mmol
of iminotris(dimethylamino)phosphorane
[(CH.sub.3).sub.2N].sub.3P.dbd.NH in 125 ml of anhydrous THF,
cooled to -15.degree. C. The mixture is left under constant
stirring at this temperature for one hour (the diylide thus
generated may be analyzed by phosphorus NMR, taking care to perform
the withdrawal under nitrogen). Under these conditions, 14 mmol (1
equivalent) of bromine predried by means of an acidic wash (36%
H.sub.2SO.sub.4) are added. The reaction mixture is then stirred
for 2 hours at a temperature of 0 to 5.degree. C. 14 mmol of
tris(dimethylamino)phosphine are finally added to this solution.
The mixture obtained is left under constant stirring for about 12
hours (overnight).
[0239] The reaction mixture is filtered and the precipitate
containing the expected product is recovered. This product is taken
up in a minimum amount of dichloromethane, to which are added a few
drops of ethanol until the slight cloudiness has totally
disappeared. The addition of a large volume of ether allows the
majority of the impurities to be removed. The ether phase is then
concentrated to dryness, taken up in ether and left at low
temperature overnight. The product in monobromo form is recovered
in pure form by simple filtration and the solid is dried over
P.sub.2O.sub.5 overnight in a desiccator.
##STR00025##
C.sub.12H.sub.36BrN.sub.7P.sub.2
[0240] 420.315 gmol.sup.-1 Beige-colored solid; 43% yield
[0241] .sup.31P NMR (ppm) (CDCl.sub.3): 19.62 (s, 2P
equivalent)
[0242] .sup.1H NMR (ppm) (CDCl.sub.3): 7.36-6.74 (t, 36H
equivalent)
[0243] .sup.13C NMR (ppm) (CDCl.sub.3): 36.50 (t,
J.sup.2.sub.PC=4.78 Hz) 2nd order system
[0244] Mass: FAB.sup.+ M-Br.sup.-; 340 [NBA matrix]
[0245] Microanalysis EXP.: C, 34.29%; H, 8.64%; N, 23.00%; BR,
19.16%
[0246] THEO.: C, 34.26%; H, 8.51%; N, 23.31%; BR, 19.03%
EXAMPLE 11
Synthesis of
[(Me.sub.2N).sub.3--P.dbd.N=PBu.sub.3].sup.+Br.sup.-
[0247] 14 mmol of a solution of dibromine diluted beforehand in 10
ml of dichloromethane at -5.degree. C. are added dropwise to a
solution of 14 mmol of tributylphosphine in 70 ml of anhydrous
dichloromethane. The mixture is stirred for 1 hour at a temperature
of 0 to -5.degree. C. (in situ formation of Bu.sub.3PBr.sub.2).
[0248] After addition of 1.5 equivalents of triethylamine, 14 mmol
of iminotris (dimethylamino) phosphorane
[(CH.sub.3).sub.2N].sub.3P.dbd.NH in 14 ml of THF are then added to
the solution of dibromotributylphosphorane Bu.sub.3PBr.sub.2. The
resulting mixture is stirred overnight at room temperature.
[0249] The solution obtained is evaporated to dryness under reduced
pressure. The residue recovered is taken up in ether and then
filtered off. The pasty, semisolid product is taken up in
dichloromethane and washed with distilled water solution. The
organic phase is dried over MgSO.sub.4, filtered and then
concentrated to dryness. The product is then suspended in ether and
left overnight at low temperature. The pasty solid contained in the
ether phase is triturated in a bath of cold alcohol at -70.degree.
C. and the solution is filtered. The pure product is finally dried
in a desiccator over P.sub.2O.sub.5.
##STR00026##
C.sub.18H.sub.45BrN.sub.4P.sub.2
[0250] 459.432 gmol.sup.-1 Pale brown solid 48.8% yield
[0251] .sup.31P NMR (ppm) (CDCl.sub.3): 29.62 (d,
J.sup.2.sub.PP=30.65 Hz); 23.18 (d, J.sup.2.sub.PP=30.65 Hz)
[0252] .sup.1H NMR (ppm) (CDCl.sub.3): 2.6 (dd, 18H); 2 to 1.8 (m,
.sup.1CH.sub.2, 6H); 1.55 to 1.3 (m, .sup.2CH.sub.2-.sup.3CH.sub.2,
12H); 0.87 (t, CH.sub.3, 9H) (ppm) (CDCl.sub.3): 36.76 (d,
J.sup.2.sub.PC=4.47 Hz, MeN); 26.85 (dd,
[0253] .sup.13C NMR J.sup.1.sub.PC=66.24 Hz, J.sup.3.sub.PC=1.49
Hz, CH.sub.2): 23.36 (d, J.sup.2.sub.PC=11.54 Hz, CH.sub.2); 23.18
(s, CH.sub.2CH.sub.3); 13.20 (s, CH.sub.3)
[0254] Mass: FAB.sup.+ M-Br.sup.-; 380 [NBA matrix]
[0255] Microanalysis EXP.: C, 45.66%; H, 9.73%; N, 11.70%; P,
12.90% THEO.: C, 47.01%; H, 9.79%; N, 12.18%; P, 13.40%;
EXAMPLE 12
Synthesis of
[(Me.sub.2N).sub.3--P.dbd.N=PPh.sub.3].sup.+Br.sup.-
[0256] 14 mmol of a solution of dibromine diluted beforehand in 10
ml of dichloromethane at -5.degree. C. are added dropwise to a
solution of 14 mmol of triphenylphosphine in 70 ml of anhydrous
dichloromethane. The mixture is stirred for 1 hour at a temperature
of 0 to -5.degree. C. (in situ formation of Ph.sub.3PBr.sub.2).
[0257] After addition of 1.5 equivalents of triethylamine, 14 mmol
of iminotris(dimethylamino)phosphorane
[(CH.sub.3).sub.2N].sub.3P.dbd.NH in 14 ml of THF are then added to
the solution of dibromotriphenylphosphorane Ph.sub.3PBr.sub.2.
[0258] After stirring overnight at room temperature, the reaction
mixture is concentrated to dryness under reduced pressure. The
solid residue is taken up in ether and then filtered off. The
recovered precipitate is dissolved in 150 ml of dichloromethane and
washed twice with 20 ml of distilled water. The organic phase is
dried over MgSO.sub.4 and then evaporate to dryness. Tre white
solid obtained is suspended in 50 ml of ether and stirred for 30
minutes. The pure product is obtained by simple filtration and
dried in a desiccator overnight over P.sub.2O.sub.5.
##STR00027##
C.sub.24H.sub.33BrN.sub.4P.sub.2
[0259] 519.4 gmol.sup.-1 White solid 67% yield
[0260] .sup.31P NMR (ppm) (CH.sub.2Cl.sub.2): 26.48 (d,
J.sup.2.sub.P-P=37.3 Hz); 13.45 (d, J.sup.2.sub.P-P=37.3 Hz)
[0261] .sup.1H NMR (ppm) (CDCl.sub.3): 2.52 (d, CH.sub.3, 18H,
J.sup.3.sub.P-H=10.35 Hz); 7.57 to 7.44 (m, aromatic, 15H) ppm
(CDCl.sub.3): 152.72 (d, J.sup.4.sub.PC=3.01 Hz); 150.92 (d,
J.sup.3.sub.PC=
[0262] .sup.13C NMR 11.06 Hz) 148.68 (d, J.sup.2.sub.PC=13.20 Hz);
147.21 (dd, J.sup.1.sub.PC=108.64 Hz, J.sup.3.sub.PC=2.54 Hz);
56.25 (d, J.sup.2.sub.PC=4.52 Hz, MeN)
Mass: FAB.sup.+ M-Br.sup.-; 439 [NBA matrix]
[0263] Microanalysis EXP.: C, 45.66%; H, 9.73%; N, 11.70%; P,
12.90% THEO.: C, 47.01%; H, 9.79%; N, 12.18%; P, 13.40%;
EXAMPLE 13
Synthesis of Bu.sub.3-P.dbd.N=PBu.sub.3.sup.+Br.sup.-
[0264] This example shows the advantage of the synthetic technique,
although the product is not among the preferred products.
[0265] Thus, 14 mmol of a solution of dibromine diluted beforehand
in 10 ml of dichloromethane at -5.degree. C. are added dropwise to
a solution of 14 mmol of tributylphosphine in 70 ml of anhydrous
dichloromethane. The mixture is stirred for 1 hour at a temperature
of 0 to -5.degree. C. (in situ formation of Bu.sub.3PBr.sub.2).
[0266] After addition of 1.5 equivalents of triethylamine, 14 mmol
of Bu.sub.3P.dbd.NH (prepared by the action of 1 equivalent of BuLi
on [Bu.sub.3PNH.sub.2].sup.+Br.sup.-) in 14 ml of THF are then
added to the solution of dibromotributylphosphorane
Bu.sub.3PBr.sub.2.
[0267] After reacting overnight, the reaction mixture is
concentrated to dryness and the residue recovered is taken up in 40
ml of THF. The solution is filtered and the organic phase
containing the expected salt is evaporated to dryness. This salt is
not entirely pure, since the residue contains about 25% of the
starting aminophosphonium salt that we did not manage to separate
out by recrystallization (on the basis of the phosphorus NMR). The
precipitate is then heated at 160.degree. C. for 5 hours until the
residual starting salt has disappeared. Recrystallization of the
residue from CCl.sub.4 thus allows the expected product to be
obtained in a yield of 52%.
##STR00028##
C.sub.24H.sub.54BrNP.sub.2
[0268] 498.549 gmol.sup.-1
YELLOW OIL
[0269] 52% yield
[0270] .sup.31P{.sup.1H} NMR (CH.sub.2Cl.sub.2): 36.3 ppm
(Bu.sub.3PNPBu.sub.3, Br) (57.2 ppm (Bu.sub.3PNH.sub.2, Br))
[0271] .sup.1H NMR (CDCl.sub.3): 0.93 ppm (t, 18H, CH.sub.3): 1.45
ppm (m, 24H, CH.sub.2--CH.sub.2); 2.03 ppm (m, 12H, --CH.sub.2--P)
(CDCl.sub.3): 13.66 ppm (s, CH.sub.3): 23.88 ppm (d,
.sup.2J.sub.P-C=15.6
[0272] .sup.13C NMR Hz, CH.sub.2); 24.02 ppm (d,
.sup.3J.sub.P-C=4.5 Hz, CH.sub.2); 27.15 ppm (d/d,
.sup.1J.sub.P-C=65.5 Hz, .sup.3J.sub.P-C.apprxeq.0.4 Hz,
CH.sub.2)
[0273] Mass: FAB.sup.+ M-Br.sup.-; 418 [NBA matrix]
[0274] Microanalysis Awaiting
* * * * *