U.S. patent number RE39,744 [Application Number 10/830,494] was granted by the patent office on 2007-07-24 for adamantane derivatives and process for producing them.
This patent grant is currently assigned to Daicel Chemical Industries, Ltd.. Invention is credited to Naruhisa Hirai, Yasutaka Ishii, Tatsuya Nakano.
United States Patent |
RE39,744 |
Ishii , et al. |
July 24, 2007 |
**Please see images for:
( Certificate of Correction ) ** |
Adamantane derivatives and process for producing them
Abstract
In the presence of an imide compound (e.g.,
N-hydroxyphthalimide) shown by the formula (2): ##STR00001##
wherein R.sup.1 and R.sup.2 independently represents a hydrogen
atom, a halogen atom, an alkyl group, an aryl group, a cycloalkyl
group; or R.sup.1 and R.sup.2 may bond together to form a double
bond or an aromatic or non-aromatic ring; Y is O or OH and n=1 to
3; or the imide compound and a co-catalyst (e.g., a transition
metal compound), an adamantane derivative having a functional group
such as a nitro group, an amino group, a hydroxyl group, a carboxyl
group, a hydroxymethyl group and an isocyanato group is oxidized
with oxygen. According to the above method, an adamantane
derivative having a hydroxyl group together with a functional group
such as a nitro group, an amino group, a hydroxyl group, a carboxyl
group, a hydroxymethyl group and an isocyanato group is efficiently
obtained.
Inventors: |
Ishii; Yasutaka (Takatsuki,
JP), Nakano; Tatsuya (Himeji, JP), Hirai;
Naruhisa (Himeji, JP) |
Assignee: |
Daicel Chemical Industries,
Ltd. (Osaka, JP)
|
Family
ID: |
26397474 |
Appl.
No.: |
10/830,494 |
Filed: |
March 5, 1998 |
PCT
Filed: |
March 05, 1998 |
PCT No.: |
PCT/JP98/00904 |
371(c)(1),(2),(4) Date: |
November 10, 1998 |
PCT
Pub. No.: |
WO98/40337 |
PCT
Pub. Date: |
September 17, 1998 |
Related U.S. Patent Documents
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Application
Number |
Filing Date |
Patent Number |
Issue Date |
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Reissue of: |
09180478 |
Nov 10, 1998 |
06392104 |
May 21, 2002 |
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Foreign Application Priority Data
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Mar 11, 1997 [JP] |
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9-056516 |
Aug 4, 1997 [JP] |
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9-209431 |
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Current U.S.
Class: |
568/818; 548/549;
548/552; 562/501; 562/502; 564/457; 564/458; 562/499; 548/551;
548/545; 548/152; 502/167 |
Current CPC
Class: |
C07C
233/74 (20130101); C07C 235/40 (20130101); C07C
69/757 (20130101); C07C 67/29 (20130101); C07C
67/31 (20130101); C07C 205/41 (20130101); C07C
62/06 (20130101); C07C 265/10 (20130101); C07C
29/50 (20130101); C07C 219/24 (20130101); C07C
69/96 (20130101); C07C 233/23 (20130101); C07C
68/02 (20130101); C07C 205/55 (20130101); C07C
67/05 (20130101); C07C 233/32 (20130101); C07C
67/08 (20130101); C07C 62/24 (20130101); C07C
35/37 (20130101); C07C 271/34 (20130101); C07C
205/18 (20130101); C07C 29/50 (20130101); C07C
35/37 (20130101); C07C 67/08 (20130101); C07C
69/753 (20130101); C07C 67/31 (20130101); C07C
69/757 (20130101); C07C 68/02 (20130101); C07C
69/96 (20130101); C07C 67/05 (20130101); C07C
69/157 (20130101); C07C 67/29 (20130101); C07C
69/157 (20130101); C07C 2603/74 (20170501) |
Current International
Class: |
C07C
35/22 (20060101); C07C 211/00 (20060101); C07C
61/12 (20060101); C07D 207/40 (20060101); C07D
207/444 (20060101) |
Field of
Search: |
;562/498,499,501.502
;548/152,545,549,551,552 ;564/457,458 ;568/818 ;502/167 |
References Cited
[Referenced By]
U.S. Patent Documents
Foreign Patent Documents
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4216621 |
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Sep 1942 |
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JP |
|
4226792 |
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Dec 1942 |
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JP |
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43-937 |
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Jan 1968 |
|
JP |
|
4412891 |
|
Jun 1969 |
|
JP |
|
4628419 |
|
Aug 1971 |
|
JP |
|
5021090 |
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Mar 1975 |
|
JP |
|
63307844 |
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Dec 1988 |
|
JP |
|
2196744 |
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Aug 1990 |
|
JP |
|
838909 |
|
Feb 1996 |
|
JP |
|
WO9640641 |
|
Dec 1996 |
|
WO |
|
Other References
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Chem. & Pharm. Bulletin, 33 (11), p. 4680-4684. cited by
examiner .
G.R. Newkome et al., J. Org. Chem, vol. 57, No. 1, 1992, pp.
358-362. cited by other .
A. Bashir-Hashemi et al., Tetrahedron Letters, vol. 36, No. 8,
1995, pp. 1233-1236. cited by other .
R.E. Moore et al., J. Org. Chem., vol. 43, No. 26, 1978, pp.
4978-4980. cited by other .
I.N. Butenko et al., Synthetic Communications, vol. 14, No. 2,
1984, pp. 113-119. cited by other .
S. Grimme et al., Chem. Ber, 127, (1994), pp. 2081-2088. cited by
other .
Dolgopolpva, T.N., et al. "Thin-layer chromatography of
oxygen-containing derivatives of adamantane" Zh. Anal. Khim.,
(1989),44(9), p. 1689-1690. cited by other .
Tadashi Sasaki et al., "Synthesis of adamantane derivatives" J.
Org. Chem., (1982), 47, p. 3219-3224. cited by other .
Kozlovskii, Ya. B. et al., (1989), 25(6), p. 1222-1226. cited by
other .
Vishnevskii, E.N. et al. (1996), 32(7), p. 1030-1035. cited by
other .
Kontani, et al., A New Combined Oxidizing Reagent System, Nov.
1985, Chem. & Pharm. Bulletin, 33(11), p. 4680-4684. cited by
other.
|
Primary Examiner: McKenzie; Thomas
Assistant Examiner: Oh; Taylor Victor
Attorney, Agent or Firm: Birch, Stewart, Kolasch &
Birch, LLP
Claims
What is claimed is:
1. An adamantane derivative shown by the following formula (1):
##STR00016## wherein X.sup.1 represents a hydroxyl group which may
be protected by a protective group, X.sup.2 represents nitro group,
an amino group or N-substituted amino group which may be protected
by a protective group, a hydroxyl group which may be protected by a
protective group, a carboxyl group which may be protected by a
protective group, a hydroxymethyl group which may be protected by a
protective group, or isocyanato group; (i) when X.sup.2 is nitro
group, X.sup.3 and X.sup.4 are the same or different from each
other and each represents a hydrogen atom, an alkyl group, a nitro
group, a hydroxyl group which may be protected by a protective
group, an amino group or N-substituted amino group which may be
protected by a protective group, a carboxyl group which may be
protected by a protective group, a hydroxymethyl group which may be
protected by a protective group, or an isocyanato group, excluding
the case where X.sup.3 and X.sup.4 are both hydrogen atoms when
X.sup.1 is hydroxyl group and excluding
1,3,5-trinitro-7-adamantanol; (ii) when X.sup.2 is an amino group
or N-substituted amino group which may be protected by a protective
group, .Iadd.X.sup.1 is a hydroxyl group, .Iaddend.X.sup.3 and
X.sup.4 are the same or different from each other and each
represents a hydrogen atom, an alkyl group, an amino group or
N-substituted amino group which may be protected by a protective
group, a hydroxyl group which may be protected by a protective
group, a carboxyl group which may be protected by a protective
group, a hydroxymethyl group which may be protected by a protective
group, or an isocyanato group, excluding the case where X.sup.3 and
X.sup.4 are both hydrogen atoms or alkyl groups .[.when X.sup.1 is
hydroxyl group.]. ; (iii) when X.sup.2 is a hydroxyl group which
may be protected by a protective group, X.sup.3 and X.sup.4 are the
same or different from each other and each represents a hydrogen
atom, an alkyl group, a hydroxyl group which may be protected by a
protective group, a carboxyl group which may be protected by a
protective group, a hydroxymethyl group which may be protected by a
protective group, or an isocyanato group, excluding the case where
X.sup.3 and X.sup.4 are both hydrogen atoms or alkyl groups when
X.sup.1 is hydroxyl group or a saturated aliphatic acyloxy group
and X.sup.2 is hydroxyl group or a saturated aliphatic acyloxy
group and the case where X.sup.3 and X.sup.4 are a combination of
hydrogen atom and a carboxyl group which may be protected by a
protective group when X.sup.1 and X.sup.2 are both hydroxyl groups
and excluding the case where each of X.sup.1, X.sup.2, X.sup.3, and
X.sup.4 are all a hydroxyl group, or all a hydroxyl group protected
by an acetyl group; (iv) when X.sup.2 is a carboxyl group which may
be protected by a protective group, X.sup.3 and X.sup.4 are the
same or different from each other and each represents a hydrogen
atom, an alkyl group, a carboxyl group which may be protected by a
protective group, a hydroxymethyl group which may be protected by a
protective group, or an isocyanato group, excluding the case where
X.sup.3 and X.sup.4 are both hydrogen atoms or alkyl groups or a
combination of a hydrogen atom and an alkyl group when X.sup.1 is a
hydroxyl group or a saturated aliphatic acyloxy group; (v) when
X.sup.2 is a hydroxymethyl group which may be protected by a
protective group, X.sup.3 and X.sup.4 are the same or different
from each other and each represents a hydrogen atom, an alkyl
group, a hydroxymethyl group which may be protected by a protective
group, or an isocyanato group, excluding the case where, X.sup.3
and X.sup.4 are both hydrogen atoms when X.sup.1 is hydroxyl group;
and (vi) when X.sup.2 is isocyanato group, X.sup.3 and X.sup.4 are
the same or different from each other and each represents a
hydrogen atom, an alkyl group or an isocyanato group, excluding the
case where, X.sup.3 and X.sup.4 are both hydrogen atoms when
X.sup.1 is hydroxyl group; or a salt thereof.
2. An adamantane derivative or a salt thereof according to claim w,
wherein X.sup.1 is hydroxyl group, a saturated C.sub.2-6aliphatic
acyloxy group, a C.sub.1-6-alkoxy-carbonyloxy group or a
carbamoyloxy group which may have a substituent and X.sup.2 is
nitro group, amino group, a C.sub.2-6acylamino group, a
C.sub.1-6alkoxy-carbonylamino group, a saturated C.sub.2-6aliphatic
acyloxy group, a C.sub.1-6alkoxy-carbonyloxy group, a carbamoyloxy
group which may have a substituent, carboxyl group, a
C.sub.1-6alkoxy-carbonyl group, a carbamoyl group which may have a
substituent, hydroxymethyl group or isocyanato group, in the
formula (1).
3. A process for producing an adamantane derivative according to
claim 1, which comprises, in the presence of an oxidation catalyst
comprising an imide compound shown by the following formula (2):
##STR00017## wherein R.sup.1 and R.sup.2 are the same or different
from each other and each represents a hydrogen atom, a halogen
atom, an alkyl group, an aryl group, a cycloalkyl group, a hydroxyl
group, an alkoxy group, a carboxyl group, an alkoxycarbonyl group,
or an acyl group; or R.sup.1 and R.sup.2 may bond together to form
a double bond or an aromatic or non-aromatic ring; Y represents
oxygen atom or hydroxyl group; and n denotes an integer of 1 to 3;
contacting an adamantane derivative shown by the ##STR00018##
wherein X.sup.2 represents an amino group or N-substituted amino
group which may be protected by a protective group, a hydroxyl
group which may be protected by a protective group, a carboxyl
group which may be protected by a protective group, a hydroxymethyl
group which may be protected by a protective group, or isocyanato
group; X.sup.3a and X.sup.4a are the same or different from each
other and each represents a hydrogen atom, an alkyl group, a
hydroxyl group which may be protected by a protective group, an
amino group or N-substituted amino group which may be protected by
a protective group, a carboxyl group which may be protected by a
protective group, a hydroxymethyl group which may be protected by a
protective group, or an isocyanato group; with oxygen.
4. A process according to claim 3, in the imide compound shown by
the formula (2) R.sup.1 and R.sup.2 bond together to form a
cycloalkane ring which may have a substituent, a cycloalkene ring
which may have a substituent, a bridged hydrocarbon ring which may
have a substituent or an aromatic ring which may have a
substituent.
5. A process according to claim 3, wherein the imide compound shown
by the formula (2) is a compound shown by the following formulae
(2a) to (2f): ##STR00019## wherein R.sup.3 to R.sup.6 are the same
or different from each other, and each represents a hydrogen atom,
an alkyl group, a hydroxyl group, an alkoxy group, a carboxyl
group, an alkoxycarbonyl group, an acyl group, a nitro group, a
cyano group, an amino group or a halogen atom; and R.sup.1,
R.sup.2, Y and n have the same meanings as defined above.
6. A process according to claim 3, wherein the imide compound shown
by the formula (2) is at least one compound selected from the group
consisting of N-hydroxysuccinimide, N-hydroxymaleimide,
N-hydroxyhexahydrophthalimide,
N,N'-dihydroxycyclohexanetetracarboximide, N-hydroxyphthalimide,
N-hydroxytetrabromophthalimide, N-hydroxytetrachlorophthalimide,
N-hydroxyhetimide, N-hydroxyhimimide, N-hydroxytrimellitimide,
N,N'-dihydroxypyromellitimide and
N,N'-dihydroxynaphthalenetetracarboximide.
7. A process according to claim 3, wherein said oxidation catalyst
comprises the imide compound shown by the formula (2) and a
co-catalyst.
8. A process according to claim 7, wherein said co-catalyst is a
compound containing at least one element selected from the group
consisting of a Group 2A element of the Periodic Table, a
transition metal element and a Group 3B element of the Periodic
Table.
9. A process according to claim 7, wherein said co-catalyst is a
compound containing at least one element selected from the group
consisting of a Group 3A element, a Group 4A element, a Group 5A
element, a Group 6A element, a Group 7A element, a Group 8 element
and a Group 1B element of the Periodic Table.
10. A process for producing an adamantane derivative according to
claim 1, wherein the adamantane derivative has at least a hydroxyl
group which comprises subjecting an adamantane derivative shown by
the following formula (1a): ##STR00020## wherein X.sup.2 represents
nitro group, an amino group or N-substituted amino group which may
be protected by a protective group, a hydroxyl group which may be
protected by a protective group, a carboxyl group which may be
protected by a protective group, a hydroxymethyl group which may be
protected by a protective group, or isocyanato group; X.sup.3a and
X.sup.4a are the same or different from each other and each
represents a hydrogen atom, an alkyl group, a nitro group, a
hydroxyl group which may be protected by a protective group, an
amino group or N-substituted amino group which may be protected by
a protective group, a carboxyl group which may be protected by a
protective group, a hydroxymethyl group which may be protected by a
protective group, or an isocyanato group; to at least one step
selected from the following oxidation step (i), nitration step (ii)
and carboxylation step (iii): (i) an oxidation step by oxygen in
the presence of a catalyst comprising an imide compound shown by
the following formula (2): ##STR00021## wherein R.sup.1 and R.sup.2
are the same or different from each other and each represents a
hydrogen atom, a halogen atom, an alkyl group, an aryl group, a
cycloalkyl group, a hydroxyl group, an alkoxy group, a carboxyl
group, an alkoxycarbonyl group, or an acyl group; or R.sup.1 and
R.sup.2 may bond together to form a double bond or an aromatic or
non-aromatic ring; Y represents oxygen atom or hydroxyl group; and
n denotes an integer of 1 to 3 provided that in the oxidation step
each of X.sup.2, X.sup.3a and X.sup.4a in the formula (1a) is not
nitro group; (ii) at least one nitration step of the following
(iia) and (iib): (iia) a nitration step by a nitrogen oxide in the
presence of a catalyst comprising the imide compound shown by the
formula (2); and (iib) a nitration step by oxygen and at least one
nitrogen oxide selected from dinitrogen oxide and nitrogen
monoxide; and (iii) a carboxylation step by carbon monoxide and
oxygen in the presence of a catalyst comprising the imide compound
shown by the formula (2).
11. A process according to claim 10, which comprises further
subjecting a reaction product to a reduction step after being
subjected to at least one step selected from said nitration step
(ii) and said carboxylation step (iii) to form at least one group
selected from an amino group and a hydroxymethyl group.
.Iadd.12. The compound 1,3,5-tricarboxyadamantane..Iaddend.
.Iadd.13. A composition comprising the compound
1,3,5-tricarboxyadamantane..Iaddend.
Description
This application is the national phase under 35 U.S.C. .sctn.371 or
prior PCT International Application No. PCT/JP98/00904 which has an
International filing date of Mar. 5, 1998 which designated the
United States of America, the entire contents of which are hereby
incorporated by reference.
TECHNICAL FIELD
This invention relates to a novel adamantane derivative, which has
a hydroxyl group together with a nitro group, an amino group, an
acyloxy group, a carboxyl group, a hydroxymethyl group or the like,
and to a process for producing the same.
BACKGROUND ART
The adamantane has a three-dimensionally symmetric structure and
skeletons which insure mutual stabilization of each ring, and, as a
result, endowed with distinctive functions. Various copolymers each
having enhanced or improved functions or characteristics can be
obtained by introducing a hydroxyl group into an adamantane and, if
necessary, inducing them into an acrylic acid derivative or a
carbonate. There have been proposed various production processes
for obtaining such copolymers from a functional group (e.g., a
hydroxyl group, an amino group, a carboxyl group)-introduced
adamantane. The processes include, for example, a process of
producing a polyester [e.g., Japanese Patent Application Laid-open
No. 21090/1975 (JP-A-50-21090)], a process of producing a
polycarbonate [e.g., U.S. Pat. No. 3,594,427], a process for
producing a polyamide or a polyimide [e.g., U.S. Pat. No.
3,832,,332], a process for producing a polyurethane [e.g., Japanese
Patent Publication No. 12891/1969 (JP-B-44-12891)], a process for
producing a polysulfone and a polysulfonate [e.g., U.S. Pat. No.
3,753,950], and a process for producing a vinyl polymer [e.g.,
Japanese Patent Publication No. 28419/1971 (JP-B-46-28419)].
Generally, these polymers provided from an adamantane derivative
have excellent functions or characteristics (high functionality)
such as, for example, small light-inducing loss, high refractive
index, double refraction index and other optical characteristics,
and moisture resistance, excellent heat resistance, coefficient of
thermal expansion and other characteristics. Such excellent
characteristics cannot be achieved by using conventional polymers.
Accordingly, they have been investigated applications of said
polymer for optical fibers, optical elements, optical lenses,
hologram, optical discs, contact lenses and other optical
materials, transparent resin coating compositions for organic
glasses, electric conductive polymers, photosensitive materials,
fluorescent materials and so forth.
Moreover, an amino derivative derived from an alcohol of an
adamantane is useful for introducing various pharmaceuticals and/or
agricultural chemicals each having excellent pharmacological
activity, and is utilized for producing a therapeutic agent for
Parkinson's disease such as "SYM-METREL" (a trade name).
Thus, an adamantane having a functional group such as a hydroxyl
group is applied to various uses.
As a process for producing an alcohol of the adamantane, there have
been proposed process, such as a process for hydrolyzing a bromide
of adamantane [Japanese Patent Application Laid-open No.
196744/1990 (JP-A-2-196744)], a process for oxidizing an adamantane
using chromic acid [Japanese Patent Publication No. 16621/1967
(JP-B-42-16621)], a process for oxidizing a fused adamantane with
oxygen using a cobalt salt as a catalyst [Japanese Patent
Publication No. 26792/1967 (JP-B-42-26792)], a biological process
[J. Chem. Soc., Chem. Comm., 1833 (1996)]. However, introduction of
a hydroxyl group (specifically, a plurality of hydroxyl groups) to
adamantane by using these processes is difficult.
Japanese Patent Application Laid-open No. 38909/1996 (JP-A-8-38909)
proposes a process for oxidizing a substrate with oxygen by using
an imide compound as a catalyst. By applying the above oxidation
process to the oxidation of a substrate such as adamantane, an
adamantanol is obtained.
It is, therefore, an object of the present invention to provide a
novel adamantane derivative and a process for producing the
same.
It is another object of the present invention to provide an
adamantane derivative having at least one hydroxyl group and at
least one functional group selected from a nitro group, an amino
group, an acylamino group, a carboxyl group, hydroxymethyl group
and other groups, and a process for producing the same.
A further object of the invention is to provide a process for
producing the above mentioned adamantane derivative effectively
with high transformation rate or conversion and selectivity even
under mild or moderate conditions.
DISCLOSURE OF INVENTION
The present inventors did intensive investigation to accomplish the
above objects, and as a result, found that oxidation of a specific
adamantane derivative with oxygen by using an oxidation catalyst
comprising a specific imide compound or the imide compound and a
co-catalyst provides a novel adamantane derivative efficiently.
Thus, a novel adamantane derivative of the present invention is
shown by the following formula (1): ##STR00002## wherein X.sup.1
represents a hydroxyl group which may be protected by a protective
group, X.sup.2 represents a nitro group, an amino group or
N-substituted amino group which may be protected by a protective
group, a hydroxyl group which may be protected by a protective
group, a carboxyl group which may be protected by a protective
group, a hydroxymethyl group which may be protected by a protective
group, or an isocyanato group; (i) when X.sup.2 is a nitro group,
X.sup.3 and X.sup.4 may be the same or different from each other
and each may represent a hydrogen atom, an alkyl group, a nitro
group, a hydroxyl group which may be protected by a protective
group, an amino group or N-substituted amino group which may be
protected by a protective group, a carboxyl group which may be
protected by a protective group, a hydroxymethyl group which may be
protected by a protection group, or an isocyanato group, excluding
the case where X.sup.3 and X.sup.4 are both hydrogen atoms when
X.sup.1 is hydroxyl group; (ii) when X.sup.2 is an amino group or
N-substituted amino group which may be protected by a protective
group, X.sup.3 and X.sup.4 may be the same or different from each
other and each may represent a hydrogen atom, an alkyl group, an
amino group or N-substituted amino group which may be protected by
a protective group, a hydroxyl group which may be protected by a
protective group, a carboxyl group which may be protected by a
protective group, a hydroxymethyl group which may be protected by a
protective group, or an isocyanato group, excluding the case where
X.sup.3 and X.sup.4 are both hydrogen atoms or alkyl groups when
X.sup.1 is hydroxyl group; (iii) when X.sup.2 is a hydroxyl group
which may be protected by a protective group, X.sup.3 and X.sup.4
may be the same or different from each other and each may represent
a hydrogen atom, an alkyl group, a hydroxyl group which may be
protected by a protective group, a carboxyl group which may be
protected by a protective group, a hydroxymethyl group which may be
protected by a protective group, or an isocyanato group, excluding
the case where X.sup.3 and X.sup.4 are both hydrogen atoms or alkyl
groups when X.sup.1 is hydroxyl group or a saturated aliphatic
acyloxy group and X.sup.2 is hydroxyl group or a saturated
aliphatic acyloxy group and excluding the case where X.sup.3 and
X.sup.4 is a combination of hydrogen atom and a carboxyl group
which may be protected by a protective group when X.sup.1 and
X.sup.2 are both hydroxyl groups; (iv) when X.sup.2 is a carboxyl
group which may be protected by a protective group, X.sup.3 and
X.sup.4 may be the same or different from each other and each may
represent a hydrogen atom, an alkyl group, a carboxyl group which
may be protected by a protective group, a hydroxymethyl group which
may be protected by a protective group, or an isocyanato group,
excluding the case where X.sup.3 and X.sup.4 are both hydrogen
atoms or alkyl groups or a combination of a hydrogen atom and an
alkyl group when X.sup.1 is a hydroxyl group or a saturated
aliphatic acyloxy group; (v) when X.sup.2 is a hydroxymethyl group
which may be protected by a protective group, X.sup.3 and X.sup.4
may be the same or different from each other and each may represent
a hydrogen atom, an alkyl group, a hydroxymethyl group which may be
protected by a protective group, or an isocyanato group, excluding
the case where, X.sup.3 and X.sup.4 are both hydrogen atoms when
X.sup.1 is hydroxyl group; (vi) when X.sup.2 is an isocyanato
group, X.sup.3 and X.sup.4 may be the same or different from each
other and each may represent a hydrogen atom, an alkyl group or an
isocyanato group, excluding the case where, X.sup.3 and X.sup.4 are
both hydrogen atoms when X.sup.1 is hydroxyl group.
The adamantane derivative can be obtained, in the presence of an
oxidation catalyst comprising an imide compound shown by the
following formula (2): ##STR00003## wherein R.sup.1 and R.sup.2 may
be the same or different from each other and each may represent a
hydrogen atom, a halogen atom, an alkyl group, an aryl group, a
cycloalkyl group, a hydroxyl group, an alkoxy group, a carboxyl
group, an alkoxycarbonyl group, or an acyl group; or R.sup.1 and
R.sup.2 may bond together to form a double bond or an aromatic or
non-aromatic ring; Y represents an oxygen atom or a hydroxyl group;
and n denotes an integer of 1 to 3; by contacting an adamantane
derivative shown by the following formula (1a): ##STR00004##
wherein X.sup.2 represents a nitro group, an amino group or
N-substituted amino group which may be protected by a protective
group, a hydroxy group which may be protected by a protective
group, a carboxyl group which may be protected by a protective
group, a hydroxymethyl group which may be protected by a protective
group, or an isocyanato group; X.sup.3a and X.sup.4a may be the
same or different from each other and each may represent a hydrogen
atom, an alkyl group, a nitro group, a hydroxyl group which may be
protected by a protective group, an amino group or N-substituted
amino group which may be protected by a protective group, a
carboxyl group which may be protected by a protective group, a
hydroxymethyl group which may be protected by a protective group,
or an isocyanato group; with oxygen.
The present invention also includes a process for producing an
adamantane derivative having at least a hydroxyl group which
comprises subjecting an adamantane derivative shown by the
following formula (1a): ##STR00005## wherein X.sup.2 represents a
nitro group, a hydroxyl group which may be protected by a
protective group, an amino group or N-substituted amino group which
may be protected by a protective group, a hydroxyl group which may
be protected by a protective group, a carboxyl group which may be
protected by a protective group, a hydroxymethyl group which may be
protected by a protective group, or an isocyanato group; X.sup.3a
and X.sup.4a may be the same or different from each other and each
may represent a hydrogen atom, an alkyl group, a nitro group, a
hydroxyl group which may be protected by a protective group, an
amino group or N-substituted amino group which may be protected by
a protective group, a carboxyl group which may be protected by a
protective group, a hydroxymethyl group which may be protected by a
protective group, or an isocyanate group; to at least one step
selected from the following oxidation step (i), nitration step (ii)
and carboxylation step (iii): (i) an oxidation step by oxygen in
the presence of a catalyst comprising an imide compound shown by
the formula (2) (ii) at least one nitration step of the following
(iia), (iib) and (iic): (iia) a nitration step by a nitrogen oxide
in the presence of a catalyst comprising an imide compound shown by
the formula (2); (iib) a nitration step by oxygen and at least one
nitrogen oxide selected from dinitrogen oxide and nitrogen
monoxide, and oxygen; and (iic) a nitration step by nitrogen
dioxide (iii) a carboxylation step by carbon monoxide and oxygen in
the presence of a catalyst comprising an imide compound shown by
the formula (2).
The catalyst may comprise an imide compound shown by the formula
(2) and a co-catalyst (e.g., a compound containing a transition
metal element).
Incidentally, in the present specification, the term "protective
group" is used in a wide sense and includes a group derived from a
free functional group. The protective group incapable of being
eliminated may be employed.
Further, the term "functional group" may be used as a general term,
simply referring to a nitro group, an amino group or N-substituted
amino group which may be protected by a protective group, a
hydroxyl group which may be protected by a protective group, a
carboxyl group which may be protected by a protective group, a
hydroxymethyl group which may be protected by a protective group,
or an isocyanato group. An amino group or N-substituted amino group
which may be protected by a protective group may be referred to
simply as an amino group.
BEST MODE FOR CARRYING OUT THE INVENTION
[Adamantane Derivative]
In the adamantane derivative shown by the formula (1), as a
protective group for hydroxyl gruop and hydroxymethyl group (a
moiety corresponding to the hydroxyl group of the hydroxymethyl
group) there may be mentioned, for instance, t-butyl group, a
cycloalkyl group (e.g., cyclohexyl group), an aryl group (e.g.,
2,4-dinitrophenyl group), an aralkyl group (e.g., benzyl group,
2,6-dichlorobenzyl group, 3-bromobenzyl group, 2-nitrobenzyl group,
4-dimethylcarbamoylbenzyl group, a benzyl group which may have a
substituent such as triphenylmethyl group), tetrahydropyranyl
group, a non-polymerizable acyl group [e.g., a saturated aliphatic
acyl group (e.g., a saturated C.sub.2-6aliphatic acyl group such as
acetyl group, propionyl group, isopropionyl group, butyryl group,
isobutyryl group, valeryl group, isovaleryl group, pyvaloyl group,
prefferably a saturated C.sub.2-4aliphatic acyl group), an aromatic
acyl group (e.g., a C.sub.7-13aromatic acyl group such as benzoyl
group, p-phenylbenzoyl, phthaloyl, naphtoyl), an alicyclic acyl
group (a cycloalkyl-carbonyl group: such as cyclohexylcarbonyl)],
an alkoxycarbonyl group such as a C.sub.1-6-alkoxy-carbonyl group
(e.g., methoxycarbonyl group, ethoxycarbonyl group,
propyloxycarbonyl group, isopropyloxycarbonyl group,
isobutyloxycarbonyl group, t-butoxycarbonyl group), an
alalkyloxycarbonyl group (e.g., benzyloxycarbonyl group,
methoxybenzyloxycarbonyl group), a carbamoyl group which may have a
substituent such as a C.sub.1-6alkyl group, a C.sub.6-14aryl group
(e.g., carbamoyl group, methylcarbamoyl group, ethylcarbamoyl
group, phenyl carbamoyl group), a dialkylphosphynotioyl group
(e.g., dimethylphosphynotioyl group), a diarylphosphynotioyl group
(e.g., diophenylphosphynotioyl group). A preferred protective group
of hydroxyl group or hydroxymethyl group includes, for instance, a
non-polymeric acyl group (specifically, a saturated
C.sub.2-6aliphatic acyl group etc., more specifically, a saturated
C.sub.2-4aliphatic acyl group etc.), a C.sub.1-6alkoxy-carbonyl
group, a carbamoyl group which may have a substituent.
A protective group for amino group includes, for example,
protective groups same as the exemplified protective groups for
hydroxyl group, such as t-butyl group, an aralkyl group, a
non-polymerizable acyl group [e.g., a saturated aliphatic acyl
group (e.g., a saturated C.sub.2-6aliphatic acyl group, in
particular a saturated C.sub.2-4aliphatic acyl group), an aromatic
acyl group (e.g., a C.sub.7-13aromatic acyl group), an alicyclic
acyl group], an alkoxy carbonyl group (e.g., a
C.sub.1-6alkoxycarbonyl group), an aralkyloxy carbonyl group, a
dialkylphosphinotioyl group, a diarylphosphinotioyl group. A
preferred protective group of amino group includes, for example, a
non-polymerizable acyl group [e.g., a saturated C.sub.2-6aliphatic
acyl group (especially, a saturated C.sub.2-4aliphatic acyl group),
a C.sub.7-13aromatic acyl group], an alkoxy carbonyl group
(especially, a C.sub.1-6 alkoxy-carbonyl group).
Examples of an N-substituted amino group include a mono- or
di-C.sub.1-6alkylamino group such as methylamino group, ethylamino
group, propylamino group, dimethylamino group, diethylamino group
(preferably, a mono- or di-C.sub.1-4alkylamino group).
A protective group for a carboxyl group includes, for instance, an
alkoxy group (e.g., a C.sub.1-10alkoxy group such as methoxy,
ethoxy, propoxy, isopropoxy, butoxy, isobutoxy, s-butoxy, t-butoxy
and hexyloxy group; preferably a C.sub.1-6alkoxy group, especially
a C.sub.1-4alkoxy group), a cycloalkyloxy group (e.g.,
cyclohexyloxy group), an aryloxy group (e.g., phenoxy group), an
aralkyloxy group (e.g., benzyloxy group, diphenylmethyloxy group),
a trialkylsilyloxy group (e.g., trimethylsilyloxy group), an amino
group which may have a substituent [amino group; an N-substituted
amino group (e.g., a mono- or di-C.sub.1-6alkylamino group such as
methylamino, dimethylamino ethylamino and diethylamino group)],
hydrazino group, an alkoxycarbonylhydrazino group (e.g.,
t-butoxycarbonylhydrazino group), an aralkylcarbonylhydrazino group
(e.g., benzyloxycarbonylhydrazino group). A preferred protective
group of carboxyl group includes an alkoxy group (especially, a
C.sub.1-6-alkoxy group), an amino group which may have a
substituent (e.g., an N-substituted amino group, especially, a
mono- or di-C.sub.1-6alkylamino group).
An alkyl group includes, for instance, a C.sub.1-6alkyl group such
as methyl, ethyl, propyl, isopropyl, butyl, isobutyl, s-butyl,
t-butyl and hexyl group (preferably, a C.sub.1-4alkyl group, more
preferably, methyl group or ethyl group).
Preferred examples of X.sup.1 include hydroxyl group, a saturated
C.sub.2-6aliphatic acyloxy group (corresponding to a hydroxyl group
protected by a saturated C.sub.2-6aliphatic acyl group), a
C.sub.1-6alkoxy-carbonyloxy group (corresponding to a hydroxyl
group protected by a C.sub.1-6alkoxy-carbonyl group), a
carbamoyloxy group which may have a substituent, (corresponding to
a hydroxyl group protected by a carbamoyl group which may have a
substituent).
Preferred examples of X.sup.2 include nitro group, amino group, a
C.sub.2-6acylamino group (corresponding to an amino group protected
by a C.sub.2-6acyl group), a C.sub.1-6alkoxycarbonylamino group
(corresponding to an amino group protected by a
C.sub.1-6alkoxy-carbonyl group), a saturated C.sub.2-6aliphatic
acyloxy group (corresponding to a hydroxyl group protected by a
saturated C.sub.2-6aliphatic acyl group), a
C.sub.1-6alkoxy-carbonyloxy group (corresponding to a hydroxyl
group protected by a C.sub.1-6alkoxy-carbonyl group), a carbamoyl
group which may have a substituent (corresponding to a hydroxyl
group protected by a carbamoyl group which may have a substituent),
carboxyl group, a C.sub.1-10alkoxy-carbonyl group (corresponding to
a carboxyl group protected by a C.sub.1-10alkoxy group)
(especially, a C.sub.1-6alkoxy-carbonyl group), a carbamoyl group
which may have a substituent (corresponding to a carboxyl group
protected by an amino group which may have a substituent),
hydroxymethyl group, isocyanato group.
Preferred examples of X.sup.3 and X.sup.4, depending on the species
of X.sup.2, include a hydrogen atom, an alkyl group, nitro group,
amino group, a C.sub.2-6acylamino group, a
C.sub.1-6alkoxycarbonylamino group, a saturated C.sub.2-6aliphatic
acyloxy group, a C.sub.1-6alkoxy-carbonyloxy group, a carbamoyloxy
group which may have a substituent, carboxyl group, a
C.sub.1-10alkoxy-carbonyl group (specifically, a
C.sub.1-6alkoxycarbonyl group), a carbamoyl group which may have a
substituent, hydroxymethyl group, isocyanato group.
In the present specification, it is sometimes described as follows:
OH for a hydroxyl group which may be protected by a protective
group, OAc for a non-polymerizable acyloxy group, NO.sub.2 for
nitro group, NH.sub.2 for an amino group or N-substituted amino
group which may be protected by a protective group, COOH for a
carboxyl group which may be protected by a protective group,
CH.sub.2OH for a hydroxymethyl group which may be protected by a
protective group, NCO for isocyanato group, H for a hydrogen atom,
and R for an alkyl group.
An adamantane derivative shown by the formula (1) is a novel
compound. A combination of X.sup.2, X.sup.3 and X.sup.4 includes
combinations of the following (1a), (2a), (3a), (4a), (5a) and
(6a).
(1a) When X.sup.2 is an NO.sub.2 and X.sup.1 is a hydroxyl group,
X.sup.3 and X.sup.4 are not H, simultaneously. That is, [1] X.sup.1
is a hydroxyl group, either X.sup.3 or X.sup.4 is H and the other
is a functional group selected from R, NO.sub.2, OH, NH.sub.2,
COOH, CH.sub.2OH and NCO, [2] X.sup.1 is a hydroxyl group, X.sup.3
and X.sup.4 are functional groups selected from R, NO.sub.2, OH,
NH.sub.2, COOH, CH.sub.2OH and NCO, or [3] X.sup.1 is a hydroxyl
group protected by a protective group, X.sup.3 and X.sup.4 are
functional groups selected from H, R, NO.sub.2, OH, NH.sub.2, COOH,
CH.sub.2OH and NCO.
(2a) When X.sup.2 is an NH.sub.2 and X.sup.1 is a hydroxyl group,
X.sup.3 and X.sup.4 are not H or R, simultaneously. That is, [1]
X.sup.1 is a hydroxyl group, either X.sup.3 or X.sup.4 is H and the
other is a functional group selected from R, NH.sub.2, OH, COOH,
CH.sub.2OH and NCO, [2] X.sup.1 is a hydroxyl group, either X.sup.3
or X.sup.4 is an R and the other is a functional group selected
from NH.sub.2, OH, COOH, CH.sub.2OH and NCO, [3] X.sup.1 is a
hydroxyl group, X.sup.3 and X.sup.4 are functional groups selected
from NH.sub.2, OH, COOH, CH.sub.2OH and NCO, or [4] X.sup.1 is a
hydroxyl group protected by a protective group, X.sup.2 is an
NH.sub.2, X.sup.3 and X.sup.4 are functional groups selected from
H, R, NH.sub.2, OH, COOH, CH.sub.2OH and NCO.
(3a) When X.sup.2 is an OH, X.sup.1 is a hydroxyl group or a
saturated aliphatic acyloxy group and X.sup.2 is a hydroxyl group
or a saturated aliphatic acyloxy group, X.sup.3 and X.sup.4 are not
H or R, simultaneously. Incidentally, when X.sup.1 and X.sup.2 are
both hydroxyl groups, X.sup.3 and X.sup.4 are not a combination of
a hydrogen atom and a carboxyl group which may be protected by a
protective group. That is, [1] X.sup.1 and X.sup.2 are both
hydroxyl groups, either X.sup.3 or X.sup.4 is H and the other is a
functional group selected from R, OH, CH.sub.2OH and NCO, [2]
X.sup.1 and X.sup.2 are both hydroxyl groups, either X.sup.3 or
X.sup.4 is R and the other is a functional group selected from OH,
COOH, CH.sub.2OH and NCO, [3] X.sup.1 and X.sup.2 are both hydroxyl
groups, X.sup.3 and X.sup.4 are functional groups selected from OH,
COOH, CH.sub.2OH and NCO, [4] X.sup.1 and X.sup.2 are both hydroxyl
groups protected by saturated aliphatic acyl groups, either X.sup.3
or X.sup.4 is H and the other is a functional group selected from
R, OH, COOH, CH.sub.2OH and NCO, [5] X.sup.1 and X.sup.2 are both
hydroxyl groups protected by saturated aliphatic acyl groups,
either X.sup.3 or X.sup.4 is R and the other is a functional group
selected from OH, COOH, CH.sub.2OH and NCO, [6] either X.sup.1 or
X.sup.2 is hydroxyl group and the other is a hydroxyl group
protected by a saturated aliphatic acyl group, either X.sup.3 or
X.sup.4 is H and the other is a functional group selected from R,
OH, COOH, CH.sub.2OH and NCO, [7] either X.sup.1 or X.sup.2 is
hydroxyl group and the other is a hydroxyl group protected by a
saturated aliphatic acyl group, either X.sup.3 or X.sup.4 is R and
the other is a functional group selected from OH, COOH, CH.sub.2OH
and NCO, or [8] X.sup.1 and X.sup.2 are hydroxyl groups protected
by protective groups excluding saturated aliphatic acyl groups,
X.sup.3 and X.sup.4 are functional groups selected from H, R, OH,
COOH, CH.sub.2OH and NCO.
(4a) When X.sup.2 is COOH and X.sup.1 is hydroxyl group or a
saturated aliphatic acyloxy group, X.sup.3 and X.sup.4 are not
simultaneously H or R, and not a combination of H and R. That is,
[1] X.sup.1 is hydroxyl group or a hydroxyl group protected by a
saturated aliphatic acyl group, either X.sup.3 or X.sup.4 is H or R
and the other is a functional group selected from COOH, CH.sub.2OH
and NCO, [2] X.sup.1 is a hydroxyl group protected by a protective
group excluding a saturated aliphatic acyl group, X.sup.3 and
X.sup.4 are functional groups selected from H, R, COOH, CH.sub.2OH
and NCO.
(5a) When X.sup.2 is CH.sub.2OH and X.sup.1 is hydroxyl group,
X.sup.3 and X.sup.4 are not H, simultaneously. That is, [1] X.sup.1
is hydroxyl group, X is CH.sub.2OH, X.sup.3 is H, and X.sup.4 is a
functional group selected from R, CH.sub.2OH and NCO, [2] X.sup.1
is hydroxyl group, X is CH.sub.2OH, X.sup.3 and X.sup.4 are
functional groups selected from R, CH.sub.2OH and NCO, [3] X.sup.1
is a hydroxyl group protected by a protective group, X is
CH.sub.2OH, X.sup.3 and X.sup.4 are functional groups selected from
H, R, CH.sub.2OH and NCO.
(6a) When X.sup.2 is isocyanato group and X.sup.1 is a hydroxyl
group, X.sup.3 and X.sup.4 are not H, simultaneously. That is, [1]
X.sup.1 is hydroxyl group, X.sup.2 is NCO, X.sup.3 is H, and
X.sup.4 is a functional group selected from R and NCO, [2] X.sup.1
is hydroxyl group, X.sup.2 is NCO, X.sup.3 and X.sup.4 are
functional groups selected from R and NCO, [3] X.sup.1 is a
hydroxyl group protected by a protective group, X.sup.2 is NCO,
X.sup.3 and X.sup.4 are functional groups selected from H, R and
NCO.
Such a novel adamantane derivative includes an adamantane
derivative having at least one kind of functional groups selected
from nitro group, amino group, hydroxyl group, carboxyl group,
hydroxymethyl group and isocyanato group, together with a hydroxyl
group. Incidentally, hydroxyl group, amino group, carboxyl group or
hydroxymethyl group may be protected by a protective group, a
nitrogen atom of an amino group may have one or two substituents.
Further, an adamantane derivative having an acidic group or a basic
group may form a salt thereof.
As an adamantane derivative containing a nitro group, there may be
exemplified a monool body such as 1-nitro-3-methyl-5-adamantanol,
1-nitro-3,5-dimethyl-7-adamantanol, 1,3-dinitro-5-adamantanol,
1,3-dinitro-5-methyl-7-adamantanol, 1,3,5-trinitro-7-adamantanol,
1-carboxy-3-nitro-5-adamantanol,
1-acetylamino-3-nitro-5-adamantanol,
1-hydroxymethyl-3-nitro-5-adamantanol; a diol body such as
1-nitro-3,5-adamantanediol, 1-nitro-3-methyl-5,7-adamantanediol,
1,3-dinitro-5,7-adamantanediol; a triol body such as
1-nitro-3,5,7-adamantanetriol; an adamantanol derivative containing
a nitro group, in which a hydroxyl group is protected by a
protective group [such as a saturated aliphatic acyl group (e.g., a
saturated C.sub.2-6aliphatic acyl group), an alkoxycarbonyl group
(e.g., a C.sub.1-6alkoxy-carbonyl group), a carbamoyl group which
may have a substituent], such as 1-acetoxy-3-nitroadamantane,
1-methoxycarbonyloxy-3-nitroadamantane,
1,3-bis(methoxycarbonyloxy)-5-nitroadamantane,
1-(N-methylcarbamoyloxy)-3-nitroadamantane.
An adamantane derivative having an amino group includes, for
example, an adamantanol derivative having a non-substituted amino
group which is not protected by a protective group (e.g., a monool
body such as 1-amino-3-methyl-5-adamantanol,
1,3-diamino-5-adamantanol, 1,3-diamino-5-methyl-7-adamantanol,
1,3,5-triamino-7-adamantanol; a diol body such as.
1-amino-3,5-adamantanediol, 1-amino-3-methyl-5,7-adamantanediol,
1,3-diamino-5,7-adamantanediol; a triol body such as
1-amino-3,5,7-adamantanetriol), an adamantanol derivative having an
N-substituted amino group (e.g., a monool body such as
1-methylamino-3-methyl-5-adamantanol,
1,3-bis(methylamino)-5-adamantanol,
1,3-bis(ethylamino)-5-adamantanol,
1,3-bis(dimethylamino)-5-adamantanol,
1,3-bis(diethylamino)-5-adamantanol,
1,3-bis(methylamino)-5-methyl-7-adamantanol,
1,3,5-tris(methylamino)-7-adamantanol,
1,3,5-tris(dimethylamino)-7-adamantanol; a diol body such as
1-methylamino-3,5-adamantanediol, 1-ethylamino-3,5-adamantanediol,
1-dimethylamino-3,5-adamantanediol,
1-diethylamino-3,5-adamantanediol,
1-methylamino-3-methyl-5,7-adamantanediol, 1,3-bis
(methylamino)-5,7-adamantanediol,
1,3-bis(ethylamino)-5,7-adamantanediol,
1,3-bis(dimethylamino)-5,7-adamantanediol,
1,3-bis(diethylamino)-5,7-adamantanediol; a triol body such as
1-methylamino-3,5,7-adamantanetriol,
1-dimethylamino-3,5,7-adamantanetriol), an adamantanol derivative
having an amino group protected by a protective group [an alcohol
body of an adamantane having a C.sub.2-6acylamino group, for
example, a monool body such as
1-acetylamino-3-methyl-5-adamantanol, 1,3-bis
(acetylamino)-5-adamantanol,
1,3-bis(acetylamino)-5-methyl-7-adamantanol,
1,3,5-tris(acetylamino)-7-adamantanol; a diol body such as
1acetylamino-3,5-adamantanediol,
1-acetylamino-3-methyl-5,7-adamantanediol,
1,3-bis(acetylamino)-5,7-adamantanediol; a triol body such as
1-acetylamino-3,5,7-adamantanetriol], an adamantanol derivative
having an amino group in which a hydroxyl group is protected by a
protective group such as a saturated aliphatic acyl group (e.g., a
saturated C.sub.2-6aliphatic acyl group), an alkoxycarbonyl group
(e.g., a C.sub.1-6alkoxy-carbonyl group), a carbamoyl group which
may have a substituent, [e.g., 1-acetoxy-3-aminoadamantane,
1-acetoxy-3-acetylaminoadamantane,
1-methoxycarbonyloxy-3-aminoadamantane,
1-acetylamino-3-methoxycarbonyloxyadamantane, 1,3-bis
(methoxycarbonyloxy)-5-aminoadamantane,
1-(N-methylcarbamoyloxy)-3-aminoadamantane].
Examples of an adamantane derivative having plural hydroxyl groups
include an adamantanepolyol derivative having a carboxyl group such
as 1-carboxy-3-methyl-5,7-adamantanediol,
1,3-dicarboxy-5,7-adamantanediol,
1-methoxycarbonyl-3-methyl-5,7-adamantanediol,
1-ethoxycarbonyl-3-methyl-5,7-adamantanediol,
1,3-di(methoxycarbonyl)-5,7-adamantanediol,
1,3-di(ethoxycarbonyl)-5,7-adamantanediol,
1-carboxy-3,5,7-adamantanetriol,
1-ethoxycarbonyl-3,5,7-adamantanetriol,
1-methoxycarbonyl-3,5,7-adamantanetriol; an adamantanepolyol
derivative having an acyloxy group (e.g., a saturated
C.sub.2-6aliphatic acyloxy group) such as
1-acetyloxy-3-methyl-5-adamantanol,
1,3-bis(acetyloxy)-5-adamantanol,
1,3-bis(acetyloxy)-5-methyl-7-adamantanol,
1,3,5-tris(acetyloxy)-7-adamantanol,
1-acetyloxy-3,5-adamantanediol,
1-acetyloxy-3-methyl-5,7-adamantanediol, 1,3-bis
(acetyloxy)-5,7-adamantanediol, 1-acetyloxy-3,5,7-adamantanetriol,
1-acetyloxy-3-methoxycarbonyloxyadamantane,
1-acetyloxy-3-(N-methylcarbamoyloxy)adamantane,
1,3,5-tris(acetyloxy) adamantane; an adamantanepolyol derivative
having an alkoxycarbonyloxy group (e.g., a
C.sub.1-6alkoxycarbonyloxy group) such as
1-methoxycarbonyloxy-3-adamantanol,
1-methoxycarbonyloxy-3,5-adamantanediol, 1,3-bis
(methoxycarbonyloxy)-5-adamantanol,
1-(N-methylcarbamoyloxy)-3-methoxycarbonyloxyadamantane,
1,3-bis(methoxycarbonyloxy)adamantane, 1,3,5-tris
(methoxycarbonyloxy)adamantane,
1-carboxy-3,5-bis(N-methylcarbamoyloxy)adamantane; an
adamantanepolyol derivative having carbamoyloxy group which may
have a substituent, such as 1-(N-methylcarbamoyloxy)-3-adamantanol,
1-(N-methylcarbamoyloxy)-3,5-adamantanediol,
1,3-bis(N-methylcarbamoyloxy)-5-adamantanol,
1,3-bis(N-methylcarbamoyloxy)adamantane,
1,3,5-tris(N-methylcarbamoyloxy)adamantane.
An adamantane derivative having a carboxyl group includes, for
example, an adamantanol derivative having a carboxyl group
protected by no protective group (an alcohol body of an adamantane
having a carboxyl group such as a monool body e.g.,
1,3-dicarboxy-5-adamantanol, 1,3-dicarboxy-5-methyl-7-adamantanol,
1,3,5-tricarboxy-7-adamantanol), an adamantanol derivative having a
carboxyl group protected by a protective group [an alcohol body of
an adamantane having a C.sub.1-10alkoxy-carbonyl group such as a
monool body e.g., 1,3-bis(methoxycarbonyl)-5-adamantanol,
1,3-bis(ethoxycarbonyl)-5-adamantanol,
1,3-bis(methoxycarbonyl)-5-methyl-7-adamantanol, 1,3-bis
(ethoxycarbonyl)-5-methyl-7-adamantanol,
1,3,5-tris(methoxycarbonyl)-7-adamantanol,
1-(N,N-dimethylcarbamoyl)-3-adamantanol], an adamantanol derivative
having a carboxyl group in which a hydroxyl group is protected by a
protective group such as a saturated aliphatic acyl group (e.g., a
saturated C.sub.2-6-aliphatic acyl group), an alkoxycarbonyl group
(e.g., a C.sub.1-6alkoxycarbonyl group), a carbamoyl group which
may have a substituent [e.g.,
1-acetoxy-3-methoxycarbonyladamantane,
1-acetoxy-3-(N,N-dimethylcarbamoyl)adamantane,
1-carboxy-3-methoxycarbonyloxyadamantane,
1-methoxycarbonyl-3-methoxycarbonyloxyadamantane,
1-(N,N-dimethylcarbamoyl)-3-methoxycarbonyloxyadamantane,
1-(N,N-dimethylcarbamoyl)-3-(N-methylcarbamoyloxy) adamantane,
1-carboxy-3-(N-methylcarbamoyloxy) adamantane,
1-methoxycarbonyl-3-(N-methylcarbamoyloxy)adamantane].
An adamantane derivative having a hydroxymethyl group includes, for
instance, an adamantanol derivative having an alkyl group and a
hydroxymethyl group such as 1-hydroxymethyl-3-methyl-5-adamantanol;
an adamantanol derivative having plural hydroxymethyl groups such
as 1,3-bis(hydroxymethyl)-5-adamantanol; an adamantanol derivative
having a hydroxymethyl group in which a hydroxyl group bound to the
adamantane backbone is protected by a protective group such as a
saturated aliphatic acyl group (e.g., a saturated
C.sub.2-6aliphatic acyl group), an alkoxycarbonyl group (e.g., a
C.sub.1-6alkoxy-carbonyl group), a carbamoyl group which may have a
substituent, such as 1-acetoxy-3-hydroxymethyladamantane,
1-hydroxymethyl-3-methoxycarbonyloxyadamantane,
1-hydroxymethyl-3-(N-methylcarbamoyl)adamantane.
An adamantane derivative having an isocyanate group includes, for
example, an adamantanol derivative having an alkyl group and an
isocyanato group such as 1-isocyanato-3-methyl-5-adamantanol
derivative having plural isocyanato groups such as
1,3-diisocyanato-5-adamantanol; an adamantanol derivative having an
isocyanato group in which a hydroxyl group is protected by a
protective group such as a saturated aliphatic acyl group (e.g., a
saturated C.sub.2-6aliphatic acyl group), such as
1-acetoxy-3-isocyanatoadamantane.
The adamantane derivative shown by the formula (1), depending on
the species of X.sup.2, may have a different substituent such as a
halogen atom, an oxo group, a hydroxyalkyl group (e.g., a hydroxy
C.sub.2-4alkyl group such as 2-hydroxyethyl group), an acyl group
(e.g., a C.sub.1-6acyl group such as formyl, acetyl, propionyl,
butyryl, isobutyryl, valeryl, isovaleryl and pivaloyl group), an
alkoxycarbonyl group (e.g., a C.sub.1-6alkoxy-carbonyl gruop such
as methoxycarbonyl, ethoxycarbonyl, propoxycarbonyl,
isopropoxycarbonyl, butoxycarbonyl, isobutoxycarbonyl,
t-butoxycarbonyl and hexylcarbonyl group), a cyano group.
The adamantane derivative shown by the formula (1) can be produced
through an oxidation step (especially, an oxidation step by oxygen
using an imide compound (2) described below). The adoption of the
oxidation step by oxygen using the imide compound realized on
efficient production of not only the novel adamantane derivative
but also the known adamantane derivatives.
According to the formula (1), the known adamantane derivatives
correspond to the following compounds (1b) to (4b) in which X.sup.1
to X.sup.4 are as follows: (1b) a compound in which X.sup.1 is
hydroxyl group and X.sup.3 and X.sup.4 are both H when X.sup.2 is
NO.sub.2 (2b) a compound in which X.sup.1 is hydroxyl group and
X.sup.3 and X.sup.4 are both H or both R when X.sup.2 is NH2 (3b) a
compound in which, when X.sup.2 is OH, [1] X.sup.1 is hydroxyl
group or a saturated aliphatic acyloxy group, X.sup.2 is hydroxyl
group or a saturated aliphatic acyloxy group, both X.sup.3 and
X.sup.4 are H or R, and [2] both X.sup.1 and X.sup.2 are hydroxyl
groups, either X.sup.3 or X.sup.4 is H and the other is COOH (4b) a
compound in which, when X.sup.2 is COOH, X.sup.1 is hydroxyl group
or a saturated aliphatic acyloxy group, X.sup.3 and X.sup.4 are
functional groups selected from an H and an R (5b) a compound in
which, when X.sup.2 is CH.sub.2OH, X.sup.1 is hydroxyl group and
both X.sup.3 and X.sup.4 are H (6b) a compound in which, when
X.sup.2 is NCO, X.sup.1 is hydroxyl group, both X.sup.3 and X.sup.4
are H.
Such known adamantane derivatives include, for example, an
adamantane derivative having a nitro group (e.g.,
1-nitro-3-adamantanol), an adamantane derivative having an amino
group (e.g., an alcohol body of an adamantane having a
C.sub.2-6acylamino group such as 1-amino-3-adamantanol,
1-amino-3,5-dimethyl-7-adamantanol, 1-methylamino-3-admantanol,
1-acetylamino-3-adamantanol, 1-dimethylamino-3-adamantanol,
1-acetylamino-3,5-dimethyl-7-adamantanol; an alcohol body of an
adamantane having a C.sub.1-6alkoxy-carbonylamino group such as
1-methoxycarbonylamino-3-adamantanol), an adamantanepolyol
derivative (e.g., 1,3-adamantanediol, 1,3,5-adamantanetriol), and
adamantane derivative having a saturated aliphatic acyloxy group
(e.g., an alcohol body of an adamantane having a C.sub.2-6acyloxy
group such as 1-acyloxy-3-adamantanol,
1-acyloxy-3,5-dimethyl-7-adamantanol), an adamantane derivative
having a carboxyl group (e.g., an alcohol body of an adamantane
having a C.sub.1-10alkoxy-carbonyl group such as
1-carboxy-3-adamantanol, 1-carboxy-3-methyl-5-adamantanol,
1-carboxy-3,5-dimethyl-7-adamantanol, 1-carboxy-3,5-adamantanediol,
1-methoxycarbonyl-3-adamantanol,
1-methoxycarbonyl-3-methyl-5-adamantanol,
1-methoxycarbonyl-3,5-dimethyl-7-adamantanol,
1-methoxycarbonyl-3,5-adamantanediol), an adamantane derivative
having a hydroxymethyl group (e.g., 1-hydroxymethyl-3-adamantanol),
an adamantane derivative having an isocyanato group (e.g.,
1-isocyanato-3-adamantanol).
[Production Process]
The adamantane derivative shown by the formula (1) and the known
adamantane derivative, that is, the adamantane derivative having a
hydroxyl group and a functional group can be produced by subjecting
an adamantane derivative shown by the following formula (1a):
##STR00006## wherein X.sup.2 represents nitro group, a hydroxyl
group which may be protected by a protective group, an amino group
or N-substituted amino group which may be protected by a protective
group, a hydroxyl group which may be protected by a protective
group, a carboxyl group which may be protected by a protective
group, a hydroxymethyl group which may be protected by a protective
group, or an isocyanato group; X.sup.3a and X.sup.4a may be the
same or different from each other and each may represent a hydrogen
atom, an alkyl group, a nitro group, a hydroxyl group which may be
protected by a protective group, an amino group or N-substituted
amino group which may be protected by a protective group, a
carboxyl group which may be protected by a protective group, a
hydroxymethyl group which may be protected by a protective group,
or an isocyanato group; to at least one step selected from the
following oxidation step (i), nitration step (ii) and carboxylation
step (iii): (i) an oxidation step by oxygen in the presence of a
catalyst comprising an imide compound shown by the formula (2):
##STR00007## wherein R.sup.1 and R.sup.2 may be the same or
different from each other and each may represent a hydrogen atom, a
halogen atom, an alkyl group, an aryl group, a cycloalkyl group, a
hydroxyl group, an alkoxy group, a carboxyl group, an
alkoxycarbonyl group, or an acyl group; or R.sup.1 and R.sup.2 may
bond together to form a double bond or an aromatic or non-aromatic
ring; Y represents an oxygen atom or a hydroxyl group; and n
denotes an integer of 1 to 3 (ii) at least one nitration step
selected from the following steps (iia), (iib) and (iic): (iia) a
nitration step by a nitrogen oxide in the presence of a catalyst
comprising an imide compound shown by the formula (2); (iib) a
nitration step by oxygen and at least one nitrogen oxide selected
from dinitrogen oxide and nitrogen monoxide; and (iic) a nitration
step by nitrogen dioxide (iii) a carboxylation step by carbon
monoxide and oxygen in the presence of a catalyst comprising an
imide compound shown by the formula (2).
An amino group, hydroxymethyl group and the like may be formed by
subjecting the adamantane (1a) to the nitration step and/or
carboxylation step followed by a reduction step. The formed amino
group may be converted into an isocyanato group by using a
conventional method.
More practically, the adamantane derivative can be obtained in
accordance with the following reaction step schemes (I) to (V).
The adamantane derivative having a nitro group or an amino group
(comprising an amino group protected by a protective group)
together with a hydroxyl group (comprising a hydroxyl group
protected by a protective group) can be obtained in accordance
with, for example, the following reaction step scheme (I).
##STR00008##
Wherein X.sup.1b represents OH, X.sup.2b represents NO.sub.2 or
NH.sub.2; X.sup.3b, X.sup.4b, X.sup.3c, X.sup.4c, X.sup.3d,
X.sup.4d, X.sup.3e, X.sup.4e, X.sup.3f, X.sup.4f, X.sup.3g and
X.sup.4g may be the same or different from each other and represent
H, R, NO.sub.2, OH, NH.sub.2, COOH, CH.sub.2OH or NCO.
[Nitration Reaction]
A nitration reaction in the reaction step scheme (I), [a nitration
reaction which derives the compound (Ic) derives from the compound
(Ib), a nitration reaction which provides the compound (Ia) or (If)
from the compound (Ie)], can be carried out by a conventional
method [for example, a method using a nitrating agent (e.g., mixed
acid of sulfuric acid and nitric acid, nitric acid, nitric acid and
an organic acid (e.g., a carboxylic acid such as acetic acid),
nitric acid salt and sulfuric acid, dinitrogen pentoxide etc.)].
Examples of a preferred nitration process include [1] a nitration
process which comprises contacting a substrate [the compound (Ib)
or the compound (Ie)] with nitrogen oxide in the presence of a
catalyst system comprising an imide compound (2) and a co-catalyst
described below, [2] a nitrating process of the substrate using
oxygen and at least one nitrogen compound selected from dinitrogen
oxide and nitrogen monoxide in the absence of a catalyst, and [3] a
nitration process which comprises contacting nitrogen dioxide with
the substrate.
The compound (Ib) includes, for example, adamantane, an adamantane
having an alkyl group (e.g., an adamantane having an alkyl group
which has one to six carbon atoms such as 1-methyladamantane,
1,3-dimethyladamantane, 1-ethyladamantane, 1-propyladamantane,
1-isopropyladamantane, 1-butyladamantane), an adamantane which has
one or more nitro groups previously (e.g., 1-nitroadamantane,
1,3-dinitroadamantane), an adamantane having a carboxyl group
(e.g., 1-carboxyadamantane), an adamantane having a hydroxymethyl
group (e.g., 1-hydroxymethyladamantane). As the compound (Ib), use
may be practically made of adamantane, an adamantane having an
alkyl group which has one to four carbon atoms (preferably, an
adamantane having an alkyl group which has one to two carbon atoms,
especially, an adamantane having a methyl group). By subjecting the
compound (Ib) to a nitration reaction, the compound (Ic) can be
obtained. For instance, when adamantane of the compound (Ib) is
subjected to the nitration, 1-nitroadamantane,
1,3-dinitroadamantane, 1,3,5-trinitroadamantane can be
obtained.
The compound (Ie) includes, for example, an adamantane having a
hydroxyl group such as 1-adamantanol, 3-methyl-1-adamantanol,
3,5-dimethyl-1-adamantanol, 1,3-adamantanediol,
5-methyl-1,3-adamantanediol, 1,3,5-adamantanetriol. When the
compound (Ie) is subjected to the nitration reaction, the compound
(Ia) or (If) can be obtained. For example, when 1-adamantanol of
the compound (Ie) is subjected to the nitration reaction,
1-nitro-3-adamantanol, 1,3-dinitro-5-adamantanol,
1,3,5-trinitro-7-adamantanol etc can be obtained. Moreover, when
1,3-adamantanediol as a substrate is subjected to the nitration
reaction, 1-nitro-3,5-adamantanediol,
1,3-dinitro-5,7-adamantanediol etc can be obtained. When
1,3,5-adamantanetriol as a substrate is subjected to the nitration
reaction, 1-nitro-3,5,7-adamantanetriol etc can be obtained.
[Catalyst Comprising an Imide Compound]
In the imide compound shown by the formula (2), a halogen atom as
the substituents R.sup.1 and R.sup.2 includes iodine, bromine,
chlorine and fluorine atoms. An alkyl group includes, for example,
a straight chain or branched chain alkyl group having about 1 to 10
carbon atoms such as methyl, ethyl, propyl, isopropyl, butyl,
isobutyl, sec-butyl, t-butyl, pentyl, hexyl, heptyl, octyl and
decyl group. Preferred examples of an alkyl group include an alkyl
group having about 1 to 6 carbon atoms, in particular a lower alkyl
group having about 1 to 4 carbon atoms.
An aryl group includes, for instance, phenyl group and naphthyl
group. A cycloalkyl group includes, for example, cyclopentyl,
cyclohexyl, and cyclooctyl group.
An alkoxy group includes, for example, an alkoxy group having about
1 to 10 carbon atoms such as methoxy, ethoxy, propoxy, isopropoxy,
butoxy, isobutoxy, t-butoxy, pentyloxy and hexyloxy group and
preferably an alkoxy group having about 1 to 6 carbon atoms, in
particular a lower alkoxy group having about 1 to 4 carbon atoms.
An alkoxycarbonyl group includes, for example, an alkoxycarbonyl
group having about 1 to 10 carbon atoms in the alkoxy moiety such
as methoxycarbonyl, ethoxycarbonyl, propoxycarbonyl,
isopropoxycarbonyl, butoxycarbonyl, isobutoxycarbonyl,
t-butoxycarbonyl, pentyloxycarbonyl and hexyloxycarbonyl group. A
preferred alkoxycarbonyl group includes an alkoxycarbonyl group
having about 1 to 6 carbon atoms in the alkoxy moiety, specifically
a lower alkoxycarbonyl group having about 1 to 4 carbon atoms in
the alkoxy moiety.
As an acyl group, there may be exemplified an acyl group having
about 1 to 6 carbon atoms such as formyl, acetyl, propionyl,
butyryl, isobutyryl, valeryl, isovaleryl and pivaloyl group.
The substituents R.sup.1 and R.sup.2 may be either the same or
different from each other. In the formula (2), R.sup.1 and R.sup.2
may bond together to form a double bond, or an aromatic or
non-aromatic ring. A preferred aromatic or non-aromatic ring may be
a 5- to 12-membered ring, in particular a 6- to 10-membered ring.
Such a ring may be a heterocyclic ring or a condensed heterocyclic
ring, but it may be practically a hydrocarbon ring. Such rings
includes, for instance, a non-aromatic alicyclic ring (e.g., a
cycloalkane ring which may have a substituent such as cyclohexane
ring, a cycloalkene ring which may have a substituent such as
cyclohexene ring), a non-aromatic bridged (cross-linked) ring
(e.g., a bridged hydrocarbon ring which may have a substituent such
as 5-norbornene ring), an aromatic ring which may have a
substituent such as benzene ring, naphthalene ring. The ring may
practically comprise an aromatic ring.
A preferred imide compound includes compounds shown by the
following formulae (2a) to (2f), ##STR00009## wherein R.sup.3 to
R.sup.6 may be the same or different from each other, and each may
represent a hydrogen atom, an alkyl group, a hydroxyl group, an
alkoxy group, a carboxyl group, an alkoxycarbonyl group, an acyl
group, a nitro group, a cyano group, an amino group or a halogen
atom; and R.sup.1, R.sup.2, Y and n have the same meanings as
defined above.
In the substituents R.sup.3 to R.sup.6, an alkyl group includes
alkyl groups similar to those exemplified in the paragraphs of
R.sup.1 and R.sup.2, in particular an alkyl group having about 1 to
6 carbon atoms. An alkoxy group includes the same alkoxy groups as
mentioned above, in particular a lower alkoxy group having about 1
to 4 carbon atoms. An alkoxycarbonyl group includes the same
alkoxycarbonyl gruops as mentioned above, especially, a lower
alkoxycarbonyl group having about 1 to 4 carbon atoms in the alkoxy
moiety. As an acyl group, there may be exemplified the same acyl
groups as mentioned above, especially an acyl group having about 1
to 6 carbon atoms. As a halogen atom, there may be exemplified
fluorine, chlorine and bromine atom. The substituents R.sup.3 to
R.sup.6 may be practically a hydrogen atom, a lower alkyl group
having about 1 to 4 carbon atoms, a carboxyl group, a nitro group
or a halogen atom.
In the formula (2), the symbol Y represents oxygen atom or hydroxyl
group, and n is usually about 1 to 3, preferably 1 or 2. The imide
compound shown by the formula (2) can be used singly or in
combination of two or more.
An acid anhydride corresponding to the imide compound shown by the
formula (2) includes, for example, a saturated or unsaturated
aliphatic polycarboxylic acid anhydride such as succinic anhydride,
maleic anhydride; a saturated or unsaturated non-aromatic
cyclicpolycarboxylic acid anhydride (an alicyclic polycarboxylic
acid anhydride) such as tetrahydrophthalic anhydride,
hexahydrophthalic anhydride (1,2-cyclohexanedicarboxylic
anhydride), 1,2,3,4-cyclohexanetetracarboxylic acid 1,2-anhydride;
a bridged cyclic polycarboxylic anhydride (an alicyclic
polycarboxylic anhydride) such as hetic anhydride, himic anhydride;
an aromatic polycarboxylic acid anhydride such as phthalic
anhydride, tetrabromophthalic anhydride, tetrachlorophthalic
anhydride, nitrophthalic anhydride, trimellitic anhydride,
methylcyclohexenetricarboxylic anhydride, pyromellitic anhydride,
mellitic anhydride, 1,8:4,5-naphthalenetetracarboxylic
dianhydride.
As a preferred imide compound, there may be mentioned, for example,
an imide compound derived from an aliphatic polycarboxylic acid
anhydride (e.g., N-hydroxysuccinimide, N-hydroxymaleimide), an
imide compound derived from an alicyclic polycarboxylic acid
anhydride or an aromatic polycarboxylic anhydride (e.g.,
N-hydroxyhexahydrophthalimide,
N,N'-dihydroxycyclohexanetetracarboximide, N-hydroxyphthalimide,
N-hydroxytetrabromophthalimide, N-hydroxytetrachlorophthalimide,
N-hydroxyhetimide, N-hydroxyhimimide, N-hydroxytrimellitimide,
N,N'-dihydroxypyromellitimide,
N,N'-dihydroxynaphthalenetetracarboximide). A typically preferable
imide compound includes an N-hydroxyimide compound derived from an
alicyclic polycarboxylic anhydride, particularly from an aromatic
polycarboxylic anhydride, such as N-hydroxyphthalimide.
The imide compound may be prepared by a conventional imidation
reaction, for example, by reating a corresponding acid anhydride
with hydroxylamine NH.sub.2OH to ring-open an acid anhydride group
followed by ring-closing and imidating.
A catalyst comprising an imide compound shown by the formula (2)
may be whichever of a homogeneous system or a heterogeneous system.
Moreover, the catalyst may be a solid catalyst comprising a
catalytic component supported on a support or carrier, as well. As
the support, use can be practically made of a porous support such
as activated carbon, zeolite, silica, silica-alumina, bentonite. As
for a supported amount of the catalytic component in the solid
catalyst, the amount of the imide compound shown by the formula (2)
is about 0.1 to 50 parts by weight, preferably about 0.5 to 30
parts by weight and more preferably about 1 to 20 parts by weight
relative to 100 parts by weight of the support.
[Nitrogen Oxide]
A nitrogen oxide employed in the nitration reaction is shown by the
formula (3) N.sub.nO.sub.m, wherein n denotes an integer of 1 or 2
and m denotes an integer of 1 to 6.
In the nitrogen oxide shown by the formula (3), when n is 1, m is
usually an integer of 1 to 3 and when n is 2, m is usually an
integer of 1 to 6.
As such nitrogen oxide, there may be exemplified N.sub.2O, NO,
N.sub.2O.sub.3, NO.sub.2 (nitrogen dioxide), N.sub.2O.sub.4,
N.sub.2O.sub.5, NO.sub.3, N.sub.2O.sub.6. The nitrogen oxide can be
employed singly or in combination of two or more.
A preferred nitrogen oxide includes, for instance, [1] a nitrogen
oxide formed by a reaction of at least one nitrogen oxide selected
from dinitrogen oxide (N.sub.2O) and nitrogen monoxide (NO) with
oxygen, specifically N.sub.2O.sub.3, or a nitrogen oxide containing
N.sub.2O.sub.3 as a main component, or [2] nitrogen dioxide
(NO.sub.2) or a nitrogen oxide containing NO.sub.2 as a main
component.
N.sub.2O.sub.3 may be easily obtained by a reaction of N.sub.2O
and/or NO with oxygen. Therefore, the nitration can be carried out
by introducing N.sub.2O and/or NO and oxygen into the reaction
system without forming N.sub.2O.sub.3 previously. Whichever of pure
oxygen or oxygen diluted with an inert gas (e.g., carbon dioxide,
nitrogen, helium or argon gas) may be used as oxygen. Air may be
employed as an oxygen source. In the above case, even if the
reaction is conducted in the absence of the catalyst, the
corresponding nitro compound can be obtained in high yield.
Moreover, also in the case where a substrate is contacted with
nitrogen dioxide, a nitro compound can be produced in good yield,
without using a catalyst.
The amount of the imide compound shown by the formula (2) may be
selected within a wide range, for instance, within a range of about
0.001 mole (0.1 mole %) to 1 mole (100 mole %), preferably about
0.001 mole (0.1 mole %) to 0.5 mole (50 mole %), more preferably
about 0.01 to 0.3 mole relative to 1 mole of a substrate. It may be
practically selected within a range of about 0.01 to 0.25 mole
relative to 1 mole of a substrate.
The imide compound (2) may constitute a catalyst system in
combination with a co-catalyst of an oxidation catalyst described
below. The species and the amount of the co-catalyst may be
selected within the same ranges as those of a co-catalyst described
below.
The amount of the nitrogen oxide can be selected according to the
amount of nitro group introduced thereto, for example, within a
range of about 1 to 50 mole, preferably about 1.5 to 30 mole, and
is usually about 2 to 25 mole, relative to 1 mole of a
substrate.
The nitration reaction is usually conducted in an organic solvent
inert to the reaction. As the organic solvent, there may be
mentioned, for example, an organic acid (e.g., a carboxylic acid
such as formic acid, acetic acid, propionic acid; a
hydroxycarboxylic acid such as oxalic acid, citric acid, tartaric
acid; a sulfonic acid such as methanesulfonic acid, ethanesulfonic
acid; and an arylsulfonic acid such as benzenesulfonic acid,
p-toluenesulfonic acid), a nitrile (e.g., acetonitrile,
propionitrile, benzonitrile), an amide (e.g., formamide, acetamide,
dimethylformamide, dimethylacetamide), an alcohol (e.g., t-butanol,
t-amyl alcohol), an aliphatic hydrocarbon (e.g., hexane, octane),
an aromatic hydrocarbon (e.g., benzene), a halogenated hydrocarbon
(e.g., chloroform, dichloromethane, dichloroethane, carbon
tetrachloride, chlorobenzene), a nitro compound (e.g.,
nitrobenzene, nitromethane, nitroethane), an ester (e.g., a
C.sub.2-10aliphatic carboxylic acid-C.sub.1-10alkyl ester such as
ethyl acetate, butyl acetate, ethyl propionate; a carboxylic aryl
ester such as phenyl acetate, phenyl propionate; a
C.sub.7-12aromatic carboxylic acid-C.sub.1-10alkyl ester), methyl
benzoate, dimethyl phthalate, an ether (e.g., dimethyl ether,
diethylether, diisopropyl ether, dioxane, tetrahydrofuran), and
mixtures of these solvents. Use may be practically made of, as the
solvent, an organic acid (e.g., a carboxylic acid such as acetic
acid), a nitrile (e.g., benzonitrile), a halogenated hydrocarbon
(e.g., dichloroethane).
The use of the catalyst comprising the imide compound allows the
nitration reaction to proceed smoothly even under comparatively
mild or moderate conditions. The reaction temperature may be
selected, according to the species of the imide compound or the
substrate, for instance, within a range of about 0 to 150.degree.
C., preferably about 25 to 125.degree. C., more preferably about 30
to 100.degree. C. The nitration reaction can be carried out at
ambient pressure (atmospheric pressure) or under a pressure (under
a load).
[Oxidation Reaction]
For the oxidation reaction in the reaction step scheme (I) [an
oxidation reaction which produces the compound (Ie) from the
compound (Ib), an oxidation reaction which leads the compound (Ic)
or the compound (Id) to the compound (Ia)], an oxidation process of
the substrate [the compound (Ib), the compound (Ic) or the compound
(Id)] by oxygen in the presence of an oxidation catalyst comprising
the imide compound shown by the formula (2) may be used.
When the compound (Ib) is subjected to the oxidation reaction (the
oxidation process by oxygen) using the imide compound (2), the
compound (Ie) can be obtained. For instance, oxidation of
adamantane of the compound (Ib) provides 1-adamantanol,
1,3-adamantanediol and soon. The oxidation of 1-carboxyadamantane
provides 1-carboxy-3-adamantanol and so forth.
The compound (Ic) includes, for example, 1-nitroadamantane,
1-nitro-3-methyladamantane, 1-nitro-3-5-dimethyladamantane,
1,3-dinitroadamantane, 1,3-dinitro-5-methyladamantane,
1,3,5-trinitroadamantane. When the oxidation process with oxygen
using the oxidation catalyst comprising the imide compound is
applied to the compound (Ic), an adamantane derivative in which
X.sup.2b of the compound (Ia) is a nitro group [the compound having
a nitro group (Ia)] can be obtained. For example, contact of
1-nitroadamantane of the compound (Ic) with oxygen in the presence
of the imide compound shown by the formula (2), provides
1-nitro-3-adamantanol, 1-nitro-3,5-adamantanediol,
1-nitro-3,5,7-adamantanetriol and so on. Moreover, according to the
present invention, oxidation of 1,3-dinitroadamantane with oxygen
provides 1,3-dinitro-5-adamantanol, 1,3-dinitro-5,7-adamantanediol
and so on.
The compound (Id) includes, for instance, 1-aminoadamantane,
1-amino-3-methyladamantane, 1-amino-3,5-dimethyladamantane,
1,3-diaminoadamantane, 1,3-diamino-5-methyladamantane,
1,3,5-triaminoadamantane. When the oxidation process with oxygen
using the imide compound is applied to the compound (Id), an
adamantane derivative in which X.sup.2b of the compound (Ia) is
amino group [the compound having an amino group (Ia)] can be
obtained. For example, when 1-aminoadamantane of the compound (Id)
is subjected to the oxidation process by oxygen,
1-amino-3-adamantanol, 1-amino-3,5-adamantanediol,
1-amino-3,5,7-adamantanetriol and the like can be obtained.
Moreover, oxidation of 1,3-diaminoadamantane by oxygen provides
1,3-diamino-5-adamantanol, 1,3-diamino-5,7-adamantanediol and so
on. Oxidation of 1,3,5-triaminoadamantane provides
1,3,5-triamino-7-adamantanol and so on.
[Oxidation Catalyst]
An oxidation catalyst may comprise the imide compound (2)
exemplified in the paragraphs of the nitration reaction, and may
comprise the imide compound and a co-catalyst.
The co-catalyst includes metal compounds such as a compound
comprising a Group 2A element of the Periodic Table (e.g.,
magnesium, calcium, strontium, barium), a transition metal
compound, or a compound comprising a Group 3B element of the
Periodic Table (e.g., boron B, aluminium Al). The co-catalyst may
be employed singly or in combination of two or more.
As an element of the transition metal, there may be mentioned, for
instance, a Group 3A element of the Periodic Table (e.g., a
lanthanoid element such as lanthanum La, cerium Ce, samarium Sm,
besides scandium Sc, yttrium Y; an actinoid element such as
actinium Ac), a Group 4A element (e.g., titanium Ti, zirconium Zr,
hafnium Hf), a Group 5A element (e.g., vanadium V, niobium Nb,
tantalum Ta), a Group 6A element (e.g., chromium Cr. molybdenum Mo,
tungsten W), a Group 7A element (e.g., manganese Mn, technetium Tc,
rhenium Re), a Group 8 element (e.g., iron Fe, ruthenium Ru, osmium
Os, cobalt Co, rhodium Rh, iridium Ir, nickel Ni, palladium Pd,
platinum Pt), a Group 1B element (e.g., copper Cu, silver Ag, gold
Au) and a Group 2B element of the Periodic Table (e.g., zinc Zn,
cadmium Cd).
A preferred element constituting the co-catalyst includes an
element of the transition metal (e.g., a Group 3A element such as a
lanthanoid element, e.g., Ce, and an actinoid element; a Group 4A
element such as Ti, Zr; a Group 5A element such as V, Nb; a Group
6A element such as Cr, Mo, W; a Group 7A element such as Mn, Tc,
Re; a Group 8 element such as Fe, Ru, Co, Rh, Ni; and a Group 1B
element of the Periodic Table such as Cu) and Group 3B elements of
the Periodic Table such as B. The oxidation number of the metal
element constituting the co-catalyst is not specifically limited
and may be, for example, 0, +2, +3, +4, +5, or +6, depending on the
species of the elements. As the co-catalyst, use may be practically
made of a divalent transition metal compound (e.g., a divalent
cobalt compound, a divalent manganese compound), a compound
comprising a trivalent Group 5A element of the Periodic Table
(e.g., a vanadium compound), a compound comprising a trivalent
Group 6A element of the Periodic Table (e.g., a molybdenum
compound) and the like.
The co-catalyst may be a simple substance or hydroxide of a metal.
The co-catalyst may practically be an oxide of a metal (a double
oxide or an oxygen acid or a salt thereof), an organic acid salt,
an inorganic acid salt, a halide, each containing the element, a
coordinate compound (a complex), a polyacid (in particular, a
heteropolyacid or an isopolyacid) or its salt, each containing the
metal element.
As the boron compound, there may be mentioned, for example, a boron
hydroxide (e.g., borane, diborane, tetraborane, pentaborane,
decaborane); aboric acid (e.g., orthoboric acid, metaboric acid ,
tetraboric acid); a borate (e.g., nickel borate, magnesium borate,
manganese borate); a boron oxide such as B.sub.2O.sub.3; a
nitrogen-containing boron compound such as borazane, borazene,
borazine, boron amide, boron imide; a halide such as BF.sub.3,
BCl.sub.3, tetrafluoroborate; an ester of boric acid (e.g., methyl
borate, phenyl borate). A preferred boron compound includes boron
hydrides, a boric acid and a salt thereof such as orthoboric acid
(particularly a boric acid).
The hydroxide includes, for example, Mn(OH).sub.2, MnO (OH),
Fe(OH).sub.2 and Fe(OH).sub.3. Examples of the metallic oxide
include Sm.sub.2O.sub.3, TiO.sub.2, ZrO.sub.2, V.sub.2O.sub.3,
V.sub.2O.sub.5, CrO, Cr.sub.2O.sub.3, MoO.sub.3, MnO,
Mn.sub.3O.sub.4, Mn.sub.2O.sub.3, MnO.sub.2, Mn.sub.2O.sub.7, FeO,
Fe.sub.2O.sub.3, Fe.sub.3O.sub.4, RuO.sub.2, RuO.sub.4, CoO,
CoO.sub.2, Co.sub.2O.sub.3, RhO.sub.2, Rh.sub.2O.sub.3,
Cu.sub.2O.sub.3, and so forth. As examples of the double oxide or
oxygen acid salt, there may be mentioned MnAl.sub.2O.sub.4,
MnTiO.sub.3, LaMnO.sub.3, K.sub.2Mn.sub.2O.sub.5, CaOxMnO.sub.2
(x=0.5, 1, 2, 3, 5), manganese salts [e.g., manganates(V) such as
Na.sub.3MnO.sub.4, Ba.sub.3[MnO.sub.4].sub.2; manganates (VI) such
as K.sub.2MnO.sub.4, Na.sub.2MnO.sub.4, BaMnO.sub.4; permanganates
such as KMnO.sub.4, NaMnO.sub.4, LiMnO.sub.4,
NH.sub.4MnO.sub.4CsMnO.sub.4, AgMnO.sub.4, Ca(MnO.sub.4).sub.2,
Zn(MnO.sub.4).sub.2, Ba(MnO.sub.4).sub.2, Mg(MnO.sub.4).sub.2,
Cd(MnO.sub.4).sub.2].
As the organic acid salts, there may be exemplified salts with a
C.sub.2-20fatty acid such as cobalt acetate, manganese acetate,
cobalt propionate, manganese propionate, cobalt naphthenate;
manganese naphthenate, cobalt stearate, manganese stearate;
manganese thiocyanate, and corresponding salts of Ce, Ti, Zr, V,
Cr, Mo, Fe, Ru, Ni, Pd, Cu and Zn. As the inorganic acid salt,
there may be mentioned, for instance, nitrates such as cobalt
nitrate, iron nitrate, manganese nitrate, nickel nitrate, copper
nitrate; and sulfates, phosphates and carbonates each corresponding
to these nitrates (e.g., cobalt sulfate, iron sulfate, manganese
sulfate, cobalt phosphate, iron phosphate, manganese phosphate, an
iron carbonate, a manganese carbonate, iron perchlorate). As the
halides, there may be mentioned, for instance, chlorides such as
SmCl.sub.3, SmI.sub.2, TiCl.sub.2, ZrCl.sub.2, ZrOCl.sub.2,
VCl.sub.3, VOCl.sub.2, MnCl.sub.2, MnCl.sub.3, FeCl.sub.2,
FeCl.sub.3, RuCl.sub.3, CoCl.sub.2, RhCl.sub.2, RhCl.sub.3,
NiCl.sub.2, PdCl.sub.2, PtCl.sub.2, CuCl, CuCl.sub.2; or fluorides,
bromides or iodides each corresponding to these chlorides (e.g.,
MnF.sub.2, MnBr.sub.2, MnF.sub.3, FeF.sub.2, FeF.sub.3, FeBr.sub.2,
FeBr.sub.3, FeI.sub.2, CuBr, CuBr.sub.2); a complex halide such as
M.sup.1MnCl.sub.3, M.sup.1.sub.2MnCl.sub.4,
M.sup.1.sub.2MnCl.sub.5, M.sup.1.sub.2MnCl.sub.6, wherein M.sup.1
represents a monovalent metal.
The ligand constituting the complex includes, for example, OH
(hydroxo); an alkoxy group such as methoxy, ethoxy, propoxy,
butoxy; an acyl group such as acetyl, propionyl; an alkoxycarbonyl
group such as methoxycarbonyl (acetato), ethoxycarbonyl;
acetylacetonato, cyclopentadienyl group; a halogen atom such as
chlorine, bromine; CO; CN; oxygen atom; H.sub.2O (aquo); a
phosphorus compound such as phosphine (e.g., triarylphosphine such
as triphenylphosphine); a nitrogen-containing compound such as
NH.sub.3 (ammine), NO, NO.sub.2 (nitro), NO.sub.3 (nitrato),
ethylenediamine, diethylenetriamine, pyridine, phenanthroline. In
the complexes or complex salts, the same or different ligands may
be coordinated singly or in combination of two or more.
The ligand is practically, for example, OH, an alkoxy group, an
acyl group, an alkoxycarbonyl group, acetylacetonato, a halogen
atom, CO, CN, H.sub.2O (aquo), phosphorus compound such as
triphenylphosphine, or a nitrogen-containing compound inclusive of
NH.sub.3, NO.sub.2 and NO.sub.3.
The transition metal element and the ligand may be suitably
employed in combination to form a complex. Such complex may be an
acetylacetonato complex [e.g., an acetylacetonato complex of Ce,
Sm, Ti, Zr, V, Cr, Mo, Mn, Fe, Ru, Co, Ni, Cu or Zn,
titanylacetylacetonato complex TiO(AA).sub.2,
zirconylacetylacetonato complex ZrO(AA).sub.2,
vanadylacetylacetonato complex VO(AA).sub.2], a cyano complex
[e.g., hexacyanomanganate(I), hexacyanoferrate(II)], a carbonyl
complex or a cyclopentadienyl complex [e.g.,
tricarbonylcyclopentadienylmanganese(I),
bixcyclopentadienylmanganese(II), biscyclopentadienyliron (II),
Fe(CO).sub.5, Fe.sub.2(CO).sub.9, Fe.sub.3(CO).sub.12], a nitrosyl
compound [e.g., Fe(NO).sub.4, Fe(CO).sub.2(NO).sub.2], a
thiocyanato complex [e.g., thiocyanatoiron], or an acetyl complex
[e.g. cobalt acetate, manganese acetate, iron acetate, copper
acetate, zirconyl acetate ZrO(OAc).sub.2, titanyl acetate
TiO(OAc).sub.2, vanadyl acetate VO(OAc).sub.2].
The polyacid is practically at least one member selected from Group
5A elements or Group 6A elements of the Periodic Table, such as V
(vanadic acid), Mo (molybdic acid) or W (tungstic acid), typically
speaking. There is no particular limit as to the central atom, and
it may be any of, for instance, Be, B, Al, Si, Ge, Sn, Ti, Zr, Th,
N, P, As, Sb, V, Nb, Ta, Cr, Mo, W, S, Se, Te, Mn, I, Fe, Co, Ni,
Rh, Os, Ir, Pt, or Cu. As illustrative examples of the
heteropolyacid, there may be mentioned cobaltmolybdic acid,
cobalttungstic acid, molybdenumtungstic acid, manganesemolybdic
acid, manganesetungstic acid, manganesemolybdenumtungstic acid,
vanadomolybdophosphoric acid, manganesevanadiummolybdic acid, and
manganesevanadomolybdophosphoric acid, vanadiummolybdic acid,
vanadiumtungstic acid, silicomolybdic acid, silicotungstic acid,
phosphomolybdic acid, phosphosungstic acid, phosphovanadomolybdic
acid, and phosphovanadotungstic acid.
Among the co-catalysts mentioned above, the use of a divalent
transition metal compound (e.g., a divalent cobalt compound, a
divalent manganese compound) or a compound containing an element
selected from a Group 4A element (e.g., Ti, Zr), a Group 5A element
(e.g., V), a Group 6A element (e.g., Cr, Mo), a Group 7A element
(e.g., Mn) and a Group 8 element (e.g., Co) of the Periodic Table
enhances oxidation activity and provides an adamantane having a
hydroxyl group with high conversion and selectivity. Specifically,
the use of a compound containing a Group 5A element (e.g., V) as a
co-catalyst insures efficient oxidation of plural positions of a
substrate (e.g., a bridge-head position or a connecting position of
adamantane) and provides an adamantane having plural hydroxyl
groups introduced thereto.
Moreover, the use of a compound containing one element selected
from a Group 4A element (e.g., Ti, Zr), a Group 5A) element (e.g.,
Cr, Mo) and a Group 7A element (e.g., Mn) of the Periodic Table
inhibits deactivation of the catalyst (specifically the imide
compound) even under severe conditions. Therefore, the substrate
can be oxidized by oxygen with commercially advantageous
efficiency.
The oxidation catalyst comprising the imide compound shown by the
formula (2) or the imide compound and the co-catalyst may be
whichever of a homogeneous system or a heterogeneous system. The
catalyst may be a solid catalyst comprising a catalytic component
supported on a support or carrier, as well. As the support or
carrier, use can be made of the exemplified supports in the
paragraphs of the nitration reaction. In the solid catalyst, the
supported amount of the imide compound of the formula (2) as the
catalyst component may be selected within the same range as the
supported amount of the imide compound in the solid catalyst
exemplified in the paragraphs of the nitration reaction. The
supported amount of the co-catalyst is about 0.1 to 30 parts by
weight, preferably about 0.5 to 25 parts by weight, and more
preferably about 1 to 20 parts by weight, relative to 100 parts by
weight of the support.
[Oxygen]
The oxygen utilized in the oxidation reaction may be whichever of
pure oxygen or oxygen diluted with an inert gas (e.g., carbon
dioxide, nitrogen, helium or argon gas). Moreover, air may be
employed as an oxygen source.
The amount of the imide compound shown by the formula (2) may be
selected from the ranges exemplified in the paragraphs of the
nitration reaction as to the amount of the imide compound.
The amount of the co-catalyst may be selected within a wide range
such as about 0.0001 mole (0.01 mole %) to 0.7 mole (70 mole %),
preferably about 0.0001 to 0.5 mole, more preferably about 0.001 to
0.3 mole, and practically about 0.0005 to 0.1 mole (e.g., 0.005 to
0.1 mole) relative to 1 mole of the substrate.
The ratio of the co-catalyst to the imide compound shown by the
formula (2) may be selected within a range not interfering with the
reaction rate or selectivity, for example, of about 0.001 to 10
mole, preferably about 0.005 to 5 mole, more preferably about 0.01
to 3 mole, and may be practically about 0.01 to 5 mole
(particularly 0.001 to 1 mole) of the co-catalyst, relative to 1
mole of the imide compound.
Activity of the imide compound sometimes deteriorates as the amount
of the co-catalyst increases. Therefore, in order to maintain the
high activity of the oxidation catalyst system, the ratio of the
co-catalyst is preferably in a range of an effective amount and
about 0.1 mole (e.g., about 0.001 to 0.1 mole, preferably about
0.005 to 0.08 mole, more preferably about 0.01 to 0.07 mole)
relative to 1 mole of the imide compound.
The amount of oxygen may be selected according to the species of
the substrate, and the range may practically be about 0.5 mole or
more (e.g., 1 mole or more), preferably about 1 to 100 mole, more
preferably about 2 to 50 mole, relative to 1 mole of the substrate.
Excess amount of oxygen relative to a substrate may practically be
employed. Specifically, the reaction under an atmosphere containing
molecular oxygen such as air or oxygen is advantageous.
The oxidation reaction may be conducted in an organic solvent inert
to the reaction. As the organic solvent, use can be made of the
organic solvents exemplified in the paragraphs of the nitration
reaction. Preferred organic solvents include organic acids (e.g.,
carboxylic aids such as acetic acid), nitrites (e.g., benzonitrile)
and the like.
In the present invention, the oxidation reaction with oxygen can be
smoothly conducted even under comparatively mild or moderate
conditions. The reaction temperature may be selected, according to
species of the imide compound or the substrate, within a range of
about 0 to 300.degree. C., preferably about 10 to 250.degree. C.
(e.g., 10 to 200.degree. C.), more preferably about 10 to
150.degree. C., and practically about 10 to 100.degree. C. (e.g.,
10 to 80.degree. C.). The reaction can be conducted at ambient
pressure (atmospheric pressure) or under a pressure (under a
load).
[Reduction Reaction]
In the reaction step scheme (I), the reduction reaction which
produces the compound (Ia) or (Id) each having an amino group by
reducing the compound (Ic) or (Ie) having a nitro group, can be
conducted by a conventional process such as the catalytic
hydrogenation process using hydrogen as a reducing agent and a
reduction process using a hydrogenation reducing agent.
In the catalytic hydrogenation, a simple substance of a metal such
as platinum, palladium, nickel, cobalt, iron and copper, a compound
containing such metal elements (e.g., platinum oxide, palladium
black, palladium carbon and copper chromite) or the like may be
used as a catalyst. The amount of the catalyst is practically about
0.02 to 1 mole relative to 1 mole of a substrate. Further, in a
catalytic hydrogenation, the reaction temperature may be, for
example, about -20 to 100.degree. C. (e.g., about 0 to 90.degree.
C.). A hydrogen pressure is practically about 1 to 100 atm (e.g.,
about 1 to 50 atm).
In the reduction process using a hydrogenation reducing agent, as
the hydrogenation reducing agent to be used, there may be
mentioned, for example, aluminium hydride, lithium aluminium
hydride, lithium trialkoxyaluminium hydride, sodium boron hydride,
diborane, bis-3-methyl-2-butylborane, a metal (e.g., zinc, tin,
iron) acid, a sulfide and hydrazine. The reducing process using a
hydrogenation reducing agent may be conducted also in the presence
of a Lewis acid such as aluminium chloride anhydride and boron
trifluoride. The amount of the hydrogenation reducing agent is
practically about 1 mole or more (e.g., about 1 to 10 mole)
relative to 1 mole of a substrate. In the reduction process using
the hydrogenation reducing agent, the reaction temperature is
practically about 0 to 200.degree. C. (e.g., about 0 to 170.degree.
C.).
Incidentally, the reduction reaction (the catalytic hydrogenation
process and the reaction by the process using the hydrogenation
reducing agent) may be carried out in the presence of a solvent
inert to the reduction reaction (e.g., an alcohol such as methanol;
a solvent exemplified in the paragraphs of the nitration reaction,
such as a carboxylic acid, an ether, an ester and an amide).
Moreover, when the reduction reaction is conducted by the catalytic
hydrogenation process, an acid such as hydrochloric acid may be
added to the reaction system in order to improve the catalytic
activity.
Reduction of the compound (Ic) provides the compound (Id), for
example, reduction of 1-nitroadamantane of the compound (Ic)
provides 1-aminoadamantane.
The compound (If) corresponds to a compound in which X.sup.2b of
the compound (Ia) is nitro group. Reduction of the compound (If)
provides a compound in which X.sup.2b is amino group. For example,
reduction of 1-nitro-3,5-adamantanediol of the compound (If)
provides 1-amino-3,5-adamantanediol, and reduction of
1-nitro-3-adamantanol provides 1-amino-3-adamantanol.
According to the species of substrate, hydroxyl group [e.g.,
hydroxyl group of the compound (Ia), the compound (Ie) or the
compound (If)], hydroxylmethyl group (a moiety corresponding to
hydroxyl group of hydroxymethyl group), amino group [e.g., amino
group of the compound (Ia) or the compound (Id)] or carboxyl group
of the reaction component or the reaction product may be optionally
protected by the protecting group before or after the nitration
reaction, oxidation reaction or the reduction reaction, or during
each reaction steps. Introduction and elimination of the protecting
group for hydroxyl group, hydroxymethyl group, amino group and
carboxyl group may be carried out by utilizing a conventional
method such as esterification, amidation, carbamation, carbonation,
hydrolysis and hydrogenolysis, if necessary, using an acid, an
alkali, an ion-exchange resin, a catalyst for hydrogenolysis or the
like.
When an acyl group is used as a protecting group for hydroxyl group
or amino group, hydroxyl group or amino group of the substrate may
be protected by allowing an acylating agent to act on the
substrate. As the acylating agent, there may be exemplified
C.sub.2-6 aliphatic monocarboxylic acids such as acetic acid,
propionic acid, n-butyric acid, isobutyric acid, valeric acid and
pivalic acid (preferably C.sub.2-4 carboxylic acids), and reactive
derivatives thereof [e.g., acid anhydrides such as acetic anhydride
and valeic anhydride, acid halides such as acid chloride (e.g.,
acetyl chloride, propionyl chloride and butyryl chloride)]. When an
acid anhydride or an acid halide is used as an acylating agent, the
reaction is practically carried out in the presence of a base in
order to capture the acid which is a by-product in the reaction. As
the base, there may be mentioned, for example, an inorganic base
(e.g., a hydroxide of an alkali metal such as sodium hydroxide; a
hydroxide of alkaline earth metal such as barium hydroxide;
carbonate of an alkaline metal such as sodium carbonate; a
carbonate of an alkaline earth metal such as barium carbonate; a
hydrogencarbonate of an alkaline metal such as sodium
hydrogencarbonate); and an organic base (e.g., a tertiary amine
such as triethylamine and N-methylpiperidine; a basic heterocyclic
compound containing a nitrogen atom such as pyridine. The acylating
agent may be used singly or in combination of two or more.
Reaction of 1-nitro-3-adamantanol of the compound having a hydroxyl
group [e.g., the compound (Ia), the compound (If)] with acetic acid
(or acetyl chloride or acetic anhydride) provides
1-nitro-3-acetyloxyadamantane. Moreover,
1-acetyloxy-3-aminoadamantane can be obtained by reducing the
1-nitro-3-acetyloxyadamantane. Similarly, 1-acetyloxy-3-adamantanol
and/or 1,3-bis(acetyloxy) adamantane from 1,3-adamantanediol;
1-acetylamino-3-adamantanol and/or
1-acetylamino-3-acetyloxyadamantane from 1-amino-3-adamantanol;
1-acetyloxy-3-carboxyadamantane from 1-carboxy-3-adamantanol;
1-acetyloxy-3-methoxycarbonyladamantane from
1-methoxycarbonyl-3-adamantanol;
1-acetyloxy-3-hydroxymethyladamantane and/or
1-acetyloxymethyl-3-adamantanol and/or
1-acetyloxy-3-acetyloxymethyladamantane from
1-hydromethyl-3-adamantanol; and 1-acetyloxy-3,5-adamantanediol
and/or 1,3-bis(acetyloxy)-5-adamantanol and/or 1,3,5-tris
(acetyloxy)adamantane from 1,3,5-adamantanetriol can be
obtained.
1-acetylamino-3-adamantanol, 1-acetylamino-3,5-adamantanediol,
1-acetylamino-3,5,7-adamantanetriol and the like are obtained by
reacting 1-aminoadamantane of the compound having an amino group
(Id) with acetic acid to oxidize with oxygen.
In the oxidation by oxygen, the use of a carboxylic acid (e.g., a
carboxylic acid such as acetic acid, propionic acid) as a solvent
insures protection of hydroxyl group and amino group by a
protective group (e.g., an acyl group) in the process of the
oxidation reaction.
When carbonate group is used as a protected hydroxyl group or when
carbamate group is used as a protected amino group, for example, a
halogenated carboxylic acid ester may be allowed to react with a
compound having a hydroxyl group or a compound having an amino
group to convert the hydroxyl group or the amino group into each
corresponding carbonate group or carbamate group. This reaction is
practically carried out in the presence of a base. As the base, use
can be made of the above exemplified bases.
For example, 1-methoxycarbonyloxy-3-adamantanol and/or
1,3-bis(methoxycarbonyloxy)adamantane can be obtained by allowing
chloromethoxycarbonyl (methyl chlorocarbonate) to react with
1,3-adamantanediol. Similarly,
1-carboxy-3-methoxycarbonyloxyadamantane from
1-carboxy-3-adamantanol;
1-methoxycarbonyl-3-methoxycarbonyloxyadamantane from
1-methoxycarbonyl-3-adamantanol;
1-acetyloxy-3-methoxycarbonyloxyadamantane from
1-acetyloxy-3-adamantanol;
1-acetylamino-3-methoxycarbonyloxyadamantane from
1-acetylamino-3-adamantanol;
1-hydroxymethyl-3-methoxycarbonyloxyadamantane and/or
1-methoxycarbonyloxymethyl-3-adamantanol and/or
1-methoxycarbonyloxy-3-methoxycarbonyloxymethyladamantane from
1-hydroxymethyl-3-adamantanol;
1-(N,N-dimethylcarbamoyl)-3-methoxycarbonyloxydadamantane from
1-(N,N-dimethylcarbamoyl)-3-adamantanol;
1-(methoxycarbonyloxy)-3-nitroadamantane from 1-nitro-3-adamatanol;
1-(methoxycarbonyloxy)-3,5-adamantanediol and/or
1,3-bis(methoxycarbonyloxy)-5-adamantanol and/or
1,3,5-tris(methoxycarbonyloxy)adamantane from
1,3,5-adamantanetriol; 1,3-bis
(methoxycarbonyloxy)-5-nitroadamantane from
1-nitro-3,5-adamantanediol; and 1-carboxy-3,5-bis
(methoxycarbonyloxy)adamantane from 1-carboxy-3,5-adamantanediol
can be obtained.
When carbamoyloxy group is used as a protected hydroxyl group, for
example, an isocyanate compound may be allowed to react with a
compound having a hydroxyl group, if necessary, in the presence of
the above exemplified base or the like to convert the hydroxyl
group into the corresponding carbamoyloxy group. For example, in
the presence of pyridine, methyl isocyanate may be allowed to react
with 1,3-adamantanediol to form
1-(N-methylcarbamoyloxy)-3-adamantanol and/or
1,3-bis(N-methylcarbamoyloxy)adamantane. Similarly,
1-(N-methylcarbamoyloxy)-3,5-adamantanediol and/or 1,3-bis
(N-methylcarbamoyloxy)-5-adamantanol and/or 1,3,5-tris
(N-methylcarbamoyloxy)adamantane can be obtained from
1,3,5-adamantanetriol.
Moreover, an adamantane derivative having an N-substituted amino
group and a hydroxyl group can be obtained, for example, (i) by
reacting the compound (Ia) having an amino group with a hydrocarbon
halide (e.g., aliphatic hydrocarbon halide such as iodomethane,
iodoethane, iodobutane, bromomethane, bromoethane, bromobutane,
chloromethane and chloroethane) or (ii) by subjecting a compound
produced by the reaction of the compound (Id) with a hydrocarbon
halide, that is, a compound in which an amino group of the compound
(Id) is converted into an N-substituted amino group, to the
oxidation reaction by oxygen with the use of the imide compound
(2). The reaction of the compound (Ia) or the compound (Id) having
an amino group with a hydrocarbon halide may be carried out in the
presence of a de-hydrogen halide agent (an agent for eliminating a
hydrogen halide). As the de-hydrogen halide agent, use can be
practically made of a basic compound [for example, an organic base
(e.g., a basic nitrogen-containing compound such as an aliphatic
amine e.g., trimethylamine, triethylamine, dimethylamine,
diethylamine, methylenediamine and ethylenediamine; a heterocyclic
amine e.g., pyridine and morpholine), an inorganic base (e.g., a
hydroxide of an alkali metal such as sodium hydroxide and potassium
hydroxide; a hydroxide of alkaline earth metal such as calcium
hydroxide; a carbonate of alkali metal such as sodium carbonate and
potassium carbonate; a carbonate of an alkaline earth metal such as
calcium carbonate; a hydrogencarbonate of an alkali metal such as
sodium bicarbonate and potassium bicarbonate; an alkoxide of an
alkali metal such as sodium methoxide and sodium ethoxide)].
The reaction of the compound (Ia) or the compound (Id) each having
an amino group with a hydrocarbon halide may be conducted in a
solvent inert to the reaction. As such solvent, use may be made of
the solvents exemplified in the paragraphs of the nitration
reaction, such as a hydrocarbon halide, an ether, an ester and an
amide.
Reaction of 1,3-diamino-5-adamantanol with iodomethane provides
1,3-di(methylamino)-5-adamantanol,
1,3-di(dimethylamino)-5-adamantanol, etc. Reaction of
1,3-diamino-5,7-adamantanediol with iodoethane provides
1,3-di(ethylamino)-5,7-adamantanediol,
1,3-di(diethylamino)-5,7-adamantanediol, etc.
When a carboxyl group is protected by an alkoxy group (when an
ester group is formed), the carboxyl group may be converted into
the corresponding ester group by reacting a carboxyl
group-containing compound or a derivative thereof (e.g., an acid
halide such as an acid chloride) with an alcohol (e.g., methanol,
ethanol) or a reactive derivative thereof (e.g., a lower alkyl
ester), if necessary, in the presence of an acid (e.g., a mineral
acid such as hydrochloric acid and sulfuric acid) or a base (e.g.,
the above exemplified base). The lower alkyl ester includes, for
example, acetic acid C.sub.1-4alkyl ester such as methyl acetate
and ethyl acetate or the corresponding propionate (e.g., methyl
propionate, ethyl propionate). For example,
1-methoxycarbonyl-3-adamantanol may be obtained by reacting
1-carboxy-3-adamantanol with methanol in the presence of an acid,
or by acting thionyl chloride on 1-carboxy-3-adamantanol followed
by reacting with methanol in the presence of an organic base such
as triethylamine.
Moreover, when a carboxyl group is converted into a group having an
amide bond, with the use of an amino group as a protecting group
for the carboxyl group (i.e., when forming an N-substituted or
unsubstituted carbamoyl group), conditions of a conventional
process for forming an amide bond may be applied. The process for
forming an amide bond may be carried out, for example, by the
following methods: (a) a method by a mixed acid anhydride, i.e., a
method which comprises reacting a compound having a carboxyl group
with an acid halide (e.g., acetyl chloride, propionyl chloride,
acetyl bromide) to produce a mixed acid anhydride followed by
reacting the given mixed acid anhydride with an amine compound; (b)
a method by an active ester, i.e., a method which comprises
converting a substrate into an active ester thereof, such as
p-nitrophenylester, an ester with N-hydroxysuccinimide, an ester
with 1-hydroxybenzotriazol or the like followed by reacting the
given ester with an amine compound; (c) a method by a carbodiimide,
i.e., a method which condenses an amine compound with a substrate
in the presence of an activating agent such as
dicyclohexylcarbodiimide and carbonyldiimidazol; or (d) a method
which comprises converting a substrate into a carboxylic anhydride
thereof by a dehydrator such as acetic anhydride followed by
reacting the given carboxylic anhydride with an amine compound, or
a method which comprises converting a substrate to an acid halide
thereof followed by reacting the acid halide with an amine
compound.
The amine compound used in the amide bond-forming reaction
includes, for example, ammonia or a derivative thereof (e.g.,
ammonium halide such as ammonium chloride), a primary amine, a
secondary amine, hydrazine or a derivative thereof (e.g.,
alkoxycarbonylhydrazine such as t-butoxycarbonylhydrazine,
alkoxycarbonylhydrazine such as benzyloxycarbonylhydrazine).
For example, the reaction of an acid halide with an amine compound
may be carried out in a suitable solvent, in the presence of an
basic compound. As the basic compound, use may be made of the basic
compounds exemplified in the paragraphs of the reaction of the
compound (Ia) having an amino group or the compound (Id) with a
hydrocarbon halide and the like.
Moreover, as the solvent, an organic solvent (e.g., an ether, an
ester, an amide) exemplified f or the nitration reaction may be
employed.
For example, reaction of 1,3-dicarboxy-5-adamantanol with ammonia
provides 1,3-dicarbamoyl-5-admatanol. Reaction of
1,3-dicarboxy-5,7-adamantanediol with hydrazine forms
1,3-di(hydrazinocarbonyl)-5,7-adamantanediol, etc.
1-(N,N-dimethylcarbamoyl)-3-adamantanol can be obtained by acting
thyonyl chloride on 1-carboxy-3-adamantanol followed by reacting
the resultant compound with dimethylamine. Similarly,
1-(N,N-dimethylcarbamoyl)-3-methoxycarbonyladamantane can be formed
from 1-carboxy-3-methoxycarbonyladamantane,
Furthermore, the compound having a carbamoyl group may also be
obtained by reacting a compound having an ester group (e.g., an
alkoxycarbonyl group, an aryloxycarbonyl group, an aralkylcarbonyl
group) as a protected carboxyl group with the amine compound in the
presence of a catalyst comprising a metal compound.
Examples of the metal compound used in the reaction (the amidation
reaction) include a conventional catalyst for trans-esterification
(including a catalyst for transferring an ester to an amide), for
example, a transition metal compound such as a compound comprising
Group 3B element of the Periodic Table (e.g., aluminum compound
such as AlCl.sub.3), a compound comprising Group 4A element of the
Periodic Table (e.g., titanium compound such as TiCl.sub.4), a
compound comprising Group 3A element (e.g., samarium compound such
as SmI.sub.2) of the Periodic Table.
The amount of the catalyst may be selected within a broad range,
for example, about 0.1 mole % to 1 equivalent, preferably about 0.5
to 50 mole %, and more preferably about 1 to 25 mole % (e.g., about
5 to 20 mole %) relative to a compound having an ester group.
The ratio of the amine compound to the ester group-containing
compound is, for example, about 0.5 to 5 mole, preferably about 0.8
mole or more (e.g., about 0.8 to 5 mole), and specifically about 1
mole or more (e.g., about 1 to 3 mole, in particular about 1 to 1.5
mole) of ammonia or the like relative to 1 equivalent of the ester
group-containing compound.
The amidation reaction may be carried out in the presence or
absence of a solvent inert to the reaction. As the reaction
solvent, there may be exemplified an aliphatic hydrocarbon, an
alicyclic hydrocarbon, an aromatic hydrocarbon, a ketone, an ether,
a non-protonic polar solvent and a mixture thereof. The reaction
temperature may be selected within the range of, for example, about
0 to 150.degree. C., and preferably about 25 to 120.degree. C.
An adamantane derivative having plural hydroxyl groups (containing
a hydroxyl group protected by a protective group) can be obtained
according to the following reaction step scheme (II).
##STR00010##
Wherein X.sup.2b and X.sup.21 represent H or OH, X.sup.3h and
X.sup.4h may be the same or different and each may represent H, R,
NO.sub.2, OH, NH.sub.2, COOH, CH.sub.2OH or NCO. X.sup.1b, X.sup.3c
and X.sup.4c have the same meanings as defined above.
In the reaction step scheme (II), the oxidation reaction which
leads the compound (IIb) to the compound (IIc) may be carried out
by the oxidation reaction (the oxidation reaction with oxygen)
using an oxidation catalyst comprising the imide compound (2). For
example, oxidation of 1-adamantanol forms 1,3-adamantanediol,
1,3,5-adamantanetriol, etc. Oxidation of 1,3-adamantanediol
provides 1,3,5-adamantanetriol, etc.
Incidentally, according to the species of substrate, hydroxyl
group, hydroxymethyl group, amino group and carboxyl group of the
reaction component or the reaction product may be protected by the
above protecting group before, after, or during the oxidation
reaction. The introduction and elimination of the protecting group
may be carried out by a method similar to the above described
method.
Specifically, an group derivative having a non-polymerizable
acyloxy group among the group derivatives having plural hydroxyl
groups (including a hydroxyl group protected by a protective group)
can be obtained in accordance with the following reaction step
scheme (II-1). ##STR00011##
Wherein X.sup.3i and X.sup.4i may be the same or different and each
may represent H, R, NO.sub.2, OH, NH.sub.2, COOH, CH.sub.2OH or
NCO, and X.sup.2r represents OAc, X.sup.1b, X.sup.3c, X.sup.4c,
X.sup.3h and X.sup.4h have the same meanings as defined above.
In the reaction step scheme (II-1), the oxidation reaction which
leads the compound (II-1) to (IIc) and the oxidation reaction which
forms the compound (IIa-1) from the compound (IIc) can be carried
out by the above mentioned oxidation process by oxygen. Moreover,
acylation may be carried out by reacting a substrate with the
acylating agent. The acylation may be conducted before, after or
during the oxidation reaction.
The compound (IIb-1) corresponds to the compound (Ib). The compound
(IIb-1) may be oxidized and reacted with an acylating agent to
produce the compound (IIc). For example, 1-acetyloxyadamantane,
1,3-acetyloxyadamantane, 1,3,5-acetyloxyadamantane or the like can
be obtained by subjecting adamantane of the compound (IIb-1) to the
oxidation by oxygen with the aid of the imide compound (2) and
reacting the resultant compound with acetic acid.
The comopound (IIc) includes, for example, an adamantane having a
C.sub.2-6acyl-oxy group such as 1-acetyloxyadamantane,
1-acetyloxy-3-methyladamantane, 1-acetyloxy-3,5-dimethyladamantane,
1,3-diacetyloxyadamantane, 1,3-diacetyloxy-5-methyladamantane,
1,3,5-triacetyloxyadamantane. The oxidation process with oxygen may
be applied to the compound (IIc) to produce the compound (IIa-1).
1-acetyloxyadamantane of the compound (IIc) maybe subjected to the
oxidation process by oxygen using the imide compound (2) to produce
1-acetyloxy-3-adamantanol, 1-acetyloxy-3,5-adamantandiol,
1-acetyloxy-3,5,7-adamantanetriol, etc. Further, according to the
present invention, 1,3-diacetyloxy-5-adamantanol and
1,3-diacetyloxy-5,7-adamantanediol can be obtained by the oxidation
of 1,3-diacetyloxyadamantane with oxygen.
1,3,5-triacetyloxy-7-adamantanol can be obtained by applying the
oxidation process with oxygen to 1,3,5-triacetyloxyadamantane.
The compound (IIa-1) may be obtained also be oxidizing the compound
(IIb-1) with oxygen to form an adamantane derivative having at
least two hydroxyl groups (e.g., 1,3-adamantanediol,
5-methyl-1,3-adamantanediol, 5,7-dimethyl-1,3-adamantanediol,
1,3,5-adamantanetriol and 1,3,5,7-adamantanetetraol) followed by
acting an acylating agent.
An adamantane derivative having a carboxyl group (containing a
carboxyl group protected by a protective group) together with a
hydroxyl group (containing a hydroxyl group protected by a
protective group) can be obtained in accordance with, for example,
the following reaction step scheme (III). ##STR00012##
Where X.sup.2j represents COOH and X.sup.3j, X.sup.4j, X.sup.3k and
X.sup.4k may be the same or different and each may represent H, R,
NO.sub.2, OH, NH.sub.2, COOH, CH.sub.2OH and NCO. X.sup.1b,
X.sup.3e, X.sup.4e, X.sup.3f and X.sup.4f have the same meanings as
defined above.
In the reaction step scheme (III), the oxidation. reaction which
leads the compound (IIb) to the compound (IIId) and the oxidation
reaction which forms the compound (IIIa) from the compound (IIIc)
can be carried out by the oxidation reaction (the oxidation
reaction with oxygen) using an oxidation catalyst comprising the
imide compound (2) or a catalyst system comprising the inside
compound (2) and a co-catalyst.
The compound (IIIb) corresponds to the compound (Ib), and oxidation
of the compound (IIIb) with oxygen provides the compound (IIId),
that is, the compound (Ie).
The compound (IIIc) includes, for example, 1-carboxyadamantane,
1-carboxy-3-methyladamantane, 1-carboxy-3,5-dimethyladamantane,
1,3-dicarboxyadamantane, 1,3-dicarboxy-5-methyladamantane,
1,3,5-tricarboxyadamantane. The compound (IIIa) can be proposed by
oxidizing the compound (IIIc) by oxygen with the aid of an
oxidation catalyst comprising the imide compound. (2) in a manner
similar to that of the oxidation reaction. The oxidation process by
oxygen with aid of the imide compound (2) may be applied to
1-carboxyadamantane of the compound (IIIc) to provide
1-carboxy-3-adamantanol, 1-carboxy-3,5-adamantandiol,
1-carboxy-3,5,7-adamantanetriol, etc. Oxidation of
1,3-dicarboxyadamantane with oxygen provides
1,3-dicarboxy-5-adamantanol, 1,3-dicarboxy-5,7-adamantanediol, etc.
Oxidation of 1,3,5-tricarboxyadamantane with oxygen provides
1,3,5-tricarboxy-7-adamantanol.
[Carboxylation Reaction]
In the reaction step scheme (III), to the carboxylation reaction
which forms the compound (IIIc) from the compound (IIIb) and the
carboxylation reaction which leads the compound (IIId) to the
compound (IIIa) may be applied a process comprising contacting the
substrate [the compound (IIIb), the compound (IIId)] with carbon
monoide and oxygen in the presence of a catalyst comprising the
imide compound shown by the formula (2).
The compound (IIIb) may be subjected to the carboxylation reaction
to provide the compound (IIIc). Adamantane of the compound (IIIb)
may be subjected to the carboxylation reaction to provide
1-carboxyadamantane, 1,3-dicarboxyadamantane,
1,3,5-tricarboxyadamantane, etc. Carboxylation of
1,3-adamantanediol provides 1-carboxy-3,5-adamantadiol, etc.
Moreover, the compound (IIId) may be subjected to the carboxylation
reaction (the carboxylation process) using the imide compound (2)
to provide the compound (IIIa). 1-adamantanol of the compound
(IIId) may be subjected to the carboxylation reaction using the
imide compound (2) to produce 1-carboxy-3-adamantanol,
1,3-dicarboxy-5-adamantanol, 1,3,5-tricarboxy-7-adamantanol,
etc.
[Catalyst]
As an imide compound in the carboxylation reaction, use can be made
of the imide compound (2) exemplified in the paragraphs of the
nitration reaction. In this carboxylation reaction, a catalyst may
comprise an imide compound (2) similar to that used in the
oxidation reaction and a co-catalyst.
[Carbon Monoxide and Oxygen]
Carbon monoxide to be used in the carboxylation reaction may be
pure carbon monoxide or diluted with an inert gas exemplified in
the paragraphs of oxygen for the oxidation reaction. Oxygen may be
one of those exemplified in the paragraphs of the oxidation
reaction.
In the carboxylation reaction, the amount of the imide compound
shown by the formula (2) may be selected within the range of the
amount of the imide compound exemplified in the paragraphs of the
nitration reaction using the inside compound (2).
The amount of the co-catalyst may be selected within the range of
the amount of the co-catalyst exemplified in the paragraphs of the
oxidation reaction with oxygen using the imide compound (2).
Similarly, the ratio of the co-catalyst to the imide compound may
be selected within the range of the ratio of the co-catalyst to the
imide compound exemplified in the paragraphs of the oxidation
reaction with oxygen.
The amount of carbon monoxide may be selected within a range of,
for example, about 1 mole or more (e.g., about 1 to 1000 mole),
preferably excess mole, for example, about 1.5 to 100 mole (e.g.,
about 2 to 50 mole), more preferably about 2 to 30 mole (e.g.,
about 5 to 25 mole), relative to 1 mole of the substrate.
The amount of oxygen may be selected within a range of about 0.5
mole or more (e.g., about 0.5 to 100 mole), preferably about 0.5 to
30 mole, more preferably about 0.5 to 25 mole, relative to 1 mole
of the substrate.
The ratio of carbon monoxide (CO) to oxygen (O.sub.2) may be
selected within a wide range, as far as the amount of each
component is within the above range, for example, of
CO/O.sub.2=about 1/99 to 99.99/0.01 (mole %). The use of the carbon
monoxide in the amount larger than that of oxygen is advantageous.
The ratio of CO to O.sub.2 may be usually selected within the range
of CO/O.sub.2=about 1/99 to 99/1 (mole %) [e.g., about 10/90 to
99/1 (mole %)], and preferably about 30/70 to 98/2 (mole %), more
preferably about 50/50 to 95/5 (mole %), particularly about 60/40
to 90/10 (mole %).
The volume ratio of carbon monoxide to oxygen in a supply line may
be selected within the range of, for example, CO/O.sub.2=about 1/99
to 99.99/0.01 (volume %), and usually about 1/99 to 99/1 (volume
%), preferably about 30/70 to 98/2 (volume %), more preferably
about 50/50 to 95/5 (volume %), specifically about 60/40 to 90/10
(volume %).
The carboxylation reaction may be conducted in an organic solvent
inert to the reaction. As the organic solvent, use can be made of
the organic solvents exemplified in the paragraphs of the nitration
reaction, and practically an organic acid (e.g., a carboxylic acid
such as acetic acid), a nitrile (e.g., acetonitrile), a hydrocarbon
halide (e.g., dichloroethane).
The carboxylation reaction using the imide compound (2) can be
smoothly conducted even under comparatively mild or moderate
conditions. The reaction temperature may be selected, according to
species of the imide compound or the substrate, within the range of
about 0 to 200.degree. C., preferably about 10 to 150.degree. C.
(e.g., about 10 to 120.degree. C.), more preferably about 10 to
100.degree. C. (e.g., about 10 to 80.degree. C.). The reaction can
be conducted at ambient pressure or under a pressure (under a
load).
According to species of the substrate, hydroxyl group [e.g.,
hydroxyl group of the compound (IIIa) and the compound (IIId)],
hydroxymethyl group, amino group and carboxyl group [e.g., carboxyl
group of the compound (IIIa) and the compound (IIIc)] of the
reaction component or the reaction product may be protected by the
above protecting group before or after the oxidation reaction or
the carboxylation reaction, or during each reaction. Introduction
and elimination of these protecting groups may be carried out by a
method similar to the above described method.
For example, 1-carboxy-3-acetyloxyadamantane,
1-carboxy-3,5-diacetyloxyadamantane,
1-carboxy-3,5,7-triacetyloxyadamantane or the like can be obtained
by oxidizing 1-carboxyadamantane of the compound (IIIc) and
reacting the produced alcohol bodies with acetic acid. Similarly,
reaction of 1-carboxy-3-adamantanol of the compound (IIIa) with
methanol provides 1-methoxycarbonyl-3-adamantanol.
1-carboxyadamantane of the compound (IIIc) may be allowed to react
with ethanol and subjected the oxidation reaction with oxygen to
produce 1-ethoxycarbonyl-3-adamantanol,
1-ethoxycarbonyl-3,5-adamantanediol,
1-ethoxycarbonyl-3,5,7-adamantanetriol, etc.
1,3-dicarboxyadamantane may be allowed to react with ethanol and
oxidized with oxygen to produce
1,3-di(ethoxycarbonyl)-5-adamantanol,
1,3-di(ethoxycarbonyl)-5,7-adamantanediol, etc.
When an alcohol or a lower alkyl ester thereof (e.g., ethyl
acetate) is used as a solvent and a substrate subjected to the
carboxylation reaction, an adamantane derivative having a carboxyl
group protected by a protective group (an alkoxy group) can be
obtained.
An adamantane derivative having a hydroxymethyl group (containing a
hydroxymethyl group protected by a protective group) together with
a hydroxyl group (containing a hydroxyl group protected by a
protective group) can be obtained in accordance with the following
reaction step scheme (IV). ##STR00013##
Wherein X.sup.2m represents CH.sub.2OH, X.sup.3n and X.sup.4n may
be the same or different and each may represent H, R, NO.sub.2, OH,
NH.sub.2, CH.sub.2OH and NCO. X.sup.1b, X.sup.2f, X.sup.3f and
X.sup.4j have the same meanings as defined above.
In the reaction step scheme (IV), the reduction reaction which
leads the compound (IIIa) to the compound (IVa) may be carried out
by a conventional method such as a catalytic hydrogenation process
using hydrogen as a reducing agent and a reduction process using a
hydrogenation reducing agent. Preferred hydrogenation reducing
agent includes, for example, sodium boron hydride-Lewis acid,
aluminium hydride, lithium aluminium hydride, lithium
trialkoxyaluminium hydride and diborane. Incidentally, the compound
(IIIa) can be obtained by the reaction step scheme (III).
For example, 1-hydroxy-3-hydroxymethyladamantane can be formed by
reducing 1-carboxy-3-adamantanol with lithium aluminium
hydride.
According to the species of the substrate, hydroxyl group,
hydroxymethyl group, amino group and carboxyl group of the reaction
component or the reaction product may be protected by the above
protecting group before or after the reduction reaction.
Introduction and elimination of these protecting groups may be
carried out by a method similar to the above described method.
An adamantane derivative having an isocyanato group together with a
hydroxyl group (containing a hydroyl group protected by a
protective group) can be obtained, for example, in accordance with
the following reaction step scheme (V). ##STR00014##
Wherein X.sup.2o represents NH.sub.2, X.sup.2p represents NCO, and
X.sup.3q and X.sup.4q may be the same or different and each may
represent H, R, NO.sub.2, OH, NH.sub.2, COOH, CH.sub.2OH and NCO.
X.sup.1b, X.sup.3b and X.sup.4b have the same meanings as defined
above.
In the reaction scheme (V), the reaction which leads the compound
(Vb) to the compound (Va) may be conducted by a conventional method
such as a method using phosgene. The compound (Vb) corresponds to a
compound in which X.sup.2b of the compound (Ia) obtained in the
reaction step scheme (I) is NH.sub.2.
The reaction of the compound (Vb) with phosgene may be conducted,
for example, in the presence or absence of a solvent at a
temperature of about -10 to 100.degree. C. The amount of phosgene
is, for example, about 0.8 to 10 mole and preferably about 1 to 2
mole relative to 1 mole of the compound (Vb).
For example, 1-acetyloxy-3-isocyanatoadamantane can be obtained by
allowing 1-acetyloxy-3-aminoadamantane to react with phosgene.
According to species of the substrate, hydroxyl group,
hydroxymethyl group, amino group and carboxyl group of the reaction
component or the reaction product may be protected by the above
protecting group before or after the isocyanation reaction.
Introduction and elimination of these protecting groups may be
carried out by a method similar to the above described method.
In the production process of adamantane derivatives mentioned
above, a nitro group and a hydroxyl group can be introduced into an
adamantane backbone in one step by, in the presence of the imide
compound, allowing an adamantane compound having at least two
methane carbon atoms in the adamantane backbone to react with a
nitrogen oxide and oxygen to be used in the nitration reaction. A
derivative in which at least two functional groups selected from a
nitro group, a hydroxyl group and a carboxyl group are introduced
to the adamantane backbone can be obtained in one step by allowing
the adamantane compound to react with a nitrogen oxide, oxygen and
carbon monoxide in the presence of the imide compound. The reaction
may be carried out in accordance with the conditions and operations
described in the paragraphs of the nitration reaction, the
oxidation reaction or the carboxylation reaction depending on the
objective compound.
For example, when adamantane is allowed to react with nitrogen
monoxide, oxygen and carbon monoxide in the presence of the imide
compound, 1-carboxy-3-nitro-5-adamantanol,
1-nitro-3,5-adamantanediol, 1-carboxy-3,5-adamantanediol,
1,3,5-adamantanetriol, 1,3-dinitro-5-adamantanol,
1,3-dicarboxy-5-adamantanol etc can be obtained.
As to the process for producing an adamantane derivative having a
hydroxyl group and a functional group, as a preferred production
process, there may be mentioned, for example, a process for
oxidizing an adamantane derivative shown by the following formula
(1a): ##STR00015## wherein X.sup.2 represents a nitro group, an
amino group or N-substituted amino group which may be protected by
a protective group, a hydroxyl group which may be protected by a
protective group, a carboxyl group which may be protected by a
protective group, a hydroxymethyl group which may be protected by a
protective group, or an isocyanato group; X.sup.3a and X.sup.4a may
be the same or different from each other and each may represent a
hydrogen atom, an alkyl group, a nitro group, a hydroxyl group
which may be protected by a protective group, an amino group or
N-substituted amino group which may be protected by a protective
group, a carboxyl group which may be protected by a protective
group, a hydroxymethyl group which may be protected by a protective
group, or an isocyanto group; with oxygen in the presence of an
oxidation catalyst comprising the imide compound shown by the
formula (2) or the imide compound and a co-catalyst.
According to the more preferable process for producing the group
derivative, in the above formula (1a), (i) when X.sup.2 is a nitro
group, X.sup.3a and X.sup.4a may be the same or different from each
other and each may represent a hydrogen atom, an alkyl group, a
nitro group; (ii) when X.sup.2 is an amino group or N-substituted
amino group which may be protected by a protective group, X.sup.3a
and X.sup.4a may be the same or different from each other and each
may represent a hydrogen atom, an alkyl group, an amino group or
N-substituted amino group which may be protected by a protective
group; (iii) when X.sup.2 is a hydroxyl group which may be
protected by a protective group, X.sup.3 and X.sup.4 may be the
same or different from each other and each may represent a hydrogen
atom, an alkyl group, a hydroxyl group which may be protected by a
protective group; (iv) when X.sup.2 is a carbonyl group which may
be protected by a protective group, X.sup.3a and X.sup.4a may be
the same or different from each other and each may represent a
hydrogen atom, an alkyl group, a carboxyl group which may be
protected by a protective group; (v) when X is a hydroxymethyl
group which may be protected by a protective group, X.sup.3 and
X.sup.4 may be the same or different from each other and each may
represent a hydrogen atom, an alkyl group, a hydroxymethyl group
which may be protected by a protective group; and (vi) when X.sup.2
is an isocyanato group, X.sup.3 and X.sup.4 may be the same or
different from each other and each may represent a hydrogen atom,
an alkyl group or an isocyanato group.
In the production of the novel adamantane derivative, a
conventional oxidation process such as an oxidation process using
nitric acid or chromic acid, oxidation process using an cobalt salt
as a catalyst, a biochemical method or the like may be employed as
an oxidation process. For the introduction of a hydroxyl group,
these may be employed a process for introducing a hydroxyl group to
a substrate which comprises introducing a halogen atom (e.g., a
bromine atom) to the substrate and then, hydrolyzing with the use
of an inorganic salt such as silver nitrate and silver sulfate.
A compound having a basic group or an acidic group among adamantane
derivatives having a hydroxyl group and a functional group may form
its salt. For example, an adamantane derivative having a carboxyl
group may form a salt by being reacted with a basic compound. As
the basic compound, use can be made of, for example, besides
ammonia, the compound (Ia) having an amino group and the compound
(Id) having an amino group, and basic compounds (e.g., an organic
base and an inorganic base) exemplified in the paragraphs of the
reaction with a hydrocarbon halide.
Moreover, among adamantane derivatives having a hydroxyl group and
a functional group, a compound having a basic group such as an
adamantane derivative having an amino group may form a salt by
being reacted with an acid. An acid includes, for example, an
inorganic acid (e.g., hydrochloric acid, sulfuric acid, nitric
acid, hydrochloric acid), an organic acid (e.g., an aliphatic
carboxylic acid such as acetic acid and propionic acid; an aromatic
carboxylic acid such as benzoic acid; an alkylsulfonic acid such as
methanesulfonic acid, ethanesulfonic acid; an arylsulfonic acid
such as benzenesulfonic acid, p-toluenesulfonic acid).
Reactions such as oxidation reaction may be effected in any of a
batch system, a semi-batch system and a continuous system. After
completion of the reaction, a reaction product can be easily
isolated and purified according to a conventional means such as
filtration, condensation, distillation, extraction,
crystallization, recrystallization and column chromatography, or a
combination of these means.
INDUSTRIAL APPLICABILITY
In the process of the present invention, an adamantane derivatives
shown by the formula (2) or a known adamantane derivative can be
efficiently produced with high conversion and selectivity.
Such adamantane derivatives are useful as raw materials for high
functional materials (e.g., optical materials such as optical
fibers, optical elements, optical lenses, hologram, optical discs
and contact lenses; transparent resin coating compositions for
organic glasses; electric conductive polymers; photosensitive
materials; fluorescent materials). Moreover, the adamantane
derivatives are also useful as raw materials of pharmaceutical
preparations having high pharmacological activity and agricultural
chemicals.
The present invention can provide a novel adamantane derivative
which is useful as a high functional material. Moreover, the use of
an oxidation catalyst comprising a specific imide compound can
provide not only the novel compound but also known adamantane
derivatives efficiently. Further, the adamantane derivatives can be
obtained in high conversion and selectivity even under mild or
moderate conditions.
EXAMPLES
The following examples are intended to describe the present
invention in more detail, but should by no means be construed to
limit the scope of the invention. Incidentally, infrared absorption
spectra were measured after purifying the reaction product by
column chromatography. The terms "Ac" and "Ph" represent acetyl
group and phenyl group, respectively.
Example 1
Mixture of 10 mmole 1-acetylaminoadamantane (Aldrich chemical
Company, Inc.), 1 mmole of N-hydroxyphthalimide (NHPI), 0.05 mmole
of vanadium (III) acetylacetonato (V(AA).sub.3) and 25 mL of acetic
acid was stirred under an oxygen atmosphere and the conditions
represented in Table 1 (temperature and time). The products in the
reaction mixture were analyzed by gas chromatography, and, as a
result, 1-acetylamino-3-adamantanol (compound 1),
1-acetylamino-3,5-adamantanediol (compound 2) and
1-acetylamino-4-adamantanone (compound 3) were obtained with
conversions and yields represented in Table 1.
TABLE-US-00001 TABLE 1 Temperature Time Conversion Yield (%)
(.degree. C.) (hr) (%) Comp.1 Comp.2 Comp.3 75 6 89 64 16 8 60 20
92 66 19 4 Comp.1 (compound 1): 1-acetylamino-3-adamantanol Comp.2
(compound 2): 1-acetylamino-3,5-adamantanediol Comp.3 (compound 3):
1-acetylamino-4-adamantanone
Example 2
A reactor was charged with 10 mmole of adamantane, 1 mmole of NHPI,
0.005 mmole of Co(AA).sub.2 and 25 mL of acetic acid, then equipped
with a gas bag of mixed gas (a mixed gas of 2 L of carbon monoxide
and 0.5 L of oxygen). The resultant mixture was stirred for 6 hours
at a temperature of 60.degree. C. to give 1-carboxyadamantane and
1,3-dicarboxyadamantane.
A mixture of 10 mmole of 1-carboxyadamantane, 1 mmole of NHPI, 0.05
mmole of V(AA).sub.3 and 25 mL of acetic acid was stirred under an
oxygen atmosphere and the conditions represented in Table 2 (time
and temperature). As a result, 1-carboxy-3-adamantanol (compound
1), 1-carboxy-3,5-adamantanediol (compound 2) and
1-carboxy-4-adamantanone (compound 3) were obtained with
conversions and yields represented in Table 2.
TABLE-US-00002 TABLE 2 Temperature Time Conversion Yield (%)
(.degree. C.) (hr) (%) Comp.1 Comp.2 Comp.3 75 1 64 44 8 3 75 2 78
59 12 4 75 5 90 64 19 4 75 8 94 52 29 5 Comp.1 (compound 1):
1-carboxy-3-adamantanol Comp.2 (compound 2):
1-carboxy-3,5-adamantanediol Comp.3 (compound 3):
1-carboxy-4-adamantanone
Example 3
In the presence of an acid catalyst (p-toluenesulfonic acid),
1-carboxyadamantane obtained in Example 2 was allowed to react with
an excess amount of ethanol to give 1-ethoxycarbonyladamantane.
A mixture of 10 mmole of the 1-ethoxycarboxyadamantane, 1 mmole of
NHPI, 0.05 mmole of V(AA).sub.3 and 25 mL of acetic acid was
stirred under an oxygen atmosphere and the conditions represented
in Table 3 (temperature and time). As a result,
1-ethoxycarbonyl-3-adamantanol (compound 1),
1-ethoxycarbonyl-3,5-adamatanediol (compound 2) and
1-ethoxy-4-carbonyladamantanone (compound 3) were obtained with
conversions and yields represented in Table 3.
TABLE-US-00003 TABLE 3 Temperature Time Conversion Yield (%)
(.degree. C.) (hr) (%) Comp.1 Comp.2 Comp.3 75 6 95 58 16 8 75 3 86
68 6 7 60 6 63 48 6 4 60 20 92 54 16 7 75 15 99 27 43 5 Comp.1
(compound 1): 1-ethoxycarbonyl-3-adamantanol Comp.2 (compound 2):
1-ethoxycarbonyl-3,5-adamantanediol Comp.3 (compound 3):
1-ethoxycarbonyl-4-adamantanone
Example 4
An eggplant type flask (50 mL) with side arm was dipped in iced
water and the pressure was reduced. Into the flask, nitrogen
monoxide was introduced from a gas bag (1 L) and further oxygen was
introduced from a gas bag (1 L). The flask was filled with
reddish-brown gas, and then a blue liquid comprising N.sub.2O.sub.3
as a main component was formed with sedimentation of the
reddish-brown gas. The introductions of the nitrogen monoxide and
oxygen were repeated to produce about 1.5 ml of the blue liquid.
The blue liquid was frozen with the use of liquid nitrogen.
1.8 g (0.024 mole based on N.sub.2O.sub.3 basis) of the frozen blue
liquid, 1 mmole of adamantane, 0.05 mmole of NHPI and 5 ml of
acetic acid were mixed, and then the mixture was reacted for 10
hours at 100.degree. C. with stirring to give 1-nitroadamantane and
1,3-dinitroadamantane.
To 25 mL of acetic acid was added 10 mmole of the
1-nitroadamantane, 1 mmole of NHPI and 0.05 mmole of V(AA).sub.3,
and the resultant mixture was stirred for 8 hours at 75.degree. C.,
under an oxygen atmosphere. The products in the reaction mixture
were analyzed by gas chromatography, and, as a result,
1-nitro-3-adamantanol (yield 48%), 1-nitro-3,5-adamantanediol
(yield 19%) and 1-nitro-3,5,7-adamantanetriol (yield 2%) were
formed with conversion of 76% of 1-nitroadamantane. Moreover, these
products were analyzed by mass spectroscopy.
(1) 1-nitro-3-adamantanol
Pale yellow solid
Mass spectral data (fragment)
[M].sup.+: 181,[M].sup.-: 163(--OH.sub.2), [M].sup.--:
117(--NO.sub.2)
(2) 1-nitro-3,5-adamantanediol
Pale yellow solid
Mass spectral data (fragment)
[M].sup.+: 197, [M].sup.-: 179(--OH.sub.2), [M].sup.--:
133(--NO.sub.2)
Example 5
A mixture of 10 mmole of 1,3-dinitroadamantane obtained in Example
4, 1 mmole of NHPI, 0.05 mmole of V(AA).sub.3 and 25 mL of acetic
acid was mixed and stirred for 8 hours at 85.degree. C., under an
oxygen atmosphere. As a result, 1,3-dinitro-5-adamantanol (yield
46%) and 1,3-dinitro-5,7-adamantanediol (yield 24%) were formed.
The conversion of 1,3-dinitroadamantane was 79%.
(1) 1,3-dinitro-5-adamantanol
Pale yellow solid
Mass spectral data (fragment)
[M].sup.+: 226, [M].sup.-: 208(--OH.sub.2), [M].sup.--:
162(--NO.sub.2), [M].sup.---: 115 (--HNO.sub.2)
(2) 1,3-dinitro-5,7-adamantanediol
Pale yellow solid
Mass spectral data (fragment)
[M].sup.+: 242, [M].sup.-: 224(--OH.sub.2), [M].sup.--:
178(--NO.sub.2), [M].sup.---: 131 (--HNO.sub.2)
Example 6
A mixture of 10 mmole of 1-carboxyadamantane obtained in Example 2,
1 mmole of NHPI, 0.05 mmole of V(AA).sub.3 and 25 mL of acetic acid
was mixed and stirred for 8 hours at 75.degree. C., under an oxygen
atmosphere. As a result, 1-carboxy-3-adamantanol (yield 28%),
1-carboxy-3,5-adamantanediol (yield 48%) and
1-carboxy-3,5,7-adamantanetriol (yield 10%) were formed. The
conversion of 1-carboxyadamantane was 94%.
(1) 1-carboxy-3-adamantanol
White solid
Mass spectral data (fragment)
[M].sup.+: 196, [M].sup.-: 178(--OH.sub.2), [M].sup.--:
133(--COOH)
(2) 1-carboxy-3,5-adamantanediol
White solid
Mass spectral data (fragment)
[M].sup.+: 212, [M].sup.-: 194(--OH.sub.2), [M].sup.-:
149(--COOH)
Example 7
A mixture of 10 mmole of 1,3-dicarboxyadamantane obtained in
Example 2, 1 mmole of NHPI, 0.05 mmole of V(AA).sub.3 and 25 mL of
acetic acid was mixed and stirred for 8 hours at 85.degree. C.,
under an oxygen atmosphere. As a result,
1,3-dicarboxy-5-adamantanol (yield 52%) and
1,3-dicarboxy-5,7-adamantanediol (yield 26%) were formed. The
conversion of 1,3-dicarboxyadamantane was 86%.
(1) 1,3-dicarboxy-5-adamantanol
White solid
Mass spectral data (fragment)
[M].sup.+: 228, [M].sup.-: 210(--OH.sub.2), [M].sup.--:
165(--COOH), [M].sup.---: 119(--HCOOH)
(2) 1,3-dicarboxy-5,7-adamantanediol
White solid
Mass spectral data (fragment)
[M].sup.+: 244, [M].sup.-: 216(--OH.sub.2), [M].sup.--:
171(--COOH), [M].sup.---: 125(--HCOOH)
Example 8
A mixture of 10 mmole of adamantane, 1 mmole of NHPI, 0.05 mmole of
cobalt(II) acetylacetonato (Co(AA).sub.2) and 25 mL of acetic acid
was stirred for 6 hours at 75.degree. C. under an oxygen atmosphere
to give 1-acetyloxyadamantane and 1,3-diacetyloxyadamantane.
To 25 mL of acetic acid were added 10 mmole of the
1-acetyloxyadamantane, 1 mmole of NHPI and 0.05 mmole of
V(AA).sub.2, and the resultant mixture was stirred for 8 hours at
75.degree. C., under an oxygen atmosphere. As a result,
1-acetyloxy-3-adamantanol (yield 37%),
1-acetyloxy-3,5-adamantanediol (yield 25%) and
1-acetyloxy-3,5,7-adamantanetriol (yield 11%) were formed. The
conversion of 1-acetyloxyadamantane was 89%.
(1) 1-acetyloxy-3-adamantanol
White solid
Mass spectral data (fragment)
[M].sup.+: 210, [M].sup.-: 151(--OAc), [M].sup.--:
133(--OH.sub.2)
(2) 1-acetyloxy-3,5-adamantanediol
White solid
Mass spectral data (fragment)
[M].sup.+: 226, [M].sup.-: 167(--OAc), [M].sup.--:
149(--OH.sub.2)
Example 9
To 25 mL of acetic acid were added 10 mmole of
1,3-diacetyloxyadamantane obtained in Example 8, 1 mmole of NHPI
and 0.05 mmole of V(AA).sub.3, and the resultant mixture was
stirred for 8 hours at 85.degree. C. under an oxygen atmosphere. As
a result, 1,3-diacetyloxy-5-adamantanol (yield 60%) and
1,3-diacetyloxy-5,7-adamantanediol (yield 19%) were formed. The
conversion of 1,3-diacetyloxyadamantane was 93%.
(1) 1,3-diacetyloxy-5-adamantanol
White solid
Mass spectral data (fragment)
[M].sup.+: 268, [M].sup.-: 209(--OAc), [M].sup.--: 191(--OH.sub.2),
[M].sup.---: 131 (--HOAc)
(2) 1,3-diacetyloxy-5,7-adamantanediol
White solid
Mass spectral data (fragment)
[M].sup.+: 284, [M].sup.-: 225(--OAc), [M].sup.--: 207(--OH.sub.2),
[M].sup.---: 147 (--HOAc)
Example 10
A mixture of 10 mmole of 1-benzoylaminoadamantane (Aldrich chemical
company, Inc.), 1 mmole of NHPI, 0.05 mmole of V(AA).sub.3 and 25
mL of acetic acid was mixed and stirred for 8 hours at 75.degree.
C. under an oxygen atmosphere. As a result,
1-benzoylamino-3-adamantanol (yield 53%),
1-benzoylamino-3,5-adamantanediol (yield 23%) and
1-benzoylamino-3,5,7-adamantanetriol (yield 7%) were formed. The
conversion of 1-benzoylaminoadamantane was 91%.
(1) 1-benzoylamino-3-adamantanol
Pale yellow solid
Mass spectral data (fragment)
[M].sup.+: 271, [M].sup.-: 253(--OH.sub.2), [M].sup.--:
133(--NHCOPh)
(2) 1-benzoylamino-3,5-adamantanediol
Pale yellow solid
Mass spectral data (fragment)
[M].sup.+: 287, [M].sup.-: 269(--OH.sub.2), [M].sup.--:
149(--NHCOPh)
Example 11
In the presence of an acid catalyst (p-toluenesulfonic acid),
1-carboxyadamantane obtained in Example 2 was allowed to react with
an excess amount of methanol to give
1-methoxycarbonyladamantane.
A mixture of 10 mmole of the 1-methoxycarbonyladamantane, 1 mmole
of NHPI, 0.05 mmole of V(AA).sub.3 and 25 mL of acetic acid was
mixed and stirred for 8 hours at 75.degree. C., under an oxygen
atmosphere. As a result, 1-methoxycarbonyl-3-adamantanol (yield
47%), 1-methoxycarbonyl-3,5-adamantanediol (yield 31%) and
1-methoxycarbonyl-3,5,7-adamantanetriol (yield 8%) were formed. The
conversion of 1-methoxycarbonyladamantane was 95%.
(1) 1-methoxycarbonyl-3-adamantanol
White solid
Mass spectral data (fragment)
[M].sup.+: 212, [M].sup.-: 194(--OH.sub.2), [M].sup.--:
179(--CH.sub.3), [M].sup.---: 135(--COO)
(2) 1-methoxycarbonyl-3,5-adamantanediol
White solid
Mass spectral data (fragment)
[M].sup.+: 228, [M].sup.-: 210(--OH.sub.2), [M].sup.--:
195(--CH.sub.3), [M].sup.---: 151 (--COO)
Example 12
In the presence of an acid catalyst (p-toluenesulfonic acid),
1,3-dicarboxyadamantane obtained in Example 2 was allowed to react
with an excess amount of methanol to give
1,3-dimethoxycarbonyladamantane.
To 25 mL of acetic acid were added the 10 mmole of the
1,3-dimethoxycarbonyladamantane, 1 mmole of NHPI and 0.05 mmole of
V(AA).sub.3, and the resultant mixture was stirred for 8 hours at
85.degree. C., under an oxygen atmosphere. As a result,
1,3-dimethoxycarbonyl-5-adamantanol (yield 42%) and
1,3-methoxycarbonyl-5,7-adamantanediol (yield 36%) were formed. The
conversion of 1,3-dimethoxycarbonyladamantane was 92%.
(1) 1,3-dimethoxycarbonyl-5-adamantanol
White solid
Mass spectral data (fragment) [M].sup.+: 272, [M].sup.-:
254(--OH.sub.2), [M].sup.--: 239(--CH.sub.3), [M].sup.---:
195(--COO)
(2) 1,3-dimethoxycarbonyl-5,7-adamantanediol
White solid
Mass spectral data (fragment)
[M].sup.+: 288, [M].sup.-: 270(--OH.sub.2), [M].sup.--:
255(--CH.sub.3), [M].sup.---: 211 (--COO)
Example 13
In an atmosphere of nitrogen, 10 mmole of 1-carboxy-3-adamantanol
obtained by the method of Example 2 was dissolved in 10 ml of
N,N-dimethylformamide (DMF). To the mixture, 15 mmole of tionyl
chloride was added dropwise over 30 minutes while heating the
mixture to the reflux temperature so as to begin to reflux at about
the time the addition is finished. After refluxing for 2 hours, the
mixture was cooled. To the mixture, 25 mmole of dimethylamine was
added dropwise over 30 minutes while keeping the temperature of the
solution at 10.degree. C. or below, and the mixture was stirred for
another 2 hours. As a result, the conversion of
1-carboxy-3-adamantanol was 99%, and
1-(N,N-dimethylcarbamoyl)-3-adamantanol (yield 95%) was formed.
Pale yellow solid
Mass spectral data [M].sup.+: 223
IR(cm.sup.-1): 3360, 1650, 700
Example 14
In an atmosphere of nitrogen, 10 mmole of 1-nitro-3-adamantanol
obtained by the method of Example 4 and 12 mmole of triethylamine
were dissolved in 10 ml of DMF. To the mixture, 11 mmole of acetyl
chloride was added dropwise over 30 minutes at 40.degree. C. The
mixture was stirred for another 3 hours at 40.degree. C. As a
result, the conversion of 1-nitro-3-adamantanol was 99%, and
1-acetyloxy-3-nitroadamantane (yield 95%) was formed.
Pale yellow liquid
Mass spectral data [M].sup.+: 210
IR(cm.sup.-1): 1720, 1570, 1340
Example 15
An autoclave was charged, 10 mmole of 1-acetyloxy-3-nitroadamantane
obtained by the method of Example 14, 5% Pd-C (10 mole % of Pd
relative to a substrate), 1 ml of dilute hydrochloric acid and 10
ml of methanol. The mixture was stirred for 2 hours at 80.degree.
C. in an atmosphere of hydrogen at 30 atm. As a result, the
conversion of 1-acetyloxy-3-nitroadamantane was 90%, and
1-acetyloxy-3-aminoadamantane (yield 70%) was formed.
Pale yellow liquid
Mass spectral data [M].sup.+: 209
IR(cm.sup.-1): 3310, 1650, 1620
Example 16
Operation was effected in the same manner as Example 15 except for
using 1-nitro-3-adamantanol obtained by the method of Example 4
instead of 1-acetyloxy-3-nitroadamantane. 1-amino-3-adamantanol
(yield 95%) was formed. The conversion of 1-nitro-3-adamantanol was
99%.
Pale yellow solid
Mass spectral data [M].sup.+: 167
IR(cm.sup.-1): 3370, 3340, 1620, 1360
In an atmosphere of nitrogen, 10 mmole of 1-amino-3-adamantanol
obtained by the above method and 24 mmole of triethylamine were
dissolved in 10 ml of DMF. To the mixture, 22 mmole of acetyl
chloride was added dropwise over 30 minutes at 40.degree. C. The
mixture was stirred for another 3 hours at 40.degree. C. As a
result, the conversion of 1-amino-3-adamantanol was 90%, and
1-acetylamino-3-acetyloxyadamantane (yield 80%) was formed.
Pale yellow liquid
Mass spectral data [M].sup.+: 251
IR(cm.sup.-1): 3300, 1680, 1620
Incidentally, another operation was effected in the same manner as
that of the above reaction except for using 1,3-adamantanediol
instead of 1-amino-3-adamantanol. 1,3-bis(acetyloxy)adamantane
(yield 95%) was obtained. The conversion of 1,3-adamantanediol was
99%.
Colorless liquid
Mass spectral data [M].sup.+: 252
IR(cm.sup.-1): 1630, 1210, 1020
Example 17
In an atmosphere of nitrogen, 10 mmole of 1-carboxy-3-adamantanol
obtained by the method of Example 2 was dissolved in 10 ml of DMF.
To the mixture, 15 mmole of tionyl chloride was added dropwise over
30 minutes while heating the mixture to the reflux temperature so
as to begin to reflux at about the time the addition is finished.
After refluxing for 2 hours, the mixture was cooled. To the
mixture, 20 mmole of triethylamine was added and 11 mmole of
methanol was added dropwise over 30 minutes while keeping the
temperature of the solution at 10.degree. C. or below, and the
mixture was stirred for another 2 hours. As a result, the
conversion of 1-carboxy-3-adamantanol was 99%, and
1-methoxycarbonyl-3-adamantanol (yield 95%) was formed.
White solid
Mass spectral data [M].sup.+: 210
IR(cm.sup.-1): 3350, 1730, 1130
Another operation was effected in the same manner as Example 14
except for using 1-methoxycarbonyl-3-adamantanol obtained by the
method of Example 14 instead of 1-nitro-3-adamantanol. As a result,
1-acetyloxy-3-methoxycarbonyadamantane (yield 80%) was formed. The
conversion of 1-methoxycarbonyl-3-adamantanol was 95%.
Colorless liquid
Mass spectral data [M].sup.+: 252
IR(cm.sup.-1): 1660, 1620, 1240
Example 18
In an atmosphere of nitrogen, 15 mmole of lithium aluminium hydride
was suspended into 15 mL of tetrahydrofurane (THF). To the
resultant mixture was slowly added 10 mmole of
1-carboxy-3-adamantanol obtained by the method of Example 2 while
keeping the temperature of the mixture at 10.degree. C. or below by
using an ice bath. After warming the mixture to room temperature,
the mixture was refluxed for 16 hours. As a result,
1-hydroxymethyl-3-adamantanol (yield 95%) was obtained. The
conversion of 1-carboxy-3-adamantanol was 99%.
White solid
Mass spectral data [M].sup.+: 182
IR(cm.sup.-1): 3370, 1380, 1120
Another operation was effected in the same manner as Example 14
except for using 1-hydroxymethyl-3-adamantanol obtained by the
above method instead of 1-nitro-3-adamantanol.
1-acetyloxy-3-hydroxymethyladamantane (yield 80%) was formed. The
conversion of 1-hydroxymethyl-3-adamantanol was 90%.
Colorless liquid
Mass spectral data [M].sup.+: 224
IR(cm.sup.-1): 3310, 1640, 1230
Example 19
Another operation was effected in the same manner as Example 14
except for using 1-carboxy-3-adamantanol obtained by the method of
Example 2 instead of 1-nitro-3-adamantanol.
1-acetyloxy-3-carboxyadamantane (yield 80%) was formed. The
conversion of 1-carboxy-3-adamantanol was 90%.
Colorless liquid
Mass spectral data [M].sup.+: 238
IR(cm.sup.-1): 3000, 1640, 1600
In an atmosphere of nitrogen, 10 mmole of
1-acetyloxy-3-carboxyadamantane obtained by the above method was
dissolved in 10 ml of DMF. To the mixture, 15 mmole of
N,N'-carbodiimidazol in the form of powder was added in one
portion. After stirring for 1 hour at the room temperature, 15
mmole of dimethylamine and 15 mmole of diazabicycloundecene were
added. The mixture was heated to 100.degree. C. and stirred for 8
hours. As a result, the conversion of
1-acetyloxy-3-carboxyadamantane was 80%, and
1-acetyloxy-3-(N,N-dimethylcarbamoyl)adamantane (yield 70%) was
formed.
Pale yellow liquid
Mass spectral data [M].sup.+: 265
IR(cm.sup.-1): 1670, 1620, 1220
Example 20
In an atmosphere of nitrogen, 10 mmole of 1,3-adamantanediol and 12
mmole of pyridine was dissolved in 10 ml of DMF. To the mixture, 11
mmole of methoxycarbonyl chloride was added dropwise with stirring
at room temperature. Cooling of the resultant mixture with ice was
started at about the time exothermic reaction began. When the
exothermic reaction is completed, the mixture was heated to
60.degree. C. and then stirred for one hour. As a result, the
conversion of 1,3-adamantanediol was 99% and
1-methoxycarbonyloxy-3-adamantanol (yield 85%) was formed.
Colorless liquid
Mass spectral data [M].sup.+: 226
IR(cm.sup.-1): 3320, 1620, 1240
Example 21
In an atmosphere of nitrogen, 10 mmole of 1,3-adamantanediol and 24
mmole of pyridine were dissolved in 10 ml of DMF. To the mixture,
22 mmole of methoxycarbonyl chloride was added dropwise with
stirring at room temperature. Cooling of the resultant mixture with
ice was started at about the time exothermic reaction began. When
the exothermic reaction is completed, the mixture was heated to
60.degree. C. and then stirred for one hour. As a result, the
conversion of 1,3-adamantanediol was 99% and 1,3-bis
(methoxycarbonyloxy)adamantane (yield 90%) was formed.
Colorless liquid
Mass spectral data [M].sup.+: 284
IR(cm.sup.-1): 1620, 1340, 1170
Example 22
In an atmosphere of nitrogen, 10 mmole of 1,3-adamantanediol and
one drop of pyridine were dissolved in 10 ml of DMF. To the
mixture, 10 mmole of methylisocyanato was added dropwise with
stirring. Cooling of the resultant mixture with ice was started at
about the time exothermic reaction began. When the exothermic
reaction is completed, the mixture was heated to 60.degree. C. and
then stirred for one hour. As a result, the conversion of
1,3-adamantanediol was 99% and
1-(N-methylcarbamoyloxy)-3-adamantanol (yield 85%) was formed.
Pale yellow liquid
Mass spectral data [M].sup.+: 225
IR(cm.sup.-1): 3300, 1660, 1270
Example 23
In an atmosphere of nitrogen, 10 mmole of 1,3-adamantanediol and
one drop of pyridine were dissolved in 10 ml of DMF. To the
mixture, 20 mmole of methylisocyanato was added dropwise with
stirring. Cooling of the resultant mixture with ice was started at
about the time exothermic reaction began. When the exothermic
reaction is completed, the mixture was heated to 60.degree. C. and
then stirred for one hour. As a result, the conversion of
1,3-adamantanediol was 99% and
1-(N-methylcarbamoyloxy)-3-adamantanol (yield 90%) was formed.
Pale yellow liquid
Mass spectral data [M].sup.+: 282
IR(cm.sup.-1): 1670, 1260, 1140
Example 24
Operation was effected in the same manner as Example 20 except for
using 1-nitro-3-adamantanol obtained by the method of Example 4
instead of 1,3-adamantanediol. The conversion of
1-nitro-3-adamantanol was 99% and
1-methoxycarbonyloxy-3-nitroadamantane (yield 90%) was
obtained.
Pale yellow liquid
Mass spectral data [M].sup.+: 255
IR(cm.sup.-1): 1620, 1560, 1340, 1170
Example 25
Operation was effected in the same manner as Example 20 except for
using 1-caboxy-3-adamantanol obtained by the method of Example 5
instead of 1,3-adamantanediol. The conversion of
1-carboxy-3-adamantanol was 99% and
1-carboxy-3-methoxycarbonyloxyadamantane (yield 90%) was
obtained.
White solid
Mass spectral data [M].sup.+: 254
IR(cm.sup.-1): 3030, 1670, 1620, 1430
Example 26
Operation was effected in the same manner as Example 20 except for
using 1-methoxycarbonyl-3-adamantanol obtained by the method of
Example 11 instead of 1,3-adamantanediol. The conversion of
1-methoxycarbonyl-3-adamantanol was 99% and
1-methoxycarbonyloxy-3-methoxycarbonyloxyadamantane (yield 90%) was
obtained.
White solid
Mass spectral data [M].sup.+: 268
IR(cm.sup.-1): 1650, 1620, 1440, 1240
Example 27
Operation was effected in the same manner as Example 1 except for
using 1-adamantanol instead of 1-acetylaminoadamantane and reacting
for 6 hours at 75.degree. C. The conversion of 1-adamantanol was
99% and 1-3-adamantanol (yield 80%) was obtained.
White solid
Mass spectral data [M].sup.+: 168
IR(cm.sup.-1): 3350, 1370, 1110
Another operation was effected in the same manner as Example 14
except for using 1,3-adamantanediol obtained by the above method
instead of 1-nitro-3-adamantanol. The conversion of
1,3-admantanediol was 99% and 1-acetyloxy-3-adamantanol (yield 95%)
was obtained.
Colorless liquid
Mass spectral data [M].sup.+: 210
IR(cm.sup.-1): 3350, 1720, 1120
Another operation was effected in the same manner as Example 20
except for using 1-acetyloxy-3-adamantanol obtained by the above
method instead of 1,3-adamantanediol. The conversion of
1-acetyloxy-3-adamantanol was 99% and
1-acetyloxy-3-methoxycarbonyloxyadamantane (yield 90%) was
obtained.
White solid
Mass spectral data [M].sup.+: 268
IR(cm.sup.-1): 1670, 1630, 1440, 1240
Example 28
In an atmosphere of nitrogen, 11 mmole of acetyl chloride and 12
mmole of triethylamine were dissolved in 2 mL of THF. To the
resultant mixture, 10 mmole of a solution of 1-amino-3-adamantanol
in DMF (10 mL) was added dropwise over 30 minutes at 40.degree. C.
The mixture was stirred for another 3 hours at 40.degree. C. As a
result, the conversion of 1-amino-3-adamantanol was 99%, and
1-acetylamino-3-adamantanol was 99%, and
1-acetylamino-3-adamantanol (yield 95%) was formed.
Pale yellow liquid
Mass spectral data [M].sup.+: 209
IR(cm.sup.-1): 3350, 1670, 690
Another operation was effected in the same manner as Example 20
except for using 1-acetylamino-3-adamantanol obtained by the above
method instead of 1,3-adamantanediol. The conversion of
1-acetylamino-3-adamantanol was 99% and
1-acetylamino-3-methoxycarbonyloxyadamantane (yield 90%) was
obtained.
Pale yellow liquid
Mass spectral data [M].sup.+: 267
IR(cm.sup.-1): 3300, 1650, 1620, 1240
Example 29
Operation was effected in the same manner as Example 20 except for
using 1-hydroxymethyl-3-adamantanol obtained by the method of
Example 18 instead of 1,3-adamantanediol. The conversion of
1-hydroxymethyl-3-adamantanol was 99% and
1-hydroxymethyl-3-methoxycarbonyloxyadamantane (yield 90%) was
obtained.
White solid
Mass spectral data [M].sup.+: 240
IR(cm.sup.-1): 3300, 1650, 1440, 1240
Example 30
Operation was effected in the same manner as Example 20 except for
using 1-(N,N-dimethylcarbamoyl)-3-adamantanol obtained by the
method of Example 13 instead of 1,3-adamantanediol. The conversion
of 1-(N,N-dimethylcarbamoyl)-3-adamantanol was 99% and
1-(N,N-dimethylcarbamoyl)-3-methoxycarbonyloxyadamantane (yield
90%) was obtained.
Pale yellow liquid
Mass spectral data [M].sup.+: 281
IR(cm.sup.-1): 1650, 1620, 1280, 1170
Example 31
In toluene (100 mL) was dissolved 10 mmole of
1-acetyloxy-3-aminoadamantane obtained by the method of Example 15.
To the resultant solution was added 12 mmole of phosgene at room
temperature and the mixture was stirred for 6 hours. As a result,
the conversion of 1-acetyloxy-3-aminoadamantane was 95% and
1-acetyloxy-3-isocyanatoadamantane (yield 85%) was obtained.
Pale yellow liquid
Mass spectral data [M].sup.+: 235
IR(cm.sup.-1): 2200, 1670, 1330, 750
Example 32
Operation was effected in the same manner as Example 1 except for
using 1,3-adamantanediol instead of 1-acetylaminoadamantane and
reacting for 6 hours at 75.degree. C. The conversion of
1,3-adamantanediol was 99% and 1,3,5-adamantanetriol (yield 80%)
was obtained.
White solid
Mass spectral data [M].sup.+: 184
IR(cm.sup.-1): 3320, 1320, 1170
Another operation was effected in the same manner as Example 14
except for using 1,3,5-adamantanetriol obtained by the above method
instead of 1-nitro-3-adamantanol. The conversion of
1,3,5-adamantanetriol was 99% and 1-acetyloxy-3,5-adamantanediol
(yield 90%) was obtained.
Colorless liquid
Mass spectral data [M].sup.+: 226
IR(cm.sup.-1): 3320, 1620, 1320, 1140
Example 33
In an atmosphere of nitrogen, 10 mmole of 1,3,5-adamantanetriol
obtained by the method of Example 32 and 24 mmole of triethylamine
were dissolved in 10 mL of DMF. To the mixture, 22 mmole of
acetylchloride was added dropwise over 30 minutes at 40.degree. C.
The mixture was stirred for another 3 hours at 40.degree. C. As a
result, the conversion of 1,3,5-adamantanetriol was 99%, and
1,3-bis(acetyloxy)-5-adamantanol (yield 80%) was formed.
Colorless liquid
Mass spectral data [M].sup.+: 268
IR(cm.sup.-1): 3300, 1610, 1310, 1150
Example 34
In an atmosphere of nitrogen, 10 mmole of 1,3,5-adamantanetriol
obtained by the method of Example 32 and 36 mmole of triethylamine
were dissolved in 10 mL of DMF. To the mixture, 33 mmole of acetyl
chloride was added dropwise over 30 minutes at 40.degree. C. The
mixture was stirred for another 3 hours at 40.degree. C. As a
result, the conversion of 1,3,5-adamantanetriol was 99%, and
1,3,5-tris(acetyloxy)adamantane (yield 95%) was formed.
Colorless liquid
Mass spectral data [M].sup.+: 310
IR(cm.sup.-1): 1620, 1320, 1140
Example 35
Operation was effected in the same manner as Example 20 except for
using 1,3,5-adamantanetriol obtained by the method of Example 32
instead of 1,3-adamantanediol. The conversion of
1,3,5-adamantanetriol was 99% and
1-methoxycarbonyloxy-3,5-adamantanediol (yield 90%) was formed.
Colorless liquid
Mass spectral data [M].sup.+: 242
IR(cm.sup.-1): 3320, 1620, 1270
Example 36
Operation was effected in the same manner as Example 21 except for
using 1,3,5-adamantanetriol obtained by the method of Example 32
instead of 1,3-adamantanediol. The conversion of
1,3,5-adamantanetriol was 99% and 1,3-bis
(methoxycarbonyloxy)-5-adamantanol (yield 80%) was obtained.
Colorless liquid
Mass spectral data [M].sup.+: 300
IR(cm.sup.-1): 3330, 1610, 1260
Example 37
In an atmosphere of nitrogen, 10 mmole of 1,3,5-adamantanetriol
obtained by the method of Example 32 and 36 mmole of pyridine were
dissolved in 10 mL of DMF. To the mixture, 33 mmole of
methoxycarbonyl chloride was added dropwise with stirring at room
temperature. Cooling of the resultant mixture with ice was started
at about the time exothermic reaction began. When the exothermic
reaction is completed, the mixture was heated to 60.degree. C. and
then stirred for one hour. As a result, the conversion of
1,3,5-adamantanetriol was 99% and 1,3,5-tris
(methoxycarbonyloxy)adamantane (yield 95%) was formed.
Colorless liquid
Mass spectral data [M].sup.+: 358
IR(cm.sup.-1): 1630, 1280, 1110
Example 38
Operation was effected in the same manner as Example 22 except for
using 1,3,5-adamantanetriol obtained by the method of Example 32
instead of 1,3-adamantanediol. The conversion of
1,3,5-adamantanetriol was 99% and
1-(N-methylcarbamoyloxy)-3,5-adamantanediol (yield 90%) was
obtained.
Pale yellow liquid
Mass spectral data [M].sup.+: 241
IR(cm.sup.-1): 3350, 1670, 1280
Example 39
Operation was effected in the same manner as Example 23 except for
using 1,3,5-adamantanetriol obtained by the method of Example 32
instead of 1,3-adamantanediol. The conversion of
1,3,5-adamantanetriol was 99% and
1,3-bis(N-methylcarbamoyloxy)-5-adamantanol (yield 80%) was
obtained.
Pale yellow liquid
Mass spectral data [M].sup.+: 298
IR(cm.sup.-1): 3340, 1680, 1310
Example 40
In an atmosphere of nitrogen, 10 mmole of 1,3,5-adamantanetriol
obtained by the method of Example 32 and one drop of pyridine were
dissolved in 10 mL of DMF. To the mixture, 30 mmole of
methylisocyanato was added dropwise with stirring. Cooling of the
resultant mixture with ice was started at about the time exothermic
reaction began. When the exothermic reaction is completed, the
mixture was heated to 60.degree. C. and then stirred for one hour.
As a result, the conversion of 1,3,5-adamantanetriol was 99% and
1,3,5-tris(methylcarbamoyloxy)adamantane (yield 95%) was
obtained.
Pale yellow liquid
Mass spectral data [M].sup.+: 339
IR(cm.sup.-1): 1670, 1310, 1140
Example 41
An eggplant type flask (50 mL) with side arm was dipped in iced
water and its pressure was reduced. Into the flask, nitrogen
monoxide was introduced from a gas bag (1 L) and further oxygen was
introduced from a gas bag (1 L). The flask was filled with
reddish-brown gas, and then a blue liquid comprising N.sub.2O.sub.3
as a main component was formed with sedimentation of the
reddish-brown gas. The introductions of the nitrogen monoxide and
oxygen were repeated to produce about 1.5 ml of the blue liquid.
The blue liquid was frozen with the use of liquid nitrogen. 1.8g
(0.024 mole based on N.sub.2O.sub.3 basis) of the frozen blue
liquid, 1 mmole of 1,3-adamantanediol obtained by the method of
Example 27, 0.05 mmole of NHPI and 5 mL of acetic acid were mixed,
and then the mixture was reacted for 10 hours at a temperature of
100.degree. C. with stirring to give 1-nitro-3,5-adamantanediol
(yield 80%). The conversion of 1,3-adamantanediol was 99%.
Pale yellow liquid
Mass spectral data [M].sup.+: 213
IR(cm.sup.-1): 3320, 1320, 1170
Example 42
Operation was effected in the same manner as Example 21 except for
using 1-nitro-3,5-adamantanediol obtained by the method of Example
41 instead of 1,3-adamantanediol. The conversion of
1-nitro-3,5-adamantanediol was 99% and
1,3-bis(methoxycarbonyloxy)-5-nitroadamantane (yield 90%).
Pale yellow liquid
Mass spectral data [M].sup.+: 349
IR(cm.sup.-1): 1650, 1590, 1360, 1120
Example 43
A reactor was charged with 10 mmole of 1,3-adamantanediol, 1 mmole
of NHPI, 0.005 mmole of Co(AA).sub.2 and 25 mL of acetic acid, then
equipped with a gas bag of mixed gas (a mixed gas of 2 L of carbon
monoxide and 0.5 L of oxygen; pressure: 5 kg/cm). The resultant
mixture was stirred for 6 hours at 60.degree. C. to give
1-carboxy-3,5-adamantanediol (yield 80%). The conversion of
1,3-adamantanediol was 99%.
White solid
Mass spectral data [M].sup.+: 212
IR(cm.sup.-1): 3320, 1320, 1170
Operation was effected in the same manner as Example 21 except for
using 1-carboxy-3,5-adamantanediol obtained by the above method
instead of 1,3-adamantanediol. The conversion of
1-carboxy-3,5-adamantanediol was 99% and
1-carboxy-3,5-bis(methoxycarbonyloxy)adamantane (yield 90%).
Colorless liquid
Mass spectral data [M].sup.+: 240
IR(cm.sup.-1): 3370, 1670, 1470, 1320
Example 44
The mixture of 10 mmole of 1-carboxyadamantane, 1 mmole of NHPI,
0.005 mmole of Co(AA).sub.2 and 25 mL of acetic acid was stirred
for 4 hours at 80.degree. C. with introducing carbon monoxide and
oxygen at a ratio of the former:the latter (molar ratio)=5:1 to
give 1-carboxy-3-nitroadamantane in a 70% yield.
In an atmosphere of oxygen, the mixture of 10 mmole of
1-carboxy-3-nitroadamantane, 1 mmole of NHPI, 0.05 mmole of
V(AA).sub.3 and 25 mL of acetic acid was allowed to react for 4
hours at 85.degree. C. The reaction products were analyzed by
gas-mass spectroscopy, and as a result,
1-carboxy-3-nitro-5-adamantanol was formed in a 80% yield.
Example 45
To a mixture of 10 mmole of adamantane, 1 mmole of NHPI, 0.005
mmole of Co(AA).sub.2 and 25 mL of acetic acid, nitrogen monoxide
(NO), carbon monoxide (CO) and oxygen (O.sub.2) were introduced at
a ratio of NO:CO:O.sub.2 (molar ratio)=10:15:1 (pressure: 26
kg/cm.sup.2). The mixture was stirred for 6 hours at 100.degree. C.
The reaction products were analyzed by gas-mass spectroscopy, and
as a result, the conversion of adamantane was 90%, and
1-carboxy-3-nitro-5-adamantanol (yield 5%),
1-nitro-3,5-adamantanediol (yield 10%),
1-carboxy-3,5-adamantanediol (yield 10%), 1,3,5-adamantanetriol
(yield 15%), 1,3-dinitro-5-adamantanol (yield 8%),
1,3-dicarboxy-5-adamantanol (yield 3%), 1,3,5-trinitroadamantane
(yield 5%), 1-carboxy-3,5-dinitroadamantane (yield 5%),
1,3-dicarboxy-5-nitroadamantane (yield 1%) and
1,3,5-tricarboxyadamantane (yield 1%) were formed.
Example 46
A reactor was charged with 10 mmole of adamantane, 1 mmole of NHPI,
0.005 mmole of Co(AA).sub.2 and 25 mL of acetic acid, then equipped
with a gas bag of a mixed gas (a mixed gas of 3 L of carbon
monoxide and 0.75 L of oxygen). The resultant mixture was stirred
for 12 hours at 60.degree. C. to give 1,3,5-tricarboxyadamantane
together with 1-carboxyadamantane and 1,3-dicarboxyadamantane.
In an atmosphere of oxygen, to 25 mL of acetic acid was added 10
mmole of the 1,3,5-tricarboxyadamantane, 1 mmole of NHPI and 0.005
mmole of Co(AA).sub.2 and the mixture was stirred for 6 hours at
75.degree. C. As a result, the conversion was 76% and
1,3,5-tricarboxy-7-adamantanol was obtained in a 70% yield.
(1) 1,3,5-tricarboxyadamantane
White solid
Mass spectral data (fragment)
[M].sup.+: 268, [M].sup.--: 223(--CO.sub.2H), [M].sup.--:
178(--CO.sub.2H), [M].sup.--: 133 (--CO.sub.2H)
(2) 1,3,5-tricarboxy-7-adamantanol
White solid
Mass spectral data (fragment)
[M].sup.+: 284, [M].sup.-: 266(--OH.sub.2), [M].sup.--:
221(--CO.sub.2H), [M].sup.---: 176 (--CO.sub.2H), [M].sup.----: 131
(--CO.sub.2H)
* * * * *