Production process and intermediate of tetrazole compound

Details Production process and intermediate of tetrazole compound Production process and intermediate of tetrazole compound

2000-09-14

2001-08-21

Gerstl, Robert (Department: 1626)

Organic compounds -- part of the class 532-570 series

Organic compounds

Heterocyclic carbon compounds containing a hetero ring...

C548S250000

Reexamination Certificate

active

06277998

ABSTRACT:

INDUSTRIAL FIELD FOR UTILIZATION
The present invention relates to production processes and intermediates of tetrazole compounds. More particularly, it relates to 2-(tetrazol-5-yl)-4-oxo-4H-benzopyran derivatives which are known to be pharmacologically useful from the viewpoint of their antagonistic action to leukotrienes such as leukotrienes C and D, and it also relates to 2-(tetrazol-5-yl)-1,1′-biphenyl derivatives which are known to be pharmacologically useful from the viewpoint of their antagonistic action to angiotensin II. Further, it relates to processes for producing 5-phenyltetrazole derivatives which are useful as intermediates of the biphenyl derivatives, and it also relates to intermediates which are useful in their production.
PRIOR ART
As the process for producing tetrazole compounds such as 2-(tetrazol-5-yl)-4-oxo-4H-benzopyran derivatives, 2-(tetrazol-5-yl)-1,1′-biphenyl derivative and 5-phenyltetrazole derivatives, there has been known a process with an azide such as sodium azide, trialkyl tin azide or trimethylsilyl azide.
However, since azides are reacted with water or acids to produce hydrogen azide having toxic and explosive properties, the concentration of hydrogen azide in the gas phase in the upper part of a reactor should be strictly controlled during the reaction. It has been known that azides are liable to form an explosive salt with heavy metals. Therefore, the application of such a process with an azide on an industrial scale is disadvantageous from the viewpoint of its safety. Further, tin reagents such as trialkyl tin azide have drawbacks that they require a complicated procedure for the isolation of a product because of its lipophilicity and that tin-containing waste matters are formed in large quantities.
As the process for producing 2-(tetrazol-5-yl)-1,1′-biphenyl derivatives or 5-phenyltetrazole derivatives, another process is described in J. Org. Chem., 1991, 56, pp. 2395-2400, in which process biphenylcarboxylic acids or phenylcarboxylic acids are converted into their amides with cyanoethylamine, followed by chlorination with phosphorous pentachloride, and reaction with hydrazine and then with dinitrogen tetroxide gas.
This process, however, has disadvantages that the yield of a desired product is not satisfactory, that the step of deprotecting a cyanoethyl group used as a protecting group is needed, and that the production on an industrial scale finds difficulty in using phosphorous pentachloride.
OBJECTS OF THE INVENTION
It is an object of the present invention to provide a process for producing tetrazole compounds with safety in an industrially favorable manner.
It is another object of the present invention to provide intermediates useful for the production of the tetrazole compounds.
These and other objects and excellent advantages will be understood from the following description.
SUMMARY OF THE INVENTION
The present inventors have intensively studied on a process for producing tetrazole compounds. As a result, they have found that the above problems can be solved and the desired products can be obtained with safety in an industrially favorable manner by a process through amidrazone compounds with nitrile compounds as the starting materials, and they have made further studies, thereby completing the present invention.
Thus, the present invention provides:
[1] a process for producing atetrazole compound of general formula (1):
wherein R
1
is as defined below, characterized in that a nitrile of general formula (2):
R
1
CN  (2)
wherein R
1
is a 4-oxo-4H-benzopyranyl group optionally substituted with R
2
or a phenyl group optionally substituted with X, in which R
2
is a hydroxy group, a halogen atom, an R
3
CONH group, a nitro group, a C
1
-C
5
alkyl or C
1
-C
5
alkoxy group; R
3
is a C
1
-C
20
alkyl group, a phenyl group, a phenyl-substituted (C
1
-C
20
) alkyl group, a phenyl-substituted (C
1
-C
20
) alkoxyphenyl group or a (C
1
-C
20
) alkoxyphenyl group; X is a halogen atom, a phenyl group optionally substituted with Y, a C
1
-C
20
alkyl group, a phenyl-substituted (C
1
-C
20
) alkyl group, a phenyl-substituted (C
1
-C
20
) alkoxy group or a C
1
-C
20
alkoxy group; and Y is a C
1
-C
20
alkyl group, a C
1
-C
20
alkyl group substituted with one or more hydroxy groups with at least one hydrogen atom in the hydroxy group being optionally replaced for protection, a C
1
-C
20
alkyl group substituted with one or more amino groups with at least one hydrogen atom in the amino group being optionally replaced for protection, a C
1
-C
20
alkyl group with at least one hydrogen atom being replaced by a halogen atom, a C
1
-C
20
alkoxy group, a C
1
-C
20
alkoxy group substituted with one or more hydroxy groups with at least one hydrogen atom in the hydroxy group being optionally replaced for protection, a C
1
-C
20
alkoxy group substituted with one or more amino groups with at least one hydrogen atom in the amino group being optionally replaced for protection, or a C
1
-C
20
alkoxy group with at least one hydrogen atom being replaced by a halogen atom, is reacted with hydrazine or a salt thereof in the presence of a catalyst, followed by reaction with a nitrous acid compound of general formula (3):
ANO
2
  (3)
wherein A is a hydrogen atom, an alkali metal, an alkaline earth metal or a C
1
-C
20
alkyl group;
[2] a process for producing tetrazole compound (1), characterized in that nitrile (2) is reacted with hydrogen sulfide, followed by reaction with an alkyl halide of general formula (4):
R
4
J  (4)
wherein R
4
is a C
1
-C
20
alkyl group and J is a halogen atom, with hydrazine or a salt thereof, and then with nitrous acid compound (3); and
[3] an amide of general formula (5):
R
1
C(═R
5
)R
6
  (5)
wherein R
1
is as defined above; R
5
is a sulfur atom or an NH group; and R
6
is an NH
2
group, an SR
4
group or an NHNH
2
group, in which when R
5
is a sulfur atom, then R
6
is an NH
2
group, and when R
5
is an NH group, then R
6
is an SR
4
group or an NHNH
2
group; and R
4
is as defined above.
DETAILED DESCRIPTION OF THE INVENTION
As the R
1
in the nitrile (2) used in the present invention, there can be mentioned 4-oxo-4H-benzopyranyl groups optionally substituted with R
2
or phenyl groups optionally substituted with X.
As the R
2
, there can be mentioned hydroxy group; halogen atoms such as fluorine, chlorine, bromine and iodine atoms; R
3
CONH groups; nitro group; straight chain or branched C
1
-C
5
alkyl groups such as methyl, ethyl, propyl, butyl and pentyl groups; and straight chain or branched C
1
-C
5
alkoxy groups such as methoxy, ethoxy, propoxy, butoxy and pentoxy groups.
As the R
3
, there can be mentioned straight chain or branched C
1
-C
20
, preferably C
1
-C
10
, and more preferably C
1
-C
5
, alkyl groups such as methyl, ethyl, propyl, butyl, pentyl, octyl, decyl, pentadecyl and octadecyl groups; phenyl group; straight chain or branched C
1
-C
20
, preferably C
1
-C
10
, and more preferably C
1
-C
5
, alkyl groups with one of the hydrogen atoms being replaced by a phenyl group, such as benzyl, phenethyl, phenylpropyl, phenylbutyl, phenyloctyl, phenylpentadecyl and l-phenylethyl groups; straight chain or branched (C
1
-C
20
, preferably C
1
-C
10
, and more preferably C
1
-C
5
) alkoxyphenyl groups with one of the hydrogen atoms in the alkoxy group being replaced by a phenyl group, such as benzyloxyphenyl, phenethyloxyphenyl, phenylpropyloxyphenyl, 4-phenylbutoxyphenyl, 3-phenylbutoxyphenyl, phenylpentadecyloxyphenyl and 1-phenylethoxyphenyl groups; and straight chain or branched (C
1
-C
20
, preferably C
1
-C
10
, and more preferably C
1
-C
5
) alkoxyphenyl groups such as methoxyphenyl, ethoxyphenyl, propoxyphenyl, butoxyphenyl, octyloxyphenyl, pentadecyloxyphenyl, octadecyloxyphenyl, 1,1-dimethylmethoxyphenyl and 1,1,1-trimethylmethoxyphenyl groups.
As the X, there can be mentioned halogen atoms; phenyl groups optionally substituted with Y; straight chain or branched C
1
-C
20
, preferably C
1
-C
10
, a

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