DD248587A1 - PROCESS FOR PREPARING SUBSTITUTED 5-AMINOPYRAZOLENE - Google Patents

Abstract

Process for the preparation of substituted 5-aminopyrazoles. Such compounds are important as starting materials for the preparation of pharmaceuticals, such as cardiovascular and azo dyes. The aim of the invention is to produce hitherto unknown 5-aminopyrazoles in a simple manner, which in the 3-position carry a saturated side chain having at least 4 members, at least the last being a heteroatom. This is done according to the invention in such a way that a nitrile with hydrazine is optionally reacted in an organic solvent to a substituted 5-aminopyrazole of the general formula I. The invention can be used in the chemical and pharmaceutical industries. Formula I

Description

where R is hydrogen, a cyano or a substituted carbophenyl group, X and Y are the same or different oxygen or sulfur or either X or Y is an amine radical and m is 0, 1, 2 or 3 and η is 1, 2, 3 or 4 or X is a substituted or unsubstituted methylene group and m is 0, 1, 2 or 3 and η is 0, 1, 2, 3 or 4, in which case the sum of m + η must be at least 2, be prepared by Reaction of a nitrile of the general formula II

with the meaning explained for R, X, Y, η and m with hydrazine optionally in an organic solvent. The process according to the invention makes it possible to prepare 5-aminopyrazoles in good yields in an economically advantageous single-step process which carry in the 3-position a saturated side chain having at least 4 members, at least the last being a heteroatom. The products are obtained after the reaction in such a quality that they can be brought by simple recrystallization in an analytically pure form. Surprisingly, both the pyrazole skeleton and the saturated side chain of the end product are simultaneously formed in the process according to the invention during the reaction, although none of the two structural elements is present in the starting material. The compounds obtained are novel and have significance as starting materials for the preparation of pharmaceuticals, for example of cardiovascular agents, as well as of azo dyes.

embodiments

The substituted 5-aminopyrazoles of the general formula I prepared according to the various variants are compiled in Table I.

option A

A mixture of 0.1 mol of Niril of general formula II with 1 mol of 72% hydrazine hydrate is refluxed for 15 minutes.

Upon cooling, the final product of the general formula I precipitates. This is filtered off and recrystallized.

Variant B "'

Analog variant A, however, 1.2 moles of 25% hydrazine hydrate is used.

Variant C

A mixture of 0.1 mole of nitrile of the general formula II, 0.15 mole of 72% hydrazine hydrate and 50 ml of methanol is heated under reflux for 3 hours. The solvent is distilled off. The residue is mixed with a little water, filtered off and recrystallized.

Variant D

Analog variant C, but acetonitrile is used as the solvent and heated under reflux for only 2 hours.

Table I: The substituted 5-aminopyrazoles of the general formula I RXY η m produced by the different variants. M.p./X yield / var.

CN CH ₂ NH 1 1 171-172 78 / A (Water) CN CH ₂ NH 0 3 168-170 82 / A (Water) CN CH ₂ NH 3 Γ 166-167 95 / A (Water) CN CH ₂ NCH ₃ 2 0 176 66 / B (Water) CN CH ₂ O 2 0 139-140 80 / D (Acetonitrile) CN NH O 2 0 143-144 54 / C (Water) CN S S 2 0 180-189 ¹ » 83 / C

1 melts with decomposition

Claims (1)

1. A process for preparing substituted 5-aminopyrazoles of general formula I, - HY- (CH ₀ ) X- (CH ₀ ), in which R is hydrogen, a cyano or a substituted carbonyl group, X and Y are identical or different and are either oxygen or sulfur or either X or Y is an amine radical and m is 0, 1, 2 or 3 and η is 1, 2, 3 or 4 or X is a substituted or unsubstituted methylene group and m is 0,1, 2 or 3 and η is 0, 1, 2, 3 or 4, in which case the sum of m + η must be at least 2, characterized in that a nitrile of the general formula II (CH₂)_n-Y/ 0Ή with the meaning explained for R, X, Y, m and η is reacted with hydrazine optionally in an organic solvent. Field of application of the invention The invention relates to a process for the preparation of substituted 5-aminopyrazoles. Such compounds are important as starting materials for the preparation of pharmaceuticals, for example of cardiovascular agents, as well as of azo dyes. Characteristic of the known technical solutions It is well known that 5-aminopyrazoles can be prepared from acrylonitriles having 3 leaving groups and hydrazines (see, for example, T.L. Jacobs in R.C. Elderfield: Heterocyclic Compounds, Vol 5, pp. 138ff, New York, 1957). This method is not suitable for the preparation of substituted 5-aminopyrazoles which carry in the 3-position a saturated side chain having at least 4 members, at least the last represents a heteroatom. Once, no corresponding starting materials are known for such substituted pyrazoles and, secondly, in the possible conceivable synthesis of such starting materials, competing intramolecular ring closure reactions must be expected, which must lead to saturated heterocyclic compounds. Object of the invention The aim of the invention is to hitherto unknown, substituted 5-aminopyrazoles which carry in the 3-position a saturated side chain having at least 4 members, wherein at least the last represents a heteroatom to make accessible in a simple manner. Explanation of the essence of the invention The invention has for its object to develop a simple process for the preparation of substituted 5-aminopyrazoles, which allows to produce representatives which carry a saturated side chain in the 3-position, wherein at least the last member of the chain represents a heteroatom. According to the invention this object is achieved in that substituted 5-aminopyrazoles of the general formula I, HY- (CH ₂ ) _n X- (CH ₂ )