DD217218A1 - PROCESS FOR PREPARING SUBSTITUTED 4-AMINO-1,3-THIAZOLENE - Google Patents

Abstract

The present invention relates to a process for the preparation of substituted 4-amino-1,3-thiazoles, which are already partially known. The representatives of this class of substances are pharmaceutically interesting compounds that can also be used as starting materials for the synthesis of other potential drugs. Due to a surprising, unexpected reaction process bypasses the already known synthetic variants for the preparation of 4-amino-1,3-thiazoles and leads because of the cheap starting materials and the good yields at the same time in an economically favorable synthesis principle. The aim of the invention is to make the class of 4-amino-1,3-thiazoles accessible by a new, generalizable method. The object is achieved by reacting N-nitroguanyl-dithiocarbimic acid monoesters in the presence of alkali metal hydroxides with benzyl halides bearing electron acceptor groups in polar, aprotic solvents at temperatures between 10 C and 80 C. The intermediates are conveniently isolated without further purification.

Description

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Title of the invention

Process for the preparation of substituted 4-amino-1,3-thiazoles

Field of application of the invention

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The invention relates to a Verfallren for the preparation of substituted 4-amino-i, 3-thlazoles.

The importance of i _f 3-thiazole or its derivatives as a central group in antibiotics and other active ingredients such as vitamin B ₁ is well known · Raise their use as potential drugs, the representatives of this class have importance in the synthesis of other compounds of interest pliarmazeutisch interesting and in crop protection.

Characteristic of the known technical solutions

The class of substituted 4-amino-1,3-thiazoles has become known in recent years by numerous representatives. "Independently from each other have D. Wobig (Iiebigs Ann. Chem ^ 1118 -1122; ibid 1977, 400-406; ibid 1972, 125 ^ 1} and W. Walek (Tetrahedron 22, 623; DDWP 131933) reacted the monoesters of H-cyano-dithiocarbimic acid with different halocarbony compounds to give a wide variety of different 1,3-thiazole derivatives, reported in 1979 by D. Wobig described a synthesis, after also benzyl which carry ülektronenacoeptoren on the aromatic ring, with the alkali salts of N-cyano-dithiocaxbinddsäuremonoesters to, can be reacted ^{2-alkylthio-4-amino-5-ary1-1,3-thiazoles;:.} ' The method according to the invention does not represent a completely new one

Foreseeable synthesis variants of the same class of substances. The starting materials used are benzyl halides which carry electron acceptor groups on the phenyl radical and N-nitroguanyldithiocarbamic acid monoesters, which in a surprising reaction sequence with elimination of nitramine, which immediately decomposes into nitrous oxide and water, the substituted 4α groups according to the invention Amino-> 1 »3-thiazoles -.form ·

Object of the invention

The object of the invention is to develop the interesting class of substituted 4-amino-1,3-thiazoles, bypassing the known processes. By using new ₉ technically easily accessible starting materials, the process should lead to a large number of such 1,5-tliiazole derivatives »

Explanation of the essence of the invention

The object is achieved in that N-Mtroguanyl-dithiocarbimidsäuremonoester of the formula J ^ in which R is substituted or unsubstituted, branched or unbranched AlkyIreste having 1 to 4 carbon atoms, or »substituted or unsubstituted Benaylreste stands: | n presence of Alkalihydroxiden of JPor ~ mel Z ₉ in the Me for any alkali metal, with benzyl halides of the formula 2 » ^{in d (Br x} any halogen and Y corresponds to an electron acceptor group, this group may be located in any position on the phenyl, to the Substituted 4-amino-i, 3-thiazoles of the formula ^, in which R and Y have the above meaning, implemented earth.

SR 4 X-CHO if-JSS ¥ MeOH

\ 2 2

-H ₂ O - " ^K 2 ° It is at temperatures between 10 ⁰ C and 80 ⁰ C below normal

pressure worked. The intermediates are conveniently obtained by pouring the reaction solution into water and reacted immediately without further purification in acetone and in the presence of tertiary amines to give the final products. The solvents used are polar, aprotic compounds, preferably DMF and acetone.

The advantage of the invention is the direct synthesis of differently substituted 4-amino-1,3-thiazoles, bypassing the known processes. The starting materials used are simple, technically easily accessible compounds. The invention is illustrated by exemplary embodiments, without being limited thereto.

Embodiment,

.1 · 4-Amino-2-methylthio-5-p-nitrophenyl-1,3-thiazole

0.03 mol of monomethyl N-nitroguanyldithiooarbamate are dissolved in 60 ml of DMP and admixed with 0.03 mol of KOH, dissolved in 10 ml of water, while stirring. 0.03 mol of p-nitrobenzyl bromide are added dropwise to the solution thus prepared in the minimum amount of DMF and heated after completion of the addition 15 minutes at 60 ⁰ C, After cooling the reaction mixture is poured into a large excess of water and sucks the crystals forming after a short time · They are suspended in acetone without further purification (about 25 ml), mixed with 15 ml of triethylamine and refluxed for 3 hours · The already forming dark red crystals during the reaction are filtered off with suction and recrystallized from ethanol / DMF.

M.p .: 73 ⁰ O (Liebigs Ann Chem 1979 757: 173 ⁰ O..) Of yield (based on p-nitro-benzyl bromide.) 60.5 # (4 | 9 g)

2 x 4-iunino-2-ethylthio-5-p-nitrophenyl-1,3-thiazole

0.03 Holem N-iJitroguanyl-dithiooarbimidsäuremoroethylester be reacted with 0.03 mol p-Uitro-benzylbromid according to the procedure under Example 1 and worked up the reaction solution »mp: 120- 122 ⁰ C (Liebigs Ann Chem. 1979, 757 : 122 ⁰ O)

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Yield (relative to p-nitrobenzylbromide) s 59 »5 # (4» 1 g) 3,4-AMno-5-p-cyanophenyl-2-methyltMo <-1,3-thiazole

Analogous to the procedure of Example 1, from 0.03 mol of N-nitroguanyl-dithiocarbamic acid monomethyl ester and 0.05 mol of p-cyanoboryl chloride _β

Ppo! 162 -163 ⁰ C (lieblgs Ann Chem 1979 757:.. 164 ⁰ O yield (based on p-cyano-benzyl chloride): 41.0 ⁰ Yes (3fo g)

Claims (3)

invention claim 1. A process for the preparation of substituted 4-amino-1,3-thiazoles of the formula ε in which E is substituted or unsubstituted, branched or unbranched Alkylr.es'te having 1 to 4 carbon atoms, or »a substituted or unsubstituted benzyl and Y is an electron acceptor group, characterized in that N-hitroguanyl dithiocarbimatesäuremonoester of formula 1, in which E has the above meaning, in the presence of alkali metal hydroxides of the formula E, in which Me is an arbitrary alkali metal, with benzyl! halides of the formula 2, in which X corresponds to an arbitrary halogen and Y represents an electron acceptor group, which may be located in any position on the phenyl radical. 1.1 · A method according to func 1, characterized in that the reactions without pressure at temperatures between 10 ⁰ C and 80 ⁰ C are performed in polar, aprotic solvents, preferably acetone and SMF · 1 * 2 * process according to item 1, characterized in that the reactions are carried out in the presence of equivalent amounts of alkali metal hydroxide and small amounts of water. 1.3. Process according to item 1, characterized in that the intermediately formed mixed diesters of N-nitroguanyldithiocarbimic acid are expediently isolated