DD285599A5 - PROCESS FOR PREPARING SUBSTITUTED 4-AMINO-1,3-THIAZOLENE - Google Patents

Abstract

The invention relates to a process for the preparation of substituted * The aim of the invention is to develop a process that allows access to differently substituted *, bypassing known variants. The substituted * are important as potential biologically active compounds and as intermediates in the synthesis. According to the invention, the substituted * of the general formula 3 in which R1 and R2, identically or differently, are substituted or unsubstituted alkyl or benzyl radicals, can be prepared by reacting N-nitroguanyl-dithiocarbimic acid monoesters with g-halocrotroic acid esters having a corresponding substituent pattern in the presence of bases {* N-nitroguanyl-dithiocarbimide-acid monoester, g-halocrotroic acid ester; nitramine; intramolecular substitution}

Description

SII

- H ₂ O

- HX

According to the invention, the substituted 4-amino-1,3-thiazoles of the formula 3 in which R 'and R ² , which may be identical or different, denote

substituted or unsubstituted alkyl or benzyl radicals, by conversion of N-Nitroguanyldithiocarbimidsäuremonoestem of formula 1, in which R ^{1 has the} above meaning, with Y-halocrotonic acid esters of the formula 2, in which X is an arbitrary halogen and R ^{2 has the} above meaning, in the presence of bases such as potassium hydroxide or

Triethylamine are produced. The reactions are carried out in polar, aprotic solvents, preferably DMF. The reaction temperatures

lie between 20 ° C and 80 ° C. The final products are obtained by pouring the reaction solution in water. After this

By filtering off the crystalline reaction products, they are further purified by recrystallization from ethanol. The individual representatives of the substance class of the invention serve as starting materials for the synthesis of new classes of substances

and have significance as intermediates for the presentation of pharmaceuticals and pesticides.

The invention is explained with reference to exemplary embodiments, without being limited thereto. embodiment

1. Trans-3- (4-amino-2-methylthio-5-thiazolyl) -acrylic acid methyl ester

Mail dissolves 0.02 mol of N-nitroguanyl-dithiocarbimic acid methyl ester in 30 ml of DMF and, while stirring, adds 0.02 mol of KOH dissolved in 5 ml of water. 0.02 mol of γ-Bromcrotonsäuromethylester without cooling to the clear solution is added dropwise. After the exothermic reaction is added dropwise with constant stirring 2 ml of triethylamine to the reaction mixture and stirred for another 30 minutes at about 5O ⁰ C. The reaction solution jießen after the A in water precipitating a tan crystals are purified by recrystallization from ethanol

M.p .: 157-8 ^C C (Lit. 152 ⁰ C) Yield: 4.4 g (95.4% of theory.).

2. trans-3- (4-amino-2-ethylthio-5-thiazolyl) -acrylic acid methyl ester

Analogously to Example 1. 0.02 mol of N-nitroguanyl-dithiocarbimic acid are ethyl ester with 0.02 mol of y-Bromcrotonsäuremethylester

implemented.

Mp: 115 ° C (Ut 117 ⁰ C) Yield: 4.1 g (85.4% of theory)

2 ή 5 SS 9 ' 3

O ₂ NN = C

NH ₂

X-CH, -CH = CH-C00R ²

^π 2 ^{| Ν} jr-NR ² OOC-CH = CH-A ₅ J-SR ¹

Claims (2)

1. A process for the preparation of substituted 4-amino-1,3-thiazoles of the general formula 3 in which R ¹ and R ² , identical or different, represent substituents or unsubstituted alkyl or benzyl radicals, characterized in that Nitroguanyl dithiocarbimatesäuremonoester of general formula 1, in which R ^{1 has the} above meaning, with γ-rialogencrotonsäureestern the general formula 2, in which X is an arbitrary halogen and R ^{2 has the} above meaning, be reacted in the presence of bases such as potassium hydroxide or triethylamine , 2. The method according to claim 1, characterized in that the reactions in polar, aprotic solvents, preferably DMF, in the presence of small amounts of water at temperatures between 20 ⁰ C and 80 ⁰ C are performed. For this 1 page formulas Field of application of the invention The invention relates to a process for the preparation of substituted 4-amino-i, 3-thiazoles. The biological activity of numerous derivatives of 1,3-tliiazole is well known. The representatives of the substance class according to the invention are interested in the preparation of pharmaceuticals and serve as starting materials for the synthesis of new, previously unknown classes of substances. Characteristic of the known state of the art Numerous representatives of the substituted 4-amino-1,3-thiazoles have been described in recent years. Independently of each other, D. Wobig (Liebigs Ann. Chem. 1977, 400-406; ibid 1972, 125-130) and W. Walek (Tetrahedron 32, 633; DD-WP 131933) succeeded in converting the monoesters of N-cyanodithiocarbimic acid into different ones Halogencarbonylverbindungen to appropriately substituted 1,3-thiazole derivatives. In 1978, D. Wobig (Liebigs Ann. Chem. 1978, 1118-1122) described a synthesis according to which bromo-crotonic acid esters can also be used successfully for the preparation of interesting 1,3-thiazole derivatives. The novel process represents a completely new, unforeseeable synthesis variant for the preparation of the same substance class. The starting compounds used are N-nitroguanyl-dithiocarbamic acid monoesters which surprisingly react with bromo-crotonic esters with the cleavage of nitroamine to give the substituted 4-amino-1,3-thiazoles according to the invention. Object of the invention The aim of the invention is the development of a new process which, bypassing known variants, makes it possible to produce an interesting class of substances whose representatives are important intermediates for pharmacy or agrochemistry and which serve for the synthesis of new hemeocyclic substance classes. Explanation of the essence of the invention The object of the invention is to produce the substituted 4-amino-1,3-thiazoles based on the N-Nitroguanyldithiocarbimidsäuremonoester. --SR ¹ -f- X-CH ₂ -CH = CH-COOR ²