DD217217A1 - METHOD FOR PRODUCING SUBSTITUTED BIS (5-THIAZOLYL) -KETONES - Google Patents

Abstract

The present invention relates to a process for the preparation of substituted bis (5-thiazolyl) ketones. The representatives of this class of substances are pharmaceutically interesting compounds, which additionally by the combination of thiazole with a carbonyl function as starting materials for the synthesis of other potential drugs have meaning. By a surprising synthetic route, which includes the unpredictable cleavage of nitramine, which in turn immediately disintegrates in nitrous oxide and water, bypassing the previously known methods for the synthesis of the 1,3-thiazole system. The aim of the invention is to make the interesting class of bis (5-thiazolyl) ketones accessible by a new, easy-to-implement method. The object is achieved by reacting N-nitroguanyl-dithiocarbimic acid monoesters in the presence of alkali metal hydroxides with 1,3-dihaloacetone. The reactions are carried out without pressure at temperatures between 20 C and 80 C in polar, aprotic solvents. The reaction products are recovered by pouring the reaction solution into water.

Description

Title of the invention

Process for the preparation of substituted bis (5-thiazolyl) ketones

Field of application of the invention

The invention relates to a process for the preparation of substituted bis (5-thiazolyl) ketones.

The biochemical importance of the 1,3-thiazole or the derivatives of 1,3-thiazole is already well known (antibiotics, vitamin B ₁ ). By combining the thiazole skeleton with a carbonyl function, the representatives of the substituted bis (5-thiazolyl) ketones not only have pharmaceutical interest, but are also important as starting materials for the synthesis of other potential drugs of importance.

Characteristic of the known technical solutions

Numerous publications have become known in recent years, in which processes for the preparation of differently substituted 4-amino-1,3-thiazoles have been described (D. Wobig, Liebigs Ann «Ghem · 1979, 757, ibid 1978, 1118, ibid 1977 W, Walek, Tetrahedron, £ 2, 623, DDJ7P 131933) All proposed synthetic variants are completely identical, based on the composition of Moiioestera of N-cyano-dithiocarbimic acid with various halocarbonyl compounds in the presence of alkali metal hydroxides An extension of this synthetic principle was achieved by the use of 1 , 3- dichloroacetone, which allowed the preparation of bis (5-thiazoly ketones) (D. Wobig, Idebigs Ann. Chem. 1976, 1166).

The inventive method represents a completely new, not voraussehbafce synthesis variant for the substance class of the substituted bis (5-thiazolyl) ketones * It N-nitroguanyl dithiocarbimidsäuremonoester be reacted with 1,3-dihaloacetone, which in a surprising course of reaction with elimination of mtramine which is immediately destroyed in nitrous oxide and water, the final products are formed »

Object of the invention

The invention has for its object to develop the interesting class of substituted bis (5-thiazolyl) ketones "Using cheap, technically readily available starting materials to circumvent the known methods a large number of substituted bis (5-thiazolyl) ketones made accessible become·

Explanation of the essence of the invention

The object is achieved in that N-nitroguanyl-dithiocarbimatesäuremonoester of the formula 1. in which R is branched or unbranched, substituted or unsubstituted alkyl radicals having 1 to 4 carbon atoms or »substituted or unsubstituted benzyl radicals, in the presence of alkali metal hydroxides For mel 2 "' Ι * · the Me is any alkali metal, with 1,3-dihaloacetone of formula 2, in which X is chlorine or bromine, to the substituted bis (5-thiazolyl) ketones of the formula A» in the R above meaning, be implemented.

2 OaN-ÜMST ^ SR f XH ₉ CC-CH ₉ -XI- 2 MeOH

-2MeX RS-C _{V /} Ö ^ _ _O ^ -C C-SR

2 H Q 2 HgO

.: '... '- 3 - f. , It is carried out at atmospheric pressure and temperatures between 20 ⁰ C and 80 ⁰ G , As a solvent polar, aprotic compounds, preferably DMFj used. The reaction products are recovered by pouring the reaction solution into water and separating the crystalline solids. The advantage of the invention is the direct pressureless synthesis of differently substituted bis (5-thiazolyl) ketones, bypassing the known processes from simple, technically readily available compounds.

The invention is explained by embodiments, without being limited thereto.

exemplary

1 x bis (4-amino-2-methylthio-5-thiazolyl) ketone

0.02 mole of N-nitroguanyl-dithiocarbamic acid monomethyl ester are dissolved in 30 ml of DMF and dissolved successively while stirring with 0.02 mole of KOH dissolved in 8 ml of water and 0.01 mole of dioxoracetone in solid form. ~ When the exothermic reaction has subsided, it is added dropwise ml of triethylamine to the reaction mixture and heated for 2 hours at 60 - 70 ⁰ O, allowed to cool the mixture, poured into a large excess of ice water and filtered off the Festpcodulct. For further purification DMF / ethanol umlcristallisiert from · ^''

Mp .: 45 -246 ⁰ O (Wobig, Ann Idebigs · Chem 1976, 1166. 238 ^p 0) yield (based on dichloroacetone.). 54 "β $> (1.7 g)

2, bis (4-amino-2-ethylthio-5-thiazolyl) ketone

0.02 mol of M-Mtroguanyl-dithiocarbimidsäuremorioethylester be with 0.01 mol of dichloroacetone analogous to Example 1 ,. reacted and worked up the reaction mixture. Mp .: 184 ⁰ C (Wobigj Idebigs Ann, Ohem 1976 "1166:. 184 ⁰ O) yield (based on dichloroacetone.): 52.1 j £ (1.8 g)

Claims (1)

  - 4 - '" invention claim 1 · Process for the preparation of substituted bis (5-thiazolyl) ketones of the formula I in which R is branched or unbranched, substituted or unsubstituted alkyl radicals having 1 to 4 C atoms or substituted or unsubstituted benzyl radicals, characterized in that that N-hitroguanyl-dithiocarbimic acid monoester of the formula V in which E has the above meaning, in the presence of alkali metal hydroxides of the formula JJ in which Me corresponds to any alkali metal, with 1,3-dihaloacetone of the formula Z ₉ in the X is chlorine or bromine stands to be implemented · 1.1. Process according to point 1, characterized in that the reactions are carried out without pressure at temperatures between 20 ^° C. and 80 ^° C. in polar solvents, preferably DMF. 1,2 · Process according to item 1, characterized in that the reactions are carried out in the presence of one equivalent of alkali hydroxide and small amounts of water.