DD258814A1 - PROCESS FOR THE PREPARATION OF NEW 2-HETEROARYL-5-AMINOTHIAZOLENE - Google Patents

Abstract

The invention relates to a process for the preparation of novel 2-heteroaryl-5-aminothiazoles which can find application in the pharmaceutical and paint industry. The object of the invention to synthesize hitherto unknown 2-heteroaryl-5-aminothiazoles of the formula III, in which R 2 is H, alkyl, aryl, aralkyl, CN, CONH 2, CO 2 alkyl, in a simple process, was achieved by reacting heteroaryldithioesters of the formula I can be reacted with aminoacetonitriles of formula II optionally with the use of a solvent and an auxiliary base. The aminoacetonitriles can be used in free form or as salts. Formula III

Description

Pleteroaryl - C.

wherein R = alkyl, aralkyl, CH ₂ COOR ¹ and R ¹ = H, alkyl, aralkyl, with aminoacetonitriles of the formula H ₂ N-CHR ² -CN

wherein R ² = H, alkyl, aryl, aralkyl, CN, CONH ₂ , CO ₂ alkyl, optionally be reacted using a solvent and from it yet unknown 2-heteroaryl-5-aminothiazole of the formula

heteroaryl ^

! ET

in which R ^{2 has} the meaning given above arise. Alcohols have proved to be favorable solvents. It may be advantageous to add catalytic amounts of an auxiliary base to accelerate the cyclization. The aminoacetonitriles are best used as far as possible in free form, but may also be released from their salts by the addition of a strong unreactive base before or during the reaction.

embodiments

General Synthesis Instructions:

0.01 mol of heteroaryl dithioester are dissolved in ethanol (60-20OmI) hot, treated with 0.011 mol aminoacetonitrile and boiled until the solution turns yellow (up to 10 min). Then, if appropriate, heating is continued with addition of 5 drops of triethylamine, during which part of the solvent is distilled off. The aminothiazole usually precipitates within 10 minutes. If this is not the case, the solution is concentrated further in vacuo or water is added until precipitation.

The strongly fluorescent, usually yellowish aminothiazole is filtered off, washed with a little water and ethanol. It is usually free of by-products, but may optionally be further purified by recrystallization.

The table contains some examples of this implementation. The dithiocarboxylic acid methyl esters I (R = Me) were used.

Table:

2-Heteroaryl-5-aminothiazoles of the formula III (Example 1-15: R ² = H, Example 16: R ² = Me)

At- Hetaryl game

Y. in % Umkrist. in Rohschmp. In G in ⁰ C

70 286-290

Ethanol 288 -

Scr Me 63 90-202

Ethanol 205-207

 N;

at

Prop 75 195-215

80 154-I6O

Ethanol 217-219

Ethanol 159-161

* v

Bn 105-128

n-hexane 127-128

At- 'Hetaryl game

, recryst -4- 258 814 , in Y. in % Mp. in ⁰ C Rohschmp. ⁰ o ethanol 70 227-228 225-228 ethanol 75 240-243 230-243

75 231-236

Ethanol 234-236

.80 155-156

Ethanol 155-156

II

"IT

85 279-289

288-291

Ti

% Ii

90 245-252

DIEB ¹ 259-261

At- Hetaryl game

Y. in % Umkrist. in Rohschmp. ⁰ C in ⁰ C

Ph

90

262-268

267-269

75

205-225

225-227

<x> 85 261-271

Ethanol / üMF 269-271

ιτ ·

Ii- Ε

Il 95

305-315

DMF 310-312

60 253-255

Ethanol 255-256

Claims (2)

1. Process for the preparation of novel 2-heteroaryl-5-aminothiazoles of the formula , S- Heteroaryl - < -MH (III) in which R ^{2 is} H, alkyl, aryl, aralkyl, CN, CONH ₂ , CO ₂ alkyl, characterized in that heteroaryl dithioester of the formula Heteroaryl - C <(I), in which R = alkyl, aralkyl, CH ₂ COOR ¹ and R ¹ = H, alkyl, aralkyl, with aminoacetonitriles of the formula H ₂ N-CHR ² -CN (II), wherein R ^{2 has} the meaning given in formula 111, if appropriate using an organic solvent and optionally with the addition of catalytic amounts of an auxiliary base are reacted. 2. The method according to item!, Characterized by the fact that alcohols are used as the solvent. Field of application of the invention The invention relates to a process for the preparation of novel 2-heteroaryl-5-aminothiazoles which can be used as valuable intermediates in pharmaceutical and paint chemistry. Characteristic of the known state of the art So far, only a few 2-substituted 5-aminothiazoles are known. They were prepared by reduction of 5-nitro compounds (for example J. Med. Chem. 15 [1972] 101) or in a few examples by reaction of alkyl and aralkyl dithioic acids or dithioesters (J. Chem. Soc. 1949, 1440). obtained with a-aminonitriles. Bis-thionooxalic acid esters have also been used to prepare 2-bis (5-aminothiazole (Arch. Pharmac., 308 [1975] 526).) Further 2-aryl or 2-heteroaryl-5-aminothiazoles are unknown (compare WEISSBERGER "The Chemistry of Hetercyclic Compounds ", Vol.34) Object of the invention The aim of the invention is to synthesize hitherto unknown 2-heteroaryl-5-aminothiazoles in a simple process. Explanation of the essence of the invention The object of the invention is to represent new 2-heteroaryl-5-aminothiazole from suitably functionalized heteroarylcarboxylic in one step. According to the invention the object is achieved in that only recently accessible Heteroaryldithioester (eg., DD-PS 141 671, 203540, 203910, 204091, 205160) of the formula