DD225129A1 - METHOD FOR THE PRODUCTION OF SUBSTITUTED THIAZOLES - Google Patents

Abstract

METHOD FOR THE PRODUCTION OF SUBSTITUTED THIAZOLES. Such compounds have significance as herbicides and as substances with immunoregulatory properties. THE INVENTION IS TO ACHIEVE SYNTHESIS IN A SIMILAR SUBSTITUTED THIAZOLE, WHICH MAY ALLOW THE SUBSTITUENTS TO BE VARYED IN RELATIVELY WIDE LIMITS. THIS HAPPENS IN THE MANNER THAT SUBSTITUTED METHYLMERCAPTOIMIDOYL COMPOUNDS WERE CARRIED OUT WITH CARBONSAFE DERIVATIVES AND, IF ANY, A BASE TO A SUBSTITUTED THIAZOL OF GENERAL FORMULA I. THE INVENTION IS IN THE CHEMICAL INDUSTRY.

Description

254364

Process for the preparation of substituted thiazoles

Field of application of the invention

The invention relates to a process for the preparation of substituted thiazoles. Such compounds are of importance as herbicides and as substances having immunoregulatory properties.

Characteristic of the known technical solutions

It is known that 4,5-disubstituted 2-aminothiazoles can be prepared from H-acylthioureas and halomethyl compounds. J. Liebscher, H, Hartmann, Z. Chem., 1_4_, 470 (1974; HH Eüttinger, H. Dehne, W. Schroth, Pharmacie, L, 218 (1976; DD 112 760) only substituted thiazoles may be prepared that carry a disubstituted amino group in position 2, U ^ herds monosubstituted H-Acylthioharastoffe used in this synthesis, formed in the reaction with d -HaIogencarbony! compounds no corresponding 2-Aminothiasole but Acyliminothiazoline. Furthermore, It is known that 5-acyl-2-arylthiazoles can be prepared from 2-aza-3-chloroprimininium salts and mercaptomethyl compounds [Liebscher, H. Hartmann, Synthesis 1976, 403]. This process has the disadvantage in that only substituted thiazoles which are unsubstituted in the 4-position and carry an aryl radical in the 2-position can be synthesized, the yields achieved being low, and according to another known process, 2,4-diarylthiazoles can be prepared from U-acylthioamides d synthesize halomethyl compounds Γ J, Liebscher,

-ι η

9.0ΚΤ.1933 * Γ-! 3049

H, Hartmann, Liebigs Ann. Chem. 1977, 10O5]. This process has the disadvantage that no substituted thiazoles can be prepared which carry different substituents in the 2- and 4-position of aryl. «

Object of the invention

The aim of the invention is to produce substituted thiazoles, wherein it is possible to vary the substituents within wide limits, in comparison to the known methods »

Explanation of the essence of the invention

The object of the invention is to develop a simple process for preparing substituted thiazoles, which allows the substituents in the synthesized products to be varied within relatively wide limits. According to the invention, this object is achieved by a substituted methylmercaptoimidoyl compound of the general formula I

R-C = HH I

or its salt, such as a hydrochloride or hydrobromide, with a carboxylic acid derivative of general formula II

x ¹

O. I ρ

 ir-c-z-11

and optionally, a base, such as an amine, an alkali metal alkoxide or hydroxide, to a substituted thiazole of the general formula

S wherein in the general formulas R is an amino group or

an alkyl, aryl or heteroaryl radical, R is an aryl ,.

2 heteroaryl or sulfonyl radical or a Uitrogruppe, R is hydrogen, alkyl, aryl, heteroaryl or an amino group,

12 3 J. , Σ and Ir are the same, or different halogen, alkoxy, acyloxy, alkylmercapto or a substituted or unsubstituted

2 3

substituted carboxylic acid derivatives of the general formula II, for example acid chlorides, acid anhydrides, orthoesters, amide acetals, imide chlorides, -. Imidoylchloride, Imidoester or Aminalester be used. The teaching of the invention makes it possible to synthesize substituted thiazoles according to a novel construction principle, wherein the substituents can be varied within wide limits. Surprisingly, substituted methylmercaptoimidoyl compounds of the general formula I which carry a monosubstituted amino group as R are not attacked by this compound. This also makes it possible to prepare substituted thiazoles which have a monosubstituted amino group in the 2-position. The starting materials used in the teaching of the invention are readily available. The final products are relatively clean and can be brought into analytically pure form without complicated separation operations.

Exemplary embodiments

The substituted thiazoles of the general formula III prepared according to the various variants are compiled in Table 1.

option A

Za a suspension of 0.01 mol of substituted Methylniercaptoimidoylverbindung the general formula I as the corresponding hydrobromide in 20 ml of methynol 0.015 moles of carbonyl

ι 2 acid derivative of the general formula II | Σ = Σ = OCH- ,;

Χ- ³ = N (CH ₂ CH ₂ ) ₂ O]. 3 ml of triethylamine are added and the mixture is boiled for 20 minutes. After cooling, the Sndprodukt of the general formula III is filtered off with suction and recrystallized.

Variant B

Analog variant A, but the substituted Methylmercaptoimidoylverbindung the general formula I is used as the corresponding hydrochloride. ,

Variant C

Analog variant A, however, the substituted Methylmercaptoimidoylverbindung the general formula I is used as the free base and dispensed with the addition of triethylamine. ; ..:. :. '' ..

Variant D

Analog variant A, but instead of the triethylamine, a sodium methoxide solution prepared from 5 ml of methynol and 0.46 g of sodium is used.

Variant E

0.01 mol of substituted methylmercaptoimidoyl compound of general formula I as the corresponding hydrobromide is prepared to a solution of 0.015 mol of carboxylic acid derivative of general formula II Γ X ¹ =, ClJ X ² X ³ = 1 (CH ₀ ) c PO ₀ Cl ₀ !

ι. , 2 5 2 2 -> '

from 0.1 mole H-formylpiperidine and 0.015 mole POCl-. The mixture was heated for 1 0 minutes 80 ⁰ C. laughing addition of 3 ml of triethylamine for another 10 minutes at 80 ⁰ C heated · supplied while cooling the mixture is treated with a little ethanol and sucked from the final product of the general formula III. This is washed briefly with water and recrystallized.

Variant F

0.01 mol of substituted methylmercaptoimidoyl compound of general formula I as the corresponding hydrobromide is dissolved in 12 ml of pyridine. After addition of 0.015 mol of carboxylic acid derivative of the general formula II (X = R COO, IT = 0), the mixture is refluxed for 10 minutes, then the mixture is mixed with 3 ml of triethylamine and boiled for a further 5 minutes. The cooled reaction mixture is poured onto ice. The final product of the general formula III is filtered off with suction and recrystallized.

Variant G

Analog variant 3, but instead of the carboxylic acid derivative of general formula II (X = R COOj JrJ? = 0) an onsäurederivat <= 0) is used.

Carboxylic acid derivative of the general formula II (X = Cl;

Table 1: The prepared according to the different variants substituted thiazoles of the general formula III

, 1 training, / Yar »mx.

  O,

C ₆ H ₅ UH

2,4- (HO ₂ O ₂ C ₆ H ₃

C ₆ H ₅ (CH ₃ ) U 4 -HO ₂ C ₆ H ₄

H 67 / A 212-213 69 / D (Acetonitrile) H 75 / A 269-271 76 / B (Ethanol) 57 / C H 44 / e 217-218 (Ethanol) H 84 / 254-255 (Ethanol) CH- 38 / S ¹ 101-102 (Ethanol) ^C 6 ^H 5 67 / G 193-194 (Ethanol)

Claims (3)

Initial application. 1 »Process for the preparation of substituted thiazoles of the general formula III III in which S is an amino group or an alkyl, aryl or heteroaryl radical, R is an aryl, heteroaryl or sulfonyl radical or a sitro group and R is hydrogen, alkyl, aryl, heteroaryl or an amino group, characterized in that a substituted methylmercaptoimidoyl compound of the general Formula I R-C = UH I SCH ₂ R ¹ with the meaning explained for R and R or a salt of the substituted methylmercaptoimidoyl compound of the general formula I, such as, for example, a hydrochloride or a "hydrobromide," with "a carboxylic acid derivative of the general formula II X ¹
R ^ -CX ^ II X ³ 2 12 with the meaning explained for R and in the X, X. and Jr are identical or different and are halogen, alkoxy, acyllosy, alkylmercapto or a substituted or unsubstituted 2 3
te amino group or XX together represent a substituted or unsubstituted nitrogen atom, oxygen or sulfur and optionally reacted with a base. 2. The method according to item 1, characterized in that as the base, for example, an amine, an alkali metal hydroxide or alcoholate is used. 18.0Κΐ1933 * 1-13049 Process according to item 1, characterized in that the carboxylic acid derivative of the general formula II used is, for example, an acid chloride, an acid anhydride, an orthoester, an amide acetal, an amide chloride, an imidoyl chloride, an imidoester © which is an iminalester.