DD246541A1 - PROCESS FOR THE PREPARATION OF 5-ARYLIDENTHIAZOLIDIN-4-ONEN - Google Patents

Abstract

The aim of the invention is the preparation of these compounds on the basis of easily accessible starting materials. According to the invention, arylpropiolic acid amides are reacted with a heterocumulum in the presence of a base. 5-Arylidenthiazolidin-4-ones are intermediates for organic syntheses. They can be widely used for the production of biologically active substances.

Description

For this 1 page formulas

Field of application of the invention, i

The invention relates to a process for the preparation of 5-Arylidenthiazolidin-4-ones of the general formula I in which R ^{1 is} an aryl group, R ^{2 is} hydrogen or an alkyl group and Z is oxygen, sulfur or the group NR ³ and R ^{3 is} a Alkyl, cycloalkyl or aryl group.

5-Arylidenthiazolidin-4-ones are intermediates for organic syntheses. They can be widely used for the production of biologically active substances.

Characteristic of the known technical solutions -

It is known that various methods exist for the preparation of 5-Arylidenthiazolidin-4-ones.

While thiazolidin-4-ones are accessible mainly by reaction of haloacetic acid derivatives with dithiocarbamates, substituted thioureas or carbamates (Chem. Rev. 81 [1981], 175-203), the 5-arylidentiazolidin-4-ones are obtained by condensation with aromatic aldehydes (Monatsh. Chem. 10 [1889], 73; Ber. Dtsch. Chem. Ges. 17, 2277; Khim. Geterotsikl. Soedin. 1985, 43, 94).

Object of the invention

The aim of the invention is the preparation of these compounds based on readily available starting materials.

Explanation of the essence of the invention

The invention has for its object to produce 5-Arylidenthiazolidin-4-one by a simple process.

According to the invention 5-Arylidenthiazolidin-4-ones of general formula I are prepared by Arylpropiolsäureamide of the general formula II, in which R ¹ and R ^{2 have} the same meaning as in formula I, with a heterocumulene in the presence of a base in a dipolar, aprotic Solvent-preferably dimethylformamide-reacted.

In the case of the 3-alkyl compounds V, either the arylpropiolic acid N-alkylamides II are reacted in the manner indicated or the N-unsubstituted compound II is used, to which an isothiocyanate, 2 equivalents of a base and then an alkylating agent are allowed to act.

Suitable heteroculenes are carbon disulfide, carbon oxysulfide or isothiocyanates.

The process according to the invention is illustrated by equations 1 to 4.

It was surprising that reactions of arylpropiolic acid amides with heterocumulenes are possible to form 5-arylidentiazolidin-4-ones.

For example, the compounds of Table 1 can be prepared by the process according to the invention.

embodiments

example 1

5-benzylidene-2-thioxo-thiazolidine-4-one

0.4 g of sodium hydride are added in portions to a solution of 2.2 g of phenylpropiolamide and 1.2 g of carbon disulfide in 45 ml of absolute dimethylformamide. To complete the reaction is stirred for 3 hrs. At room temperature, then hydrolyzed with ice water and carefully acidified with hydrochloric acid. The precipitated solid is filtered off, dried and recrystallized from water or carbon tetrachloride.

Example 2

5-Benzylidene-thiazolidine-2,4-dione '

A stirred solution of 2.2 g Phenylpropiolsäureamid in 45 ml of absolute dimethylformamide is added in portions with 0.4 g of sodium hydride. After 30 minutes, the mixture is cooled to 0 ° C. and a moderately strong stream of carbon oxysulfide is introduced for about 20 minutes. The mixture is then stirred for 3 hrs. At room temperature and worked up as in Example 1.

Example 3:

5-benzylidene-2-phenylimino-thiazolidin-4-one

Method A: 0.5 g of sodium hydride are added in portions to a solution of 2.9 g of phenylpropiolamide and 2.7 g of phenylisothiocyanate in 80 ml of absolute dimethylformamide, and the mixture is then stirred for a further 3 hours at room temperature. The solution is then mixed with ice-water and carefully acidified with hydrochloric acid, whereby a solid is obtained. It is filtered off, dried and recrystallized from methanol.

Method B: To 2.9 g of phenylpropiolamide in 80 ml of dimethylformamide is added dropwise a solution of 1.2 g of potassium hydroxide in 5 ml of water and stirred for a further 30 min. To the resulting reaction mixture, 2.7 g of phenyl isothiocyanate are added, stirring at room temperature for 3 hr continues. The isolation of the reaction product is carried out according to method A.

Example 4: '...

5-benzylidene-3-methyl-2-phyenylimino-thiazolidin-4-one

Method C: Dissolve 2.9 g of phenylpropiolamide and 2.7 g of phenylisothiocyanate in 80 ml of absolute dimethylformamide, add in portions 0.5 g of sodium hydride and allow to stir for 30 min. After another 0.5 g were added, after 1 hr.

2.9 g of methyl iodide was added dropwise. To complete the reaction, the mixture is stirred for a further 1 hr. At room temperature and worked up analogously to Example 3, method A.

Method D: 0.5 g of sodium hydride are added in portions to 3.2 g of phenylpropiolic acid N-methylamide and 2.7 g of phenyl isothiocyanate in 80 ml of absolute dimethylformamide and the mixture is stirred for a further 2 hours at room temperature. The solution is mixed with ice-water and acidified with hydrochloric acid. The solid is filtered off with suction and crystallized from alcohol.

Table 1 R ¹ R ² Z M.p. ( ⁰ C) Yield (%) CeHs- H S 204-206 • 57 C ₆ H ₆ H O 244-246 47 C ₆ H ₅ - H NR ³ 261-263 A: 74 (R ³ IC ₆ Hs) B: 46 C ₆ H ₅ - H NR ³ 183-185 A: 65 (R ³ : nC ₃ H ₇ -) B: 48 C ₆ H ₅ - H NR ³ ' 168-170 A: 58 (R ³ : CH ₂ = CH-CH ₂ -) B: 35 ; C ₆ H ₅ - H 'NR ³ 201-261 A: 60 (R ³ : ^ ₁ -CH ₃ -C ₆ H ₄ -) ^; C ₆ H ₅ - H NR ³ 259-261 A: 68 (R ³ IC ₆ H ₁₁ -) ; C ₆ H ₅ - H NR ³ 23Ϊ-233 A: 59 (R ³ : CH ₃ -) C ₆ H ₆ - CH ₃ NR ³ 132-134 C: 68 (R ³ : C ₆ H ₅ -) D: 56)

Claims (3)

Invention claim: A process for the preparation of 5-Arylidenthiazolidin-4-ones of the general formula in which R ^{1 is} an aryl group, R ^{2 is} hydrogen or a. Alkyl group and Z is oxygen, sulfur or the group NR ³ and R ^{3 is} an alkyl, cycloalkyl or aryl group, characterized in that Arylpropiolsäu.reamide the general formula II, in which R ¹ and R ^{2 have} the same meaning as in Formula I have to be reacted with a heterocumulum in the presence of a base in a dipolar, aprotic solvent - preferably dimethylformamide. 2.) Process according to item 1, characterized in that the 3-alkyl compounds of I can be obtained by a) the arylpropiolic acid-N-alkylamides of the general formula II in the manner indicated or b) the N-unsubstituted compounds II are reacted with an isothiocyanate, 2 equivalents of a base and then an alkylating agent. 3. The method according to item 1, characterized in that find as heterocumulenes carbon disulfide, carbonyl sulfide and isothiocyanates use.