DD267492A1 - PROCESS FOR THE PREPARATION OF THIAZOLIDINE DERIVATIVES - Google Patents

Abstract

The invention relates to a process for the preparation of thiazolidine derivatives. The aim of the invention is to develop a process for the preparation of N-furfuryl (3-aryl, aralkyl or hetaralkyl-5-aryl or hetarylmethylene-4-oxo-thiazolidin-2-ylidene) cyanoacetamides. These thiazolidine derivatives can be used as organic intermediates for further syntheses. They are particularly suitable for the preparation of potentially biologically active compounds. According to the invention, the thiazolidine derivatives of general formula VII in which R is an optionally substituted phenyl, aralkyl or heteroaralkyl radical and R 2 is an optionally substituted phenyl or hetaryl radical may be N, N-difurfuryl-1,3-dithietane -2,4-diylidene bis (cyanoacetamide) I by reaction with the amines of the general formula II, in which R has the above meaning, to the ammonium thiolates of the general formula III, in which R is as defined above, their subsequent reaction with Haloacetic esters of the general formula IV, in which X is a halogen atom and R 1 is an alkyl radical, to the Thiazolidinderivaten of the general formula V, in which R has the above meaning, and their subsequent reaction with aldehydes of the general formula VI, in the R2 as is defined above.

Description

-2- 267 Exemplary Example

Exercise booklet 1

N-Furfuryi- (4-oxo-3-phenyl-thiazclidin-2-ylidene) -cyanacetamide A mixture of 0.005mol N, N'-difurfuryl-1,3-dithietane-2,4-diylidene bis -cyanacetamide), 0.02 mol of aniline and 10 mM of dimethylformamide is refluxed for 2 minutes. After cooling to room temperature, the reaction mixture is admixed with 0.015 mol of ethyl chloroacetate and again refluxed for 5 minutes. The mixture is cooled to 20 ^v C, mixed with stirring with 150 ml of water, the precipitate formed is filtered off, washed with water and recrystallized from ethanol / glacial acetic acid.

Ausb.:82%d.Th. Mp. 195-197 ⁰ C

C ₁₇ H ₁₃ N ₃ O ₃ S (339.4) Ber. C60,17 H3,83 N 12,38 S9.43

Gef. C 59.59 H 3.90 N 11.79 S 9.49

IR (KBr): NH 3320, CN 2220, CO 1720, 1640 cm ^-1 ;

¹ H-NMR (CDCl 2 _a ): CH ₂ CO 3.75 (s, 2H), CH ₂ 4.38 (d, 2H), furan protons: H-3.4C, 6.17 (m, 2H), H- 5C, 7.13 (m, 1H), aromatic protons: 7.25-7.52 (m, 5H), NH 6.37 (broad signal, 1H) ppm.

Implementation Example 2

N-Furfuryl- [3- (p-methoxy-phenyl) -4-oxo-thiazolidin-2-ylidene-cyanoacetamide 0.005 moles of N, N'-difurfuryl-IS-dithietane ^^ - diylidene bis-1-cyanacetamide), 0.02 mol p-Anisidine and 0.015 mol of methyl bromoacetate are reacted as described in Example 1.

Ausb.:54%d.Th. M.p .: 199-200 ⁰ C N 11.38 S 8,67 C ₁₈ H ₁₆ N ₃ O ₄ S (369.4) Ber. C 58.53 H 4.06 N 10.87 S 8,51 Gef. C 582 H 4,40

Implementation Example 3

N-Furfuryl- (3-furfuryl-4-oxo-thiazolidin-2-ylidene) cyanoacetamide O.OOSmol N.N'-difurfuryl-IS-dithietane ^^ - diylidene bis-lycanacetamide), 0.02 mol furfurylamine and 0.015 mol Chloroacetylethylosijr are reacted as described in Example 1.

Ausb.:85%d.Th. M .: 222-223 ⁰ C

C ₁₆ H ₁₃ N ₃ O ₄ S (343.4) Calcd. C 55.97 H 3.79 N 12.24 S 9.32

Gef. C 55.55 H 3.90 N 11.98 S 9.15

Execution badge 4

N-Furfuryl- (5-Benzylidene-4-oxo-3-phenyl-thiazolidin-2-ylidene) -cyanacetamide A mixture of 0.01 moles of N-furfuryl- (4-oxo-3-phenyl-thiazolidin-2-ylidene ) Cyanoacetamide, 0.01 mol of benzaldehyde, 0.01 mol sodium ethoxide and 25 ml of absolute ethanol is stirred for 4 hours at 2O ⁰ C. The precipitate is filtered off, washed with a little ethanol and recrystallized from dimethylformamide / ethanol.

Ausb.:60%d.Th. M .: 282-285 ⁰ C

C ₂₄ H ₁₇ N ₃ O ₃ S (427.5) boron. C 67.44 Η3.9Γ N 9.83 S 7.49

C 66.95 H 4.08 N 9.15 S 7.09

¹ H-NMR (CDCl ₃ ): CH ₂ 4,20 (d, 2H), furan protons: H-3,4-C6,22 (m, 2H), H-5C7,25 (m, 1H), aromatic protons: 7 , 17-7.47 (m, 5H). CH 7.65 (s, 1H), NH 6.47 (broad signal) ppm.

Implementation Bills 5

N-Furfuryl-to-furfurylidene ^ -oxo-S-phenyl-thiazolidine ^ -ylideneacyaneacetamide 0.01 mol of NFurfuryl (4-oxo-3-phenyl-thiazolidin-2-ylidene) cyanoacetamide, 0.01 mol of furfural and 0, 01 mol of sodium ethoxide are reacted as described under Ausführungsbeispial 4.

Ausb.:85%d.Th. M.p .: 285-286 ° C

C ₂₂ H ₁₆ N ₃ O ₄ S (417.5) Calcd. C63.30 H 3.59 N 10.07 S 7.67

Gef. C63.10 H3.60 N10,12 S7.68

Embodiment 6

N-Furfury HS-IS-nitro-furfurylidene M-oxo-S-phenyl-thiazolidine ^ -ylideneacyaneacetamide 0.01 M N-Furfuryl- (4-oxo-3-phenyl-thiazolidin-2-ylidene) cyanoacetamide, 0.01 mol 5 Nitro-furfural and 0.01 mol of sodium ethanolate are reacted as described in Example 4.

Ausb.:90%d.Th. M.p .: 260-262 ⁰ C

C ₂₂ H ₁₄ N ₄ O ₆ S! 462.5) Ber. C57.14 H3.03 N 12.12 S6.92

Gof. C 57.04 H 3.48 N 11.98 S 6.38

H ι

O = O. "- KU

IIA

O = O] O) OODHm ² HO-I

O ² H Z -

IA

HH0 = 0

H j

0 = 0K

O = (BO) OOO HN

2 *

no

HO ^ H Z -

XH 2 - ^<S HH 2 -

ΛΙ

, HOOO ² HOX Z

III HHN (H ^ HKf + .S) O = (KO) DOO HK ² HO "

II 'HNH 17 +

1- ² HOHNOD (KO) O = OO = OiO) OOOHK ² HD-

'S Sii t-VZ

Claims (3)

1. A process for the preparation of thiazolidine derivatives of the general formula VII in which R is an optionally substituted phenyl, aralkyl or hetaryl radical and R ^{2 is} an optionally substituted phenyl or hetaryl radical, characterized in that N, N'- Difurfuryl-1,3-dithietane-2,4-diylidene-bis (cyanoacetamide) I with amines of general formula II, in which R has the above meaning, to the ammonium thiolates of general formula III, in which R is as defined above, These are subsequently reacted with haloacetic esters of the general formula IV, in which X is a halogen atom and R ^{1 is} an alkyl radical into which thiazolidine derivatives of the general formula V, in which R has the above meaning, and these then r-. aldehydes of the general formula VI, in which R ^{2 is} as defined above, are reacted. 2. The method according to claim 1, characterized in that the ammonium thiolates III are reacted without isolation in the reaction mixture with the haloacetic esters IV IV. 3. The method according to claim 1, characterized in that the reaction of the thiazolidine derivatives V takes place with the aldehydes VI in the presence of sodium alcohols. For this 1 page formulas Field of application of the invention The invention relates to a process for the preparation of NTurfuryl- (3-aryl, aralkyl or hetaralkyl-5-aryl or hetarylmethylene-4-oxo-thiazolidin-2-ylidene) cyanacelamiden. These thiazolidine derivatives can be used as organic intermediates for further syntheses. They are particularly suitable for the preparation of potentially biologically active compounds. Characteristic of the known state of the art N-Furfuryl- (3-aryl-, aralkyl- or hetaralkyl-5-aryl- or hetarylmethylene ^ -oxothiazolidine) -ylidene-1-cyanoacetamides are not yet known. Object of the invention The aim of the invention is the development of a process for the preparation of new pharmaceutical active ingredients. Explanation of the essence of the invention The object of the invention is to develop a process for the preparation of N-furfuryl- (3-aryl-, aralkyl-, b-, hetaralkyl-5-aryl- or hetarylmethylene-oxo-thiazolidine) -ylidene-cyanoacetamides. According to the invention, the thiazolidine derivatives of general formula VII, in which R is an optionally substituted phenyl, aralkyl or hetaralkyl radical and R ^{2 is} an optionally substituted phenyl or hetaryl radical, can be prepared from dtm N, N'-difurfuryl-1,3 -dithietai-2,4-di-ylidene-bis (cyanoacetamide) I by reaction with the amines of the general formula II in which R has the above meaning, to the ammonium thiolates of the general formula III in which R is as defined above, whose subsequent reaction with haloacetic esters of the general formula IV, indor Xfor ein'ialogenatom and R ^{1 is} an alkyl radical, to the Thiazolidinderivaten of the general formula V, in which R has the above meaning Be¬, and their subsequent reaction with aldehydes of the general formula VI, in which R 'is the same as defined. The reaction of the N.N'-Difurfurvl-IS-dithietane ^ Adiyliden-bislcyanacetamid) I with the Aminin II is carried out in an organic solvent, preferably dimethylformamide. The compound I and the amines II are reacted in a molar ratio of 1: 4. The reaction temperatures are at the boiling temperatures of the solvents used. The reaction times are only a few minutes. It is not necessary to isolate the Amnioniumthiolate III. These can be reacted in the reaction mixture with the haloacetic esters IV. This reaction also takes place at reflux temperatures. The reaction times are only minutes. After cooling the reaction mixtures, they are mixed with water. The precipitates formed (compounds V) are filtered off, washed with water and recrystallized from organic solvents. The reaction of the thiazolidine derivatives V with the aldehydes VI takes place in the presence of sodium alcoholates in alcohols. It is convenient to stir the reaction mixtures. The reaction temperatures are 2O ⁰ C to 3O ⁰ C. The reaction times range from 2-6 hours. After completion of the reaction, the products VII are filtered off, washed with water and recrystallized from organic solvents.