DD295366A5 - PROCESS FOR THE PREPARATION OF 2-HYDRAZONO-DELTA [EXP4] -THIAZOLINES - Google Patents

Abstract

The invention relates to a process for the preparation of 2-hydrazono-D4-thiazolines. The title compounds are of interest as spasmolytics and as a coupling component for the preparation of dyes that can be used in biochemistry and clinical chemistry laboratory diagnostics. According to the invention, the 2-hydrazono-D4-thiazolines are prepared by hydrolysis of 2-acylhydrazono-D4-thiazolines with mineral acids. {2-hydrazono-D4-thiazolines; 2-Acylhydrazono-D4-thiazolines; Coupling component; antispasmodics; dyes; Biochemistry; Clinical chemical laboratory diagnostics; mineral acids}

Description

According to the invention, this object is achieved in that 2-acylhydrazono-A ⁴ -thiazoline of the general formula I.

»3

in organic solvents, preferably in alcohols, with the addition of mineral acids under mild conditions, to give 2-hydrazono-A ⁴ -thiazolines of the general formula II.

This variant is particularly suitable for the preparation of 2-hydrazono-A * -thiazolines, which already undergo rearrangement reactions in dil. Mineral acids to 2-alkyl (aryl) imino-3-amino-A ⁴ -thiazolinen. More stable 2-hydrazono-A ⁴ -thiazolines can also be prepared by heating in dilute mineral acids. In the general formulas, R ¹ and R ² denote an alkyl, aryl, alkoxycarbonyl, acyl radical or a Η atom, R ³ and R ⁴ denote an alkyl or aryl radical. The 2-acylhydrazono-A ⁴ -thiazolines are accessible by condensation of 4-substituted 1-acyl-thiosemicarbaziden with a-halo-carbonyl compounds.

embodiments example 1

2-hydrazono-3-methyl-4,5-diphenyl-A ⁴ -thiazoline

3.23 g (10 mmol) of 2-acetylhydrazono-3-methyl-4,5-diphenyl-A ^4- thiazoline are dissolved in 140 ml of 2m hydrochloric acid for 2 h. under reflux. After completion of the reaction is neutralized with ammonia, wherein a yellow precipitate precipitates. Y. 2.4 g (85%). Yellow needles (from ethanol), mp 178 ⁰ C.

Example 2

2-hydrazono-3-n-propyl-4,5-diphenyl-A ⁴ -thiazoline

3.51 g (10 mmol) of 2-acetylhydrazono-3-n-propyl-4,5-diphenyl-A ⁴ -thiazoline are dissolved in 50 ml of ethylene glycol monomethyl ether

Addition of 2 ml conc. Hydrochloric acid 4h heated to reflux. The reaction solution is cooled and treated with ammonia solution

added. Here, a yellow substance separates out. Y. 2.7g (87%). Dark yellow rods (made of ethanol), mp 156 ° C.

Example 3

2-hydrazone-3-n-butyl-4,5-diphenyl-A ⁴ -thiazoline

4.27 g (10 mmol) of 2-benzoylhydrazono-3-n-butyl-4,5-diphenyl-A ⁴ -thiazoline were dissolved in 120 ml of 50% sulfuric acid 1.5 h. one

Subjected to steam distillation. Upon cooling, an oil separates, which solidifies on addition of ammonia solution. Y. 2.7g (83%). Yellow rods (from ethanol), mp 152 ^° C. Example 4

2-hydrazono-3-allyl-4,5-diphenyl-A ⁴ -thiazoline

3.49 g (10 mmol) of 2-acetylhydrazono-3-allyl-4,5-diphenyl-A ⁴ -thiazoline are concentrated in 40 ml of ethanol and 2 ml of conc. Hydrochloric acid 3h

heated to reflux. The solution smelling clearly of ethyl acetate is filtered hot and neutralized with ammonia, precipitating a yellow precipitate which is filtered off with suction and washed with water. 2.8g (91%). Yellow prisms (from ethanol),

Example 5

2-hydrazone-3,5-dimethyl-4-phenyl-A ⁴ -thiazoline hydrochloride

2.97 g (10 mmol) of 2-acetylhydrazono-3,4-dimethyl-5-phenyl-A ⁴ -thiazoline are dissolved in 50 ml of 2M hydrochloric acid for 1.5 h. under reflux. After the reaction has ended, the mixture is mixed with ammonia, whereby an oil precipitates, which is dissolved in a little ethanol with the addition of 1 ml ethanol. Hydrochloric acid is dissolved. Upon addition of ether, a crystalline precipitate separates out. Y. 2.3g (90%). Colorless

Prisms (from ethanol / ether), m.p. 184-185 ⁰ C.

Example β

2-Hydrazono-3-methyl-4-phenyl-5-ethyl-A ⁴ -thiazoline hydrochloride

3.11 g (10 mmol) of 2-acetylhydrazono-3-methyl-4-phenyl-5-ethyl-A ⁴ -thiazoline are dissolved in 50 ml of 2M hydrochloric acid for 2 h. under reflux. Further workup is carried out as described in Example 5 be ichrieben. Y. 2.35g (87%). Colorless needles (made of ethanol),

F. 114-115 ⁰ C.

Example 7

2-Hydrazono-3,4-dimethyl-5-ethoxycarbonyl-A ⁴ -thiazoline 2.57 g (10 mmol) of 2-acetylhydrazono-3,4-dimethyl-5-ethoxycarbonyl-A ^4- thiazoline are in 5OmI ethanol and 2ml conc ,

Hydrochloric acid for 3 hrs. Heated under reflux. The filtrate is mixed with ammonia, whereby a dark yellow crystal lead precipitates. After cooling in ice is filtered off with suction and washed with water. Y. 1.9g (88%). Yellow rods (diluted from. Ethanol), mp 118 ⁰ C.

Example 8

2-Hydrazono-3-ethyl-4-methyl-5-ethoxycarbonyl-A ⁴ -thiazoline 2.66 g (10 mmol) of 2-acetylhydrazono-3-ethyl-4-methyl-5-ethoxycarbonyl-A ⁴ -thiazoline are dissolved in 25 ml Ethanol and 1 ml conc.

Hydrochloric acid 2.5h. One reflux heated. The precipitated with verd. Ammonia crystal slurry is washed twice with 100ml of hot water. Y. 2g (87%). Light yellow needles (from dil. Ethanol), mp 102-103 ⁰ C.

Claims (2)

A process for the preparation of 2-hydrazono-A4-thiazolines, characterized by reacting 2-acylhydrazono-A4-thiazolines of the general formula I by heating in organic solvents with addition of mineral acids or in dil. Or conc. Hydrolyzed mineral acids to give 2-hydrazono-A4-thiazolines of general formula II, ¹ - / R ³ where R ¹ and R ² denote an alkyl, aryl, alkoxycarbonyl, acyl radical or a Η-atom, R ³ and R ⁴ denote an alkyl or aryl radical. Field of application of the invention The invention relates to a process for the preparation of 2-hydrazono-A ⁴ -thiazolinen, which are of interest as spasmolytics, as reagents for biochemistry, the clinical chemical laboratory diagnostics and as organic intermediates for the production of dyes. Characteristic of the known state of the art 2-hydrazono-A ⁴ -thiazolines are formed as by-products in the condensation of 4-alkylthiosemicarbazides with a-halo ketones (H.Beyer, Z. Chem., 1969, 361, WD Pfeiffer, E. DiIk and E. Bulka Z. Ernst-Moritz-Arndt-University Greifswald, Math.-nat. Wiss. Reihe 27 [1978] 135). In the acidic hydrolysis of 2-isopropylidenehydrazono-3-alkyl (aryl) -A ⁴ -thiazolines, 2-hydrazone-3-alkyl (aryl) -A ⁴ -thiazolines can be isolated (E.Bulka, H.G. Rohde and H. Beyer, Chem. Ber.93 [1965] 259; WD Pfeiffer, E. DiIk and E. Bulka, Z. Chem. 17 [19771218; E. Bulka, WD Pfeiffer, C.Trolzsch, E. DiIk, H. Gärtner and D. Daniel, Collection Czechoslov Chem. Commun.43 [1978] 1227). However, these processes have the disadvantage that acid-sensitive 2-hydrazono-A ⁴ -thiazolines are rearranged into 2-alkyl (aryl) imino-3-amino-A ⁴ -thiazolines. Some 2-hydrazono-3-alkyl-4-phenyl-A ⁴ -thiazoline undergo heating on heating in conc. Hydrochloric a ring extension to the corresponding 1,3,4-thiadiazines. 2-hydrazono-A ⁴ -thiazolines can also be prepared by quaternization of the corresponding A ⁴ -thiazoline-2-thiones with dimethyl sulfate and subsequent hydrazinolysis (S. Hünig and W. Lampe, J. prakt. Chem. 8 [1959] 264) , Object of the invention The aim of the invention is the preparation of new 2-hydrazono-A ⁴ -thiazoline with potential spasmolytic activity and as coupling components for dyes. Presentation of the essence of the invention The object of the invention is to produce 2-hydrazono-A ⁴ -thiazoline from easily accessible starting components in a simple manner.