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Synthesis of substituted 5‐oxo‐1‐thiocarbamoyl‐3‐pyrazoline‐4‐alkanoic acid derivatives
Author(s) -
Santilli Arthur A.,
Hofmann Bruce R.,
Kim Dong H.
Publication year - 1974
Publication title -
journal of heterocyclic chemistry
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 0.321
H-Index - 59
eISSN - 1943-5193
pISSN - 0022-152X
DOI - 10.1002/jhet.5570110607
Subject(s) - chemistry , pyrazoline , acetamide , ammonium acetate , ammonium hydroxide , medicinal chemistry , ethyl acetate , reagent , methyl acetate , organic chemistry , acetic acid , high performance liquid chromatography
Cyclization of the 4‐methyl‐3‐thiosemicarbazone of diethyl acetylsuccinate (1a) by the action of ammonium hydroxide followed by acidification afforded ethyl 3‐methyl‐1‐methylthiocarbamoyl‐5‐oxo‐3‐pyrazoline‐4‐acetate (11a). Pmr spectral analyses using shift reagent, Eu(fod) 3 , in deuteriochloroform indicated the presence also of approximately 15% of a second tautomer, ethyl 5‐hydroxy‐3‐methyl‐1‐(methylthiocarbamoyl)pyrazole‐4‐acetate (11a'). 3‐Methyl‐1‐methyl‐thiocarbamoyl‐5‐oxo‐pyrazoline‐4‐acetamide (11b) was prepared by extending the reaction time of 1a with ammonium hydroxide. Alkaline hydrolysis of 11a provided the corresponding acid 3‐methyl‐1‐methylthiocarbamoyl‐5‐oxo‐3‐pyrazoline‐4‐acetie acid (11c). Regeneration of 11a was achieved by the reaction of ethyl 3‐methyl‐5‐oxo‐3‐pyrazoline‐4‐acetate (IV) with methyl isothiocyanate. The latter reaction provided confirmation of structure for 11a. The preparation of other pyrazolin‐5‐ones by cyclization of thiosemicarbazones of ethyl formylsuccinate and ethyl acetylglutarate also is presented. All spectra are in accord with the proposed structures.