Hydrazides of 4-aryl(hetaryl)-2-oxopyrrolidine-3-carboxylic acids: Synthesis and structure

Synthesis, structure, and biological activity of 4-hetaryl-2-pyrrolidones containing a pyrazole ring

“…Indeed, the spin-spin coupling constants of 3,4-CH methine protons ( 3 J 3-4 = 10.7-11.2 Hz) in 1 Н NMR spectra of compounds 5a-e and 4,5-CH methine protons ( 3 J 4-5 = 8.2-8.7 Hz) in the spectra of compounds 6a-g indicated their trans and cis orientation relative to the lactam ring plane. This orientation corresponded to (3R*,4S*) and (4R*,5R*) configurations of the chiral centers and was in good agreement with the spin-spin coupling соnstants established by us for the starting carbohydrazides 1a-e, 2a-g, [20][21][22] as well as the literature data available for trans-and cis-isomers of similar molecules. [23][24][25] The formation of pyrazole ring was confirmed by the presence of characteristic =CH proton quartet signals in 1 Н NMR spectra of compounds 5a-e, 6a-g, and 7a-d in the region of 5.88-6.20 ppm.…”

“…The starting materials 1a-e, 2a-g, and 3a-d were synthesized according to our previously developed procedures. [20][21][22] The successful completion of these reactions was found to substantially depend on the catalyst that was used. For example, the interaction of hydrazides 1a-с with 2,4-pentanedione under the conditions described in earlier publications [14][15][16][17][18][19] (catalyst hydrochloric acid, solvent i-PrOH) was accompanied by rapid hydrolysis of compounds 1а-с, followed by esterification of the intermediate pyrrolidone carboxylic acids and resulting in the isolation of the respective isopropyl esters 4a-c (Scheme 2).…”

“…The synthesis of (3R*,4S*)-4-hetaryl-2-pyrrolidone-3-carbohydrazides 1a-e, (4R*,5R*)-4-hetaryl-2-pyrrolidone-5-carbohydrazides 2a-g, and 2-[4-aryl-2-pyrrolidon-1-yl]acetohydrazides 3a-d was accomplished by following published procedures. [20][21][22] Synthesis of isopropyl (3R*,4S*)-4-aryl-2-oxopyrrolidine-3-carboxylates 4a-c (General method). A mixture of the appropriate 4-aryl-2-oxopyrrolidine-3-carbohydrazide 1а-с (5 mmol), 2,4-pentanedione (15 mmol), and 6 N HCl (0.25 ml) in i-PrOH (20 ml) was heated at reflux for 2 h. The solvent was evaporated at reduced pressure (15-20 mmHg) by 2/3 of the initial volume, and the residue was treated with H 2 O (4 ml).…”