Synthesis of 2-amino-4-aryl-3-cyano-5-hydroxyimino-4,5-dihydrothiophenes

Abstract

Aliphatic nitro compounds are of interest as reactive starting materials in the synthesis of heterocycles both with and without a nitro group [1]. We made a systematic study of the reactions of α-carbonyl and α,β-unsaturated nitro compounds with various CH-nucleophiles and determined their regioselectivity, which depends on the structure of the initial compounds and the reaction conditions. It has been shown that the products from the reactions of the nitro compounds with the CH-nucleophiles can be both acyclic compounds and heterocycles of the indolizine, thiophene, and pyridine series [2][3][4][5].We established that the reaction between the nitrostyrenes 1a-e, cyanothioacetamide 2, and an equivalent of tetramethylethylenediamine (TMEDA) or morpholine takes place in ethanol at room temperature with the formation of compounds 3a-f with yields of 30-60%. S Ar N NH 2 B N O H Ar NO 2 3a-f 2 B 1a-e + + NCCH 2 CSNH 2 1a, 3a,f Ar = Ph; 1, 3 b Ar = 4-ClC 6 H 4 , c Ar = 2-C 4 H 3 S, d Ar = 4-FC 6 H 4 , e Ar = 4-MeOC 6 H 4 ; 3 a-e B = 0.5(Me 2 NCH 2 CH 2 NMe 2 ), f B = O N HCompounds 3a-f are complexes of 2-amino-4-aryl-3-cyano-5-hydroxyimino-4,5-dihydrothiophenes with the bases in ratios of 2:1 in the case of TMEDA 3a-e and 1:1 in the case of morpholine 3f. By conducting the reaction in the presence of ethyl ether it is possible to obtain compounds 3a-f with yields of 50-80% [6].Further study of the reaction showed that compounds not containing the base combined into a complex can be isolated. Thus, 2-amino-4-aryl-3-cyano-5-hydroxyimino-4,5-dihydrothiophene 4a is formed with an almost quantitative yield when the nitrostyrene 1a is briefly boiled with cyanothioacetamide 2 in the presence of __________________________________________________________________________________________

2-Amino-4,5-dihydrothiophene-3-carbonitriles: A New Synthesis, Quantum Chemical Studies, and Mannich-Type Reactions Leading to New Hexahydrothieno[2,3-d]pyrimidines

“…However, the available methods for the synthesis of ADHTs are somewhat limited and the studies are somewhat hampered by the lack of common practical procedures and by the narrow scope of useful substrates. ADHTs can be prepared (Scheme ) by the reaction of γ-haloacetoacetic acid derivatives with isothiocyanates, , treatment of Michael adducts prepared from cyanoacetic esters and chalcone with elemental sulfur, recyclization of thiiranes, , diastereoselective cycloadditions of aminothioisomünchnones with chiral 1,2-diaza-1,3-butadienes, condensation of S -acetylmercaptosuccinic anhydride with methyl cyanoacetate, reaction of cyanothioacetamide with β-nitrostyrene, reductive recyclization of functionalized thiazolidinones, and cyclocondensation of benzoylpyruvate with PhNCS or β-ketothioamides with oxalyl chloride . Very recently, the organotin-catalyzed reaction of arylmethylene malononitriles with α-mercaptoketones was reported to produce ADHTs as a mixture of diastereomers .…”