A Unique Approach to Catalyst-Free, One-Pot Synthesis of Spirooxindole-Pyrazolines

Abstract

A pseudo-five-component synthesis of spirooxindolepyrazolines via a one-pot and catalyst-free reaction under mild conditions is reported. The 1,1-bishydrazino-2-nitroethylene intermediate generated in situ from the addition of aqueous hydrazine to 1,1-bis(methylthio)-2-nitroethylene is trapped by two equivalents of isatin derivatives to obtain the title compounds.

Multicomponent reactions in unconventional solvents: state of the art

“…128 A pseudo-five-component reaction of isatin, 1,1-bis-(methylthio)-2-nitroethylene and hydrazine hydrate could also be performed under a catalyst-free aqueous condition, providing very a complex spirooxindolepyrazoline 49 in good yields (Scheme 25). 129 In the beginning of the reaction, a 1,1-bishydrazino-2-nitroethylene intermediate might be generated in situ from the addition of aqueous hydrazine to 1,1-bis(methylthio)-2-nitroethylene, which was then trapped by two equivalents of isatin derivatives to form the final products.…”

Recent developments of ketene dithioacetal chemistry

“…In addition, pyrazolo [3,4-b]pyridines 398 and pyrazolo[1,5-a]pyrimidines 399, 232 dihyroindeno[1,2-b]pyrroles 400, 233 pyridinols 401, 234 spirooxindole-pyrazolines 402, 235 and imidazo[1,2-c]pyrimidines 403 etc. 236 were prepared based on multi-component reactions of ketene dithioacetals (Fig.…”

“…10). [232][233][234][235][236][237][238] It is worth noting that the chemistry of ketene dithioacetals and dithioesters is closely related because the latter can be the precursor of the former. 212,239,240 Recently, a convergent and regioselective synthesis of highly substituted 2-amino-4-(aryl/ alkyl)-5-(aroyl/heteroaroyl)-3-(cyano/carboalkoxy)-6-methylthio-4-H-thiopyran derivatives 405 from the three-component domino coupling of b-oxodithioesters 404, aldehydes, and malononitriles/ethyl or methyl cyanoacetates promoted by 4-dimethylamino pyridine (DMAP) was reported by Singh and co-workers (Scheme 103, for the reaction mechanism, also see Scheme 27).…”

Part I: Nitroalkenes in the synthesis of heterocyclic compounds

“…Finally, Alizadeh and Zohreh developed a novel method for preparation of spirooxindole-pyrazoline derivatives 243 in high yields via a one-pot pseudo-ve-component reaction of hydrazine hydrate 241, 1,1-bis(methylthio)-2-nitroethylene 92, and isatin derivatives 242 (Scheme 80). 159 The products are polynitrogen compounds with potential synthetic and pharmacological interest that will be suitable for further elaboration. The products are strongly colored with high heat resistance.…”