An Efficient Synthesis of Spiro-oxindole Derivatives by Three-Component Reactions in Water

• Published in: Helvetica chimica acta Vol. 98; no. 4; pp. 546 - 551
• Main Authors: Alizadeh, Abdolali, Moafi, Leila
• Format: Journal Article
• Language: English
• Published: Zürich WILEY-VCH Verlag 01.04.2015; WILEY‐VCH Verlag; Wiley; Wiley Subscription Services, Inc
• Subjects: 2-a]pyrimidine; Acetate; Acetate, ethyl 2‐cyano; Chemistry; Chemistry, Multidisciplinary; ethyl 2-cyano; hexahydro-2-(nitromethylidene); Isatin; Multicomponent reactions; Oxindole; Physical Sciences; Pyrido; Pyrido[1,2‐a]pyrimidine; Pyrimidine; Pyrimidine, hexahydro‐2‐(nitromethylidene); Science & Technology; Spiro-oxindole
• ISSN: 0018-019X; 1522-2675
• DOI: 10.1002/hlca.201400263

An efficient synthesis of (3S)‐1,1′,2,2′,3′,4′,6′,7′‐octahydro‐9′‐nitro‐2,6′‐dioxospiro[3H‐indole‐3,8′‐[8H]pyrido[1,2‐a]pyrimidine]‐7′‐carbonitrile is achieved via a three‐component reaction of isatin, ethyl cyanoacetate, and 1,2,3,4,5,6‐hexahydro‐2‐(nitromethylidene)pyrimidine. The present method does not involve any hazardous organic solvents or catalysts. Also the synthesis of ethyl 6′‐amino‐1,1′,2,2′,3′,4′‐hexahydro‐9′‐nitro‐2‐oxospiro[3H‐indole‐3,8′‐[8H]pyrido[1,2‐a]pyrimidine]‐7′‐carboxylates in high yields, at reflux, using a catalytic amount of piperidine, is described. The structures were confirmed spectroscopically (IR, 1H‐ and 13C‐NMR, and EI‐MS data) and by elemental analyses. A plausible mechanism for this reaction is proposed (Scheme 2).