One-pot sequential synthesis of isocyanates and urea derivatives via a microwave-assisted Staudinger–aza-Wittig reaction

• DOI: 10.3762/bjoc.9.274
• Publication Date: 2013-11-06T15:26:51Z
• Authors: Diego Carnaroglio; Katia Martina; Giovanni Palmisano; Andrea Penoni; Claudia Domini; Giancarlo Cravotto
• Keywords: urea derivatives; one-pot reaction; Science; Q; Organic chemistry; tandem Staudinger–aza-Wittig reaction; 01 natural sciences; Full Research Paper; microwave-assisted reaction; 0104 chemical sciences; QD241-441; Isocyanates; Microwave-assisted reaction; One-pot reaction; Tandem Staudinger-aza-Wittig reaction; Urea derivatives; isocyanates

A fast and efficient protocol for the synthesis of N,N'-disubstituted urea derivatives from alkyl halides and primary or secondary amines has been developed. The synthetic pathway combines nucleophilic substitutions and a Staudinger–aza-Wittig reaction in the presence of polymer-bound diphenylphosphine under 14 bar of CO2 pressure and has been performed in a one-pot two-step process. The protocol has been optimized under microwave irradiation and the scale-up experiment has been conducted under conventional conditions in a Parr reactor. The final compounds were isolated after simple filtration in almost quantitative overall yields which makes this procedure facile and rapid to execute.