Zinc chloride catalyzed three-component Ugi reaction: synthesis of N-cyclohexyl-2-(2-hydroxyphenylamino)acetamide derivatives

The ability of zinc chloride as a catalyst to promote the three-component Ugi reaction of 2-aminophenols, aliphatic or aromatic aldehydes, and cyclohexyl isocyanide in methanol at room temperature is described. The N-cyclohexyl-2-(2-hydroxyphenylamino) amide products are obtained in high yields. When N,N-dimethylformamide dimethyl acetal and triethyl orthoformate, as two new components of the three-component Ugi reaction are used instead of the aldehyde the reaction gives N-cyclohexyl-2-(dimethylamino)-2-(2-hydroxyphenylamino)acetamide and N-cyclohexyl-2-(2-hydroxyphenylamino)-2-ethoxyacetamide derivatives, respectively. (C) 2012 Elsevier Ltd. All rights reserved.