2-cyanoacetamide

Abstract

(A) 2-Cyanoacetamide (1) can be readily alkylated at C2. Nucleophilic substitution in (benzamidomethyl)triethylammonium chloride (5) occurred under mild conditions in aqueous media and at ambient temperature to give disubstituted cyanoacetamide 6 without any catalyst. (B) Triarylstibine-modified Co2 (CO) 8 appeared to be an efficient homogeneous catalytic system for the synthesis of secondary amides by direct reductive N-alkylation of a variety of substituted aryl aldehydes with aryl-, heteroaryl- and aliphatic primary amides. Reaction of 4-tert-butyl benzaldehyde (7) and 2-cyanoacetamide (1) gave compound 8 in 90% yield. (C) The triethylamine- catalyzed alkylation of 2-cyanoacetamide (1) with 2-chloroacetoacetate (9) followed by nucleophilic attack of the amide nitrogen on the carbonyl group and acid-catalyzed dehydration led to the formation of substituted pyrrole 10 in good yield. (D) The Gewald reaction of a ketone or aldehyde with 2-cyanoacetamide in the presence of a base and elemental sulfur affords substituted 2-aminothiophenes. T. Horiuchi and co-workers described the preparation of thiophene 12 from butyraldehyde (11), 2-cyanoacetamide (1) and elemental sulfur in DMF. (E) α,β-Unsaturated nitrile derivatives (Knoevenagel condensation products) are among the most important precursors of heterocycles. Various aliphatic, aromatic and heteroaromatic aldehydes 13 reacted with 2-cyanoacetamide (1) in the presence of N-methylpiperazine under solvent-free conditions to give the Knoevenagel condensation products 14. (F) 1,4-Conjugate addition (Michael reaction) of 2-cyanoacetamide (1) to butenonyl C-glycoside 15 was carried out in the presence of various organic bases in organic solvents and under a nitrogen atmosphere followed by oxidative aromatization to form glycopyranosyl methylpyridone 16. (G) [3+2] Dipolar cycloaddition of azides and 2-cyanoacetamide gave substituted 5-amine-4-carbamoyl-1,2,3-triazoles. Cycloaddition of diethyl (R)-3-azidophosphonate 17 and 2-cyanoacetamide (1) in DMSO in the presence of potassium carbonate provided phosphonate 18 in 70% yield. © Georg Thieme Verlag Stuttgart New York.