Multicomponent reaction for the synthesis of new highly functionalized nicotine derivatives from alkynes, trichloroacet-amidine(imidate), and 2-(1-amino-2,2,2-trichloroethylidene) malononitrile

An efficient and straightforward multicomponent synthesis protocol has been developed for the preparation of a novel series of 4-amino-5-cyano-6-trichloromethyl nicotinimidamide and nicotinimidate derivatives. The protocol involves a one-pot reaction of terminal alkynes with 2-(1-amino-2,2,2-trichloroethylidene) malononitrile, trichloroacetonitrile, and a variety of amines or alcohols in THF under ultrasonic irradiation, using copper(I) iodide as a catalyst. The reaction proceeds efficiently in the absence of additional ligands or external oxidants, affording the desired products in good to excellent yields within 45 min. Ultrasonic irradiation substantially accelerates the reaction and enhances the overall performance of the catalytic system under mild conditions. In addition to its high efficiency, the developed protocol offers several practical advantages, including the use of readily available and inexpensive starting materials, a simple catalytic system, mild reaction conditions, a short reaction time, and straightforward product isolation.