Synthesis Involving Formation of Three or More Bonds

2 Synthesis Involving Formation of Three or More Bonds Me Me 

Another versatile approach to pyrimidine synthesis uses the N-C fragments. Nitriles are a common N-C source and have been used to form pyrimidines in many syntheses. Cyanamide is a particularly useful nitrile derivative in the synthesis of pyrimidines as illustrated.  

An improved and convenient preparation of pyrimidines and condensed pyrimidines from ketones and nitriles was reported. In the presence of acetonitrile, the cation generated from methyl ethyl ketone with trifluoromethanesulfonic anhydride is trapped by the nucleophile, whereby a resonance-stabilized nitrilium species is formed. A second molecule of nitrile reacts with nitrilium intermediate, and after elimination of triflic acid, cyclization, and loss of a proton, the pyrimidine product was obtained in a useful yield. The formation of pyrimidines is accompanied by a minimum 

The Bredereck-type synthesis, which is well known as a conventional preparation of pyrimidine derivatives, generally requires a reaction temperature of more than 160 °C, and the product yield is moderate. A simple, high-yielding synthesis of pyrimidines from ketones in the presence of HMDS and formamide is reported. Under microwave irradiation, heteroaromatic, aryl, aliphatic, and cyclic ketones cyclized to give pyrimidines in good yields. 

Phosphonium-based reagents PyBOP and PyBroP were found to be very effective in this transformation, affording oxytripyrrolidino-phosphonium intermediates in high yields, with PyBroP being slightly superior to PyBOP. Weak nucleophiles such as iV-methyl benzenesulfonamide, imidazole, indole, diethyl malonate, and phenol were coupled smoothly with oxytripyrrolidino-phosphonium in high yields. Sodium terr-butoxide was found to be an excellent base to ensure a clean and complete reaction. 

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