Versatility of Alternative Reaction Media: Water-Mediated Domino and Green Chemical Synthesis of Pyrimido[1,2-a]benzimidazole Under Nonconventional Conditions

Abstract

A convenient and clean water-mediated synthesis of a series of 4-amino-2-aryl-1,2-dihydro pyrimido[1,2-a]benzimidazoles (4) is reported using alternative nonconventional energy sources. The products are obtained in shorter times with excellent yields (78–89%) from the multicomponent reaction of 2-aminobenzimidazole (1), malononitrile/ethylcyanoacetate (2a/b), and carbonyl compounds (3). The reaction is found to be general with respect to the cyclic and acyclic carbonyl compounds. The procedure does not involve the use of any additional reagent/catalyst, produces no waste, and represents a green synthetic protocol with high atom economy.

Keywords:

• Aqueous media
• microwave irradiations
• pyrimido[1, 2-a]benzimidazole

ACKNOWLEDGMENTS

Financial assistance from the Council for Scientific and Industrial Research (01/2248/08/EMR-II) (9/149/398/2005/EMR-I), New Delhi are gratefully acknowledged. We are also thankful to the Regional Sophisticated Instrumentation Centre Chandigarh, and Central Drug Research Institute, Lucknow, for the elemental and spectral analyses.

Notes

Note. Power = 600 W for water and 360 W for alcohol.

^a Multicomponent reactions carried out in one pot.

^b Cetyl trimethyl ammonium bromide is used as phase-transfer catalyst for entries ix and x.

^c Alkene-nitrile synthesized in situ by malononitrile (2)+carbonyl compound (3).

^d Anil synthesized in situ by 2-aminobenzimidazole (1)+carbonyl compound (3).

^e 5 + 4 indicates that first irradiation for 5 min gave intermediate alkene-nitrile (detected by TLC), which was synthesized in situ, and then further irradiation for 4 min after adding 2-aminobenzimidazole.

^f 4 + 5 indicates that first irradiation for 4 min gave intermediate anil (detected by TLC), which was synthesized in situ, and then further irradiation for 5 min after adding malononitrile.