Title:Fast and Efficient One-Pot Three-Component Synthesis of Some 1,2,3,4- Tetrahydro-6-methyl-N-phenyl-5-pyrimidinecarboxamide Derivatives via Biginelli Condensation Reaction
VOLUME: 17 ISSUE: 5
Author(s):Şirin Gülten*, Ufuk Gezer and Elmas Aksanli Gündoğan
Affiliation:Department of Chemistry, Faculty of Arts and Sciences, Canakkale Onsekiz Mart University, 17020, Canakkale, Department of Chemistry, Faculty of Arts and Sciences, Canakkale Onsekiz Mart University, 17020, Canakkale, Department of Chemistry, Faculty of Arts and Sciences, Canakkale Onsekiz Mart University, 17020, Canakkale
Keywords:Acetoacetanilide, Biginelli condensation,
one-pot condensation, tetrahydropyrimidines,
thiourea, urea.
Abstract:Tetrahydropyrimidine (THPM) synthesis has an enormous importance in organic chemistry
and especially in pharmaceutical applications. Pyrimidines are the most active class of N-containing
heterocyclic compounds and have different biological properties. The heterocyclic ring system with a
thio group occupy a unique position in medicinal chemistry. This type of compounds play an important
role in synthetic drugs and in biological processes. Dihydropyrimidinethione derivatives occur widely
in nature. Several modifications of THPM-5-carboxamides have attracted considerable interest of medicinal
chemists due to their pharmacological and therapeutic properties. A series of 1,2,3,4-tetrahydro-
2-pyrimidinone/thione derivatives bearing a phenylcarbamoyl group at C-5 position were synthesized
by one-pot three-component Biginelli condensation reaction. The reaction of acetoacetanilide as the
1,3-dicarbonyl component with various aromatic aldehydes and urea/thiourea in the presence of a catalytic
amount of p-toluenesulfonic acid monohydrate (PTSA·H2O) or concentrated HCl as an efficient
catalyst leads to Biginelli compounds. We have prepared eight THPM 5-carboxamide derivatives, four
of them are new compounds. Their structures were confirmed by spectroscopic techniques and elemental
analysis. These compounds have potential applications in organic synthesis and medicinal
chemistry. We have synthesized a series of THPM-5-carboxamides by simple and efficient threecomponent
Biginelli condensation reaction. Significant benefits of the present procedure include: a)
application of inexpensive, non-toxic, environmentally friendly and easily available catalysts, b) the
reactions are easy to carry out without high temperature and the workup is very simple, c) the required
reaction times are relatively short (30-80 min with HCl and 8-24 h with PTSA·H2O), d) compatibility
with various functional groups, e) the products are isolated in good to excellent yields (50-95%).
