Highly regioselective, base-catalyzed, biginelli-type reaction of aldehyde, phenylacetone and urea/thiourea kinetic vs. thermodynamic control

ABSTRACT

An efficient one-pot regioselective synthesis of various novel 3,4-dihydropyrimidin-2(1H)-one (DHPMs) via a three-component Biginelli-type condensation of aldehyde, phenylacetone and urea/thiourea under two different based-catalyzed conditions is described. In kinetic control path, lithium N, N-diisopropylamide (LDA-20 mol % generated in situ from n-BuLi and diisopropylamine) was used as the base, in tetrahydroforane (THF) as the solvent at 0°C. Thermodynamic control path was run with NaH as the base, in EtOH as the solvent under reflux status. The simple procedure, mild base-catalytic reaction conditions, no column chromatography and good to high yields are important features of this protocol.

GRAPHICAL ABSTRACT

KEYWORDS:

• 3,4-Dihydropyrimidin-2(1H)-one
• lithium N,N-diisopropylamide
• biginelli- type
• phenylacetone
• urea/thiourea
• kinetic-thermodynamic

Disclosure statement

No potential conflict of interest was reported by the authors.

Additional information

Funding

This work was supported by a grant from the Research Council of Shahid Beheshti University of Medical Sciences [grant no. 10445].