Conformational analysis of 1-aryl-2-H and 2-alkyl-1,4,5,6-tetrahydropyrimidines

L. R. ORELLI, I. A. PERILLO

Montana, EEUU

Congreso; XVI International Congress of Heterocyclic Chemistry; 1997

CONFORMATIONAL ANALYSIS OF 1-ARYL-2-H AND 2-ALKYL-1,4,5,6-TETRAHYDROPYRIMIDINES   Liliana R. Orelli and Isabel A. Perillo   Departamento de Química Orgánica.  Facultad de Farmacia y Bioquímica.  Universidad de Buenos Aires.  Junín 956 (1113) Buenos Aires.  Argentina                 Over the past few years, a number of groups have explored the utility of 1,4,5,6-tetrahydropirimidine moiety as a suitable replacement (bioisostere) for the ammonium group of acetylcholine.  Although many properly substituted tetrahydropyrimidine derivatives have been synthesized and evaluated as selective M1 muscarinic agonists, only few conformational studies concerning the tetrahydropyrimidine system are available in the literature.             In this communication we present the computational chemical study of a series of 1-aryl-2-alkyl -1,4,5,6,-tetrahydropyrimidines (1) (R1 = 4-Cl C6H4, R2 = H, Me, Et, iPr, tBu) together with 1H and 13C NMR data.             Minimum-energy conformations of compounds (1) were generated using the program PCMODEL (version 5.1).  In a first step, potential energy surfaces corresponding to rotation of R1 and R2, as well as ring torsional angles were obtained (Dihedral driver option).  Redundant structures were eliminated after minimization using the MMX force field as implemented in the program.  Geometries thus obtained were then optimized employing the semiempirical method AM1 (HYPERCHEM version3.0).  Correlations between computational chemical study and nmr data are discussed.  A comparison is made with 1,2-diaryl-1,4,5,6-tetrahydropyrimidines.