Microwave-assisted synthesis and stereochemical study of N-aryl-N´-acylhexahydropyrimidines

JUAN A. BISCEGLIA; ROMINA A. TORRES; LILIANA R. ORELLI

Florianópolis. Brasil

Conferencia; CLAFQO 10; 2009

MICROWAVE-ASSISTED SYNTHESIS AND STEREOCHEMICAL STUDY OF N-ARYL-N´-ACYLHEXAHYDROPYRIMIDINES Juan A. Bisceglia, Romina A. Torres, Liliana R. Orelli. Departamento de Química Orgánica. Facultad de Farmacia y Bioquímica. Universidad de Buenos Aires. CONICET. Junin 956. (1113) Buenos Aires. Argentina. Email: jab@ffyb.uba.ar. Structural features of amides have been widely studied by NMR spectroscopy and molecular modeling, as they represent model compounds for the peptide bond. Cyclic aminals are interesting as bioprecursors of 1,n-diamines or carbonyl compounds with pharmacological properties. In this communication we present the stereochemical study of some novel tertiary amides derived from the hexahydropyrimidine nucleus (1), together with a new method for their synthesis. Compounds 1 were prepared with satisfactory yields by microwave assisted condensation of the corresponding aminoamides and aqueous formaldehyde. The planar arrangement of the substituents in amides, due to partial (O)C-N double bond character, entails the existence of non isolable E/Z diastereoisomers , which can be observed as two separate species in the corresponding NMR spectra.In particular, tertiary amides show comparable populations of both rotamers. We present here the assignment of the 1H and 13C NMR spectra of the E/Z diastereoisomers of compounds 1. Differential assignment of 1H resonances was made on the basis of chemical shifts of model compounds, and confirmed by NOESY. Relative populations of both isomers were determined by integration of suitable 1H signals. The corresponding bidimensional HSQC spectra were used to assign 13C signals, by correlation with the previously assigned proton resonances. We also report the complete conformational analysis of some representative members, performed with the RHF/6-311G** method. The relative stabilities of E/Z diastereoisomers were influenced by the steric hindrance of the R substituent and, to a lesser extent, by the stereoelectronic nature of the substituents in the aryl moiety.