E/Z equilibrium in tertiary amides: stereochemical study of N-aryl-N´-acylhexahydro-1,3-diazepines

JUAN A. BISCEGLIA; LILIANA R. ORELLI

Cancún

Conferencia; 11th. Latin American Conference on Physical Organic Chemistry; 2011

CLAFQO

E/Z EQUILIBRIUM IN TERTIARY AMIDES: STEREOCHEMICAL STUDY OF N-ARYL-N´-ACYLHEXAHYDRO-1,3-DIAZEPINES Juan A. Bisceglia, Liliana R. Orelli.Departamento de Química Orgánica. Facultad de Farmacia y Bioquímica. Universidad de Buenos Aires. CONICET. Junin 956. (1113) Buenos Aires. Argentina. Email: lorelli@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 hexahydro-1,3-diazepine nucleus (1). Compounds 1 were prepared with satisfactory yields by microwave assisted condensation of the corresponding aminoamides and aqueous formaldehyde. Ar= 4-Cl-C6H4, C6H5, 4-CH3-C6H4; R= H, CH3, C2H5, C6H5a) 4-NO2C6H4OCHO/THF (R=H), or (RCO)2O/DCM/NaOH (R≠H); b) 37%H2CO/H2O/μWThe 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 sets of signals in the corresponding NMR spectra. In particular, tertiary amides 1 show comparable populations of both rotamers. We present here the unambiguous assignment of the 1H and 13C NMR spectra of the E/Z diastereoisomers of compounds 1. Differential assignment of 1H NMR resonances was made on the basis of anisotropic solvent induced shifts (ASIS) of N-CH2¬-N signals, and confirmed by NOESY. Relative populations of both rotamers were determined by integration of suitable 1H NMR signals. The corresponding HSQC spectra were used to assign 13C signals, by correlation with the previously assigned proton resonances. Analysis of the results showed that the population distribution of E/Z diastereoisomers of compounds 1 is influenced by the steric hindrance of the R substituent. N-acyl-N´-arylhexahydro-1,3-diazepines show a comparatively higher preference for the Z rotamer if compared to the corresponding six-membered cyclic aminals (hexahydropyrimidines).