engleski

First example of the solvent effect on absolute conformation of chiral 3, 3-disubstituted 1, 4-benzodiazepin-2-ones

Chiral 3, 3-disubstituted 1, 4-benzodiazepin-2-ones (3S)-7 and (3S)-8 reveal solvent dependent conformational equilibria. The conformer with absolute P-conformation, with CH2X (X= p-tosyl, Cl) group in a pseudoaxial position and CH2OAc group in a pseudoequatorial position, prevails in nonpolar solvents, as shown by 1H-NMR and CD spectra. For (3S)-7 only a small shift of the conformational equilibrium in a polar solvent (DMSO) is observed, whereas compound (3S)-8 inverts to a prevailing M-conformer. The inversion barrier for M/P equilibrium is estimated on the bases of TDNMR data. For compounds (3R)-5 and (3S)-7, 8 the relative stability of the M/P conformers in the ground state is calculated by the MM2 method ; comparison of these results with CD and 1H-NMR data reveal that nonpolar solvents invert the relative stability calculated for the two conformers.

benzodiazepines; conformation; circular dichroism; Nmr

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