Conformations and conformational changes of 3-isobutyl- and 3-neopentyl-rhodanines. A case of steric attraction studied by X-ray crystallography, NOE effects and force-field calculations

Abstract

An X-ray crystallographic study of 3-neopentyl-5-phenylrhodanine [3-neopentyl-5-phenyl-2-thioxo-2,3dihydro-1,3-thiazol-4(5H)-one 4] shows that the crystal is composed of the syn form, previously supposed to be less stable than the anti form. MM2(91) calculations also predict the syn form to be the most stable one due to an attractive steric effect, mainly between two methyl groups of the tert-butyl group and the nearest carbon and hydrogen atoms in the benzene ring. MM2 calculations of the barriers to rotation the 3-isobutylrhodanines 1 and 3 and on the 3-neopentyl analogues 2 and 4 reproduce the experimental barriers quite well and indicate that the preferred path of rotation of the 3-substituent is with the isopropyl or tert-butyl group passing the carbonyl rather than passing the thiocarbonyl group.

A substantial NOE enhancement was observed between tert-butyl and phenyl protons, but this was not strong enough to exclude the possibility that it was caused by a minor form present in ca. 30%.