The generalized anomeric effect in the 1,3-thiazolidines: Evidence for both sulphur and nitrogen as electron donors. Crystal structures of various N-acylthiazolidines including mercury(II) complexes. Possible relevance to penicillin action

Abstract

Evidence for the generalized anomeric effect (GAE) in the N-acyl-1,3-thiazolidines, an important structural motif in the penicillins, was sought in the crystal structures of N-(4-nitrobenzoyl)-1,3-thiazolidine and its (2:1) complex with mercuric chloride, N-acetyl-2-phenyl-1,3-thiazolidine, and the (2:1) complex of N-benzoyl-1,3-thiazolidine with mercuric bromide. An inverse relationship was generally observed between the C 2– N and C 2– S bond lengths of the thiazolidine ring, supporting the existence of the GAE. (Maximal bond length changes were ∼0.04 Å for C 2– N 3, S 1– C 2, and ∼0.08 Å for N 3– C 6.) Comparison with N-acylpyrrolidines and tetrahydrothiophenes indicates that both the nitrogen-to-sulphur and sulphur-to-nitrogen GAE’s operate simultaneously in the 1,3-thiazolidines, the former being dominant. (This is analogous to the normal and exo-anomeric effects in pyranoses, and also leads to an interesting application of Baldwin’s rules.) The nitrogen-to-sulphur GAE is generally enhanced in the mercury(II) complexes (presumably via coordination at the sulphur); a ‘competition’ between the GAE and the amide resonance of the N-acyl moiety is apparent. There is evidence for a ‘push–pull’ charge transfer between the thiazolidine moieties in the mercury(II) complexes, and for a ‘back-donation’ of charge from the bromine atoms to the thiazolidine moieties in the HgBr 2 complex. (The sulphur atom appears to be sp 2 hybridised in the mercury(II) complexes, possibly for stereoelectronic reasons.) These results are apparently relevant to the mode of action of the penicillins.