Stereoespecific synthesis, 1H and 13C spectroscopy, and X-ray crystallographic studies of 6,6 dibromo-3-ciano-2,2 dimethyl penam-(1R)-S-oxide

SALOMON C.J.; MASCARETTI A.; STROUSE C.; PUNTE G.

CANADIAN JOURNAL OF CHEMISTRY

NATL RESEARCH COUNCIL CANADA-N R C RESEARCH PRESS

Lugar: Ottawa; Año: 1991 vol. 69 p. 578 - 583

0008-4042

A stereospecific synthesis of 6,6-dibromo-3a-cyano-2,2-dimethylpenam-(1R)-S-oxide (2) is described. The X-ray single crystal investigation of this compound show! that it crystallizes in the mono~linic system, space group P2´, with cell parameters a = 6.194(1), b = 9.363(1), c = 9.869(1) A, P = 96.55(2)", V = 568(1) A~, and two molecules per unit cell. The structure was solved, from low temperature data, by direct methods, and refined, by least-squares procedures, to a final R = 3.17%, R,,, = 3.38%, for 122 1 observe: independent reflections. The sulfoxide configuration is R. The thiazolidine presents an envelope shape with the C(3) atom 0.56 A above the other four members of the ring mean plane. Therefore, it exhibits the conformation with a-CH3 pseudoequatorial and P-CH3 and a-CN both pseudoaxial. This conformation is different from the one reported for other penicillin sulfoxide derivatives. The geometry of the p-lactam ring is typical of the fused bicyclic penam nucleus. The ring is non-planar. The N(4) atom displays a pyramidial arrangement. The examination of crystal packing shows that molecules along a are connected by a short C-H.. .O contact. Reported single crystal studies showed two dominant conformations for the thiazolidine ring in the fused bicyclic penam nucleus: the C(3) or 2P-3a substituents both pseudoaxial, as found in 2, and the S(1) or 2P-3a substituents both pseudoequatorial, adopted by most sulfoxides. Neither of these conformations can explain the nuclear Overhauser effect data. A conformation with the substituents C2-P-methylLC3-a-H and C2-a-methyl-C3-a-CN fully eclipsed is in accordance with the experimental results in the solution. The ´H nuclear magnetic resonance data reflect the influence of the magnetic anisotropy of the CN triple bond on the gemdimethyl groups, particularly in relation with the geometrical features of the molecule. Comparison of I3C nuclear magnetic resonance chemical shifts for 2 and its parent penicillin sulfide (1) indicates configurationally dependent substituent effects, the magnitude of which can be used for the stereochemical assignment of sulfoxide groups in this series.