Conformational Analysis of Some Cyclic Compounds by Molecular Mechanics and X-Ray Diffraction

Guy, Michael Henry Patrick (1976) Conformational Analysis of Some Cyclic Compounds by Molecular Mechanics and X-Ray Diffraction. PhD thesis, University of Glasgow.

Abstract

This thesis is composed of two parts. In part I the x-ray structural analyses of two sesquiterpenoids and two derivatives of 2-naphthol are reported, while in part II the results from molecular mechanics calculations are used to investigate the conformational processes occurring in a series of cyclo-octa-1,5-dienes and to interpret some of the stereochemical peculiarities of germacrane based sesquiterpenoids. The crystal structure analysis of the germacranolide, costunolide, was undertaken to determine its structure and stereochemistry. An incomplete structure was available at the commencement of this study, derived partially from x-ray diffraction measurements using Mo - Ka radiation and partially from synthetic and spectral observations. The diffraction data were recollected using Cu - Ka radiation in order to obtain more accurate measurements of the weaker reflexions. This technique was completely successful and allowed the structure and stereochemistry to be determined. Crystals of the guianolide, mikanokryptin, were supplied by Professor W. Hertz who, on the basis of UV, IR, and NMR spectra, had elucidated most of the stereochemistry. The configurations at C(1), C(6), and C(10) remained uncertain and the x-ray analysis removed the ambiguities at these chiral atoms. In addition, molecular mechanics calculations were carried out for the isolated 1-methylidene-cycloheptane system of mikanokryptin and these allowed observations to be made pertaining to the stereochemistry of this and other guianolides. Structure analyses of 1-methyl- and 1-isopropyl-2-naphthyl acetate were carried out as part of a series of investigations, by Dr. J. Carnduff, into the autoxidation of 2-naphthols. It was anticipated that the isopropyl derivative would have been substantially more strained than the 1-methyl compound because of differences in the rates of autoxidation of the corresponding 2-naphthols. The observed structures did not support this view. Molecular mechanics calculations for syn-3,7-dibromo-cis, cis-cyclo-octa-1,5-diene found the twist-boat conformation as the global minimum, the geometry of which was very similar to that found in an earlier x-ray analysis. The complete pseudorotational cycle was also investigated using this technique. A similar study was carried out for the anti-3,7-dibromo isomer. The conformational processes in the parent diene, cis,cis-cyclo-octa-1,5-diene, were the subject of a variable temperature NMR investigation by Professor P. A. L. Anet and molecular mechanics calculations were used to interpret these spectra and to reproduce the minimum energy geometry found by electron diffraction measurements. The anti-3,7-dimethyl derivative has recently been synthesized by Professor P. Heimbach. He kindly supplied a sample of his product for variable temperature NMR analysis and molecular mechanics calculations have been performed with a view to interpreting the spectra. The final chapter reports a series of calculations on the stereochemistry of germacranolides. The force field used was able to reproduce the geometry of costunolide,which had been the subject of an x-ray analysis described earlier in this thesis. Subsequent calculations on the two frequently occurring conformations of the cyclodecadiene system in germacranolides have been used to investigate the stabilities of the various modes of lactone-cyclodecadiene fusion apparent in these sesquiterpenoids and to correlate the conformation of the lactone function with both the fusion and the Cotton effect at 260nm.

• Item Type: Thesis (PhD)
• Qualification Level: Doctoral
• Keywords: Physical chemistry, Organic chemistry, Analytical chemistry
• Date of Award: 1976
• Depositing User: Enlighten Team
• Unique ID: glathesis:1976-78730
• Copyright: Copyright of this thesis is held by the author.
• Date Deposited: 30 Jan 2020 14:58
• Last Modified: 30 Jan 2020 14:58
• URI: https://theses.gla.ac.uk/id/eprint/78730