Schneider, Gschwendtner, Weigand zyxwvutsrq / Empirical Force Field Calculations 7195 (15) E. V. Waage and B. S. Rabinovitch, Chem. Rev., 70, 377 (1970). (16) zyxwvutsrqpon C. F. Batten, J. Ashley Taylor, and G. G. Meisels, J. Chem. Phys., 65,3316 (1976). (17) C. F. Batten, J. Ashley Taylor, Bilin P. Tsai, and G. G. Meisels, J. Chern. Phys., 69, 2547 (1978). (18) H. M. Rosenstock, U. Dray, 8. W. Steiner, and J. T. Herron, J. Phys. Chern. Ref. Data, Suppl. I, 6 (1977). (19) P. Masclet, D. Grosjean, G. Mourier, and J. Dubois, J. Electron Spectrosc. Relat. Phenom., 2, 225 (1973). (20) The error is caused by the unnormalized nature of the ratio zyxwvutsrqp kllk2. The correct approach averages the fraction zyxwvutsrqpon kll(kl t k2) and then obtains (kll(k1 t k~))/(k2/(kl + k2)). The numerical difference between the process we use and the correct one is negligible in this case. We appreciate the helpful comments of Mr. Lew zyxwvutsrqpon Bass and Professor Michael Bowers, who pointed this out to us. (21) (a) W. Forst, "Theory of Unimolecular Reactions", Academic Press, New York, 1973, (b) P. J. Robinson and K. A. Holbrook, "Unimolecular Reac- tions", Wiley-lnterscience, New York, 1972. (22) G. G. Meisels, J. Chem. Phys., 42, 2328 (1965); Adv. Chern. Ser., zyxwvutsr 58, 243 (1966). (23) 2. Herman, Y. T. Lee, and R. Wolfgang, J. Chem. Phys., 51, 452 (1969). (24) (a) G. G. Meisels, J. Y. Park, and B. G. Giessner, J. zyxwvuts Am. Chem. SOC., 91, 1555 (1969); (b) bid., 92, 254 (1970). M. S. H. Lin and A. G. Harrison, Can. J. Chern., 52, 1813 (1974). H. Budzikiewicz, C. Djerassi. and D. H. Williams, "Mass Spectrometry of Organic Compounds", Holden-Day, San Francisco, Calif., 1967. F. P.Lossing, Can. J. Chern., 50, 3973 (1972). T. Baer, D. Smith, B. P. Tsai. and A. S. Werner, Adv. Mass Spectrorn., 7, (1978). M. Vestal and G. Lerner, Aerospace Research Laboratory Report 67-01 14 (1967). S. W. Benson. "Thermochemical Kinetics", 2nd ed., Wiley-lnterscience, New York, 1976. R. Change, "Basic Principles of Spectroscopy", McGraw-Hill, New York, 1971, p 156 ff. S. G. Lias and P. Ausloos, J. Res. Natl. Bur. Stand., 75, 589 (1971). P. Warneck, Ber. Bunsenges. Phys. Chern., 76,421 (1972). P. R. LeBreton. A. D. Williamson, J. L. Beauchamp, and W. T. Huntress, J. Chern. Phys., 62, 1623 (1975). J. K. Kim, V. G. Anicich, and W. T. Huntress, Jr., J. Phys. Chern., 81, 1798 (1977). R. A. Marcus, J. Chern. Phys., 62, 372 (1975). G. M. L. Verboom, Doctoral Dissertation, University of Nebraska-Lincoln, Oct 1978. Conformational Relaxation as Limitation of Chemical Models. Empirical Force Field Calculations and 13C NMR Shielding Effects for Some Cyclohexanes, Bicyclo[2.2.1 ]heptanes, Bicyclo[3.3. llnonane, and 1 lp-Substituted Estrenes] Hans-Jorg Schneider,* Wolfgang Gschwendtner, and Eckehard F. Weigand Contribution from the Fachrichtung Organische Chemie, Universitat des Saarlandes, D 6600 Saarbriicken 11, West Germany. Received May 7, 1979 Abstract: Molecular mechanics calculations on the title compounds demonstrate the redistribution of steric effects of concep- tual single origin over the whole molecule. Sterically induced substituent effects on I3C NMR shifts are obtained as the sum of up to ten single forces; use of nonrelaxed structures leads to gross overestimations of the interactions. A potential surface comparison between bicyclo[3.3.l]nonane and cyclohexane reveals that introduction of the bridge into cyclohexane rather ex- tends than limits the number of conformations with similar energy in the chair inversion transition state. Considerable differ- ences are found between published X-ray and force field derived structures of estrene derivatives, although the reflex angle be- tween diaxial methyl groups is similar and comparable to that in isolated cyclohexanes. A potential surface calculation shows that both the C-ring distortion and the skeleton curvature brought about by axial substituents on the steroidal 6 side induce little strain energy variation in comparison to the binding energy to steroid hormone receptors. In many studies of structure/energy relations and particu- larly of steric substituent effects, geometry variation is allowed for only in the molecule part under focus, while other parts are treated as rigid. The advent of highly efficient energy mini- mizing force fields2 enables one to calculate molecular energies for any steric distortion with relaxation of all structural pa- rameters. In a study of acetylcholine and derivatives, Gelin and Karpl~s,~ e.g., have shown that the structural flexibility thus accessible can lead to significant variations in calculated minimum geometries and transition energies. Pursuing steri- cally induced substituent effects on I3C N M R shifts, which are a most sensitive tool for recognition of remote steric dis- tortions, we realized the importance of overall conformational relaxation for the observed hi el ding.^ I3C N M R shielding variations can be obtained by calculation of intramolecular steric forces F exerted on C-H bonds,5 but it is necessary to localize the F contributions and to account for the redistri- bution of steric substituent effects with the aid of a suitable force field.4 Because of their restricted mobility, cyclohexanes, bridged analogues, and steroids lend themselves as seemingly simple mode models for the evaluation of shielding mecha- nisms. The present paper is addressed to the impact of full 0002-7863/79/1501-7195$01.00/0 conformational relaxation in these molecules, which contain some classical problems of conformational analysis. The structures were investigated with the Allinger MMl force field,2a which provides rapid access to a large range of com- pounds, including hetero-substituted ones. Some recognized shortcomings of the MMl version6 will not alter the conclu- sions of the present investigation, which aims more at relative energy distributions than at accurate minima. In view of the particular sensitivity of nonbonded interactions to parame- trization ambiguities we have also used an equation for the evaluation of nonbonded steric forces4 which is based on the Lifson-Warshel force' field. Substituted Cyclohexanes and Bicyclo[2.2. lbeptanes. Strain energy redistribution by relaxation is well known for axial substituted cyclohexanes, where repulsion between the sub- stituent and 1,3-diaxial hydrogens is not solely the destabilizing fa~tor.~ Although numerical values dissecting the different strain contributions depend on the potential functions and parametrizations used in the force fields,2,6it is not disputable that the gauche hydrogen effect between the equatorial hy- drogen at Ca (H8 in 1) and the equatorial hydrogen at Cp (H9 in 1) can be a significant factor destabilizing the conformer 0 1979 American Chemical Society