AB-INITIO MOLECULAR-ORBITAL CALCULATION ON CARBOHYDRATE MODEL COMPOUNDS .1. THE ANOMERIC EFFECT IN FLUORO AND CHLORO DERIVATIVES OF TETRAHYDROPYRAN

Ab initio calculations have been carried out on model compounds for th e pyranose halides 2-fluoro- and 2-chlorotetrahydropyran with either a n axially or an equatorially oriented halogen atom. Energy minimizatio n has been carried out at the STO-3G, 3-21G, 6-31G, 6-31G, 6-31+G*, a nd MP2/6-31G levels. The optimized geometries were used to calculate the energy difference between the axial and equatorial conformers with STO-3G, 3-21G, 4-31c, 6-31G, 6-31G, 6-31G**, 6-31+G*, 6-311G*, 6-31S G*, 6-311++G**, and MP2/ 6-31G* basis sets. Large differences in C-Ha l bond lengths and O-C-Hal bond angles were found between the axial an d equatorial conformers. After including the zero-point energy, therma l energy, entropy, and MP3 electron correlation corrections to energy differences calculated at 6-311++G*//6-31+G* basis set, these calcula tions favored the axial conformers by 2.4 and 2.5 kcal/mol. Solvent ef fects considerably reduce this energy difference; in the extreme case, in water, values of 0.5 and 1.5 kcal/mol were obtained for fluoro and chloro derivatives, respectively. The magnitude of the anomeric effec t depends on the solvent and was estimated to be in the range 0.9-2.8 kcal/mol for the fluoro and 2.3-3.1 kcal/mol for the chloro forms. On the basis of these results, we suggest that the 6-31+G//6-31G* proced ure is suitable for calculations of the geometry and the conformationa l energies of carbohydrate molecules. The calculated energies and geom etries provide additional data which should prove useful in the repara metrization of existing force fields to better reproduce the behavior of C-O-Hal systems.