Proton chemical shifts in NMR .10. Bromine and iodine substituent chemical shifts (SCS) and an analysis of the contributions to the SCS in halocyclohexanes

A model for the prediction of the proton chemical shifts in substituted alkanes (CHARGE4) has been extended to include a variety of bromo-and iodo-alkanes. These include iodo-and bromo-cyclohexane and trans-1,2-dibromocyclohexane, for which the proton chemical shifts in the distinct conformers have been obtained at low temperatures where the ring inversion is slow on the NMR timescale. The bromine and iodine SCS are shown to be multifunctional. The short range effects (three bonds or less) are calculated from the partial atomic charges obtained from the CHARGE scheme. Bromine and iodine substituents beta to a methine proton produce an enhanced SCS, which increases with the number of attached carbons, i.e. RR'CHX > RCHXY (R,R' = alkyl group). The long range (>three bonds) effects are shown to be due to the electric field of the C-X (X = Br or I) bond plus the steric effect of the halogen atom. This model predicts bromine SCS in a variety of cyclic bromoalkanes over 118 data points with an error of 0.07 ppm, and iodine SCS over 96 data points to 0.09 ppm. Systems considered include haloethanes, -propanes, -cyclohexanes, -bornanes, -norbornanes, -adamantanes and -steroids. The accurate prediction of bromine and iodine SCS together with the previous analyses of the chloro and fluoro SCS allows the proton SCS in axial and equatorial halocyclohexanes to be analysed in terms of the calculated contributions in CHARGE4, Le. charge, steric, linear electric field and magnetic anisotropy terms. The beta- and gamma-halogen SCS are determined by charge effects. The beta (CHX) proton chemical shifts are in the order F > I > Br > CI for both the axial and equatorial conformers. This order is accounted for by a general electronegativity function plus a heavy atom effect (where I > Br > Cl). In contrast the gamma (vicinal) proton SCS are in the order F < Cl < Br < I and also show no orientation dependence. These are given by a polarisability functional dependence in CHARGE4. Protons in a 1,3-syn-diaxial orientation with the substituent, i.e. H-3,5-ax, in the axial conformer are heavily influenced by the direct steric effect of the halogen substituent for Cl, Br and I, but, the influence of the C-X linear electric field is also appreciable. The other proton of this methylene group (H-3,5-eq) has a compensating 'push-pull' upheld shift. For fluorine no steric effects are observed. The C-X linear electric field term is the dominant interaction for the remaining protons. In particular all the proton SCS in the equatorial conformer (except the beta and gamma SCS) are given by this term. The general good agreement with the observed SCS supports this interpretation,though the influence of other interactions is possible for certain protons. No C-X anisotropy term was needed in this scheme. The characterisation of the chlorine, bromine and iodine steric terms shows that the steric term coefficients are proportional to the polarisability, but not to the ionisation energy of the substituent, supporting the interpretation that this term is due to van der Waal's interactions and not to the quadratic electric field.