Methyl substitution effects

Furthermore, it has been demonstrated in acetals of phenyl alkyl ketones that the presence of the aromatic moiety at the anomeric carbon induces a further stabilization resulting in very strong anomeric stabilization.29 This phenomenon is reminiscent of the stronger methyl substitution effects discussed above for 1,3-dioxolane and 1,3-dioxane (see also Table 1) than for alkyl ethers and alkanes. 

It was shown that the protonation regioselectivity was strongly controlled by methoxy and hydroxyl substituents, whose directive effects overwhelmed the methyl substitution effects." Regiocontrol by —OMe and —OH substituents, and its stronger influence relative to methyl groups, was also observed in the nitration and bromination reactions (Fig. 21). Regioselectivities observed in the nitration and bromination reactions in representative cases were the same as those via protonations. 

An experimental Acan be derived from the temperature dependence of the second-order rate constant, which yielded a value of 25.9 kcal/mol.59 Although it appears that this disagrees with the computed free energy of activation (16.6 kcal/ mol) for the reaction of H3N + CH3SH2 in water, the difference actually originates from the intrinsic reactivity of the two reactions. The additional methyl group substitutions both on the nucleophile and substrate raise the gas-phase barrier by 10 kcal/mol to a value of 10.5 kcal/mol at the HF/6-31G(d) level. Taking the methyl substitution effect into account, the computed solvation effect in fact is in accord with experiment,59 which is about 15 kcal/mol (25.9 — 10.5 kcal/mol). 

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