Methyl effects

This technique provides quantitative information about tautomeric equilibria in the gas phase. The results are often complementary to those obtained by mass spectrometry (Section VII,E). In principle, gas-phase proton affinities, as determined by ICR, should provide quantitative data on tautomeric equilibria. The problem is the need to correct the measured values for the model compounds, generally methyl derivatives, by the so-called N-, 0-, or S-methylation effect. Since the difference in stability between tautomers is generally not too large (otherwise determination of the most stable tautomer is trivial) and since the methylation effects are difficult to calculate, the result is that proton affinity measurements allow only semi-quantitative estimates of individual tautomer stabilities. This is a problem similar to but more severe than that encountered in the method using solution basicities (76AHCS1, p. 20). 

In the field of azoles, Catalan, Abboud, and Elguero [87AHC(41)187] carried out a series of studies which show the interest of the ICR method for a case where the correction always corresponds to an N-methylation effect which can be estimated accurately. This is the case for (1) the annular tautomerism of indazole and its relationship with the annulation effect... 

Pawlowska D, Moniuszko-Jakoniuk J, Soltys M. 1985a. Parathion-methyl effect on the activity of hydrolytic enzymes after single physical exercise in rats. Pol J Pharmacol 37 629-638. 

Fig. 7 Comparison of the X-dependence of the a-methyl effect in bromination and hydration of X-substituted styrenes (data from Ruasse et al, 1978).

An unusually large ( + 7.45 ppm) 7-SCS of a methyl group at C(7) was observed in cis-pinane (327) when compared with norpinane (326) (499). This difference does not originate only in the methyl effect transmitted through the bonds also, the 7g-effect from C(3) is missing due to the flip of the six-membered ring (499). In the trans isomer 328 the C(7) signal shows an upfield shift of 3.5 ppm, as expected (499). 

A significant decrease in reactivity was observed when the IV-aryl zinc enamide generated from 4-methylaniline was used. It was suggested that this 2-methyl effect on reactivity may arise from a steric effect contributing to the conformational stabilization of the transition state. These recent results have thus greatly expanded the scope of the so-called olefinic aldol condensation as the experimental procedure is quite simple and applicable to a variety of monosubstituted or aqa-disubstituted alkenes. 

Examination of plots of the enthalpies of formation of the various halide homologous series in the gaseous or liquid phase versus the number of carbon atoms immediately reveals at least two features. First, the enthalpy of formation of the methyl halide23 in any monohalogenated -alkyl series deviates from the otherwise apparently linear relationship established by the higher members of the series. This methyl effect is well-known2,24 and is dependent on specific interactions of adjacent nonbonded atoms which become... 

Table 4 Methyl Effects in Alkenes at the Position of Electrophilic Attack (Reactions with the p-Methoxy-Substituted Benz-hydryl Cation, An(Ph)CH+, CH2C12, -70° C)...

Swanson, R, V, Glazer, A, N, (1990), Phycobiliprotein methylation. Effect of the y-N-methy-lasparagine residue on energy transfer in phycocyanin and the phycobilisome. J. Mol. Biol. 214, 787-796. 

The effect of introducing a methyl group at the P-position is to decrease the rate by a factor of 4. The second methyl produces a more pronounced reduction by a factor of 9 as the transition state becomes more crowded. The third methyl group produces a massive rate decrease by a factor of 7000 this last methyl effectively blocks access to the ethoxide ion as it approaches the reaction centre. 

However, there are many cases where an open-chain radical gives stereoselectivity that is less obvious. The radical 7.103 can be expected to attack anti to the donor substituent, but the major product 7.104 in the capture of a bromine atom implies a conformation which is no longer obviously the preferred one, since the two alkyl substituents are gauche rather than anti.1035 This is another inside methyl effect (see pp. 233 and 242) allowing the bromide to attack close to the small substituent, the hydrogen atom. 

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