Substituents effects, electronic steric

The chemoselectivity of olefin bromination is reported84 to occur after the attack of the bromine on the double bond, but the formation of the bromonium ion is the slow step of the reaction. As a consequence, the distribution of products and the selectivity of addition of nucleophiles can hardly be explained by substituent effects (both steric and electronic) bonded to the C=C double bond in a fast step of the reaction. 

Hydrolysis reactions involving tetrahedral intermediates are subject to steric and electronic effects. Electron-withdrawing substituents faciUtate, but electron-donating and bulky substituents retard basic hydrolysis. Steric effects in acid-cataly2ed hydrolysis are similar to those in base-cataly2ed hydrolysis, but electronic effects are much less important in acid-cataly2ed reactions. Higher temperatures also accelerate the reaction. 

Hydroboration is highly regioselective and stereospecific. The boron becomes bonded primarily to the less-substituted carbon atom of the alkene. A combination of steric and electronic effects works to favor this orientation. Borane is an electrophilic reagent. The reaction with substituted styrenes exhibits a weakly negative p value (-0.5).156 Compared with bromination (p+ = -4.3),157 this is a small substituent effect, but it does favor addition of the electrophilic boron at the less-substituted end of the double bond. In contrast to the case of addition of protic acids to alkenes, it is the boron, not the hydrogen, that is the more electrophilic atom. This electronic effect is reinforced by steric factors. Hydroboration is usually done under conditions in which the borane eventually reacts with three alkene molecules to give a trialkylborane. The... 

Wedekind and Stauwe" studied the oxidation of 3-substituted formazans and concluded that ease of oxidation depended on the steric effects of the 3-substituent. More recently, Hegoraty et al. 100 studied the reaction of formazans with bromine. It proceeds via an odd-electron species such as 52 favoring an electronic substituent effect (Scheme 5). The rate of reaction increases with electron-donating substituents. Similar conclusions have been reached using thalium(III) as the oxidant.101,102... 

There has been a HO study of the stereoelectronic effects in methy1phosphines (90). Steric effects were found to concentrate in the HOHO and accounted for half the substituent effects on the pK values, whilst electronic effects on the HOHO was minimal.242 The relative basicities of polymethoxytriarylphosphines have been measured. Tris(2,4,6-trimethoxyphenyl)phosphine was considerably more basic than piperidine.243 The basicities of P-N compounds have been reviewed and their correlation with P-N bond lengths invest igated.2 4 4... 

The most frequently encountered hydrolysis reaction in drug instability is that of the ester, but curtain esters can be stable for many years when properly formulated. Substituents can have a dramatic effect on reaction rates. For example, the tert-butyl ester of acetic acid is about 120 times more stable than the methyl ester, which, in turn, is approximately 60 times more stable than the vinyl analog [16]. Structure-reactivity relationships are dealt with in the discipline of physical organic chemistry. Substituent groups may exert electronic (inductive and resonance), steric, and/or hydrogen-bonding effects that can drastically affect the stability of compounds. A detailed treatment of substituent effects can be found in a review by Hansch et al. [17] and in the classical reference text by Hammett [18]. 

Riichardt, Ch., and Beckhaus, H.-D. Steric and Electronic Substituent Effects on the Carbon-Carbon Bond. 130, 1-22 (1985). 

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