Electrophilic addition substituent effects

Substituent effect, additivity of, 570 electrophilic aromatic substitution and, 560-563 summary of. 569 Substitution reaction, 138 Substrate (enzyme), 1041 Succinic acid, structure of, 753 Sucralose, structure of. 1006 sweetness of, 1005 Sucrose, molecular model of. 999 specific rotation of, 296 structure of, 999 sweetness of, 1005 Sugar, complex, 974 d, 980 L, 980... 

With regard to the composition of the electrical effect, examination of the p values reported in Table XVII shows that in six of the sets which gave significant correlation, the localized effect is predominant (in these sets, either Pr < 50 or / is not significant). Thus it would appear that in so far as substituent effects are concerned, there are two major classes of electrophilic addition to the carbon-carbon double bond predominance of the localized effect or predominance of the delocalized effect. This behavior may well be accounted for in terms of the reaction mechanism. The rate-determining step in the electrophilic addition reaction is believed to be the formation of an intermediate which may be either bridged or a free carbonium ion. 

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... 

Numerous p-values for various electrophilic additions to styrene itself are available (Schmid and Garratt, 1977). Strictly speaking, the reaction constants measure only the sensitivity of the reaction to substituent effects they depend at the same time on the solvent, on the position of the transition state on the reaction coordinate (charge magnitude) and on the way in which substituent effects are transmitted (charge location). In particular, the observed trend of p-values for the chlorination ( — 3.22 Yates and Leung, 1980), bromination (—5.7 Ruasse et al, 1978) and sulfenylation ( — 2.41 ... 

The very small p- and m-values observed for the fast bromination of a-methoxystyrenes deserve comment since they are the smallest found for this electrophilic addition. The rates, almost but not quite diffusion-controlled, are amongst the highest. The sensitivity to polar effects of ring substituents is very attenuated but still significant that to resonance is nil. These unusually low p-values for a reaction leading to a benzylic carbocation are accompanied by a very small sensitivity to the solvent. All these data support a very early transition state for this olefin series. Accordingly, for the still more reactive acetophenone enols, the bromination of which is diffusion-controlled, the usual sensitivity to substituents is annulled. 

In this chapter, both intermolecular and intramolecular electrophilic [1] and nucleophilic additions [2, 3] to allenes will be discussed. For electrophilic addition, the regio- and stereoselectivity depend on the steric and electronic effects of the substituents on the allenes and the nature of the electrophiles. However, nucleophilic addition usually occurs at the central carbon atom with very limited exceptions. 

The cumulated Jt-system of allenes has been described as consisting of two comparatively unperturbed double bonds with regard to its reactivity towards nucleophiles or electrophiles [10]. Early reports on radical additions to 1,2-dienes, however, already pointed to peculiarities of the allene system concerning its reactivity towards intermediates with unpaired electrons [11-14], It was soon realized that no such correlation between polar and steric substituent effects existed, similar to what had been uncovered for the reaction of radicals with olefins, in order to predict selectivities in radical additions to cumulated dienes [4, 15],... 

Substituent effects on the solvomercuration reaction differ markedly from those on many other electrophilic additions and these have been explained by assuming that the formation of the intermediate is often rate limiting in electrophilic additions whereas the reaction of the ionic intermediate with nucleophiles is rate limiting in solvomercuration147. In other words, the solvomercuration involves a fast pre-equilibrium formation of an intermediate, followed by rate-limiting attack of the nucleophile on this species. 

The addition-elimination mechanism is also very common in the monocyclic oxygen and sulfur heterocycles (e.g. equation 20), a fact frequently cited as evidence for their low aromaticity. Pyran-2-ones can react with electrophiles at the 3- and 5-positions and pyran-4-ones at the 3-position (they also react at the carbonyl oxygen atom, but this is classified as a substituent reaction). Moreover, while the position of substitution can often be predicted on the basis of charge distribution and substituent effects, the choice of experimental conditions can also profoundly affect the outcome of the reaction, as illustrated in Schemes 2 and 3. 

The normal course of reaction of alkenes involves addition of Lewis acids (electrophiles) yielding an intermediate carbocation which is trapped by a weak nucleophile [114]. The most common electrophilic addition reactions are summarized in Ligure 6.1. If the olefin is unsymmetrically substituted, the question of regioselectivity arises. We begin by examining the effects on the olefin n system of three classes of substituents as... 

The pKa of a nitrogen is a convenient measure of its nucleophilicity in proton addition steric effects are unimportant. All other types of electrophilic attack at nitrogen are sensitive in varying degrees to steric effects from a-substituents. (Exception certain ring formation reactions as in metal chelation.)... 

Bromination of allylic positions cannot be achieved specifically by using elementary bromine, unless electrophilic addition to the rc-bond (Eq. 18) is unfavorable because the substituents have a high negative inductive effect. Efficiency of electrophilic addition of Br2 may also be diminished by steric effects. In addition to these secondary thermal reactions, the specificity of photochemical brominations of allylic positions using Br2 will also suffer from the competing (radical) addition of Br to the double bond (Eq. 19) [31]. 

Another interesting set of results relating to additivity of substituent effects in heterocyclic systems is provided by the work of Katritzky and co-workers on electrophilic substitution in acidic media for... 

It is subsequently interesting to enquire the degree of additivity of effects in electrophilic substitution and carbonium ion reactions of substituted five-membered rings, using aj, for 4-substituents and at for 5-substituents. As reasoned previously, the p values for such correlations compared with those for the equivalent reactions in benzene indicate the status of the o+ values for the heteroatoms. If the p values are the same... 

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