Electrophilic substitution relative rates

Reactivity-selectivity relationships play an important part in free radical chemistry for the same reasons as in carbene chemistry and electrophilic substitution. Absolute rate constants for free radical reactions are not generally available (and when they are known they are often associated with large systematic errors), and the use of relative rate studies is an important technique in the study of free radical reactions. A comprehensive monograph dealing with various... 

Aromatic compounds (eqs 16 and 17) are acylated by PhCOCI in the presence of a Lewis acid such as AICI3, TiCU, BF3, SnCU, ZnClz, or FeClz, or of a strong acid such as polyphos-phoric acid or CF3SO3H. Metallic A1 or Fe and iodine (in situ formation of a Lewis acid) can also act as a catalyst. Various solvents that have been used to perform this reaction are CSz, CH2CI2, 1,2-dichloroethane, nitrobenzene, and nitromethane. PhCOCI is less reactive than aliphatic carboxylic acid chlorides (with benzene in nitromethane the relative reaction rates are Ph-COCl MeCOCl = 6 100). As for all electrophilic substitutions, the rate and the regioselectivity of the acylation closely depend on the nature and on the position of the substituents on the aromatic system (eqs 16 and 18 ). The nature of the solvent can also exert a strong influence. ... 

The relative basicities of aromatic hydrocarbons, as represented by the equilibrium constants for their protonation in mixtures of hydrogen fluoride and boron trifluoride, have been measured. The effects of substituents upon these basicities resemble their effects upon the rates of electrophilic substitutions a linear relationship exists between the logarithms of the relative basicities and the logarithms of the relative rate constants for various substitutions, such as chlorination and... 

The heats of formation of Tt-complexes are small thus, — A//2soc for complexes of benzene and mesitylene with iodine in carbon tetrachloride are 5-5 and i2-o kj mol , respectively. Although substituent effects which increase the rates of electrophilic substitutions also increase the stabilities of the 7r-complexes, these effects are very much weaker in the latter circumstances than in the former the heats of formation just quoted should be compared with the relative rates of chlorination and bromination of benzene and mesitylene (i 3 o6 x 10 and i a-Sq x 10 , respectively, in acetic acid at 25 °C). 

Rate data are also available for the solvolysis of l-(2-heteroaryl)ethyl acetates in aqueous ethanol. Side-chain reactions such as this, in which a delocalizable positive charge is developed in the transition state, are frequently regarded as analogous to electrophilic aromatic substitution reactions. In solvolysis the relative order of reactivity is tellurienyl> furyl > selenienyl > thienyl whereas in electrophilic substitutions the reactivity sequence is furan > tellurophene > selenophene > thiophene. This discrepancy has been explained in terms of different charge distributions in the transition states of these two classes of reaction (77AHC(21)119>. 

The effect of substituents on electrophilic substitution can be placed on a quantitative basis by use ofpartial rate factors. The reactivity of each position in a substituted aromatic compound can be compared with that of benzene by measuring the overall rate, relative to benzene, and dissecting the total rate by dividing it among the ortho, meta, and para... 

These relative rate data per position are experimentally detennined and are known as partial rate factors. They offer a convenient way to express substituent effects in electrophilic aromatic substitution reactions. 

Evidently S, is a measure of intramolecular selectivity because it involves a ratio, the contribution of the benzene substitution rate disappears, and the selectivity factor expresses the selectivity of the reagent X in Eq. (7-83) for the para position relative to the meta position. Each individual partial rate factor, on the other hand, is expressive of an inteimolecular selectivity thus p is a measure of the selectivity of the reagent for the para position in CgHsY relative to benzene. It was observed that Eq. (7-85), where Cmc is a constant, is satisfied for a large number of electrophilic substitutions of toluene. 

Bromodeboronation has acquired a particular significance in recent theories of electrophilic substitution and briefly this has arisen since it was supposed to have a very high r factor relative to its p factor in a Yukawa-Tsuno analysis. (For a fuller discussion see ref. 729). It had been suggested729 that some of the rate coefficients determined for the reaction (Table 254) may be in error due to concurrent bromodeprotonation, and a reinvestigation730 of this possibility has revealed a number of points ... 

Waters61 have measured relative rates of p-toluenesulfonyl radical addition to substituted styrenes, deducing from the value of p + = — 0.50 in the Hammett plot that the sulfonyl radical has an electrophilic character (equation 21). Further indications that sulfonyl radicals are strongly electrophilic have been obtained by Takahara and coworkers62, who measured relative reactivities for the addition reactions of benzenesulfonyl radicals to various vinyl monomers and plotted rate constants versus Hammett s Alfrey-Price s e values these relative rates are spread over a wide range, for example, acrylonitrile (0.006), methyl methacrylate (0.08), styrene (1.00) and a-methylstyrene (3.21). The relative rates for the addition reaction of p-methylstyrene to styrene towards methane- and p-substituted benzenesulfonyl radicals are almost the same in accord with their type structure discussed earlier in this chapter. 

TABLE 11.3 Relative Rates and Product Distributions in Some Electrophilic Substitutions on Toluene and Benzene... 

What we shall be doing in the discussion that follows is comparing the effect that a particular Y would be expected to have on the rate of attack on positions o-/p- and m-, respectively, to the substituent Y. This assumes that the proportions of isomers formed are determined entirely by their relative rates of formation, i.e. that the control is wholly kinetic (cf. p. 163). Strictly we should seek to compare the effect of Y on the different transition states for o-, m- and p-attack, but this is not usually possible. Instead we shall use Wheland intermediates as models for the transition states that immediately precede them in the rate-limiting step, just as we have done already in discussing the individual electrophilic substitution reactions (cf. p. 136). It will be convenient to discuss several different types of Y in turn. 

So far as the overall substitution reaction (— 107) is concerned, marked differences from electrophilic and nucleophilic attack become apparent as soon as the behaviour of substituted benzene derivatives (C6HjY) is considered. Thus homolytic attack on C6H5Y is found to be faster than on C6H6, no matter whether Y is electron-attracting or -withdrawing, as shown by the relative rate data for attack by Ph ... 

The very small spread in relative rate, as Y is varied, is in marked contrast to electrophilic substitution, e.g. nitration, on the same substrates where the spread in relative rate would have been =108. Though it should be remembered that phenylation involves attack by a species of low polarity. 

Electrophilic substitution in furan, thiophene, selenophene and pyrrole has, up to 1970, been comprehensively reviewed by Marino.66 Italian workers have determined the relative reactivities of selenophene and thiophene as well67 relative rates are given in Table I. Including furan, the order of reactivity is furan > selenophene > thiophene. 

Relative Rates of Electrophilic Substitution for Selenophene and Thiophene... 

Individual substitutions may not necessarily be true electrophilic aromatic substitution reactions. Usually it is assumed that they are, however, and with this assumption the furan nucleus can be compared with others. For tri-fluoroacetylation by trifluoroacetic anhydride at 75 C relative rates have been established, by means of competition experiments 149 thiophene, 1 selenophene, 6.5 furan, 1.4 x 102 2-methylfuran, 1.2 x 105 pyrrole, 5.3 x 107. While nitrogen is usually a better source of electrons for an incoming electrophile (as in pyrrole versus furan) there are exceptions. For example, the enamine 63 reacts with Eschenmoser s salt at the 5-position and not at the enamine grouping.150 Also amusing is an attempted Fischer indole synthesis in which a furan ring is near the reaction site and diverted the reaction into a pyrazole synthesis.151... 

According to results from laser flash photolysis, the p-(methoxyphenyl) sulfanyl radical adds exclusively to the central atom in of 2,4-dimethylpenta-2,3-diene (If) with a rate constant of 1.1 x 10s M-1 s-1 (23 1 °C) (Scheme 11.6) [45], A correlation between the measured rate constants for addition of para-substituted arylsulfanyl radicals to allene If was feasible using Brown and Okomoto s o+ constant [46], The p+ value of 1.83, which was obtained from this analysis, was interpreted in terms of a polar transition state for C-S bond formation with the sulfanyl radical being the electrophilic part [45]. This observation is in agreement with an increase in relative rate constant for phenylsulfanyl radical addition to 1-substituted allene in the series of methoxyallene lg, via dimethylallene Id, to phenylsulfanylallene lh, to ester-substituted 1,2-diene li (Table 11.2). 

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