Substituent rate factors

The extensive kinetic data available for quaternization of substituted pyridines and derivatives, such as benzologs and diazines, under a uniform set of conditions make possible the calculation of substituent rate factors that are of considerable value in dealing with new substrates. When a heteroaromatic molecule has two or more nucleophilic annular positions that can react, often it is possible to estimate, in some cases very accurately, the ratio of quaternized products using these rate factors. 

Substituent Rate Factors for the Calculation of Isomer Ratios Resulting from the Quaternization of Azines with Methyl Iodide in DMSO°... 

An extensive set of substituent rate factors has been derived for the N-methylation of pyridazines. They differ from those reported in Table II in that they represent differences between ortho and meta rate factors, rather than factors for individual positions. They should be consulted when considering pyridazines because the steric effects are likely to be more similar for ortho-substituted pyridazines than for pyridines.108 In some cases the pyridazine rate factors give calculated isomer ratios that are in better agreement with observed values than those using the data in Table II. 

Substituent Rate Factors (Logarithmic Values) from /V-Methylation of Pyridine Derivatives by Methyl Iodide in DMSO to be Used for Predicting the Regioselectivity in Polyazines Quaternization... 

Substituents in pyridinium salt Relative rates Isomer proportions (partial rate factors) i 0 p-ratio... 

The applicability of the two-parameter equation and the constants devised by Brown to electrophilic aromatic substitutions was tested by plotting values of the partial rate factors for a reaction against the appropriate substituent constants. It was maintained that such comparisons yielded satisfactory linear correlations for the results of many electrophilic substitutions, the slopes of the correlations giving the values of the reaction constants. If the existence of linear free energy relationships in electrophilic aromatic substitutions were not in dispute, the above procedure would suffice, and the precision of the correlation would measure the usefulness of the p+cr+ equation. However, a point at issue was whether the effect of a substituent could be represented by a constant, or whether its nature depended on the specific reaction. To investigate the effect of a particular substituent in different reactions, the values for the various reactions of the logarithms of the partial rate factors for the substituent were plotted against the p+ values of the reactions. This procedure should show more readily whether the effect of a substituent depends on the reaction, in which case deviations from a hnear relationship would occur. It was concluded that any variation in substituent effects was random, and not a function of electron demand by the electrophile. ... 

As has been noted above, there is no gross change in the mechanism of nitration of PhNH3+ down to 82 % sulphuric acid. The increase in o- andp-substitution at lower acidities has been attributed differential salt effects upon nitration at the individual positions. The two sets of partial rate factors quoted for PhNH3+ in table 9.3 show the effect of the substituent on the Gibbs function of activation at the m- and -positions to be roughly equal for reaction in 98 % sulphuric acid, and about 28 % greater at the -position in 82 % sulphuric acid. ... 

The nitration of nitro- and dinitro-biphenyls has been examined by several workers. i - As would be expected, nitration of the nitro-biphenyls occurs in the phenyl ring. Like a phenyl group, a nitrophenyl group is 0 -directing, but like certain substituents of the type CH CHA ( 9.1.6) it is, except in the case of w-nitrophenyl, deactivating. Partial rate factors for the nitration at o °C of biphenyl and the nitro-biphenyls with solutions prepared from nitric acid and acetic anhydride are given below. The high o p-v2X o found for nitration of biphenyl... 

These and other studies of the relative substituent effects of X and CH X in nitration were considered in terms of the transmission factor a of the methylene group. To avoid complications from conjugative interactions, attention was focussed mainly on substitution at the meta-position, and ct was defined in terms of partial rate factors by the equation ... 

These relative rate data per position are experimentally determined and are known as partial rate factors They offer a convenient way to express substituent effects m elec trophilic aromatic substitution reactions... 

Of the groups shown which is the most likely candidate for substituent X based on the par tial rate factors for chlonnation ... 

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... 

Partial rate factors have the significance that a factor greater than unity represents activation of that site by the substituent Y relative to hydrogen, and a factor less than unity represents deactivation. 

Nesmeyanov et a/.546 have also measured the effects of substituents in deuteration of ferrocene by deuterated trifluoroacetic acid in dichloromethane at 25 °C. Rate coefficients were measured for ferrocene and its derivative in a range of such acid mixtures, the composition of which was omitted, and in some cases the rate of exchange for ferrocene was calculated on the basis of a linear relationship between log and —H0. Results including the calculated knl values are given in Table 161. It should be noted that, in discussing those results, the authors quoted the incorrect partial rate factors for dedeuteration of toluene arising from the use of the incorrect data for benzene (see p. 199). This should be taken into account... 

The lack of steric hindrance is also shown by the kinetic data for p-xylene, mesitylene, and durene, the observed reactivities being close to those calculated by the additivity principle. The additivity principle has also been tested for the last seven compounds in Table 177, and for the first five of these it holds very well. If one assumes a value for/3Me0 of ca. 4.0 and takes the average of the values listed in the table for the methyl substituent partial rate factors, then the observed calculated reactivity ratios are 1.6, 0.85, 0.75, 1.4 and 1.0. For the last two compounds in the table the ratios are 5.3 and 4.1, the reason for this being unknown. 

Once we know the partial rate factors, we can predict the proportions of isomers to be obtained when two or more groups are present on a ring, if we make the assumption that the effect of substituents is independent. For example, if the two methyl groups in m-xylene have the same effect as the methyl group in toluene, we can calculate the theoretical partial rate factors at each position by multiplying those from toluene, so they should be as indicated ... 

Substituents have a much smaller effect than in electrophilic or nucleophilic substitution hence the partial rate factors (see p. 690) are not great. Partial rate factors for a few groups are given in Table 14.2. ... 

Abramovitch, Roy, and Uma 51> disagreed with this, pointing out a number of inconsistencies with that conclusion. Thus, while the total rate ratios are not much different from unity, as expected for a homolytic substitution, the values of °h A = 1.0, °HeA = 0.96, and °hA = 0.80 do not support this mechanism since such electron-donating substituents should facilitate attack by an electrophilic free radical 59-60> and lead to total rate ratios greater than unity. Also, the partial rate factor calculated for attack at the meta position of toluene was unusually low, and it is not clear why this position should be deactivated towards attack either by a free radical or by an electrophilic species. 

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