Substituent effects alkylation

Hammett s equation, and substituent effects, 137-43 heteromolecules, 130 Holleman s product rule, 3 hyperconjugation, in nitration of alkyl-benzenes, 165-7 in nitration of positive poles, 169... 

Here again it is possible to find a linear relationship between the log (k/feo) (ko = methyl) values of 2-alkyl- and 2,4-dialkylthiazoles and between the latter value and Tafts Eg parameter (256). The value of 5 for 2,4-dialkylthiazoles is 1.472 with a correlation coefficient of 0.9994. Thus the sensitivity to substituent effects is more marked than in the case of a single substituent in the 2-position. Furthermore, the 4-position is again more sensitive than the 2-position. 

A mechanism has been proposed to rationalize the results shown in Figure 23. The relative proportion of the A -pyrazolines obtained by the reduction of pyrazolium salts depends on steric and electronic effects. When all the substituents are alkyl groups, the hydride ion attacks the less hindered carbon atom for example when = Bu only C-5 is attacked. The smaller deuterohydride ion is less sensitive to steric effects and consequently the reaction is less selective (73BSF288). Phenyl substituents, both on the nitrogen atom and on the carbon atoms, direct the hydride attack selectively to one carbon atom and the isolated A -pyrazoline has the C—C double bond conjugated with the phenyl (328 R or R = Ph). Open-chain compounds are always formed during the reduction of pyrazolium salts, becoming predominant in the reduction of amino substituted pyrazoliums. 

If, however, hydrogen is present in the a-position of the iV-alkyl substituent, 2-alkyl-oxaziridines are easily decomposed by alkali. Base attack on this H atom effects 1,2-elimination at the C—N bond. From (86) and aldimine (87) forms, and a mixture of ammonia and two carbonyl compounds is finally obtained, one of them containing the carbon atom of the original oxaziridine ring, the other originating from the IV-alkyl group (57JA5739). 

This is opposite from the order in solution as revealed by the pK data in water and DMSO shown in Table 4.14. These changes in relative acidity can again be traced to solvation effects. In the gas phase, any substituent effect can be analyzed directly in terms of its stabilizing or destabilizing effect on the anion. Replacement of hydrogen by alkyl substituents normally increases electron density at the site of substitution, but this effect cannot be the dominant one, because it would lead to an ordering of gas-phase acidity opposite to that observed. The dominant effect is believed to be polarizability. The methyl... 

The net effect is, therefore, a balance of these two components. Some of the results of the separation may be surprising, such as the relatively small contribution that resonance makes to the overall substituent effect of p-NOj. Another interesting result is the predominant resonance contribution in the alkyl series this (if real) must be attributed to hyperconjugation. 

To understand the unpredictable nature of the Pictet-Gams reaction, Hartwig and Whaley conducted the first mechanistic studies in 1949. Their work focused on substituent effects when directly attached to the ethylamine side chain. They also investigated a variety of dehydration agents in order to identify optimal reaction conditions. It was determined that formation of the isoquinoline structure was virtually impossible when alkyl or phenyl substituents were placed in the 4-position of the ethylamine side chain. 

Nitration by nitric acid in sulphuric acid has also been by Modro and Ridd52 in a kinetic study of the mechanism by which the substituent effects of positive poles are transmitted in electrophilic substitution. The rate coefficients for nitration of the compounds Pl CHi NMej (n = 0-3) given in Table 10 show that insertion of methylene groups causes a substantial decrease in deactivation by the NMej group as expected. Since analysis of this effect is complicated by the superimposed activation by the introduced alkyl group, the reactivities of the... 

Arrhenius parameters for nitration of 4-aikylphenyltrimethyiammonium ions in nitric acid-sulphuric acid mixtures (Table 12). It was argued that the observed Baker-Nathan order of alkyl substituent effect was, in fact, the result of a steric effect superimposed upon an inductive order. However, a number of assumptions were involved in this deduction, and these render the conclusion less reliable than one would like it would be useful to have the thermodynamic parameters for nitration of the methyl substituted compound in particular, in order to compare with the data for the /-butyl compound, though experimental difficulties may preclude this. It would not be surprising if a true Baker-Nathan order were observed because it is observed for all other electrophilic substitutions in this medium1. 

Table 5 shows the rate ratios between ethylenes differing by an increase by two in number of alkyl substituents. It can be observed that in solvents as different as methanol, ethanol, and acetic acid, the rate ratio is always around 10, that is of the same order of magnitude of the increase in Kf. This indicates that substituent effects are not much more influential on the kinetic constants that on Kf. A possible rationalization of the lower accelerating effects by alkyl substituents on the bromination rate, relative to what could be expected for an AdgCl mechanism on... 

The present results show that the first step of the interaction between olefins and Bt2 is the formation of CTCs, whose Kf are highly sensitive to structural effects. Both Kf ratios and reactivity ratios of olefins are scarcely affected by the solvent. An increase by two in number of alkyl substituents on the double bond increases both Kf and kobsd roughly by a factor of 103. Therefore, at variance with the expectation for an AdgCl mechanism, substituent effects are not much more influential on k tsd than on Kf. This suggests that the rates of CTC ionization be actually reduced by reversal. 

The existence of open carbocation intermediates is supported by the contrast in the pattern of alkyl substituent effects with that found in brominations, where cyclic intermediates are involved. In the latter case substitution of alkyl groups on H2C=CH2 causes a cumulative rate acceleration until all four... 

---