Nitration steric effects

If, on the other hand, the encounter pair were an oriented structure, positional selectivity could be retained for a different reason and in a different quantitative sense. Thus, a monosubstituted benzene derivative in which the substituent was sufficiently powerfully activating would react with the electrophile to give three different encounter pairs two of these would more readily proceed to the substitution products than to the starting materials, whilst the third might more readily break up than go to products. In the limit the first two would be giving substitution at the encounter rate and, in the absence of steric effects, products in the statistical ratio whilst the third would not. If we consider particular cases, there is nothing in the rather inadequate data available to discourage the view that, for example, in the cases of toluene or phenol, which in sulphuric acid are nitrated at or near the encounter rate, the... 

The importance of a primary steric effect in the nitration of alkyl-benzenes has been mentioned ( 9.1.1). The idea was first introduced by Le Fevre to account for the fact that -alkyltoluenes (alkyl = Et, -Pr,68a t-Bu ) are nitrated mainly adjacent to the methyl group. Without the rate data reported for the alkylbenzenes the effect might equally well have been accounted for by hyperconjugation. 

Davies and Warren have investigated the nitration of naphthalene, ace-naphthene and eight dimethylnaphthalenes in acetic anhydride at o °C. Rates relative to naphthalene were determined by the competition method, and the nitro-isomers formed were separated by chromatographic and identified by spectrophotometric means. The results, which are summarised in the table, were discussed in terms of various steric effects, and the applicability of the additivity rule was examined. For the latter purpose use was made of the data of Alcorn and Wells (table 10.2) relating to the nitration of monomethyl-naphthalenes at 25 °C. The additivity rule was found to have only limited utility, and it was suggested that the discrepancies might be due in part to the... 

When two positions aie compaiably activated by alkyl groups, substitution usually occurs at the less hindered site. Nitration of p-terr-butyltoluene takes place at positions ortho to the methyl group in preference to those ortho to the larger rerr-butyl group. This is an example of a steric effect. 

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. 

The X-ray structure of the unsubstituted tris(pyrazolyl)borato zinc nitrate has been solved showing a unidentate coordination mode for nitrate, in contrast with the t-butyl substituted ligand, which shows anisobidentate nitrate coordination due to the steric effects.232 A partial explanation of the reduced activity of cadmium-substituted carbonic anhydrase is offered by Parkin on the basis of the comparison of nitrate coordination to cadmium and zinc trispyrazo-lylborate moieties. A contributing factor may be the bidentate coordination supported by the cadmium that does not allow the facile access to a unidentate bicarbonate intermediate, which could be highly important to carbonic anhydrase activity.233... 

Although the intermolecular selectivity of the nitration of alkylbenzenes by nitric acid in trifluoroacetic acid is controlled by both electronic and steric factors, it is argued that intramolecular selectivity is controlled by steric effects on transition state solvation. 

Ordinarily, alkyl nitrate esters will not nitrate amines under neutral conditions. However, Schmitt, Bedford and Bottaro have reported the use of some novel electron-deficient nitrate esters for the direct At-nitration of secondary amines. The most useful of these is 2-(trifluoromethyl)-2-propyl nitrate, which nitrates a range of aliphatic secondary amines to the corresponding nitramines in good to excellent yields. Nitrosamine formation is insignificant in these reactions. 2-(Trifluoromethyl)-2-propyl nitrate cannot be used for the nitration of primary amines, or secondary amines containing ethylenediamine functionality like that in piperazine. Its use is limited with highly hindered amines or amines of diminished nucleophilicity due to inductive or steric effects. 

The high -selectivity in bicydoaimelated benzenes toward nitration has previously been partially attributed to increased steric effects. See Section 2.2. For previous attempts to establish relative steric effects in benzocycloalkenes, see Arnold, R. T. Webers, V. J. Dodson, R. M. J. Am. Chem. Soc. 1952, 74,368 and references diereia... 

Given this behavior (little selectivity in distinguishing between different substrate molecules), the selectivity relationship would predict that positional selectivity should also be very small. However, it is not. For example, under conditions where nitration of p-xylene and 1,2,4-trimethylbenzene takes place at about equal rates, there was no corresponding lack of selectivity at positions within the latter.83 Though steric effects are about the same at both positions, more than 10 times as much 5-nitro product was formed as 6-nitro product. 

The importance of the steric effect accounts for the spread of the data for lf-N in the substitution reactions. Nitration and non-catalytic chlorination, reactions of modest steric requirements, define points which fall above the arbitrary reference line. Bromination, a reaction of somewhat greater steric requirements, is not accelerated to the extent anticipated on the basis of the results for nitration or chlorination. The benzoylation reaction with large steric requirements is two orders of magnitude slower than the equally selective chlorination reaction. The unusually small ratio for lf-N/2f-N for the acylation reaction is a further indication of the steric effects. Apparently, the direct substitution reactions of naphthalene respond to the retarding steric influence of the peri hydrogen in much the same way as for other ortho substituents. 

Consider the nitration of toluene (Following fig.). The amount of meta substitution is very small as expected and there is a preference for the ortho and para products. The formation of more ortho substitution compared to para substitution is due to the fact that there are two ortho sites on the molecule to one para site and so there is double the chance of ortho attack to para attack. Based on pure statistics it would be expected that the ratio of ortho to para attack to be 2 1. In fact, the ratio is closer to 1.5 1. In other words, there is less ortho substitution than expected. This is because the ortho sites are immediately next door to the methyl substituents and the size of the substituent tends to inference with ortho attack— a steric effect. The significance of the steric effect will vary according... 

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