Reactivity and positional selectivity

Table 9.7. Relative Reactivity and Position Selectivity for Nitration of Some Aromatic...

Solutions of aroyl nitrates are prepared by reaction of aroyl chlorides and silver nitrate in an inert organic solvent. These solutions react as nitrating agents in a manner similar to acetyl nitrate. The reactivity and position selectivity of toluene has been determined for a series of aroyl nitrates. The data are given below. What information do these data furnish about the mechanism of nitration by aroyl nitrates ... 

Relative reactivity and position selectivity for nitration of some aromatic compounds... 

Several research groups have also used theoretical methods in an effort to understand the activating and deactivating effects of the substituents in S Ar reactions. For example, Galabov and coworkers have developed a computational approach for determining electrophile affinity, Ea, as a measure to determine arene reactivity and positional selectivity in S Ar reactions [36]. Other recent approaches to this problem include the development of reactive hybrid orbital analysis [37], the topological analysis of electron localization function [38], the calculations of electrostatic potentials at the arene carbons [39], and several other methods. A comprehensive summary of this area is beyond the scope of this chapter however, the interested reader may consult one of the recent reviews of this topic [40]. 

Absolute rate data for Friedel-Crafts reactions are difficult to obtain. The reaction is complicated by sensitivity to moisture and heterogeneity. For this reason, most of the structure-reactivity trends have been developed using competitive methods, rather than by direct measurements. Relative rates are established by allowing the electrophile to compete for an excess of the two reagents. The product ratio establishes the relative reactivity. These studies reveal low substrate and position selectivity. 

The table below gives first-order rate constants for reaction of substituted benzenes with w-nitrobenzenesulfonyl peroxide. From these data, calculate the overall relative reactivity and partial rate factors. Does this reaction fit the pattern of an electrophilic aromatic substitution If so, does the active electrophile exhibit low, moderate, or high substrate and position selectivity ... 

Free-radical arylation of heterocyclic compounds is a relatively inefficient process in which yields of particular products greater than 50% are rare. This is the inevitable result of the high reactivity and low selectivity of aryl radicals not only is it usual for the heterocyclic compound to be attacked at each of its available positions, but, as shown in preceding sections, other by-products are numerous. Nevertheless, the method often presents the only short route to a given compound and it has been widely applied. Preparative uses are grouped in this section under the heading of the heterocyclic system concerned. 

The alcohols are intermediates in the formation of ketones. Isomerization of the products is not observed. Hydroxylation at the 2-position is favored over that at the 3-position, and the latter is preferred over hydroxylation at the 4-position. Solubility and concentration in the reaction medium, intrazeolite diffusion of the reactants, steric hindrance at the reactive carbon center, and C-H bond strength influence the reactivity and H202 selectivity (Table XXIV). The advantage of the large-pore Ti-beta over TS-1 in the oxidation of bulky alkane molecules is shown by the results in Table XXV. 

Dewar,120 as well as Brown and Olah, respectively, raised the importance of initial n complexing of aromatics in alkylations.109121 Relevant information was derived from both substrate selectivities (usually determined in competitive alkylations of benzene and toluene, or other alkylbenzenes), and from positional selectivities in the alkylation of substituted benzenes. Olah realized that with reactive alkylating agents substrate and positional selectivities are determined in two separate steps. 

The effect of additives and of modified aluminum and borohydrides has been extensively examined in efforts to enhance reactivity and improve selectivity. The system of LAH and aluminum chloride was early applied to achieving opposite regioselectivity. For example, the reduction of styrene oxide with this system takes place at the benzylic position to give 3-phenethyl alcohol as the major product, and the same effect is observed with 1,4-dialkylcyclohexene oxide (equation 17). 4... 

These substitutions are facilitated by electron release from the heteroatom pyrroles are more reactive than furans, which are in turn more reactive than thiophenes. Quantitative comparisons of the relative reactivities of the three heterocycles vary from electrophile to electrophile, but for trifluoroacetylation, for example, the pyrrole furan thiophene ratio is 5 x 10 1.5 x 10 I " in formylation, furan is 12 times more reactive than thiophene, and for acetylation, the value is 9.3. In hydrogen exchange (deuteriodeproton-ation), the partial rate factors for the a and p positions of A-methylpyrrole are 3.9 x 10 ° and 2.0 x 10 ° respectively for this same process, the values for furan are 1.6 x 10 and 3.2 x l(f and for thiophene, 3.9 X 10 and 1.0 x 10 respectively, and in a study of thiophene, a P ratios ranging from 100 1 to 1000 1 were found for different electrophiles. Relative substrate reactivity parallels positional selectivity i.e. the a P ratio decreases in the order furan > thiophene > pyrrole. ° Nice illustrations of these relative reactivities are found in acylations of compounds containing two different systems linked together. ... 

The interrelationships among catalyst activity, carbonium-ion stability, and positional selectivity have been studied in detail, with the use of substituted benzyl halides and a wide variety of Friedel-Crafts catalysts. These data indicate that no single mechanistic description can encompass all Friedel-Crafts alkylations. With very reactive catalysts, there is little selectivity with respect to competing aromatic substrates. In less reactive systems, substrate selectivity increases. Quantitative description of catalyst activity has not been achieved, but a number of Lewis acids have been grouped into four broad categories, based on their activity in catalyzing the benzylation of benzene. Some of the catalysts are listed in Table 7.1. 

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