Nucleophiles benzenes

In Brown s classification a diazonium ion is a reagent of very low reactivity and correspondingly high substrate selectivity and regioselectivity. This follows from the fact that benzenediazonium salts do not normally react with weakly nucleophilic benzene derivatives such as toluene. More reactive heteroaromatic diazonium ions such as substituted imidazole-2-diazonium ions will even react with benzene (see Sec. 12.5). 

The polarized Br molecule is then attacked by the rr electron systeu of the nucleophilic benzene ring in a slow, ru te limiting step to yield nenaromallc carbocation intermediate. This carbocotion is doubly all frecall the allyl cation. Section 11.9) and has three resonance forms ... 

In early phenol alkylation studies 61), we noticed that alkylation of phenol with ethylene occurred at 204°C, a temperature much higher than that required for ethylation of the much less nucleophilic benzene nucleus (121°C) under similar conditions. Superficially, at least, this appears to violate the classical laws of electrophilic substitution (24). Closer examination of this system 62, 64), however, showed that phenol, at moderately low temperatures, was specifically adsorbed at sites active for alkylation, thus hindering adsorption of ethylene at these same sites, and preventing generation of the electrophile necessary for attack on the phenyl nucleus. That is, alkylation by a Rideal-type mechanism see Scheme 5) cannot occur until temperatures high enough to desorb phenol from the active sites—and allow ethylene to compete for adsorption— are obtained. In such systems, alkylation can be facilitated by imposition of pressure (in the case of ethylene), or use of more polar or higher... 

An electrophilic aromatic substitution reaction begins in a similar way, but there are a number of differences. One difference is that aromatic rings are less reactive toward electrophiles than alkenes are. For example, Bi in CH2CI2 solution reacts instantly with most alkenes but does not react with benzene at room temperature. For bromination of benzene to take place, a catalyst such as FeBr is needed. The catalyst makes the Br2 molecule more electrophilic by polarizing it to give an FeBi " Br species that reacts as if it were Br. The polarized Br2 molecule then reacts with the nucleophilic benzene ring to yield a nonaromatic carbocation intermediate that is doubly allylic (Section 11.5) and has three resonance forms. 

A new catalyst 106, also derived from phenylalanine but with extra chirality, is needed for conjugate additions to crotonaldehyde. Nucleophilic benzene rings such as 107 react with good regio- and stereoselectivity24 in the same sense as 105. 

The relationship between the formylation reactions carried out with formamide derivatives and the formation of ketones when using amides of other carboxylic acids has been pointed out. The method has not been as widely exploited as one might have expected. A -Methylacetamide and N,N-dimethylaceta-mide both give substituted acetophenones when they are allowed to interact with phosphoryl chloride in the presence of nucleophilic benzene derivatives. The initial product has to be hydrolyzed. Similarly, benzamide derivatives give substituted benzophenones as exemplified in equation (62). 

The weakly nucleophilic benzene has evidently added in conjugate fashion to the enone in a kind of Friedel-Crafts reaction and we can use the Lewis add to make the enone into the necessary cation. 

The acid chloride reacts with the powerful Lewis acid, AICI3, to give an acylium cation (resonance stabilised), which is very electrophilic and reacts with the good nucleophile, benzene, in an electrophilic substitution rea ct io n. 

Analogous ort/ o-substituents on the benzoyl group show comparatively large variations in rates of cyclization. All ort/io-substituted compounds cyclize more slowly than the unsubstituted 2-benzylbenzophe-none. The variation appears to be due to the increasing steric requirements of the substituents in the expected order Br > Cl > F. In this case, the steric bulk of the substituent inhibits the attack of the electropositive carbon atom on the nucleophilic benzene ring. 

In summary, the rate of cyclization of o-benzylbenzophenones depends on several factors, the most important of which appear to be (1) the steric nature of R (and perhaps also Ri), (2) the effective positive character of the carbonyl carbon of the conjugate acid, (3) electron density at the ortho position of the nucleophilic benzene ring, and (4) the number of such positions available. 

The electrophile (Y ) adds to the nucleophilic benzene ring, thereby forming a carbocation intermediate. The structure of the carbocation intermediate can be approximated by three resonance contributors. 

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