Side-chain alkylation of aromatics

While alkylation of aromatics with olefins or alcohols occurs at the aromatic ring over acid catalysts, alkylation of the alkyl groups proceeds over basic catalysts. Pines and coworkers reported that the side-chain alkylation of toluene with ethylene is effectively catalyzed by the use of a mixture of sodium and a promotor such as anthracene or o-chlorotoluene.  

Podall and Foster reported that the reaction of toluene with olefins with KCs, a graphite inclusion compound, gave the alkylation of the side chain. A 50% conversion of toluene to 3-phenylpentane was obtained together with higher alkylbenzenes at 298 K from toluene and ethylene. At 323 K, the main product was propylbenzene (48%) together with 3-phenylpentane and a small quantity of higher alkylated products. Similarly, the reaction of isopropylbenzene with ethylene gave a 42% yield of -amylbenzene at 473 K. 

In recent years, particular attention has been paid to the side-chain alkylation of toluene with methanol to styrene aind ethylbenzene. The commercial incentive stems from using toluene, instead of more expensive benzene, as the raw material for the 

Unland et made an extensive study of the side-chain alkylation of toluene with methanol. They confirmed the general features of the alkylation, which had been reported by other investigators. In addition, they found that the addition of certain inorganic materials such as phosphoric acid or boric acid to the ion-exchange solution improved the selectivity for the side-chain alkylation. The borate-promoted CsX 

Itoh et al. found that Rb, Li — X zeolite (Li/Rb -1- Li = 0.1) showed a higher activity than RbX for the side-chain alkylation.The assemblage of acid cmd base sites was assumed to be essential the basic sites activate the carbon atom of the side chain of toluene and the acid sites adsorb and stabilize toluene molecules. They further suggest that weakly acidic sites are generated by incorporation of Li cations and this serves also to suppress the decomposition of formaldehyde.  

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The second important use of superbases is side-chain alkylation of aromatic compounds [22, 34]. In these reactions a benzyl anion generated by the superbase catalyst subsequently attacks olefins such as ethene or propene as a nucleophile. The result of such a nucleophilic addition of a carbanion is side-chain alkylation of the arene by ethene. The reaction was commercialized by Sumitomo for the side-chain alkylation of cumene (Scheme 5, a) [34]. 

Further examples of bifunciional acid-basc catalysis are a Idol and Knoevenagel conden.salions 239, 286. 287] or side-chain alkylation of aromatic rings [I48. The better... 

Typical base-catalysed reactions that occur over alkali metal-exchanged zeolites include dehydrogenations, double bond isomerisations, side-chain alkylation of aromatics, conversion of methyl halides and a range of condensations. The reaction of alcohols over zeolites can be used to determine whether acid or base catalysis predominates. Whereas acid forms of zeolites catalyse dehydrations, leading to alkenes and the products of their subsequent reactions, basic sites catalyse dehydrogenations, leading to aldehydes and ketones. 

Basic catalysts also show very different behaviour from acid catalysts for the alkylation of aromatics. Whereas acid catalysts promote alkylation of the aromatic ring, with high shape selectivity in the important case of ZSM-5 (Chapter 8), alkali metal zeolites catalyse side chain alkylation. In the case of the reaction of toluene with methanol over Cs-X, for example, the products include ethylbenzene and styrene. The side chain alkylation proceeds by the following base-catalysed steps, (i) formation of formaldehyde from methanol, (ii) activation of the toluene by polarisation of the methyl group (tending towards carbanion formation) and (iii) nucleophilic attack of the carbanion of toluene on the carboxyl group of formaldehyde. Side chain alkylation of aromatics is therefore a special case of aldol condensation. Reactions of this... 

The benzotriazole derivatives 101 (R1 = alkyl) formed from aliphatic aldehydes, ben-zotriazole and primary aromatic amines are reduced by lithium aluminium hydride or sodium borohydride to secondary amines 102, while Grignard reagents yield compounds of type 103116. The reaction has been used for the side-chain alkylation of 2-aminopyridine (equation 42) (direct alkylation occurs predominantly at the ring nitrogen atom). 

The alkylation of toluene with nrethanol is readily catalyzed on synthetic zeolites. Previous work has shown that the aromatic-ring alkylation of toluene with methanol takes place over acid zeolites [1], while the side-chain alkylation occurs preferentialty over basic zeolites [2,3]. The side-chain alkylation of toluene with methanol, for producing a mbrtuie of styrene and ethylbenzene offers economical advantages conpared with the conventional homogeneously catalyzed Friedel-Crafts process, which use ethylene and benzene as reactants [4]. 

The side-chain alkylation reaction of aromatic hydrocarbons has also been studied using unsaturated aromatic olefins, especially styrene. Pines and Wunderlich 43) found that phenylethylated aromatics resulted from the reaction of styrenes with arylalkanes at 80-125° in the presence of sodium with a promoter. The mechanism of reaction is similar to that suggested for monoolefins, but addition does not take place to yield a primary carbanion a resonance stabilized benzylic carbanion is formed [Reaction (23a, b)j. 

The alkylation product of benzene (W) and ferf-butylbenzene (S4) with ethylene yields predominantly sec-butyl alkylates. This is the case because the ethylbenzene alkylate formed reacts very rapidly in the normal side-chain alkylation reaction. The sec-butyl aromatic alkylates much less readily. The much greater ease of side-chain alkylation over nuclear alkylation also accounts for the exclusive formation of side-chain alkylates from compounds, such as cumene, that are predominantly metalated on the ring by alkylalkali metal compounds. 

Side-chain oxidations of alkyl aromatic compounds to aromatic carboxylic acids by electrogenerated and regenerated chromic acid have been studied extensively in the case of saccharin formation from o-toluene sulfonamide This... 

Side-chain acetoxylations of alkyl aromatic compounds can be performed selectively by use of internally electrogenerated cobalt(ni) acetate (Eq. (17))... 

Side-Chain Chlorination of Arylalkanes. Alkyl-substituted aromatic compounds can easily be halogenated at the benzylic position with chlorine or bromine.107 108,142 143 a-Monohaloalkylaromatics are usually the main products with both reagents. 

Side-chain substitutions of alkyl aromatic compounds are applied in industry (Eq. 

The electrolyte may also influence the product distribution. This can be demonstrated in the case of the side-chain oxidation of alkyl aromatics [73] ... 

In all photooxidation of the toluenes, the initial step was observed to be oxidation of the side chains on the aromatic nucleus. Two oxidation sites were observed for the alkyltoluenes, either the -CH3 or the para-alkyl, and oxidation of these sites led to formation of alkylbenzaldehydes and a-ketones, respectively. Table 9.3 presents the compounds studied and percent conversion to the desired products. 

The Selectivity Relationship was shown to be applicable for substitution in the meta and para positions of toluene (Section II). The fine adherence of the -methyl group to a linear free-energy relationship (Fig. 37) is apparently typical of the behavior of the other alkyl substituents, as illustrated for the p-ethyl, p-i-propyl, and p-t-butyl groups (Figs. 38-40). Indeed, the data for electrophilic substitution in toluene are better correlated by a linear relationship than are the data for ordinary side-chain reactions of p-tolyl derivatives (Stock and Brown, 1959a). In the Extended Selectivity Treatment (Fig. 25) the side-chain reactions show a slightly greater scatter from the correlation line than the aromatic substitution reactions. 

In comparison with molecular catalysts, solid catalysts can be isolated from the reaction mixtures by filtration or used in continuous processes this is both environmentally friendly and useful in laboratory-scale experiments. The most important reactions catalyzed by solid superbases are isomerization reactions and the alkylation of substituted arenes in the side chain (Scheme 2). They proceed at room temperature or below with high yield (typically >99%). The surperbase-cata-lyzed alkylation of aromatic compounds complements the acid-type Friedel-Crafts alkylation and acylation, because the latter results in ring alkylation, whereas the former results in side-chain alkylation. 

These are particularly important as they allow the synthesis of larger organic molecules by adding alkyl (R) or acyl (RCO) side chains to an aromatic ring. 

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