The Friedel-Crafts Alkylation

Biphenyl is two benzene rings joined by a single bond. The site of substitution for a biphenyl is determined by (1) which phenyl ring is more activated (or less deactivated), and (2) which position on that ring is most reactive, using the fact that a phenyl substituent is ortho, para-directing. 

Carbocations are perhaps the most important electrophiles capable of substituting onto aromatic rings, because this substitution forms a new carbon-carbon bond. Reactions of carbocations with aromatic compounds were first studied in 1877 by the French alkaloid chemist Charles Friedel and his American partner, James Crafts. In the presence of Lewis acid catalysts such as aluminum chloride (AIQ3) or ferric chloride (FeQ3), alkyl halides were found to alkylate benzene to give alkylbenzenes. This useful reaction is called the Friedel-Crafts alkylation. 

For example, aluminum chloride catalyzes the alkylation of benzene by r-butyl chloride. HCl gas is evolved. 

This alkylation is a typical electrophilic aromatic substitution, with the /-butyl cation acting as the electrophile. The /-butyl cation is formed by reaction of /-butyl chloride with the catalyst, aluminum chloride. The /-butyl cation reacts with benzene to form a sigma complex. Loss of a proton gives the product, /-butylbenzene. The aluminum chloride catalyst is regenerated in the final step. 

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Other catalysts which may be used in the Friedel - Crafts alkylation reaction include ferric chloride, antimony pentachloride, zirconium tetrachloride, boron trifluoride, zinc chloride and hydrogen fluoride but these are generally not so effective in academic laboratories. The alkylating agents include alkyl halides, alcohols and olefines. 

It should be noted that the Friedel-Crafts acylation differs from the Friedel-Crafts alkylation (compare Sections IV,3-4 and discussion preceding Section IV,1) in one important respect. The alkylation requires catal3d.ic quantities of aluminium chloride, but for acylation a molecular equivalent of aluminium chloride is necessary for each carbonyl group present in the acylating agent. This is because aluminium chloride is capable of forming rather stable complexes with the carbonyl group these complexes probably possess an oxonium... 

Isopropylbenzene is prepared by the Friedel-Crafts alkylation of benzene y using isopropyl chloride and aluminum chloride (Section 12 6) j... 

Optically active 2-arylalkanoic acid esters have been prepared by the Friedel-Crafts alkylation of arenes with optically active a-sulfonyloxy esters (40). Friedel-Crafts alkylation of ben2ene with (5)-methyl 2-(chlorosulfonyloxy)- or 2-(mesyloxy)propionate proceeded with predorninant inversion of configuration (<97%) to give (5)-methyl 2-phenylpropionate. 

Catalysts used in the polymerization of C-5 diolefins and olefins, and monovinyl aromatic monomers, foUow closely with the systems used in the synthesis of aHphatic resins. Typical catalyst systems are AlCl, AIBr., AlCl —HCl—o-xylene complexes and sludges obtained from the Friedel-Crafts alkylation of benzene. Boron trifluoride and its complexes, as weU as TiCl and SnCl, have been found to result in lower yields and higher oligomer content in C-5 and aromatic modified C-5 polymerizations. 

Drawbacks as known from the Friedel-Crafts alkylation are not found for the Friedel-Crafts acylation. In some cases a decarbonylation may be observed as a side-reaction, e.g. if loss of CO from the acylium ion will lead to a stable carbenium species 8. The reaction product of the attempted acylation will then be rather an alkylated aromatic compound 9 ... 

The synthesis of an alkylated aromatic compound 3 by reaction of an aromatic substrate 1 with an alkyl halide 2, catalyzed by a Lewis acid, is called the Friedel-Crafts alkylation This method is closely related to the Friedel-Crafts acylation. Instead of the alkyl halide, an alcohol or alkene can be used as reactant for the aromatic substrate under Friedel-Crafts conditions. The general principle is the intermediate formation of a carbenium ion species, which is capable of reacting as the electrophile in an electrophilic aromatic substitution reaction. 

The intramolecular variant of the Friedel-Crafts alkylation is also synthetically useful, especially for the closure of six-membered rings, e.g. the synthesis of tetraline 8 but five- and seven-membered ring products are also accessible ... 

Scheme 5.1-44 The Friedel-Crafts alkylation reaction (R = alkyl, X = leaving group).

Mechanism of the Friedel-Crafts alkylation reaction of benzene with 2-chloropropane to yield isopropylbenzene (cumene). 

Despite its utility, the Friedel-Crafts alkylation has several limitations. For one thing, only alkyl halides can be used. Aromatic (atyl) halides and vinylic halides do not react because aryl and vinylic carbocations are too high in energy to form under Friedel-Crafts conditions. 

An important use of the Friedel-Crafts alkylation reaction is to effect ring closure. The most common method is to heat with aluminum chloride an aromatic compound having a halogen, hydroxy, or alkene group in the proper position, as, for example, in the preparation of tetralin ... 

In this section, the reactivities of organosilicon compounds for the Friedel-Crafts alkylation of aromatic compounds in the presence of aluminum chloride catalyst and the mechanism of the alkylation reactions will be discus.sed, along with the orientation and isomer distribution in the products and associated problems such as the decomposition of chloroalkylsilanes to chlorosilanes.. Side reactions such as transalkylation and reorientation of alkylated products will also be mentioned, and the insertion reaction of allylsilylation and other related reactions will be explained. 

This section will describe the Friedel-Crafts alkylation reactions of aromatic hydrocarbons with alkenylchlorosilanes containing short chain alkenyl groups such as allyl and vinyl. The reaction will be discussed in terms of the substituent effect on silicon and the arene rings. 

Ferrocene behaves in many respects like an aromatic electron-rich organic compound which is activated toward electrophilic reactions.In Friedel-Crafts type acylation of aromatic compounds with acyl halides, ferrocene is lO times more reactive than benzene and gives yields over 80%. However, ferrocene is different from benzene in respect to reactivity and yields in the Friedel-Crafts alkylation with alkyl halides or olefins. The yields of ferrocene alkylation are often very low. and the separations of the polysubstituted byproducts are tedious. 

Vinylchlorosilanes react with aromatic compounds in the presence of Lewis acid to give the alkylation products 2-(chlorosilyl)ethylarenes. In the Friedel-Crafts alkylation of aromatic compounds, the reactivity of vinylchlorosilanes is slightly lower than that of allylchlorosilanes.Friedel-Crafts alkylation of benzene derivatives with vinylsilanes to give 2-(chlorosilyl)ethylarenes was first reported by the Andrianov group (Eq. (5))." The reactivity of vinylsilanes in the... 

The Friedel-Crafts alkylation of aromatic compounds with alkyl halides in the presence of Lewis acid is well defined in organic chemistry. However, alky-... 

Dichloroalkyl)chlorosilanes undergo the Friedel-Crafts alkylation type reaction with biphenyl in the presence of aluniinurn chloride catalyst to afford 9-((chlorosilyl)alkyl)fluorenes through two step reactions (Eq. (16)). The results obtained from the alkylation of biphenyl and the cyclization reaction to 5-membered-ring product are summarized in Table XIIE... 

The mechanism for the production of 9-((chlorosilyl)alkyl)(luorenes from the Friedel-Crafts alkylation reaction of biphenyl with (l,2-dichloroethyl)silane in the presence of aluminum chloride as catalyst is outlined in Scheme 4. At the beginning stage of the reaction, one of two C—Cl bondsof (1,2-dichloroethyl)silane (CICH2—CICH—SiXi) interacts with aluminum chloride catalyst to give intermediate 1 (a polar +C-CI - ( +C-C1—Al CI3) or a carbocation C AICU ... 

Among the Friedel-Crafts alkylations of aromatic compounds with (chlorinated alkyl)silanes, the alkylation of benzene with (tt>-chloroalkyl)silanes in the presence of aluminum chloride catalyst was generally affected by two factors the spacer length between the Cl and silicon and the electronic nature of substituents on the silicon atom of (w-chloroalkyl)silanes. As the spacer length between the C—Cl and silicon increases from (chloromethyl)silane to (/i-chloroethyl)silane to (/-chloropropyl)silane, the reactivity of the silanes increases. As the number of chloro-groups on the silicon decreases from (chloromethyl)trichlorosilanes to (chloromethyl)methyldichlorosilanes to (chloromethyl)trimethylsilanes, the... 

Zinc chloride exchanged clay catalysts have been reported to be highly active for the Friedel-Crafts alkylation and acylation reactions these are commercially sold by Contract Catalysts under the name Envirocats. These are montmorillonite catalysts modified by ZnCU and FeCli. Some of the reported examples of Friedel-Crafts reactions are given below there are claims that some of the processes are commercially practised. 

The Friedel-Crafts alkylation reaction does not proceed successfully with aromatic reactants having EWG substituents. Another limitation is that each alkyl group that is introduced increases the reactivity of the ring toward further substitution, so polyalkylation can be a problem. Polyalkylation can be minimized by using the aromatic... 

Pseudo-C3-symmetrical trisoxazoline copper(II) complexes prove to be excellent catalysts in the Friedel-Crafts alkylation of indoles with alkylidene malonates (Eq. 7.13). Water tolerance of chiral catalyst trisoxazoline/Cu(OTf)2 was examined, and it was found that the addition of up to 200 equivalents of water relative to the catalyst in /,vo-butyl... 

Reaction type (d) also complicates the Friedel-Crafts alkylation of benzene (a type c/b reaction, p. 141) by 1-bromopropane, MeCH2-CH2Br, in the presence of gallium bromide, GaBr3, as Lewis acid... 

In all that has gone before a tacit assumption has been made that the proportions of alternative products formed in a reaction, e.g. o-, m- and p-isomers, are determined by their relative rates of formation, i.e. that the control is kinetic (p. 42). This is not, however, always what is observed in practice thus in the Friedel-Crafts alkylation of methyl-benzene (Me o-/p-directing) with benzyl bromide and GaBr3 (as Lewis acid catalyst) at 25°, the isomer distribution is found to be ... 

A number of reactions have been explained on the basis of generation of carbocations. The examples include the Friedel-Crafts alkylation and arylation reactions. Besides pinacol-pinacolne rearrangement, Beckmann rearrangement and Wagner-Merwein rearrangement are other examples. 

The Friedel-Crafts alkylation of 2,5-dimethylthiophene was also studied (57). In contradistinction to thiophene itself, it was reported that this substituted thiophene alkylated readily with only a minor amount of polymerization when an active halide such as t-butyl chloride was used. With less reactive halides, e.g. n-butyl chloride, some replacement of the methyl groups in 2,5-dimethylthiophene occurred and polymerization increased. 

Messina, N. V. The Friedel-Crafts Alkylation in the Thiophene Series. 

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