Halides, alkyl reaction with aromatic compounds

With the development of the cross coupling methodology, many 6-C-substituted purines have been prepared in the past decade. Thus, 6 halopurine derivatives react with arylmagnesium halides,25 alkyl(aryl)zinc or tin reagents,26 trialkylaluminum,27 or alkylcuprates28 to give the 6-alkylpurine derivatives. Also a reverse approach based on the reaction of purine-6-zinc iodide with aryl or vinyl halides has recently been described.29 For the synthesis of 6-arylpurines, an alternative approach makes use of radical photochemical reactions of adenine derivatives with aromatic compounds,30 but this method is very unselective and for substituted benzenes, mixtures of ortho-, meta-, and para substituted derivatives were obtained. 

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 (A1C13) or ferric chloride (FeCl3), alkyl halides were found to alkylate benzene to give alkylbenzenes. This useful reaction is called the Friedel-Crafts alkylation. 

Uncatalyzed nncleophihc snbstitution reactions of Grignard reagents with aromatic compounds is much more difficult than with alkyl species, unless the leaving gronp (sometimes halide nsnally alkoxide is preferred) is activated by one or more potent electron-withdrawing substituents, snch as an oxazoline, nitro, or ester moiety, most often at the ortho... 

Carbonium ions can be generated at a variety of oxidation levels. The alkyl carbocation can be generated from alkyl halides by reaction with a Lewis acid (RCl + AICI3) or by protonation of alcohols or alkenes. The reaction of an alkyl halide and aluminium trichloride with an aromatic ring is known as the Friedel-Crafts alkylation. The order of stability of a carbocation is tertiary > secondary > primary. Since many alkylation processes are slower than rearrangements, a secondary or tertiary carbocation may be formed before aromatic substitution occurs. Alkylation of benzene with 1-chloropropane in the presence of aluminium trichloride at 35 °C for 5 hours gave a 2 3 mixture of n- and isopropylbenzene (Scheme 4.5). Since the alkylbenzenes such as toluene and the xylenes (dimethylbenzenes) are more electron rich than benzene itself, it is difficult to prevent polysubsiitution and consequently mixtures of polyalkylated benzenes may be obtained. On the other hand, nitro compounds are sufficiently deactivated for the reaction to be unsuccessful. 

The first kinetic study of the Friedel-Crafts alkylation reaction was repotted by Brown and Grayson in 1953. This involved the reactions of some substituted benzyl halides with aromatic compounds in the presence of AlClj-PhNOa catalyst. The transition state for the rate-determining step (attack of the aromatic component on a polar alkyl halide-AlCb addition compound) was depicted as a o -complex. 

Electron transfer is also crucial to a series of alkylation reactions involving aromatic and aliphatic nitro compounds. These reactions were discovered as the result of efforts to explain the mechanistic basis for high-yield carbon alkylation of the 2-nitropropane anion by p-nitrobenzyl chloride. The corresponding bromide and iodide and benzyl halides that do not contain a nitro substituent give mainly the unstable oxygen alkylation product with this ambident anion. The mixture of... 

Triflates of aluminum, gallium and boron, which are readily available by the reaction of the corresponding chlorides with triflic acid, are effective Fnedel-Crafis catalysis for alkylation and acylation of aromatic compounds [119, 120] Thus alkylation of toluene with various alkyl halides m the presence of these catalysts proceeds rapidly at room temperature 111 methylene chloride or ni-tromethane Favorable properties of the triflates in comparison with the correspond mg fluorides or chlorides are considerably decreased volatility and higher catalytic activity [120]... 

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 Friedel-Crafts allcylation reaction usually involves the interaction of an allcy-lation agent such as an alkyl halide, alcohol, or alkene with an aromatic compound, to form an alkylated aromatic compound (Scheme 5.1-44). 

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