Benzene with alkyl halides

Alkylation of benzene with alkyl halides m the presence of aluminum chloride was discovered by Charles Friedel and James M Crafts m 1877 Crafts who later became president of the Massachusetts Institute of Technology collaborated with Friedel at the Sorbonne m Pans and together they developed what we now call the Friedel-Crafts reaction into one of the most useful synthetic methods m organic chemistry... 

Demonstrated here is the mechanism for the alkylation of benzene with alkyl halide using AICI3 as the catalyst. 

Organolithium compounds can readily be prepared from metallic Li and this is one of the major uses of the metal. Because of the great reactivity both of the reactants and the products, air and moisture must be rigorously excluded by use of an inert atmosphere. Lithium can be reacted directly with alkyl halides in light petroleum, cyclohexane, benzene or ether, the chlorides generally being preferred ... 

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. 

Valentine and Curtis (1975) extended the synthetic utility of potassium peroxide by reporting the successful solubilization of K02 in dry dimethyl sulfoxide using dicyclohexyl- 18-crown-6 ([20] + [21]). Corey et al. (1975) used 18-crown-6 to solubilize KOz in dimethylformamide, dimethoxyethane and diethyl ether, whilst Johnson and Nidy (1975) reported its solubilization in benzene. A wide variety of chemical transformations have been realized with K02 complexes of crown ethers. With alkyl halides the main reaction products are peroxides, alcohols and olefins (Johnson and Nidy, 1975). Peroxides are... 

Protic acids are usually used as catalysts for alkylation with olefins rather than with alkyl halides. Anhydrous hydrogen chloride, in the absence of metal halides, is a catalyst for the alkylation of benzene with terf-butyl chloride only at elevated temperatures96 where an equilibrium with isobutylene may exist. Other alkyl halides and cyclohexene were also reacted with benzene and toluene using this catalyst. 

Di- and polyalkylation can occur during alkylation with alkyl halides since the product alkylbenzenes are more reactive, although the reactivity difference with reactive alkylation systems is small. Toluene, for example, reacts only about 2-5 times faster in some benzylations than benzene.118,119 As alkylbenzenes, however, dissolve preferentially in the catalyst containing layer, heterogeneous systems can cause enhanced polysubstitution. The use of appropriate solvents and reaction conditions as well as of an excess of aromatics allow the preparation of monoalkyl-ated products in high yields. 

A much more general method for acyl silane synthesis involving silyl diazo intermediates is illustrated in Scheme 1688. The lithiated derivative of trimethylsilyl diazomethane reacts smoothly with alkyl halides in THF solution to give a-trimethylsilyl diazoalkanes in good yields. Oxidative cleavage of the diazo moiety is effected using 3-chloroperbenzoic acid in benzene solution, to give access to a wide variety of acyl silanes in yields of up to 71%. A phosphate buffer (pH 7.6) is used to prevent side reactions. Aromatic acyl silanes clearly cannot be prepared by this chemistry since an aromatic nucleophilic substitution reaction would be required. 

Tetrakis-Cp uranium complexes are readily prepared via metathesis of UC14 and KCp in refluxing benzene. These complexes are a relatively rare example of a pseudotetrahedral complex with four r 5-Cp tings, (r -ring)4U (25). The Cp derivative has been shown to react with CO and C02 to give acyl and carboxylato complexes. This complex also reacts with alkyl halides to afford the U(TV) complex, Cp3UX (X = halide). 

At elevated temperatures and in a sealed tube pentaphenylstiborane reacts with alkyl halides such as chloroform, tetrachloromethane142) or iodomethane143> to give tetraptenylstibonium halides, benzene, halobenzene and other products. Homo-lytic cleavage of Sb—C bonds is assumed to play a leading role here. In a more detailed study, a radical chain reaction was proposed for such decompositions,... 

N-Alkylation of 1,2,3-triazoles and benzotriazoles is readily achieved using (1) alkyl halides, dialkyl sulfates, diazoalkanes, and jS-tosylates or (2) the Mannich reaction. When alkyl halides are used, sodium alkoxide, sodium hydride, or sodium hydroxide is usually employed as the base. The N-alkylation of benzotriazole with alkyl halides proceeds efficiently using powdered NaOH as the base in DMF. The highest yields (80100%) of the alkylated benzotriazoles are obtained when a fourfold excess of NaOFl is employed. A-Alkylbenzotriazoles have been prepared from benzotriazole and alkyl halides using phase-transfer catalysts, e.g., KOFI, benzene, tetrabutyl-ammonium salts or KOH, benzene, polyethylene glycol. 

Esterification. Carboxylic acids can be esterified by reaction with alkyl halides and DBU in benzene at 25 or 80° (equation I). The reaction is widely applicable to hindered or unstable acids and to BOC- or CBZ-protected amino atids. Yields are invariably high. Triethylamine is of less value as the base. Presumably the hydrogen-bonded complex of DBU and the acid plays a significant role in the reaction. The DBU can be recovered by treatment of the hydrohalide with sodium hydroxide. ... 

Alkyl mesylates undergo alkylation reaction with benzene rings in the presence of Sc(OTf)3. " Allylic acetates undergo alkylation with Mo(CO)g and allylic chlorides react in the presence of ZnCl2/Si02. " Montmorillonite clay (KIO) is an effective medium for alkylation reactions.Nafion-H, a super acidic perfluori-nated resin sulfonic acid, is a very good catalyst for gas phase alkylations with alkyl halides, alcohols,or alkenes. 

Alkylboronic acids are coupled to aryl halides using a palladium catalyst, " analogous to the Suzuki reaction in 13-12. Conversely, arylboronic acids can be coupled to aliphatic halides Arylboronic acids can be coupled to allylic alcohols as well. " Arylboronic acids (12-28) were shown to react directly with benzene in the presence of Mn(OAc)3. " Arylboronic acids also couple with alkyl halides in... 

The sodium salt of diethyl N-(r-butoxycarbonyl)phosphoramidate (98) reacted with alkyl halides in boiling benzene in the presence of tetrabutylammonium bromide to give the corresponding N-alkyl derivatives (99) in 71-95% yields for primary alkyl halides and 38-58% yields for secondary a-halo esters (in MeCN). The phosphoryl and r-butoxycarbonyl groups were removed by treatment overnight with benzene saturated with dry HCl (Scheme 41). ... 

In conclusion it should be pointed out that the unusual success of the Wurtz-Fittig reaction in coupling two unlike halides can be understood if we assume that phenyl sodium predominates over the alkyl sodium in the first phase of the reaction and that phenyl sodium reacts preferentially with alkyl halides in the second phase of the reaction. These assumptions seem very reasonable, since arbmatic halides are always more inert to displacement reactions than alkyl halides and ethyl sodium has been shown to react even with benzene to give phenyl sodium and ethane.11 Consequently, when a solution of ethyl bromide and bromo-... 

Uses. Tetramethylene sulfone has high solvent power for aromatics and has been used extensively by Olah and co-workers for Friedel-Crafts type nitrations and for studies of the mechanism of nitronium tetrafluoroborate nitration of alkyl-benzenes and halobenzenes in homogeneous solution. It is a superior solvent for quaternization of tertiary amines with alkyl halides, since it has a high dielectric constant and does not enter into side reactions observed with nitrobenzene and dimethylformamide. For example in the synthesis of the acridizinium salt (3), Bradsher and Parham effected quaternization of (1) with benzyl bromide in tetramethylene sulfone at room temperature in excellent yield. Several other salts analagous to (2) were obtained in good yield and in crystalline form with use of tetramethylene sulfone, whereas with other solvents the products were colored... 

A similar S-alkylation took place to give the (alkylsulfanyl)-substituted cydopropenylium salts when 2,3-bis(diisopropylamino)cyclopropenethionc (29) ° and 2,3-diphenylcyclopropene-thione (27) ° were treated with alkyl halides in benzene. 

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