Alkylation with alkenes

Alkylation with Alkenes. Besides alkyl halides, alkenes,86,148-151 alkynes,152 alcohols and ethers,86,151,153 and esters86,151,154 are most frequently used for alkylation of arenes. Of all alkylating agents, alkenes are practically the most important. 

When an alkene is used in the alkylation of arenes, metal halides with hydrogen halide or water as cocatalyst, protic acids, and acidic oxides can be used as catalysts. Both linear and cyclic alkenes are used in alkylations. Alkylation with alkenes is usually preferred in industry because the processes are simpler and olefins are readily and cheaply available in pure form from petroleum refining processes. 

The related manufacture of cumene (isopropylbenzene) through the alkylation of benzene with propylene is a further industrially important process, since cumene is used in the synthesis of phenol and acetone. Alkylation with propylene occurs more readily (at lower temperature) with catalysts (but also with hydrogen fluoride and acidic resins) similar to those used with ethylene, as well as with weaker acids, such as supported phosphoric acid (see further discussion in Section 5.5.3). 

In alkylation of benzene with both ethylene and propylene di- and polyalkylates are also formed. In alkylation with propylene 1,2,4,5-tetraisopropylbenzene is the most highly substituted product steric requirements prevent formation of penta-and hexaisopropylbenzene. On the other hand, alkylation of benzene with ethylene readily even yields hexaethylbenzene. Alkylation with higher alkenes occurs more readily than with ethylene or propylene, particularly when the alkenes are branched. Both promoted metal chlorides and protic acids catalyze the reactions. 

Carbocations formed through protonation of alkenes by proton acids are usually assumed as intermediates in alkylation with alkenes. Metal halides, when free of protic impurities, do not catalyze alkylation with alkenes except when a cocatalyst is present. It was shown that no neat conjugate Friedel-Crafts acids such as HA1C14 or HBF4 are formed from 1 1 molar compositions in the absence of excess HC1 or HF, or another proton acceptor.163-166 In the presence of a proton acceptor (alkene), however, the Lewis acid halides—hydrogen halide systems are readily able to generate carbocations  

ALKYLATION OF AROMATIC HYDROCARBONS 5.2.1. Alkylation with Alkenes 

Cumene is industrially produced by propylating benzene over supported acidic catalysts such as phosphoric acid. On the other hand, the largest-scale single industrial alkylation process—that is, ethylation of benzene with ethylene—is still carried out to a significant degree in the liquid phase using acid catalysts since ethylene is less polar than propylene, it requires more forcing conditions in the protolytic initiation step [Eq. (5.71)]. 

Consequently, stronger solid acids were needed to activate the ethylation reaction. The solid acids that were available earlier exhibited only limited acidity, which was sufficient to promote the propylation of benzene with propylene at reasonable temperatures and pressures, but it was not high enough to promote ethylation of benzene with ethylene under similar conditions. 

The conventional resinsulfonic acids such as sulfonated polystyrenes (Dowex-50, Amberlite IR-112, and Permutit Q) are of moderate acidity with limited thermal stability. Therefore, they can be used only to catalyze alkylation of relatively reactive aromatic compounds (like phenol) with alkenes, alcohols, and alkyl halides. Nafion-H, however, has been found to be a suitable superacid catalyst in the 110-190°C temperature range to alkylate benzene with ethylene (vide infra) 16 Furthermore, various solid acid catalysts (ZSM-5, zeolite /3, MCM-22) are applied in industrial ethylbenzene technologies in the vapor phase.177 

In addition to alkenes, functionalized alkenes can also be used as alkylating agents. Koltunov, Walspurger, and Sommer, have reported the alkylation of benzene with a,/3-unsaturated carboxamides in the presence of excess aluminum chloride [Eq. (5.72)]. The reaction takes place under mild conditions and gives the products in near-quantitative yields. Results with ortlro-dichlorobenzene and triflic acid are usually inferior. Triflic acid, however, can catalyze similar reactions of cyclic and open-chain unsaturated amines with benzene to give phenylalkylamines in excellent yields.180 The transformations are interpreted by invoking the involvement of dica-tionic intermediates 39 and 40. 

Further evidence against the formation of a free carbonium ion in the alkylation reaction is obtained from the fact that in the presence of boron trifluoride-phosphoric acid catalyst, but-l-ene, but-2-ene, and i-butene react at different rates with alkylbenzenes, yet they would each give the same carbonium ion. In addition, only the latter alkene gave the usual activation order (in this case the hyper- 

FIRST-ORDER RATE COEFFICIENTS FOR REACTION OF CYCLOHEXENE WITH BENZENE 

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C-Alkylations may be discussed under the headings of alkene reactions and A/-alkyl rearrangements. The isopropylation of benzene and naphthalene are two important examples of alkylation with alkenes (see Alkylation). Manufacture of j butylaniline, by heating /V-butylaniline with 2inc chloride, typifies the rearrangement reaction appropriate to and higher alkyl derivatives. 

Fluorobenzene is readily alkylated with alkenes in the presence of protic acids, however, the isomenc purity of the product is poor, and polysubstitution can result Thus, propene and sulfuric acid alkylate fluorobenzene at 20 C to yield a 45 55 ortho/para ratio of the inonoalkyl product m addition to di- and triiso propylfluorobenzene [i5] The reaction of benzene and trifluoropropene at 25 °C in HF-BF3 gives a mixture of mono-, bis-, and tns(3,3,3-trifluoropropyl)ben zene [72, 75] (equation 12)... 

The alkylation with alkenes can be catalyzed by protons. The carbon-carbon double bond of the alkene is protonated according to Markow nikojfs rule, to give a carbenium ion 10, which then reacts by the above mechanism to yield the alkylated aromatic product 11 ... 

These observations demonstrate that multiplicity of products is a characteristic feature of acid-catalyzed alkylation with alkenes indicating the involvement of isomerizations. Some of the compounds isolated cannot be formed by the reaction of one molecule of the alkane with one or more of the alkenes. This points to secondary reactions accompanying alkylation. 

Reaction conditions in alkylation with alkenes exert a strong effect on product distribution151 [Eq. (5.37)]171 similar to that in alkylation with alkyl halides ... 

Similarly, benzo[6]thiophene also yields mixtures of 2- and 3-alkyl derivatives on alkylation with alkenes or alkanols in the presence of acids <70AHC(11)177). Thus with isopropyl chloride, isopropanol or propene, mixtures of 2- and 3-isopropyl derivatives are formed. Alkylation by 2-methylpropene in the presence of PPA gives 2-7-butyl- (22%) and 3-7-butyl-(71%) benzo[6]thiophenes with 7-butanol and cone. H2S04, the yields are 2-7-butyl (6%) and 3-7-butyl (89%) (72JCS(Pl)414). 

The procedure described here is typical for the catalytic alkylation of aromatic ketones at the ortho position by alkenes. Aromatic ketones are readily available by Friedel-Crafts acylation and many other methods, and many of these ketones are suitable substrates for the present catalytic alkylation with alkenes affording the corresponding ortho-alkylated ketones. The present method provides a direct way to alkylate aromatics with olefins. Moreover, the C-C bond formation takes place with exclusive ortho selectivity, while mixtures of 0-, m-, p-isomers are usually obtained in the conventional Friedel-Crafts alkylation of aromatic compounds. 

Ipatieff and coworkers carried out the first alkylation with alkenes and branched and normal chain alkanes (except methane and ethane) in the presence of AlCb as the catalyst. The sulfuric acid catalyzed alkylation reaction of arenes and isoalkanes, developed in 1938, is a still widely used industrial process to produce alkylates with high octane numbers. For synthetic applications, however, Friedel-Crafts-type alkylations of alkenes and alkanes have limited value since they tend to give mixtures of products, including oligomers of alkenes. ... 

Friedel-Crafts alkylation. Secondary alkyl mesylates are adequate alkyl donors in this reaction." Both Sc(OTf)3 and TfOH can be used as the catalyst. It has also been reported that Sc(OTf js immobilized in ionic liquid forms a recyclable system for arene alkylation with alkenes. ... 

C. Friedel-Crafts Alkylation with Alkenes and Alcohols... 

Envirocat EPIC General acid catalysis Beckmann rearrangements Acylations with carboxylic acids and alkylations with alkenes Strong, solid Bronsted acid Improved product quality Easier separation... 

Envirocat EPZIO Benzylations Alkylations with alkenes or alkyl halides Truly catalytic Promotion of reactions at low temperatures High yields and good selectivity... 

In 2012, Maes and co-workers reported a new transition-metal-catalyzed methodology for the direct C2-H functionalization of piperidines [67], via pyridine-directed Ru-catalyzed C(sp )-H alkylation with alkenes [68]. Based on previous work [69-73], they discovered that a combination of a bulky alcohol (2,4-dimethyl-3-pentanol) and a catalytic amount of a carboxylic acid [74] is necessary to avoid side reactions such as isomerization and/or reduction of the alkene reactant (Scheme 11). They successfully applied this method to the total synthesis of ( )-... 

More recently, Yoshikai [135] developed a cobalt-catalyzed chelation-assisted C-H bond alkylation with alkenes. The reaction was initially developed with 2-arylpyridines (Scheme 19.92) [136], The authors demonstrated the influence of the ligand on the reaction, leading selectively to the formation of the linear or the branched product. 

Phenol alkylation, with alkenes Coumarin synthesis (Pechman reaction)... 

Scheme 2 Proposed catalytic cycle for sp C-H alkylation with alkenes...

Alkylation with Alkenes. The alkylation of phenols by olefins and cyclo-olefins has been reviewed, in Russia Several papers on the alkylation of phenols have appeared. Thus, p-t-butyiphenol has been prepared with good selectivity by treatment of phenol with isobutene and a Lewis acid catalyst followed by HCIO4 as an isomerization catalyst. The ort/io-alkylation of phenol by alkenes can be improved by using Al(OPh)3 and an aluminosilicate catalyst.Much greater ortho-selectivity in the alkylation of phenol with 4-bromostyrene is obtained if aluminium diphenylphosphorodithioate rather than BF3-OEt2 or BF3-H3P04 is used as catalyst. Relative reactivities of the various ring positions towards... 

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