Toluene Friedel-Craft alkylation

The selectivity of an electrophile, measured by the extent to which it discriminated either between benzene and toluene, or between the meta- and ara-positions in toluene, was considered to be related to its reactivity. Thus, powerful electrophiles, of which the species operating in Friedel-Crafts alkylation reactions were considered to be examples, would be less able to distinguish between compounds and positions than a weakly electrophilic reagent. The ultimate electrophilic species would be entirely insensitive to the differences between compounds and positions, and would bring about reaction in the statistical ratio of the various sites for substitution available to it. The idea has gained wide acceptance that the electrophiles operative in reactions which have low selectivity factors Sf) or reaction constants (p+), are intrinsically more reactive than the effective electrophiles in reactions which have higher values of these parameters. However, there are several aspects of this supposed relationship which merit discussion. 

All attempts to prepare selenazole derivatives by the Gatterman (for-mylation) or Friedel-Crafts (alkylation) methods failed (19, 26). indicating that the electrophilic reactivity of the 5-position is less than that of benzene or toluene. 

In addition, boron, aluminum, and gallium tris(triduoromethanesulfonates) (tridates), M(OTf)2 and related perduoroalkanesulfonates were found effective for Friedel-Crafts alkylations under mild conditions (200). These Lewis acids behave as pseudo haUdes. Boron tris(tridate) shows the highest catalytic activity among these catalysts. A systematic study of these catalysts in the alkylation of aromatics such as benzene and toluene has been reported (201). 

Steric effects play a major role in determining the ortho para ratio in Friedel-Crafts alkylations. The amount of ortho substitution of toluene decreases as the size of the entering alkyl group increases along the series methyl, ethyl, /-propyl. No ortho product is found when the entering group is /-butyl. ... 

Friedel-Crafts alkylation of benzene or toluene by allyl chloride in presence of ethylaluminium chlorides is vigorous even at — 70°C, and explosions have occurred. See Lewis acids, etc., next below... 

The topics analysed here include reversible termination and the formation of p-tolyl end-groups on polystyrenes made in toluene. For unknown reasons, most authors have very largely ignored this Friedel-Crafts alkylation, which in a polymer context is a transfer reaction. It was unfortunately termed molecular termination by Overberger and was explored by his and Smets groups. 

To demonstrate the catalytic efficiency of thiourea 9 and urea 16 (each 10mol% loading), Friedel-Crafts alkylation of various aromatic and heteroaromatic substrates was performed at room temperature in toluene as well as under solvent-free conditions. The results for the products 1-7 shown in Scheme 6.6 revealed that in all cases the 9-catalyzed reactions gave higher yields. In toluene N-methylpyrroIe reacted smoothly to give the 2-substituted Friedel-Crafts adduct 1, while the adducts 3-5 and 7 formed slowly and required longer reaction times (72 h). The... 

Scheme 6.6 Products resulting from 9-catalyzed Friedel-Crafts alkylation of aromatic and heteroaromatic N-containing substrates performed in toluene and without solvent.

Here, the term no-solvent means the absence of a traditional solvent—the reactants are neat and may well be sohds. Where one reactant is in sufficiently large excess to qualify as a solvent, for example in Friedel-Crafts alkylations or acylations with excess benzene or toluene, the reactions are not normally classified as no-sol-vent. The phrase solid-phase (solid-state) reaction today often describes a reaction carried out on a solid phase, like a resin, to which the reaction intermediates are bound by adding reagents in solution. These reactions have become very important in combinatorial chemistry, but they do not meet the definition of no-solvent. The nosolvent reactions refer only to the primary reactions themselves and not to workup conditions which may or may not involve solvents (Dittmer, 1997). 

The Friedel-Crafts alkylation of aromatic compounds by oxetanes in the presence of aluminum chloride is mechanistically similar to the solvolyses above, since the first step is electrophilic attack on the ring oxygen by aluminum chloride, followed by a nucleophilic attack on an a-carbon atom by the aromatic compound present. The reaction of 2-methyloxetane and 2-phenyloxetane with benzene, toluene and mesitylene gave 3-aryl-3 -methyl-1-propanols and 3-aryl-3-phenyl-l-propanols as the main products and in good yields (equation 27). Minor amounts of 3-chloro-l-butanol and 4-chloro-2-butanol are formed as by-products from 2-methyloxetane, and of 3-phenyl-l-propanol from 2-phenyloxetane (73ACS3944). 

Silica-alumina particles coated with a permselective silicalite membrane is almost completely selective in the formation of p-xylene in the disproportionation of toluene.402 Friedel-Crafts alkylations were performed in ionic liquids. The strong polarity and high electrostatic fields of these materials usually bring about enhanced activity.403 404 Easy recycling is an additional benefit. Good characteristics in the alkylation of benzene with dodecene were reported for catalysts immobilized on silica or MCM-41 405... 

Friedel-Crafts alkylation of benzene,220 221 toluene,222para-xylene,220 and naphthalene223 with benzyl alcohols have been studied over Nafion-silica nano-composite catalysts, including the kinetics of alkylation.221,223 In most cases, 13% Nafion-silica showed the highest activity, testifying again to the much higher accessibility of the active sites. Complete conversion of para-xylene was found in the presence of triflic acid, and it was the only reaction when ether formation as side reaction did not occur. 

Fujiwara et al.227 tested a nanocomposite material having Nafion immobilized in MCM-41 mesoporous silica in Friedel-Crafts alkylations with benzyl alcohol. Whereas Nafion-MCM-41 showed lower activity in the alkylation of toluene than 13% Nafion SAC-13 under identical conditions, it exhibited increased activity when used in the alkylation of para-xylene. 

The selectivity of the reagents in the Friedel-Crafts alkylation and in acylation reactions is remarkably distinct. The procedures for the preparation of p-ethyltoluene represent a classic case of the different behavior of the effective species. The direct ethylation of toluene... 

Benzylation of toluene with benzyl chloride, which is a typical example of Friedel-Crafts alkylation, is known to be catalyzed by Lewis-type superacids such as A1C13 and BF3. This type of catalyst has been mostly used for the Friedel-Crafts reaction, which is one of the most studied of organic reactions. This reaction was performed over several metal oxides and sulfates, and iron sulfates showed an unexpected effectiveness for the reaction (102-104). The catalytic activities of FeS04 and Fe2(S04)3 for the reaction were examined in detail the activities were remarkably dependent on calcination temperature, the maximum activity being observed with calcination at 700°C (105-107). Catalytic actions analogous to the above case were also observed with other Friedel-Crafts reactions, the benzoyl-ation of toluene with benzoyl chloride (108), the isopropylation of toluene with isopropyl halides (109), and the polycondensation of benzyl chloride UIO). 

For the synthesis of orfbo-bromotoluene we use a sulphonic acid. o-Bromotoluene could be synthesised by bromination of toluene or by Friedel-Crafts alkylation of bromobenzene (Fig. T). However, the reaction would also give the para substitution product and this is more likely if the electrophile is hindered from approaching the ortho position by unfavourable steric interactions. Alternatively we can substitute a group at the para position before carrying out the bromination. 

Route A works fine. Toluene is readily nitrated, and the methyl group is an ortho/para director. The only problem is that both the desired compound and its ortho-isomer are produced and must be separated. (This is a common problem, and we usually assume that the separation can be accomplished, although it is not always easy in the laboratory.) Route B is unsatisfactory because the Friedel-Crafts alkylation reaction does not work with deactivated compounds such as nitrobenzene. Furthermore, even if the alkylation could be made to go, the nitro group is a meta director, so the desired product would not be formed. 

Vinylchlorosilanes undergo Friedel-Crafts alkylation with aromatic compounds in the presence of Lewis acids to give 2-(chlorosilyl)ethylarenes [Eq. (17)].lb 32,33 The reactivity of vinylchlorosilanes for the alkylation of aromatic compounds is slightly lower than that of allylchlorosilanes.lb 3,32 The reactivity of vinylsilanes for alkylation depends on the substituents on the silicon of the vinylsilane. The reactivity of vinylchlorosilanes decreases in the following order dichloro(methyl)vinyl-silane > trichlorovinylsilane > chloro(dimethyl)vinylsilane. The alkylation of mono-substituted benzenes such as toluene, chlorobenzene, and biphenyl with di-chloro(methyl)vinylsilane (lc) at 75-80 °C for 2h affords alkylated products in 50-63% yields.32... 

Phenol > Toluene > p-Bromotoluene > Bromobenzene Aniline and nitrobenzene don t undergo Friedel-Crafts alkylations. 

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