Friedel-Crafts acylation benzene alkylation

Electrophilic Aromatic Bromination 673 Nitration of Benzene 675 Sulfonation of Benzene 676 Friedel-Crafts Alkylation 677 Friedel-Crafts Acylation 680 Benzylic Halogenation 701 Birch Reduction 710... 

An important difference between Friedel-Crafts alkylations and acylations is that acyl cations do not rearrange. The acyl group of the acyl chloride or acid anhydride is transfened to the benzene ring unchanged. The reason for this is that an acyl cation is so strongly stabilized by resonance that it is more stable than any ion that could conceivably arise from it by a hydride or alkyl group shift. 

Because acylation of an aromatic ring can be accomplished without reanangement, it is frequently used as the first step in a procedure for the alkylation of aromatic compounds by acylation-reduction. As we saw in Section 12.6, Friedel-Crafts alkylation of benzene with primary alkyl halides nonrrally yields products having rearranged alkyl groups as substituents. When a compound of the type ArCFl2R is desued, a two-step sequence is used in which the first step is a Friedel-Crafts acylation. 

Ualike the multiple substitutions that often occur in Friedel-Crafts alkylations, acylations never occur more than once on a ring because the product acyl-benzene is less reactive than the nonacylated starting material. We ll account for this reactivity difference in the next section. 

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. 

Bismuth tra-tri lluoromcthancsulfonate, Bi(OTf)3, and BiCh were found to be effective catalysts for the Friedel-Crafts acylation of both activated and deactivated benzene derivatives such as fluorobenzene.19 Ga(III) triflate is also effective for Friedel-Crafts alkylation and acylation in alcohols and can tolerate water.20 This catalyst is water-stable... 

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). 

Direct electrophilic substitution of benz- and dibenz-azepines remains relatively unexplored. Most substituted benzazepines have been prepared from benzene precursors bearing the desired substituents (74AHC(17)45). The bulk of the reported electrophilic substitutions have been carried out on 5//-dibenz[6,/]azepine (74CRV101), MO calculations on which predict that substitution should occur at the 2- and 4-positions, i.e. para and ortho to the azepine ring nitrogen. These predictions are borne out by Friedel-Crafts alkylation and acylation studies, although it is apparent that a second alkyl group enters at the 8- rather than at the 4-position. Formylation under Vilsmeier conditions yields the 2-aldehyde. As noted earlier (Section 5.16.3.4), however, the 10,11-dihydro system exhibits different behavior and acylates at the benzylic 10,11-positions. Nitration with mixed acids of the... 

Electrophilic aromatic substitution is a reaction where a hydrogen atom in an aromatic system, e.g. benzene, is replaced by an electrophile. Some of the important electrophilic substitution reactions are Friedel-Crafts alkylation and acylation, nitration, halogenation and sulphonation of benzene. 

Tetralone 31 could also be synthesized much more efficiently by employing a chemoselective ketone reduction of 32 to give the lactone 33. A double Friedel-Crafts alkylation/acylation sequence employing a variety of Lewis or protic acids and benzene gave the tetralone 31 directly. Triflic acid and HF produced the highest yields of tetralone, presumably through the intermediacy of the diaryl acid 34 (Scheme 6)... 

Alkyl halide Benzylic halide Acyl halide These will not react with benzene under Friedel-Crafts conditions ... 

The Friedel-Crafts acylation reaction, another example of an electrophilic aromatic substitution reaction, is similar to the Friedel-Crafts alkylation reaction except that the substance that reacts with benzene is an acyl halide,... 

Substrates of Friedel-Crafts acylations are benzene and naphthalene, as well as their halogen, alkyl, aryl, alkoxy, or acylamino derivatives. Acceptor-substituted aromatic compounds are inert. Because Friedel-Crafts acylations introduce an acceptor into the aromatic substrate, no multiple substitutions take place. This distinguishes them from Friedel-Crafts alkylations. Free OH and NH2 groups in the aromatic compound prevent Friedel-Crafts acylations because they themselves are acylated. However, the O-acylphenols available in this way can later be rearranged with A1C1, into orf/zo-acylated isomers (Fries rearrangement). 

In the presence of aluminum chloride, an acyl chloride reacts with benzene (or an activated benzene derivative) to give a phenyl ketone an acylbenzene. The Friedel-Crafts acylation is analogous to the Friedel-Crafts alkylation, except that the reagent is an acyl chloride instead of an alkyl halide and the product is an acylbenzene (a phenone ) instead of an alkylbenzene. 

This two-step sequence can synthesize many alkylbenzenes that are impossible to make by direct alkylation. For example, we saw earlier that n-propylbenzene cannot be made by Friedel-Crafts alkylation. Benzene reacts with n-propyl chloride and AICI3 to give isopropylbenzene, together with some diisopropylbenzene. In the acylation, however, benzene reacts with propanoyl chloride and A1C13 to give ethyl phenyl ketone (propiophenone), which is easily reduced to n-propylbenzene. 

Friedel-Crafts alkylation with t-alkyl chlorides and Lewis acids (usually AICI3) gives t-alkyl benzenes. The more reliable Friedel-Crafts acylation with acid chlorides and Lewis acids (usually AICI3) gives aryl ketones. 

Ferrocene reacts with acetyl chloride and aluminum chloride to afford the acylated product (287) (Scheme 84). The Friedel-Crafts acylation of (284) is about 3.3 x 10 times faster than that of benzene. Use of these conditions it is difficult to avoid the formation of a disubstituted product unless only a stoichiometric amount of AlCft is used. Thus, while the acyl substituent present in (287) is somewhat deactivating, the relative rate of acylation of (287) is still rapid (1.9 x 10 faster than benzene). Formation of the diacylated product may be avoided by use of acetic anhydride and BF3-Et20. Electrophilic substitution of (284) under Vilsmeyer formylation, Maimich aminomethylation, or acetoxymercuration conditions gives (288), (289), and (290/291), respectively, in good yields. Racemic amine (289) (also available in two steps from (287)) is readily resolved, providing the classic entry to enantiomerically pure ferrocene derivatives that possess central chirality and/or planar chirality. Friedel Crafts alkylation of (284) proceeds with the formation of a mixture of mono- and polyalkyl-substituted ferrocenes. The reaction of (284) with other... 

Recall from Section 18.5C that propylbenzene cannot be prepared by a Friedel-Crafts alkylation. Instead, when benzene is treated with 1-chloropropane and AICI3, isopropylbenzene is formed by a rearrangement reaction. Propylbenzene can be made, however, by a two-step procedure using Friedel-Crafts acylation followed by reduction. 

You have learned two ways to make an alkyl benzene Friedel-Crafts alkylation, and Friedel-Crafts acylation followed by... 

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