Friedel-Crafts reaction with acid anhydrides

This type of duality of action is presumably present in other situations, such as the Fries rearrangement (78), the Friedel-Crafts reaction with acid chlorides (65) or acid anhydrides (21), and the catalytic chlorination of nitrobenzene (17). In these reactions it appears that the uncoordinated Lewis acid is the effective catalyst. The same situation is illustrated by recent work on aromatic amination (32, 33) and halogenation (57, 58, 71) and seems to be general feature of Lewis acid-catalyzed electrophilic reactions of aromatic compounds containing suitable donor groups. 

Aminophenols from anilines, 35, 2 Anhydrides of aliphatic dibasic acids, Friedel-Crafts reaction with, 5, 5 Anion-assisted sigmatropic rearrangements, 43, 2 Anthracene homologs, synthesis of, 1, 6 Anti-Markownikoff hydration of alkenes, 13, 1... 

There are two main synthetic routes to naphthalene the Haworth synthesis and a Diels-Alder approach. In the Haworth synthesis (Scheme 12.1), benzene is reacted under Friedel-Crafts conditions with succinic anhydride (butanedioic anhydride) to produce 4-oxo-4-phenylbutanoic acid, which is reduced with either amalgamated zinc and HCl (the Clemmensen reduction) or hydrazine, ethane-1,2-diol and potassium hydroxide (the Wolff-Kischner reaction) to 4-phenylbutanoic acid. Ring closure is achieved by heating in polyphosphoric acid (PPA). The product is 1-tetraione and reduction of the carbonyl group then gives 1,2,3,4-tetrahydronaphthalene (tetralin). Aromatization is achieved by dehydrogenation over a palladium catalyst. 

Friedel-Crafts reaction of phthalic anhydride with benzene in the presence of aluminium chloride followed by cyclization under acidic conditions gives anthra-9,10-quinone (Scheme 12.10). Distillation over zinc dust gives anthracene. 

The Friedel-Crafts reaction of phthalic anhydride with excess benzene as solvent and two equivalents of aluminum chloride proceeds rapidly and gives a complex salt of 2-benzoylbenzoic acid in which one mole of aluminum chloride has reacted with the acid function to form the salt RCOj AlClj" and a second mole is bound to the carbonyl group. On addition of ice and hydrochloric acid the complex is decomposed and basic aluminum salts are brought into solution. 

Clemmensen reaction. The Clemmensen method of reduction (1913) consists in refluxing a ketone with amalgamated zinc and hydrochloric acid. Acetophenone, for example, is reduced to ethylbenzene. The method is applicable to the reduction of most aromatic-aliphatic ketones to at least some aliphatic and alicyclic ketones, to the y-keto acids obtainable by Friedel-Crafts condensations with succinic anhydride (succinolylation), and to the cyclic ketones formed by intramolecular condensation. 

Phthalic anhydride undergoes Friedel-Crafts reaction with benzene to yield ortho-henzoyl benzoic acid, which gets cyclized to anthraquinone, and it gets reduced to produce anthrone . Explain the sequence of reactions involved briefly. 

Two diphenylaminophthalides have been synthesized The 3,3-diphenyl-6-aminophthalide [24] was synthesized in 20% yield by the following sequence of reactions which was patterned after early work °. This series involved nitration of phthalimide, hydrolysis and dehydration to 4-nitrophthalic anhydride, Friedel-Crafts reaction with benzene to 2-benzoyl-5-nitrobenzoic acid, cyclization with thionyl chloride to the pseudoacid chloride, Friedel-Crafts reactions with benzene, and, finally reduction of the nitro group to the amino function with Adams catalyst. 

As shown in the sixth entry of Table 24 4 C acylation of phenols is observed under the customary conditions of the Friedel-Crafts reaction (treatment with an acyl chloride or acid anhydride m the presence of aluminum chloride) In the absence of aluminum chloride however O acylation occurs instead... 

Sulfonylation. Under Friedel-Crafts reaction conditions, sulfonyl haUdes and sulfonic acid anhydrides sulfonylate aromatics (139), a reaction that can be considered the analogue of the related acylation with acyl haUdes and anhydrides. The products are sulfones. Sulfonyl chlorides are the most frequently used reagents, although the bromides and fluorides also react ... 

Isopropylnaphthalenes produced by alkylation of naphthalene with propjdene have gained commercial importance as chemical intermediates, eg, 2-isopropylnaphthalene [2027-17-OJ, and as multipurpose solvents, eg, mixed isopropylnaphthalenes. Alkylation of naphthalene with alkyl haUdes (except methyl hahdes), acid chlorides, and acid anhydrides proceeds in the presence of anhydrous aluminum chloride by Friedel-Crafts reactions (qv). The products are alkylnaphthalenes or alkyl naphthyl ketones, respectively (see Alkylation). 

Friedel-Grafts Reaction. Until quite recently, the manufacture of anthraquiaone ia the United States was by the Friedel-Crafts reaction benzene [71-43-2] and phthaUc anhydride [85-44-9] condense ia the preseace of anhydrous aluminum chloride to give o-benzoylbenzoic acid [85-52-9] which, on treatment with concentrated sulfuric acid, is converted iato anthraquiaoae ia high yields and purity (33). 

Although all four tocopherols have been synthesized as their all-rac forms, the commercially significant form of tocopherol is i7//-n7i a-tocopheryl acetate. The commercial processes ia use are based on the work reported by several groups ia 1938 (15—17). These processes utilize a Friedel-Crafts-type condensation of 2,3,5-trimethylhydroquinone with either phytol (16), a phytyl haUde (7,16,17), or phytadiene (7). The principal synthesis (Fig. 3) ia current commercial use iavolves condensation of 2,3,5-trimethylhydroquiQone (13) with synthetic isophytol (14) ia an iaert solvent, such as benzene or hexane, with an acid catalyst, such as ziac chloride, boron trifluoride, or orthoboric acid/oxaUc acid (7,8,18) to give the all-rac-acetate ester (15b) by reaction with acetic anhydride. Purification of tocopheryl acetate is readily accompHshed by high vacuum molecular distillation and rectification (<1 mm Hg) to achieve the required USP standard. 

Diaryl sulfones can be formed by treatment of aromatic compounds with aryl sulfonyl chlorides and a Friedel-Crafts catalyst. This reaction is analogous to Friedel-Crafts acylation with carboxylic acid halides (11-14). In a better procedure, the aromatic compound is treated with an aryl sulfonic acid and P2O5 in polypho-sphoric acid. Still another method uses an arylsulfonic trifluoromethanesulfonic anhydride (ArS020S02CF3) (generated in situ from ArS02Br and CF3S03Ag) without a catalyst. ... 

Several other heterohelicenes resist this reaction even when the Friedel-Crafts catalyst (A1C13) is exchanged for FSOjH, 90% HjSO, 40% HF and other strong acids. Some dehydroheterohelicenes have been used to prepare heterocirculenes by a Diels-Alder reaction with maleic anhydride and subsequent hydrolysis and removal of the carboxylic acid groups167). 

The statine-like moiety in one of the first drugs, saquinovir (23-8), comprises a transition state mimic for the cleavage of phenylalanylprolyl and tyrosylprolyl sequences. Constmction starts with the protection of the amino group of phenylalanine as its phthaloyl derivative (Phth) by reaction with phthalic anhydride this is then converted to acid chloride. The chain is then extended by one carbon using a Friedel-Crafts-like reaction. The required reagent (21-2) is prepared by reaction of the enolate obtained from the /7A-silyl ether (21-3) of glyoxylic acid and lithio... 

Triflates of boron, aluminum, and gallium were found to be efficient catalysts in Friedel-Crafts acylations.46 However, these are water-sensitive materials and were required to be used in equimolar quantities to be effective. More recently various water-tolerant and recyclable triflate salts, which were also tested in alkylation, were found to exhibit similar good characteristics in Friedel-Crafts acylations. Although benzene cannot be acylated, Sc triflate,47 48 lanthanum triflates,48-51 and Hf triflate52 usually give high yields of aryl ketones in acylation with acid anhydrides. In many cases, Li perchlorate was found to accelerate the reactions.48 52... 

Friedel-Crafts reactions have found application to form the 1,2-bond of pyrrolizines. Treatment of anhydride 78 with aluminum chloride gave 93% of acid 79, which on heating in the presence of copper gave a 91% yield of 2,3-benzo-1 H-pyrrolizin-1 -one (17).55 Benzopyrrolizinones (81) have been obtained from acid chlorides (80) by a similar route.56,57 Houben-Hoesch cyclization of nitrile 82 gave 2,3-benzo-lf/-pyrrolizin-l-one (17) in a reaction that resembles the formation of 17 from 16a.58... 

Aroylation of an aromatic system by reaction with phthalic anhydride under Friedel-Crafts conditions yields the o-aroylbenzoic acid. These readily available compounds have characteristic melting points which make them useful as derivatives in the characterisation of aromatic hydrocarbons and of aryl halides (Section 9.6.3, p. 1238). 

The aroylation of an aromatic system by reaction with phthalic anhydride under Friedel-Crafts conditions is described in Section 6.11.1, p. 1006. The cyclisation of the derived o-aroylbenzoic acid with polyphosphoric acid is a convenient route to substituted anthraquinones. The reaction is illustrated by the formation of 2-methylanthraquinone from o-(p-toluoyl)benzoic acid (Expt 6.132). 

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