0-Aroylbenzoic acids

Aroylbenzoic acids. Aromatic hydrocarbons condense with phthalic anhydride in the presence of anhydrous aluminium chloride producing aroylbenzoic acids in good yields ... 

Place a mixture of 1 0 g. of the hydrocarbon, 10 ml. of dry methylene chloride or ethylene dichloride or syw.-tetrachloroethane, 2 5 g. of powdered anhydrous aluminium chloride and 1-2 g. of pure phthalic anhydride in a 50 ml. round-bottomed flask fitted with a short reflux condenser. Heat on a water bath for 30 minutes (or until no more hydrogen chloride fumes are evolved), and then cool in ice. Add 10 ml. of concentrated hydrochloric acid cautiously and shake the flask gently for 5 min utes. Filter oflf the solid at the pump and wash it with 10-15 ml. of cold water. Boil the resulting crude aroylbenzoic acid with 10 ml. of 2 -5N sodium carbonate solution and 0 2 g. of decolourising carbon for 5 minutes, and filter the hot solution. Cool, add about 10 g. of crushed ice and acidify... 

The isomeric pyrimido[2,l-tf]phthalazine 121 and its partly saturated analogue 122 could also be synthesized by a RDA reaction, analogously to 118, starting from 115 and aroylbenzoic acid or fA-2-aroylcyclohexanecarboxylic acid, respectively <2001J(P1)558>. 

Cyclocondensation of 2-aroylbenzoic acid 223 with hydrazine gave the phthalazine derivative 224, which was alkylated with ethyl chloroacetate in aqueous sodium hydroxide or pyridine to give the N-substituted derivative 225. Condensation of the latter with hydrazine afforded the hydra-zide 226, which could be cyclized to give the 2//[l,2,4]triazino[3,4-a]phthalazin-3(4tf)-one 227 (91MI3). 

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). 

With benzene the product is o-benzoylbenzoic acid (Expt 6.124), and with toluene, o-(p-toluoyl)benzoic acid (Expt 6.132). The aroylbenzoic acids are important starting materials for the synthesis of quinones (Section 6.11.3, p. 1022), into which they are cyclised using polyphosphoric acid (Expt 6.132). 

An excellent survey of the various methods of synthesis is available53 this section includes some of the illustrative methods of synthesis of the simpler analogues. These methods may be considered under the following headings (a) the oxidation of hydrocarbons (b) the oxidation of phenols and the oxidative coupling of phenols (c) the oxidation of dihydric phenols and aminophenols and (d) the cyclisation of aroylbenzoic acids. 

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). 

The intramolecular condensation of o-aroylbenzoic acids in the presence of concentrated sulfuric acid gives substituted anthraquinones. The acid strength, reaction temperature, and period of heating are carefully controlled to insure optimum yields and to avoid sulfonation products. Boric acid has been added as a sulfonation inhibitor. Substitution in the para position of the aroyl group leads to 2-alkyl-, 2-chloro-, and 2-bromo-anthraquinones. ... 

Access to the pharmacologically useful hexahydro-2,5-diazocines (see Section V) has been provided by reductive ring opening of imidazoisoindolones. Sulkowski and co-workers, in most of such reports, reacted o-aroylbenzoic acids with 1,2-diamines, producing compounds 46. These latter compounds were reduced with lithium aluminum hydride, aflbrding diazocines 47... 

J. W. Cook introduced the method of cyclizing an o-aroylbenzoic acid to an anthraquinone by heating the keto acid with phosphorus pentoxide in nitrobenzene at 150-165 . For example, the isomeric acids (3) and (4) resulting from the Friedel-Crafts reaction of 1,2-naphthalic anhydride with thiophene are cyclized to the same quinone (5). ... 

Because it appears as a neutral product, the methyl ester chloride of phthalic acid has various advantages over the anhydride for preparation of aroylbenzoic acids and esters 552 reaction times are shorter, the required temperatures are lower, yields are good, and the products are more easily isolated. 

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