Phthalic anhydride, Friedel-Crafts reaction

Dichloro-2,2 -dimethyl-1,1 -dianthraquinonyl can be synthesized by Friedel-Crafts reaction from phthalic anhydride and 2,6-dichlorotoluene. Subsequent cyclization of the resulting substituted benzoylbenzoic acid 102 in sulfuric acid affords the corresponding anthraquinone derivative 103, which is dimerized by Ullmann reaction ... 

Friedel-Crafts). (A., 291, 9 C. r., 119, 139.)—When the dichloride of phthalic anhydride reacts with the hydrocarbon, benzene, in presence of anhydrous aluminium chloride, phthalophenone (diphenylphthalide) is formed (see p. 107). With phthalic anhydride itself the reaction can be made to take the same or a different course. Using an excess of hydrocarbon, condensation and hydrolysis occur, and o-benzoyl-benzoic acid or its homologues are obtained according to the reacting hydrocarbon. Not only can the latter be varied, but derivatives of phthalic anhydride may be used, so that a great number of compounds can be synthesised in this way. 

Annulation of pyrrolizines may be carried out using the Friedel-Crafts reaction. Quinone derivative 191 was synthesized from pyrrolizine 190 with phthalic anhydride.113 Formation of l-chloro-3//-pyrrolizine (192) was observed in an investigation of the Vilsmeier reaction of 2,3-dihydro-IH-pyrrolizin-l-one (3a).17... 

More recently, Biswas and Chatteijee have prepared polystyrene electro-philically substituted with phthalic anhydride pyromellitic diianhydride tri-mellitic anhydride and 1,2,3,4-tetrahydrophthalic anhydride by Friedel-Crafts reaction. These anhydride-modified polystyrenes have further been converted into sulfonic acid resins by conventional sulfonation reaction. The thermal stabilities of these modified polymers are comparatively better than that of unmodified polystyrene. Ion-exchange capacities also compare favourably with the polystyrene-based commercial resins. 

The benzenedisulfonic acids are of little interest, except that benzene-1,3-disulfonic acid is a source of 1,3-dihydroxybenzene (see Chapter 4). The benzene dicarboxylic acids are more important. Benzene-1,2-dicarboxylic acid (phthalic acid, 8) can be converted into phthalic anhydride (9), which is a typical acid anhydride, reacting with amines and alcohols and also taking part in Friedel-Crafts reactions. Phthalimide (10), produced by reaction of the anhydride with ammonia, is weakly acidic and forms a potassium salt with ethanolic potassium hydroxide. 

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. 

Pyrrolo[l,2-a]indolequinones were prepared also by cyclization reactions. One of them involves copper-catalyzed pyrolysis of 2-azido-5-methoxy-6-methyl-3-(2,4-pentadienyl)-l,4-benzoquinone to give compound 45 (87JOC3956). The second pyrrole ring was also formed from a 2-hydroxy-propyl side chain of an indolo-4,7-dione (80JOC5057). Benzo analogs were prepared in a Friedel-Crafts reaction from either phthalic anhydride (67TL765) or 2-pyrrolidinylcarbonyl chloride (86H2797). 

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. 

Similar structures can be realised in low yield from the Friedel-Crafts reaction of 1,4-dimethoxybenzene with substituted phthalic anhydrides (R = Me, Et, i-Pr), which were obtained by the appropriate Diels-Alder synthesis. The acylations were effected in the presence of boron trifluoride etherate as catalyst, followed by demethylation of the product (ref.55). 

Chromic acid in hot glacial acetic acid oxidizes anthracene quantitatively to antlmaquinone in a very smooth reaction, but the method is too expensive for coxnmercial application in competition with synthetic anthraquinone made from cheap phthalic anhydride and benzene by means of the Friedel-Crafts reaction Prior to the development of the present methods of phthalic anhydride manufacture, the process was used extensively for anthraquinone production in Europe. The method has been recommended for anthracene analysis. 

In the dyestuff industry, anthraquinone stiU ranks high as an intermediate for the production of dyes and pigments having properties unattainable by any other class of dyes or pigments. Its cost is relatively high and will remain so because of the equipment and operations involved in its manufacture. As of May 1991, anthraquinone sold for 4.4/kg in ton quantities. In the United States and abroad, anthraquinone is manufactured by a few large chemical companies (62). At present, only two processes for its production come into consideration manufacture by the Friedel-Crafts reaction utilizing benzene, phthalic anhydride, and anhydrous aluminum chloride, and by the vapor-phase catalytic oxidation of anthracene the latter method is preferred. 

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. 

The Friedel-Crafts reaction is an important reaction in organic synthesis and is widely used for the substitution of a side chain in an aromatic ring with AICI3 as catalyst. The reaction between benzene and phthalic anhydride, which constitutes a step in the preparation of anthraquinone, is one such reaction. We give below the chemist s and the chemical engineer s ways of looking at this reaction (see Rose, 1981, for a detailed discussion). ... 

Where selective introduction of substituents into the anthraquinone molecule is difficult, synthesis from smaller components is frequently used. The most important reaction component in this context is phthalic anhydride, which undergoes Friedel-Crafts reaction with other substituted aromatics such as chlorobenzene, chlorophenol or toluene to yield the desired anthraquinone derivative. 

The reaction of chlorobenzene with phthalic anhydride to yield 2-chloro-anthraquinone is also industrially important. The flow diagram for this Friedel-Crafts reaction is shown in Figure 11.5. 

The first example of a Friedel-Crafts acylation reaction in a molten salt was carried out by Raudnitz and Laube [90]. It involved the reaction between phthalic anhydride and hydroquinone at 200 °C in NaCl/AlCl3 (X(A1C13) = 0.69) (Scheme 5.1-58). 

An alternative route to anthraquinone, which involves Friedel-Crafts acylation, is illustrated in Scheme 4.3. This route uses benzene and phthalic anhydride as starting materials. In the presence of aluminium(m) chloride, a Lewis acid catalyst, these compounds react to form 2-benzoyl-benzene-1-carboxylic acid, 74. The intermediate 74 is then heated with concentrated sulfuric acid under which conditions cyclisation to anthraquinone 52 takes place. Both stages of this reaction sequence involve Friedel-Crafts acylation reactions. In the first stage the reaction is inter-molecular, while the second step in which cyclisation takes place, involves an intramolecular reaction. In contrast to the oxidation route, the Friedel-Crafts route offers considerable versatility. A range of substituted... 

Anthraquinone itself is traditionally available from the anthracene of coal tar by oxidation, often with chromic acid or nitric acid a more modern alternative method is that of air oxidation using vanadium(V) oxide as catalyst. Anthraquinone is also produced in the reaction of benzene with benzene-1,2-dicarboxylic anhydride (6.4 phthalic anhydride) using a Lewis acid catalyst, typically aluminium chloride. This Friedel-Crafts acylation gives o-benzoylbenzoic acid (6.5) which undergoes cyclodehydration when heated in concentrated sulphuric acid (Scheme 6.2). Phthalic anhydride is readily available from naphthalene or from 1,2-dimethylbenzene (o-xylene) by catalytic air oxidation. 

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... 

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). 

Preparation from Phthalic Acid.—In discussing phthalic acid (p. 691) we spoke of the fact that phthalic anhydride or phthalyl chloride with phenol yields phenolphthalein. The reaction takes place in the presence of anhydrous zinc chloride as a dehydrating agent or in the presence of aluminium chloride (Friedel-Craft). Phthalyl chloride being the unsymmetrical compound (p. 692), the two reactions are represented as follows ... 

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