Anthraquinones Friedel-Crafts reaction

In the dyestuff industry, anthraquinone still 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, phthahc anhydride, and anhydrous aluminum chloride, and by the vapor-phase catalytic oxidation of anthracene the latter method is preferred. 

Olah et al. (1999) have been able to realize selective cyclisation of o-benzoyl benzoic acid to anthraquinone using dichlorobenzene as a solvent and Nafion-H as a catalyst. This may lead to avoidance of the Friedel-Crafts reaction using a stoichiometric amount of aluminium chloride and resulting in a lot of wa,ste. Many other examples of similar reactions have been reported. 

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 ... 

The Friedel-Crafts reaction, which proceeds via electrophilic aromatic substitution, as illustrated in the following scheme, is unique to the manufacture of anthanthrone pigments. Most other polycyclic anthraquinone pigments are synthesized via nucleophilic ring closure. 

Another application that demonstrates the advantages of using NPC for the separation of analytes prone to hydrolysis is the reaction monitoring for the formation of 9,10-anthraquinone [29]. Anthraquinone is an important intermediate in the manufacturing of various dye products but also is used as a catalyst in the isomerization of vegetable oils. It is produced in large amount by Friedel-Crafts reaction of phthaUc anhydride with benzene in the presence of AICI3 catalyst. 

Chapter 53 The Friedel-Crafts Reaction Anthraquinone and Anthracene... 

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). ... 

A number of important technical and economic considerations are involved in the use of sodium anthraquinone-2-sulfonate (silver salt) for the preparation of 2-Bminoanthraquinone. The cost of chloroanthra-quinone is approximately the same as anthraquinone when they are prepared according to the Friedel-Crafts reaction. The former lends itself to the direct production of an amine of 97-98.5 per cent purity. The product from silver salt is, however, of a higher purity and can, furthermore, be prepared at a lower operating temperature (viz., 170-180 C) so that steam-jacketed equipment can be employed. Consequently, despite economic handicaps, the silver-salt process is firmly entrenched and is used to a considerable extent. 

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. 

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. 

Anthraquinone dyes are derived from several key compounds called dye intermediates, and the methods for preparing these key intermediates can be divided into two types (/) introduction of substituent(s) onto the anthraquinone nucleus, and (2) synthesis of an anthraquinone nucleus having the desired substituents, starting from benzene or naphthalene derivatives (nucleus synthesis). The principal reactions ate nitration and sulfonation, which are very important ia preparing a-substituted anthraquiaones by electrophilic substitution. Nucleus synthesis is important for the production of P-substituted anthraquiaones such as 2-methylanthraquiQone and 2-chloroanthraquiaone. Friedel-Crafts acylation usiag aluminum chloride is appHed for this purpose. Synthesis of quinizatia (1,4-dihydroxyanthraquiQone) is also important. 

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. 

An alternative focus based on known antitumor activity of adriamycin-type systems stimulated the synthesis of the aza-anthraquinones 599 and 600 (Scheme 177) (84CC897). Thus, synergistic chloro-oxazoline directed metalation of 597 with methyllithium followed by treatment with 2,5-dimethoxybenzaldehyde and acid-promoted cyclization provided the lactone 598. Radical bromination and base-induced hydrolysis gave an intermediate keto acid which, upon Friedel-Crafts cyclization with methanesulfonic acid, led to the aza-anthraquinone 599 in modest yield. The azanaphthacene dione 600 was prepared by an analogous series of reactions starting with 597. 

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). 

Many of the more recent applications of intramolecular Friedel-Crafts acylation reactions have involved the synthesis of biologically active tetracycline derivatives. In the synthesis of aclacinomycin- the acid shown in equation (42) was cyclized efficiently to the anthrone using trifluoroacetic anhydride in dichloromethane and then converted immediately into the anthraquinone shown. 

The hydroxylated anthraquinone chromophore of the anthracyclines would seem an ideal candidate for synthesis through two Friedel-Crafts acylations, either in a concurrent or a stepwise manner with formation of ring C. However, the fact that the first acylation deactivates the future ring B toward further electrophilic substitution necessitates vigorous reaction conditions, and this... 

From the established carbon-carbon connectivities in 304a, it was proposed that a possible precursor of the bicyclo[7.3.1]enediyne substructure could be C-14 chains such as 329 or 330, or their biogenetic analog, which can be connected with the anthraquinone moiety through a Friedel-Crafts type acylation reaction to form the C-8-C-9 bond and can also cyclize to the bicycle structure through two condensation reactions to form the C-3-C-4 and C-7-C-8 bonds. Introduction of an additional acetate unit at C-5 followed by oxidative degradation to form the carboxyl group and O-methylation from methionine should occur at some point. Tentatively, a heptacar-bonyl acid such as 331 was proposed as a possible precursor of the anthraquinone moiety. Moreover, an enediyne chain such as 329 is also conceivable as a precursor of the anthraquinone portion [332]. 

Friedel-Crafts acylation is related to Friedel-Crafts alkylation, with an acylium cation acting as the electrophile. However, in industrial aromatic chemistry, because of the high consumption of catalyst, this reaction is of much less importance than Friedel-Crafts alkylation. Nonetheless, it has been used, for example, in the manufacture of anthraquinone from phthalic anhydride and benzene. 

Synthetic production of anthraquinone is based on Friedel-Crafts acylation of benzene with phthalic anhydride, and the Diels-Alder reaction of naphthoquinone with butadiene. 

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