Friedel-Crafts reaction cyclisation

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. 

The synthesis of 2,4-diarylchromen-2-ols through the reaction of phenols with an excess of a chalcone in TFA involves sequential Friedel-Crafts alkylation, cyclisation to a 4/7-1-benzo-pyran, an intermolecular hydrogen transfer generates the 4-arylflavylium ion which is hydrated to give the final product (Scheme 12) <07JOC9383>. 

Haworth reaction A reaction in which an aryl compound is treated with a cyclic anhydride, such as succinic anhydride, and the intermediate Friedel-Crafts product is reduced and then cyclised via an internal Friedel-Crafts reaction to give a 1,2-disubstituted aromatic compound with a carbonyl group in the new ring. The whole sequence is called the Haworth reaction. 

There are no problems of orientation in the Friedel-Crafts reaction as all positions in the aromatic ring are the same. Reformatsky (Chapter 20) is usually the best method of control for /3-hydroxy esters (12) so we shall need to protect the COjH group as an ester (15). The final cyclisation occurs during ork-up. 

Searchable data bases have for some time now simplified the search for the more routine methods of 7-membered ring synthesis. For this reason it seems reasonable to omit yet further examples of cyclisation by cyclocondensation or intramolecular Friedel-Crafts reaction, as well as new examples Schmidt and Beckmann ring expansion reactions, unless specific mechanistic or stereochemical features are of interest. 

Clayzic has been used to catalyze various Friedel-Crafts reactions including those of aromatic substrates with alkyl halides, aldehydes and alcohols. Other applications include the preparation of benzothiophenes by cyclisations of... 

This chapter collects miscellaneous enantioselective nickel-catalysed reactions that could not be included in other chapters, such as cyclisation reactions, amination reactions, ring-opening reactions, Friedel-Crafts reactions, allylation reactions of aldehydes, and other reactions. It well demonstrates the remarkably diverse chemical reactivity exhibited by chiral nickel catalysts. 

Substituted Cp rings can be made to undergo intramolecular cyclisation via a simple Friedel-Crafts reaction giving (16) which is derived from the parent benzyl complex. Other reactions reported for the CpFe fragment include the first report of an arsalkenyl complex (17) and migration of the phenyl group of... 

The Y-phenylbutyric acid is cyclised to a-tetralone by converting it into the acid chloride with thionyl chloride or phosphorus pentachloride and then an intramolecular Friedel and Crafts reaction is carried out ... 

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... 

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 Robinson annelation is by no means the only ionic reaction that makes six-membered rings. Six-membered rings form easily so trapping a Nazarov intermediate (chapter 35) makes good sense. The Friedel-Crafts-like disconnection 18 suggests a most unlikely cation 19 until we realise that it would be formed in the Nazarov cyclisation of the dienone 20 whose synthesis is discussed in the workbook. 

Another advantage of this approach is that we can now use electrophilic substitution on the pyrrole to add the rest of the molecule. So the secondary benzylic alcohol 106 might well cyclise to 105 with Lewis acid catalysis as the cation will be reasonably stable and the reaction is intramolecular. But the Friedel-Crafts alkylation to give 107 will not succeed as the cation would be primary. 

The Claisen rearrangement is normally performed without a catalyst, however, the use of certain catalysts can increase the rate of the reaction, e.g. BF3, AICI3 and CF3COOH [1,3]. In this case the mechanism is often no longer cyclic, but may become a Friedel-Crafts type reaction, which can result in side products. Furthermore, the Claisen rearrangement in the presence of acids is often accompanied by the cyclisation of the initial rearrangement product [2,3]. 

Pivaloylindole gives high yields of 6-substituted ketones on reaction with a-halo-acid-chlorides and aluminium chloride simple acid chlorides react only at 0-3. The sequence below shows how a 1-pivaloyl-3-(indol-3-yl)propanoic acid undergoes Friedel-Crafts cyclisation to C-4, away from the deactivated heterocyclic ring. °... 

The main synthesis of oxindoles is simple and direct and involves an intramolecular Friedel-Crafts alkylation reaction as the cyclising step. Also straightforward in concept is the displacement of halogen from an ort/to-halo-nitroarene with malonate, this leading to an oxindole after decarboxylation and reduction of the nitro group with spontaneous lactamisation. ... 

The alternative Friedel-Crafts disconnection requires (18)—a rather unstable compound. This is hardly a problem as (18) is unstable because it cyclises readily to (17). The reaction occurs at 35 C and (18) need not be... 

Other synthetic strategies based on cyclisation of ring B involve synthesis of an intermediate DCA entity through anionic reactions followed by ring closure under Friedel-Crafts conditions. Thus Michael addition of the nitrile 34 to the... 

Numerous synthetic approaches to anthracyclines are based on carbanion mediated cyclisations. These reactions often occur under mild conditions, allowing incorporation of highly functionalised precursors. Some approaches follow an initial base-catalysed coupling of two fragments by cyclisation under Friedel-Crafts conditions (previous section), while other strategies bring about both condensation and cyclisation under basic conditions. Syntheses based on closure of rings C, B or A have been described. 

Many of the homochiral AB synthons described above have been utilised in syntheses of anthracyclinones which are based on Friedel-Crafts cyclisations. As was noted earlier such reactions often require vigorous conditions, and there is some controversy concerning the enantiomeric purity of the products so obtained. While some groups claim that condensation of the hydroxy ketone 174 with phthalic anhydride in an intimate mixture of sodium chloride and aluminium chloride yields optically pure ( —)-4-demethoxy-7-deoxydauno-mycinone [16, 141] others report a considerable degree of racemisation under virtually identical conditions [135, 142], although the problem may be avoided under the somewhat milder conditions employed in a recent condensation of 174 with phthaloyl dichloride [143]. In contrast, stereochemical integrity of the product is assured under the mild conditions employed in Swenton s carbanion based synthesis of (4-)-daunomycinone 5 [53] and in our Diels-Alder based... 

The main synthesis of oxindoles is simple and direct and involves an intramolecular Friedel-Crafts alkylation reaction as the cyclising step. ... 

Because of their negligible vapor pressure, thermal stability and easy recyclability, neutral ILs have been referred to as environmentally benign solvents. These ILs have been employed as excellent and recyclable medium for a wide array of reactions e.g., Heck reaction [Park Alper, 2003], Bischler-Napierlaski cyclisation [fudeh et al, 2002], Beckmann rearrangement [Ren et al., 2001], addition of thiols to unsaturated ketones [Yadav et al., 2003], 1-proline catalysed aldol reaction [Loh et al., 2002], and Pechmann condensation of phenols and ethyl acetoacetate (EAA) catalyzed by POCI3 in [bmim]PF6 and [bmim]BF4 ILs [Potdar et al., 2005]. Other examples where ILs have been used as a reaction media include, but not limited to, Diels-Alder reactions [Reinhardt, 2009 Doherty, 2004 Song, 2001], Friedel-Crafts alkylation and acylation reactions [Xiao, 2006 Xiao Malhotra, 2005 ... 

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