Carboxylic acids indoles, 1-acyl

Indole-2-carboxylic acid, 5-hydroxy-ethyl ester acylation, 4, 219... 

Changing the functionality on the alicyclic ring from an amine to a carboxylic acid leads to a compound that shows antiallergic activity, acting possibly by means of inhibition of the release of allergic mediators. Thus, condensation of acylated indole with cyclohexanone carboxylic acid affords directly oxarbazole (29). ... 

The 2H-and 3//-pyrroles and -indoles are considerably more basic than the corresponding H-isomers and they readily undergo alkylation to give the quaternary salts, which are then highly susceptible to nucleophilic attack. Thus, for example, methylation of the trialkyl-3//-indole (507), followed by reaction with aqueous base, yields the indolin-2-ol (508). A similar reaction sequence results from the acylation of (507) under Schotten-Baumann conditions to give (509 X = OH). When the benzoylation is conducted in benzene in the absence of the base, the 2-chloroindoline (509 X = C1) is formed and acylation of (507) with a carboxylic acid anhydride produces the ester (509 X = OCOR) (79HC(25-3)l). 

N-Acylation of indole.1 Indole can be N-acylated by a carboxylic acid in the presence of boric acid (0.3 equiv.) in 45-80% yield. 

Enantioselective additions of a,f)-unsaturated 2-acyl imidazoles, catalyzed by bis(oxazolinyl)pyridine-scandium(III)triflate complex, were used for the asymmetric synthesis of 3-substituted indoles. The complex 114 was one of the most promising catalysts. The choice of acetonitrile as the solvent and the use of 4 A molecular sieves were also found to be advantageous. The 2-acyl imidazole residue in the alkylation products of u,(i-unsaturated 2-acyl imidazoles could be transformed into synthetically useful amides, esters, carboxylic acid, ketones, and aldehydes (Scheme 32) [105]. Moreover, the catalyst 114 produced both the intramolecular indole alkylation and the 2-substituted indoles in good yield and enantioselectivity (Scheme 33) [106]. The complex... 

Syntheses of 2-substituted indoles from (2-aminobenzyl)triphenylphosphonium salts have been achieved either by cyclization with carboxylic acid anhydrides in the presence of triethylamine, or acyl chlorides in 2,6-lutidine <02TL2885>. In a related study, the acylated indoles 65 have been prepared from the phosphonium salts 66 in a process involving extrusion of a one-carbon fragment. A mechanistic rationale for these findings was also provided by the authors <02TL8893>. 

Reaction of enaminones and carboxylic acids is mainly interesting as a route for cyclization of suitable substituted enaminoketones to N-heterocycles45. In this way iV-cyclohexenylglycines can cyclize to indoxyl derivatives (equation 30). By a similar intramolecular acylation at the / -carbon of enaminones, fused indoles or pyrrole derivatives are obtained46-48. 

A second, more versatile, method involves the O-acyl thiohydroxamates. These compounds are generally prepared by reaction of acyl chlorides with the commercial sodium salt (1) of 2-mercapto-pyridine A(-oxide (equation 6 X = Cl). Use of mixed anhydrides formed by reaction of the carboxylic acid with isobutyl chloroformate (equation 6 X = OCC>2CH2CHMe2) renders the procedure compatible with unprotected indoles, phenols, secondary and, presumably, tertiary alcohols. An alternative mode of preparation of the 0-acyl thlohydroxamates involves the s t (2) in reaction with the carboxylic acid (equation 7). 

Indole can be condensed directly with a variety of carboxylic acids in the presence of boric acid [9], Traditional methods are unsatisfactory because of low yields and the production of 3-acylated and 1,3-diacylated side products. 

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