GB796665A - Process for the preparation of indole carboxylic acids - Google Patents

Abstract

Indole carboxylic acids or salts or derivatives thereof are prepared by heating indole or a substituted indole which contains a hydrogen atom in the 2 and/or 3 position with carbon dioxide under pressure in the presence of an acid-binding agent. The salts of indole carboxylic acids thus obtained, the carboxyl groups of which are in the 2- or 3-position, may be converted in known manner into the free acids or derivatives thereof. The starting materials may be substituted in either or both rings, and may include: 1-, 2- or 3-alkyl- or aryl-indoles, 3-indolyl acetic acid, 1,3-dimethylindole (1-methylskatol), 4-methylindole, 7-methylindole, 2,5 - dimethylindole, 3,5 - dimethylindole, 2 - phenyl - 7 - methylindole, 1 - ethyl - 5 - methyl-indole, 2 - phenyl - 7 - methylindole, 5 - chloro-2 - ethylindole, 2,4,7 - trimethylindole, indole-carboxylic acid - 6, 4,5 - benzindole and 6,7 - benzindole. Preferred acid-binding agents are basically-reacting alkali metal salts such as the carbonates, oxides, hydroxides, bicarbonates, formates or oxalates; particularly preferred is potassium carbonate. The agent should be as anhydrous as possible, although small amounts of water do not disturb the reaction. They are used in at least the quantity necessary for the formation of the carboxylic acid salt, but preferably in 10-100 per cent or more excess. The temperature is generally 150-500 DEG C., usually optimally 200-350 DEG C. At least the calculated quantity of CO2 is used, preferably an excess, the pressure reaching, for example, 10-500 atm. The CO2 may be diluted by inert gases such as nitrogen. Catalysts may be present such as zinc, cadmium, lead, mercury or iron or compounds thereof such as the oxides or salts with inorganic or organic acids. Inert fillers may also be used such as sand, finely-divided carbon, kieselguhr, bentonite, metal powder or chippings and inert salts such as sodium sulphate and potassium sulphate. Organic diluents may also be added, e.g. pyridine, dioxan, tetrahydrofuran, benzene, toluene, xylene, and high-boiling benzines. The reaction product may be worked up by dissolving in water, filtering, if desired with the addition of active carbon or other decolorizing agent; and liberating the desired acids by acidification, e.g. with HCl, H2SO4 or other strong acids. In many cases the reaction products can also be isolated by utilizing the low solubility of the potassium salts in saturated K2CO3 solution. Alternatively the crude reaction product may be directly converted in known manner to derivatives such as the chlorides or esters of the indole carboxylic acids formed. The products are useful intermediates in the synthesis of pharmaceuticals and plant-growth promoters. In examples, the following are prepared in the presence of K2CO3: (1), (2) and (3) indole-3-carboxylic acid from indole, CdF2 being present in (2) and (3); (4) skatol-2-carboxylic acid from skatol; (5) 2-methylindole-3-carboxylic acid from 2-methylindole, CdCl2 being present; (6) N-methylindole-2-carboxylic acid from N-methylindole.