Patent GB-326523-A (GB)
Title: Improvements in the manufacture and production of reduction products of indoxyl, naphthindoxyl, their homologues and acyl derivatives
IPC: C07D209/36
Filed: 1928-11-06
Abstract: 326,523. Johnson, J. Y., (I. G. Farbenindustrie Akt.-Ges.). Nov. 6, 1928. Dihydroindoxyls, dihydroindoles, indoles, and their acyl derivatives.-Dihydroindoxyls and dihydroindoles are prepared by the catalytic hydrogenation of indoxyl, naphthindoxyl, their homologues and acyl derivatives. From the dihydroindoxyls, indoles are obtained by splitting off water. For the production of dihydroindoxyls, the hydrogenation is carried out under mild conditions, e.g. at ordinary temperature with or without the employment of pressure; if elevated temperatures, e.g. 80‹ C., are employed, the pressure should not substantially exceed atmospheric pressure; in some cases, however, by working in the absence of dehydrating materials and interrupting the process when two atomic proportions of hydrogen have been absorbed, both elevated temperature and pressure may be employed. Dihydroindoles are formed when the hydrogenation is effected at elevated temperature, e.g. 80‹ C. and above, and preferably also at elevated pressure; the presence of a dehydrating agent is advantageous. Of the hydrogenation catalysts employed, those containing metals of the first or eighth periodic group, or mixtures thereof, are especially suitable; activating metals or compounds may be added and carriers may be employed; when using catalysts containing noble metals such as platinum, the hydrogenation is effected in acid media, e.g. acetic acid. In all cases a solvent or diluent, such as water, ethyl alcohol, acetic acid, ethyl acetate and decahydronaphthalene, is desirably present during the hydrogenation, with or without the addition of basic substances or salts, e.g. caustic alkalies, organic bases, phosphates, bicarbonates, carbonates, acetates and borates. The use of salts is advantageous in the hydrogenation of N : O.diarylindoxyls, for the separation of the O-acyl residues is facilitated thereby. For the hydrogenation of indoxyls, aqueous solutions of salts having a pH between 7 and 9.5 are particularly suitable. In the conversion of dehydroindoxyls (which need not be isolated from the hydrogenation product) into indoles, the splitting off of water is effected by treatment with mineral or organic acids, alkalis or salts, or by merely raising the temperature. When N-acylindoles comprise the product, the indole may be prepared therefrom by saponification, or the indole mav be obtained by splitting off water from a simultaneous saponification of N-acyldihydroindoxyls. The products are useful as perfumes, for pharmaceutical purposes and as intermediates in the manufacture of dyestuffs; whilst in the case of the dihydroindoxyls and dihydroindoles, they may be employed as vulcanization accelerators. Examples are given of the catalytic hydrogenation under the conditions specified of (1) indoxyl to dihydroindoxyl, using a nickel (22.5 per cent)-copper (2.5 per cent)- kieselguhr catalyst, 15-35‹ C. and 100 atmospheres pressure; acetylation of the product yields N-acetyldihydroindoxyl; (2) indoxyl to dihydroindoxyl using copper (12.5 per cent)-cobalt (12.5 per cent)-kieselguhr, 26' C. and 100 atmospheres; (3) indoxyl to dihydroindole using nickel-copperkieselguhr, 25‹ C. for some time and then 95- 100‹ C., and 140 atmospheres; acetylation of the product gives N-acetyl-2:3-dihydroindole; (4) N : O-diacetylindoxyl to N-acetyldihydroindoxyl using nickel-kieselguhr, 20-85‹ C. and atmospheric pressure, or 25-30‹ C. and 100 atmospheres; (5) N-monoacetylindoxyl to N-monoacetyldihydroindoxyl using nickel (25 per cent)-kieselguhr, 25-35‹ C. and 100 atmospheres; (6) N : O- diacetylindoxyl to N-acetyldihydroindole, together with some N-acetyldihydroindoxyl, using nickelkieselguhr or nickel-tungsten, 80-90‹ C. and 100 atmospheres; (7) N-acetyldihydroindoxyl to N- acetyldifiydroindole using nickel-kieselguhr, 95- 100‹ C. and 80 atmospheres; (8) indoxyl to dihydroindoxyl using copper (12.5 per cent)-cobalt (12.5 per cent)-kieselguhr, 25‹ C. and 100 atmospheres; then to indole, together with some dihydroindole, by raising the temperature to 80' C. whilst maintaining the pressure; (9) 7-methyl- N : 0-diacetylindoxyl (prepared by fusing otoluylglycine with caustic soda and treating the resulting 7-methylindoxyl with acetic anhydride) to 7-methyl-2 : 3-dihydroindoxyl using nickel (25 per cent)-kieselguhr, 20‹ C. and 100 atmospheres; (10) N : O - diacetyl-2 : 3-naphthindoxyl to N- acetyl-2 3-naphthdihydroindole using nickel (25 per cent)-kieselguhr, 25‹ C. for some time and then 50‹ C., and 100 atmospheres; (11) N-acetyl- 2: 3-naphthindoxyl (prepared by partial saponification of N : O-diacetyl-2 : 3-naphthindoxyl) to N-acetyl- : 3-naphthdihydroindoxyl using nickel (25 per cent)-kieselguhr, 25‹ C. and 100 atmospheres. Examples are also given of the preparation of (1) indole from 2 : 3-dihydroindoxyl by acidifying with dilute sulphuric acid and distilling with steam ; in the same way N-acetylindole and 7-methylindole are obtained from N-acetyldihydroindoxyl and 7-methyldihydroindoxyl respectively; caustic soda. treatment of the N-acetylindole gives indole ; (2) indole by heating N-acetyldihydroindoxyl with caustic soda; (3) N-acetyl-2 : 3- naphthindole by boiling N-acetyl-2 : 3-naphthdihydroindoxyl in ethyl alcohol with sulphuric acid; saponification of the product gives 2 : 3-naphthindole.