Emetic tetralones and the use thereof for inducing regurgitation

#This invention relates to certain .beta.-tetralones useful as chemical intermediates and to the emetic 2-aminotetralins prepared therefrom.

#Certain 2-amino-5,6-dimethoxytetralins have been reported to have emetic activity. Emetics are useful for quickly inducing regurgitation, i.e. vomiting, to empty the stomach, for example, after certain toxic materials have been ingested. Potent emetics may also be incorporated into certain formulations to prevent accidental poisonings by ingestion, e.g. by small children, of said formulations. Similarly, emetics may be incorporated into pharmaceutical formulations of medicinals which might be prone to misuse to induce emesis whenever an overdose was taken.

#However, the synthetic routes available to the 2-amino-5,6-dialkoxytetralins have been inconvenient ones. The applicants have now discovered a novel class of intermediates useful in the synthesis of these 2-amino-5,6-dialkoxytetralins and methods for preparing these intermediates.

#The following examples illustrate but should not be construed to limit the invention.

#1,2,6-Trimethoxynaphthalene (5.0 g.; 23 m mol) was dissolved in ethanol (55 ml.). Under nitrogen, sodium metal (5.5 g; 240 m mol) was added in small pieces at a rate adequate to maintain refluxing. After all this sodium was added, the flask was heated to reflux until all the metal was dissolved. After cooling slightly, water (20 ml.) was added down the condenser followed cautiously by concentrated HCl (40 ml.). The resulting suspension was refluxed for 30 minutes. After cooling, sufficient water was added to dissolve the solid present. Extraction with methylene chloride followed by drying and evaporation of the solvent yielded I as a viscous oil. This oil was shaken with saturated NaHSO.sub.3 solution (75 ml.) to form the bisulphite adduct of I. After 30 minutes the adduct was collected by filtration and washed, first with ethanol and then with ether, yielding 5.2 g. (17 m mole, 73%) of white powder. The free, purified ketone, m.p. 50.degree. C., was obtained as needed by adding the bisulphite adduct to a stirred mixture of ether and excess 10% aqueous Na.sub.2 CO.sub.3 solution, followed by separating, washing, drying, and evaporating the other layer.

#Compound I, R.dbd.R'.dbd.CH.sub.3 (2.8 g., 13.6 m moles), diethylamine (6 g., 82 m moles), 5 A molecular sieves (5 g.), and p-toluenesulfonic acid monohydrate (0.2 g., 1 m mole) were combined in benzene (75 ml.) under nitrogen in a pressure bottle. The bottle was stoppered, clamped shut and heated in a steam bath for 3 days. After cooling, the bottle was opened, the molecular sieves were removed and rinsed with ethanol (75 ml.). Platinum oxide (150 mg.) was added to the combined filtrate. Hydrogenation was performed on a Parr apparatus just above atmospheric pressure. The theoretical amount of hydrogen was absorbed in 45 minutes. Removal of catalyst and evaporation of the solvent left 3.4 g. of a dark oil, which was chromatographed on a column of activity I alumina (38 g.) eluting with 85% hexane/15% benzene. This produced the pure amine as an oil (2.8 g., 79%. The hydrochloride was obtained by dissolution in a little HCI/methanol and trituration with ethyl acetate, m.p. 177.degree.-179.degree. C.