Patented Jan. 9, 1945 2,366,760 UNITED STATES PATENT OFFICE PRODUCTION OF TROPINE Jacob van de Kamp, Westfield, N.J., and Meyer Sletzinger, Bronx, N.Y., assignors to Merck & Co.,Jersey Inc., Rahway, N.J. ., a corporation of New No Drawing. Application June 5, 1942, '. Serial No. 445,988 4 Claims. (C1.260-292) This invention relates to the preparation of the hydrogen may be brought to reaction with tropine from tropinone. the tropinone solution in any other suitable man Several methods have been proposed in th ner Well known in the hydrogenation art. prior art for the reduction of tropinone to tropine, When operating within the preferred Scope. Of Such as electrolytic reduction, in acid or alka the invention, the conversion of tropinone to line media, reduction with zinc dust and hydro tropine is substantially quantitative. iodic acid and similar procedures. However, such The following example illustrates a method of prior art methods yield products containing rela tively large amounts of objectionable impurities, carrying out the present invention, but it is to be comprising among other products, pseudotropine understood that this example is given by way. and tropane (the oxygen-free base of tropine). 10 of illustration and not of limitation. . . . ." Tropine is used in the synthesis of atropine, and Eacample When So used, the presence of appreciable To 10 parts by weight of tropinone dissolved amounts of the pseudo product causes difficulties in 100 parts by volume of absolute ethanol is in isolating a good yield of pure atropine or its added 0.5 part by weight of Raney nickel catalyst. salts. Methods for the purification of crude Hydrogen is then introduced into the solution at tropine give relatively poor yields and necessitate a pressure of a few inches of Water, the tem cumbersome and time-consuming procedures. operature being maintained at about room tem - We have now discovered that by catalytic hy perature. The hydrogenation reaction is com drogenation of a solution of tropinone in a suit 20 pleted upon absorption of the calculated amount, able organic solvent and in the presence of a of hydrogen. The solution is then filtered from suitable hydrogenation catalyst, preferably of the the catalyst and evaporated to dryness in vacuo. metal type, a tropine is obtained which is char Tropine, in the form of white crystals M. P. 62° acterized by a relatively low pseudotropine con C., is obtained in substantially quantitative yield tent. When operating within the preferred em 25 and the product is substantially free from iso bodiment of our invention, the pseudotropine con meric pseudotropine. . . " tent may even be reduced to practically zero. The identity of the product was established The organic solvent used in accordance with through preparation of tropine picrate (M. P. our invention may be any suitable solvent in 275°). Also, the product was condensed with which tropinone is soluble and which is substan 30 tropic acid to form an addition product, tropine tially inert against tropinone or tropine, and tropate, of melting point 140-142 C. The tro against hydrogenation. It should be such that pine-tropate so prepared was identical with tro it may be evaporated in vacuo substantially with pine-tropate prepared from tropine obtained by Out decomposing tropine dissolved therein. Pref hydrolysis of atropine, and a mixed melting point erably, the solvent should be a lower aliphatic 35 determination of the two 'samples of tropine alcohol. Within the preferred embodiment of tropate showed no depression, Our invention we use absolute ethanol, Modifications may be made in carrying out The concentration of the tropine solution to be the present invention, without departing from the Subjected to the hydrogenation procedure in ac spirit and scope thereof, and we are to be lim cordance with our invention is not critical ex ited only by the appended claims. . cept that for practical reasons it is preferred to We claim: . use concentrations between 5 and 15% tropinone 1. The process comprising hydrogenating tro in the solvent used. pinone, in organic solvent solution, in the pres The catalyst in accordance with the invention ence of a nickel catalyst, and recovering tropine. may be any suitable hydrogenation catalyst of the 45 2. The process comprising hydrogenating tro metal type. Within our preferred procedure we pinone, in organic solvent solution, and in the find it of advantage to use a nickel catalyst and preferably a Raney nickel catalyst. The catalyst presencepine. of Raney. . nickel,. and recovering tro is preferably finely dispersed throughout the 3. The process comprising hydrogenating tro tropinone solution. The same may be used either 50 pinone in ethanol. Solution, in the presence of a as such or adsorbed on a suitable carrier. nickel catalyst, and recovering tropine. The hydrogenation is carried out by introduc 4. The process comprising hydrogenating tro ing hydrogen gas into the tropinone solution. pinOne in ethanol, solution, in the presence of For best results, it is of advantage to provide for Raney nickel, and recovering tropine. the proper distribution of the hydrogen gas in 55. - - JACOB WAN DEKAMP. the Solution such as by agitation. Alternatively, MEYER SLETZINGER.