The purpose of this investigation was t u synthesize compounds in which the keto group of the potent analgetic drug methadon is incorporated in a saturated ring. As examples of this type of structure we have prepared a number of amino substituted 2,2-diphenylcyclohexanone derivatives of types I1 and V. In addition, the amino alcohols 111 and the amine VI1 have been prepared for general pharmacodynamic screening tests.Our starting material, 2,2-diphenylcyclohexanone (I), was prepared essentially according to the directions of M e e r~e i n .~ The @-amino ketones I1 were obtained smoothly by the Xannich reaction and could be hydrogenated uneventfully to the amino alcohols 111. The a-amino ketones V were synthesized by treating the readily available bromo ketone IV with secondary amines. When 2,2-diphenyl-fi-brornocyclohexarione (IV) was heated with collidine, hydrogen bromide was eliminated and 2,2-diphenylcyclohexen-~i-one-l (VI) was formed.Reduction of 2,2-diphenylcyclohexanone oxime with lithium aluminum hydride furnished 2,2diphenylcyclohexylamine (VII) in good yield. In view of the ease of this reduction, and of the hydrogenation of the &amino ketones I1 to the amino alcohols 111, we attempted to hydrogenate the a-amino ketones V to the corresponding amino alcohols. These experiments were unsuccessful, and we tried therefore to reduce the bromo ketone Ponndorff-Xeerweinthis step could not be I V to a bromohydrin by the Verley method. However, accomplished, either. 0 ii Vol. 7 2 cicntly stirred mixture of 1395 g. of cyclopentanone and a solution of 980 g. of sodium cyanide in 3750 cc. of water was added over a period of 40 minutes a solution of 2000 g. of sodium bisulfite in 2700 cc. of water. The temperature mas maintained below 30 a by periodical addition of ice.The solution was filtered, the layers were separated, the aqueous layer was extracted with ether, and the latter evaporated. The crude cyanohydrin was refluxed with 7.5 1. of 37% hydrochloric acid for one hour, and the solution evaporated. The yield of 1 -hydroxycyclopentanecarboxylic acid was 1306 g. (60Oj,).The ester, obtained from the acid and methanol in the presence of concentrated sulfuric acid in a yield of 77y0, reacted with a twofold excess of phenylmagnesium bromide to give yields of 80 to 91% of diphenyl-(1-hydroxy-1cyclopentyl) -carbinol. We were unable to get good yields of 2,2-diphenylcyclohexanone from the pinacol rearrangement with sulfuric acid as described by Meerwein, but found' that refluxing 50 g. of the pinacol in 350 cc. of glacial acetic acid containing 0.3 g. of iodine for thirty minutes, cooling, and pouring onto ice led to a yield of 98% of a product melting a t 96.599". Recrystallization from ethanol gave 39.5 g. (85%) of colorless prisms, m . p. 98.5-99.5".Preparation of 2,2-Diphenyl-6-diakylaminomethylcyclohexanones (11) .-These compounds were prepared by dissolving 0.12 mole of the secondary amine hydrochloride and 0.1 mole of 2,2-diphenylcyclohexanone in isoamyl alcohol, heating to reflux, adding a fivefold exces of par...
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Two hundred grams of cellulose acetate was dissolved in two liters of acetic acid. The solution was heated by total immersion in a steam-bath and vigorously stirred during the addition of 200 g. of acetic anhydride and for one hour afterward. Samples were taken as indicated in Table II. Portions of the solution were poured into distilled water with vigorous stirring to precipitate the product, which was then washed to neutrality and dried in a current of air at 70°. The portions used for analyses were further dried at 105°.Acetylation with Perchloric Acid Catalyst.-Two hundred grams of cellulose acetate was dissolved in two liters of acetic acid at room temperature, and 200 g. of acetic anhydride at 0°was added with good stirring. Then 80 ml. of acetic acid containing 0.10 ml. of perchloric acid was•added. Samples were taken during the course of one hour at room temperature, constant stirring being maintained.Acetylation with Sulfuric Acid Catalyst.-This acetylation was similar to the above, except that 0.70 ml. of sulfuric acid was added. The sulfuric acid combined quantitatively with the cellulose acetate during this acetylation,5 6 giving products containing 0.17-0.18% sulfur. They were rendered stable to drying by adding sufficient sodium carbonate to the last wash to impart a pink color to phenolphthalein indicator.Acetylation in Solution with Pyridine Catalyst.-Eighty grams of cellulose acetate was dissolved in 1000 ml. of acetic acid and 200 g. of pyridine. The mixture was heated to 65°and 80 g. of acetic anhydride was added with stirring. Samples were taken during the course of one hour.Acetylation in Suspension with Pyridine Catalyst.-These acetylations were carried out in individual screw-cap bottles on a tumbler heated to 65°. Each bottle was charged with 20 g. of cellulose acetate, 280 ml. of benzene, 20 g. of pyridine and 20 g. of acetic anhydride. The products were filtered off and washed with benzene.Acetylation with Zinc Chloride Catalyst.-Fifty grams of cellulose acetate was dissolved in 500 ml. of acetic acid, and 50 g. of acetic anhydride was added with good stirring at room temperature. This was followed by a solution of 10 g. of zinc chloride dissolved in 20 ml. of acetic acid. Samples were taken during the course of seven hours. Triacetates were prepared by acetylating several of the starting materials with two parts of acetic anhydride and one part of zinc chloride for two hours at 50°. These products contained the theoretical amount of acetyl, no free hydroxyl, and had an optical rotation of -23 ± 1°.Acetylation with Acetyl Chloride and Pyridine.-Fifty grams of cellulose acetate was dissolved in a mixture of 60(5) C.
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