New carbamates and related compounds

Abstract

Tables I and I1 give constants of the new compounds. Anilinoalkylamines. The anilinoethyl halides were prepared according to published directions (15, 20, 24) from commercially available anilinoethanol. The N(dialkylaminoethy1)anilines (IV, R' = H, R = alkyl, x = 2,3) were prepared from the anilinoethyl halide by reaction with the desired dialkylamine (4 , 8, 17). The higher members of the homologous series of IV, x > 2, were not made easily from the intermediate halides because of ring closure, and were prepared, therefore, by reaction of aniline with the haloalkynitrile to yield the anilinoalkyl cyanides (10, 25). These cyanides were reduced to the amines by the use of high pressure and a Raney nickel catalyst (25). Lithium aluminum hydride reduction also was used according to the directions of Nystrom and Brown (9, 19) except that dilute hydrochloric acid instead of sodium potassium tartrate was used to hydrolyze the lithium aluminum complex. Since these diamines are soluble in both ether and water, a minimum of water was employed. N-Phenyl-N-(alkylphtha1imido)-N-carbamoyl Halide (11, R = COX, x = 2,4). These compounds were synthesized via the reaction of phosgene with the anilinoalkylphthalimides, according to the directions of Raiford and Alexander (21). The fluoro derivatives were made by reacting the chloro compounds with antimony trifluoride (18). Ethyl N-Phenyl-N-(2-phthalimidoethyl)carbamate (11, R = 0 II --C-OGHs, x = 2). This carbamate was prepared from the anilinoethylphthalimide (2, 24) and ethyl chloroformate according to published directions (6,11, 12, 17, 27). The final product was obtained pure only after many recrystallizations. Other similar carbamates, not reported, were used as intermediates after several recrystallizations if their ana:, ical data were reasonable. Alkyl or Aryl N-Phenyl-N-(dialkylaminoalkyl)carbamate, Hydrochloride (I, R = alkyl, R t = alkoxy or aryloxy, x = 2,3). The following synthesis of phenyl N-phenyl-N(2diethylaminoethyl)carbamate, hydrochloride is typical for this series. Approximately grams, (0.1 mole) of N-(diethylaminoethyl) aniline (IV, R' = H, R =ethyl) was placed in a 500-ml., three-necked round-bottomed flask equipped with a mechanical stirrer, drying tube, condenser, and dropping funnel; dry ethyl acetate, 250 ml., was added, and the mixture was cooled to about 20 C. (No appreciable difference in yield was observed when the reactions were run a t any temperature between 5' and 25 C., Phenyl chloroformate (16 grams, 0.1 mole) was added dropwise to the well-stirred mixture; precipitation of the carbamate-hydrochloride occurred immediately. The whole was stirred a t 25 C. for 3 hours, filtered, and the recovered crystals were washed with dry ethyl acetate and ether. After drying in vacuo over CaC1and recrystallizing three times from ethyl acetate plus a small amount of absolute ethanol, a pure product was obtained. Hydrolysis Rate of Carbamates. The above phenylor p-nitrophenyl N-phenyl-N-(2-diethylaminoethyl)carbamate was placed in buffered 0.066M sodium phosphate a t pH 8.30. The half-life of the phenyl carbamate was 15 minutes which gives a first-order hydrolysis constant of 4.9 x 10-2 per minute. The hydrolysis of