Sept., 19-16
PREPARATION OF SOME SUBSTITUTED LEPIDYLAMINES [CONTRIBUTION FROM THE
DEPARTMENT OF CHEMISTRY,
UNIVERSITY O F NOTRE
1851
DAME]
Studies in. the Quinoline Series. VI. The Preparation of Some Substituted Lepidylamines I3Y KENNETH 14. CAMPBELL, ARMIGERH. SOMMERS,~ JAMES F. K E R W I N 3 AND B A R B A R A K. CAMPBELL
In view of the high antimalarial activity shown by the 4-aminoquinolines, i t became desirable to learn whether any of that activity would be retained if a methylene group were interposed between the amino side chain and the quinoline nucleus. In this connection we undertook the synthesis of some lepidylamines derived from 6chloro- and 7-chlorolepidines. Work4 prepared several substituted lepidylamines by converting the corresponding Nalkylcinchonamides to the amido dichlorides, and reducing these with stannous chloride. While the present wo:rk was in progress Tarbell and his co-workers5 reported the preparation of some 2phenyllepidylamines. In most cases these were made by the method of Work4 but in one case the lepidylalclehyde was condensed with a primary amine, and the product hydrogenated. Axany 1epidi:nes can now be prepared in good yield and in one step from the substituted anilinee and lepidines can in general be oxidized in one step to the corresponding aldehydes by means of selenium d i o ~ i c l e .It ~ ~seemed ~ ~ ~ to us, therefore, that the :;horte:jt route to lepidylamines lay in the hydrogenation of the corresponding aldimines ; this method was found to be very satisfactory in the cases reported here.
Experimental8 6-Chloro-4-quinoline Aldehyde.-A solution of 18.3 g. (0.165 mole) of sublimed selenium dioxide9 in a mixture of 50 ml. of purified dioxane10and 12 ml. of water was added during one hour to a well-stirred solution of 29.3 g. (0.165 mole) of B-~hlorolepidine~~ in 55 ml. of purified dioxane, kept a t 65-75". The mixture was stirred a t 85-90' for five hours and then filtered through a sintered glass funnel. The dioxane was evaporated from the filtrate to give 31 g. of crude aldehyde. Attempts to free this material of traces of selenium by recrystallization and treatment with Norite were unsucccssful, and it was finally purified by steam distillation. The aldehyde crystallized from the steam distillate in long white needles, m. p. 152-153 ', obtained (1) T h e m , r k reported here was carried o u t under a contract, recclmmended by t h e Committee on Medical Research, between t h e
Ofice of Scientific Research and Development a n d t h e University of
S o t r e Dame (2) Present addretis: Department of Chemistry, Columbia University. ( 3 1 Present atlrIre.;s Smith, Kline and French Laboratories, Pa. ( k ) W f r k , J . C h e ~ ~Siii., i 42(j (l!l-t'2). ( 3 ) Tarbell, Runnctt, Carlin and Wystrach, THISJ O U R N A L , 67, l i R 2 (1045). ( 6 ) Campbell a n d Schaffner. i b i d . . 67, 86 (1945). ( 7 ) Levitz a n d Boi:ert, 1.O r g . C h e m . , 10, 341 (1945).
I'hil.idelphia
(8) N o s t of t h e analyses reported here were carried o u t a t Northwestern Ilniversity. (9) "Organic Syntheses," Coll. Vol. 11, 510 (1943). ( 1 0 ) Fiesei-, "Laboratory Experiments in Organic Chemistry." :lid rd , 1). 1: H e a t h a n d Co., New York, N. Y.,1941,p. 369. ( 1 1)
