June 20, 1954
3213
NOTES
XI1 was acetylated under conditions similar to those reTesting data on I and current studies on related corded by de Arce, Greene and Cappss for the acetylation compounds with flocculating activity will be reof 5-amino-&bromo-6-methylquinoline; yield 67%, n1.p. ported in forthcoming publications. >330° (uncor.) from 95% ethanol. ExperirnentaF.6 Anal. Calcd. for C12H12Ns02: N, 12.96. Found: N, 13.11. Ethyl 3a-Hydroxy-A11-cholenate (11).-3a-Hydroxy-A"XI1 was berizoylated under conditions similar to those cholenic acid7.8 was esterified with absolute ethanol essentiused by de Arce, Greene and Cappss for the benzoylation of ally according to the method used by Kendall and his associ~5-arnino-8-bromo-6-methylquinoline; yield 42%, m.p. > ates for the preparation of the methyl ester.9 However, whereas esterification with methanol is complete in less 315". Anal. Calcd. for C17H14Nn02: N, 10.07. Found: N, than an hour, with ethanol 27% of unreacted acid was recovered even after 22 hours. The ethyl ester did not 10.00. crystallize from aqueous ethanol, but separated satisfac8-Methyl-5-quinoline~usonic Acid (XV) , 2-Chloro-8- torily from purified Skellysolve F as colorless needles melting methyl-5-quinolinearsonic Acid (XVIII) and 2-Hydroxy-8- a t 81-82', [ a I z 8 D 30' (c 2.01, chf.). Anal. Calcd. for methyl-5-quinolinearsonic Acid (XXI) .-The hydrochlorides C2&203: C,77.56; H, 10.52. Found: C,77.3; H, 10.6. of X (12.0 g.), XI (9.0 g.) and XI1 (10.0 g.) were diazotized Ethyl 3P-Chl0ro-A~~-cholenate (I).lO-To a stirred solution and converted into arsonic acids according tcr t h e p r m d r e of 500 mg. of I1 in 28 ml. of chloroform, in a flask equipped reported by Capps and Hamilton" for changing certain 2- with a drying tube and immersed in an ice-bath maintained chloroaminoquinolines into khloroquinolinearsonic acids. a t O', 800 mg. of powdered calcium carbonate and, in two XV, XVIII and XXI resulted in yields of 12.8, 11.9 and portions with a 20-minute interval, 1.2 g. of phosphorus 14 S'%, respectively. X V melted a t 224-226' while XVIII pentachloride were added. Stirring was continued for 100 dud XXI melted above 315" (uncor.). minutes a t 0'. The reaction product was poured into 200 Anal. Ccilctl for CIOHIOASXO~: As, 28.05; N, 5.27. ml. of 5% sodium bicarbonate solution containing ice, and Found: As, 27 92; S , 5.09. Calcd. for CIOH~ASCINO~:ether was added. The resulting mixture was stirred until As, 24 84; S , 4 65. Found: As, 24.69; N, 4.75. Calcd. the ice had melted, transferred to a separatory funnel and for CIOHIOASNO~ H10: As, 24.87; N, 4.65. Found: As, shaken thoroughly. The organic layer, which still retained 24.79; N, 4.67. a small amount of an insoluble, colorless, inorganic solid, was washed with water, dried (Drierite), filtered and evapoD Capps and C. S. Hamilton, THIS JOURNAL, 60, 2105 (11) J rated (reduced pressure) to a colorless residual oil. This oil (1938). dissolved in the minimum amount of warm methanol, on refrigeration for 2 hoours yielded 380 mg. (73%) of colorless Ross CHEMICAL LABORATORY Two recrystallizat$ms from methacrystals m.p. 69-73 ALABAMA POLYTECHNIC INSTITUTE nol gave thin plates melting at 74-76 , [ C Y ] ~ ~ D25" AUBURN, ALABAMA (c 2.05, chf.). Anal. Calcd. for C&,102Cl: C, 74.16; H, 9.82; CL8.42. Found: C, 74.3; H, 9.8; C1,8.8. Catalytic Hydrogenation.-I in acetic acid solution and Seroflocculating Steroids. I. Ethyl 3p-Chlorothe presence of Adams catalyst absorbed 1.03 moles of A1l-cholenate hydrogen within 20 minutes. After removal of catalyst and solvent, two crystallizations of the product from BY FREDERIC e. CAASGA N D DOUGLAS H. S P K U N T methanol gave colorless, feathery crystals, m.p. 59-60.5', RECEIVED APRIL2, 1954 which did not depress the melting point of ethyl 3p-chlorocholanate (111) prepared from ethyl lithocholatellJ* by the During the course of our study of the relationship same method as used for the unsaturated derivative, crysof steroids2 to ininiunological phenomena associ- tallizing in methanol as colorless needles, m.p. 59-61.5', ~ (c 1.27, chf.). Anal. Calcd. for C2sHtaO&1: ated with injury, we have had the occasion to [ a I z e +18.5" investigate the seroflocculating reagents described C, 73.81; H, 10.24; C1, 8.38. Found: C, 73.5; H, 10.5; c1, 8.2.
+
.
+
by Penn and his associate^.^ These reagents4 (5) Microanalyses by the Microchemical Laboratory of New York cause flocculation in a high percentage of the sera University. of patients with cancer and other diseases. (6) Melting points were taken on an electrically heated micro Our investigation of the flocculating reaction hot-stage and are uncorrected. led us to prepare ethyl 3P-~hloro-A~~-cholenate (7) J. Press and T. Reichstein, Helu. Chim. Acla, 26, 878 (1912); (I) which in preliminary testing we have found to B. F. McKenzie, W. F. McGuckin and E. C. Kendall, J. Biol. Chcm., 555 (1946) be a very satisfactory flocculating reagent. The 162, (8) Generously supplied by Merck and Co. through the kindness of conipuund. is c r y s t a l h e a d stable -m&ror&my Dr: M;rx Tishier conditions. I r e will discuss in detail elsewhere (9) L. L. Engle, V. R. Mattox, B. F. McKenzie, W. F. McGuckin implications of general significance in this field sug- and E. C. Kendall, J. B i d . Chem., 162, 565 (1946). (10) Although a double bond shift is considered unlikely under the gested to us by this finding. conditions of this reaction. experiments are under way to confirm the 'Treatmext of ethyl 3a-hydroxy-A1Wiolenate position of unsaturation. ( I 1) with phosphorus pentachloride in chloroforni (11) F. Reindel and K. Niederlander, Bey., 68, 1969 (1935). (12) We are indebted to Ciba Pharmaceutical Products, Inc.. and at 0" yielded ethyl 3~-chloro-A11-cholenate(I), which could be quantitatively hydrogenated to Dr. H. B. MacPhillamy for a supply of lithocholic acid. AND ethyl 3,b-chlorocholanate (111). The latter was DIVISIONOF CHEMISTRY, DiVi310N O F PATHOLOGY AND- BACTERIOLOGY found- to be identicar by meiting point comparison UNIVERSITY O F TENNESSEE with the product of reaction between ethyl litho- MEMPHIS,TENNESSEE cholate and phosphorus pentachloride. (1) Aided in part by a grant from the United States Public Ifealth Service. (2) D. 1%.Sprunt, A. D. Dulaney and R. P. Conger, Cancer Research, 2 , 282 (1951). (3) H. S.Penn. J . S n l l C Q J I C P Y ~12, I S ~1389 . , (1952); A. H. Dowdy, H S. Penn, C i . Hall and A. Brllamy, Proc. A m . Assoc. for Cancer R P s r i l r < h . 1, I2 (19.54). ( 4 ) We wish to thank 131s. D o w d y and Penn aud their group for their
coijperation in making available to us procedures for preparing and testing both the liver and desoxycholic acid-derived flocculating reagents which they designate as "antigens."
The Preparation of Sarcosine and Methyl aMethylamino-0- (3-indolyl)-propionate BY F. F. BLICKEA N D PAULE. NORRIS RECEIVED FEBRUARY 15, 1954
The preparation of methyl a-methylaniino-P-(3indoly1)-propionate was undertaken since a supply of this ester was required as an intermediate.
