NOTES
Dec., 1946
2-M ethoxy -6-chloro-9(dialkylaminoalkylamino)-acridines BY
G. BRYANT BACHMAN AND 1). E. WELTON'
'These compounds were prepared from 2-methoxy-($9-dichloroacridine (I) and the appropriate rlialkylamitioalk~laminesby the general procedure
2725
and 5 showed activity against P. lopiiuvue in ducks. Compounds 2, 3, 6 and 7 showed little or no trypanocidal activity. Compounds :< and 7 were inactive toward Strebtococcus hemolvticus. influenza-virus and Tetanus toxemia. Acknowledgment.-The authors are indebted t o Eli Lillp and Company, Indianapolis, Tndi-
TABLE I
~-METHOXY-~-CHLORO-~-(DIALKYLAMINOALKPLAMISO) -ACRIDINES SO.
Substituent. -R
M. p..'" "C.
Salt
Yield. method
Crystallization solvent-diluent
--
Analyses, %-----Carbon Hydro~en Calcd. F o u n d Calcd. Found
56.67 5 6 . M 6 . 3 0 6.44 36.25 6.51 2 -CH?C(CHs)lCH*S(C2Hs!2 2HCl 243-245 29 Water-dioxane 37.66 57.63 fj.!',!) 7.84 1/3H20bpC 5 7 , 7.5 7.01 :j -CH?C(CHp)iCH4N(n-C4He) 2HC1 31 5-220 33 Water-dioxane 61.27 61.07 7,,3i 7.44 6 0 , 77 7.71 4 -CHCH3CHpS(n-CpHp)y BHCl 4- 217-221 83 95% Ethanol-diethyl 58.80 58.39 7. :I:; 7 . 4 5 2/3H20b9d ether 58. 87 7.fi3 5 -(CH;)FJiCI~a~, 2HC1 281-282 ti4 Water-dioxane 57.55 57.41 tj.5S 8 . 7 2 5 7 . 87 l i , 73 6 -CH[--CH2:~(C€13is]2C 3HCl 347-748 89 Acetic acid-none 49.62 49.49 ii 14 ti.08 .HOAc' 1 9 .ti8 r; ,:;w 7 -CH[--CH2:i(1z-C3H1)2]zP 3HC1 280-?21 13 Methanol-diethyl 57.59 5 7 . 0 2 7 . 3 i 7.4tj ether .X. $10 7.50 a Corrected; all melted with decomposition. Dried to constant weight a t 140' over phosphorus pentoside. Calcd. : S , 8.77. Found: S,8.63.0 Ionizable C1: Calcd., 14.83; found, 14.55. % Ionizable C1: C_alcd.,13.85; found, 18.86. * Free base, in. p. 120-121 . Y0C: Calcd., 65.17; found, 65.19. O/CH: Calcd., 7.03; found, I .13. Dried to constant weight over calcium oxide a t l.OOO. 0 Free base, m. p. 99-101)". %C: Calcd., 69.91; found, 69.77. C/'OH: Calcd., 8.50; found, 8.64. 1 -CH2C(CH3)~CHzX(CH3,2
2HC1
255-286
fi4
Water-dioxane
+
+
of Magidson and Grigorovskii.2 The products are ana, and to the Purdue Research Foundation for financial assistance. listed in Table I. In spite of their general structural similarity, PCRDCE RESEARCH FOUNDATIOS A\D the products show considerable differences in ease DEPARTMENT OF CHEMISTRY UNIVERSITY of hydrolysis. Those in which the substituted PURDUE IKDIANA RECEIVED AUGUST22, 194ti ethylenediamine structure is present in the sub- LAFAYETTE, stituent group (Table I, nos. 4, G and 7 ) hydrolyze immediately in hot dilute hydrochloric acid solu- The Freezing Point of Pure Phthalic Anhydride tion to give a precipitate of 2-methoxy-6-chloroBY D. E. DEBEAU acridone, whereas those in which the amino groups are further separated are not affected unPhthalic anhydride is an article of great conider these conditions for a t least one hour. mercial importance and is sold on the basis o f Only the 1,3-bis-(dialkylamino)-2-propylamine derivatives (Table I, nos. 6 and 7) form crystalline. purity as determined by freezing point. Hence, free bases, but all yield crystalline polyhydrochlo- it is important to know accurately the freezing rides which form hydrates of varying stabilities; point of this material with zero impurity. The the derivatives listed in Table I are the most nearly values to be found in the literature vary from anhydrous materials obtainable in each case. 130.841to 131.60°.2 To reach a decision as to which of these values Kecrystallization of these salts from a mixture of solvents generally gives much more effective puri- is the more reliable i t was necessary to make the measurements reported below. tication and recovery than a single solvent. The phthalic anhydride used was supplied by the OroPharmacological Testing.-All of the acridine nite Company and was manufactured from oderivatives listed in Table I were submitted for xyleneChemical by air oxidation. Several methods of purification testing as antimalarial agents. The results of of the phthalic anhydride were tried. They were slow these tests will be reported in detail elsewhere. fractional crystallization, recrystallization from acetone, It may be noted, however, that compounds 1, 2 , 3 and sublimation a t atmospheric pressure. Samples pre-
j
(1) Present .iddress d u P o n t Experimental Station. E. I du Pont de Kernours and Company, Wilmington. Delaware 12) 0 Y Mnxidson a n d A Irl Grtgornvsku. Aer 69B, 3Qfi-412 1 WCi)
pared by sublitnation had the highest freezing points and gave the most reproducible results. ( 1 ) K P.Monroe, Znd. E n g . Chcm., 11, 1116 (1919). ( 2 ) F. Burriel-Marti. Bull Soc Chim. Belg.. 39. 590 (1930).
