INDUSTRIAL A N D ENGINEERING CHEMISTRY
To46
heated with agitation t o 58-60' C. and filtered through a preheated press. It was necessary to maintain the temperature carefully within these limits. Above 60" C. objectionable quantities of impurities were carried through into the finished product. Below 58 " considerable quantities of quinacrine hydrochloride were left on the carbon.
Val. 37, No. 11
solubility, and the minimum solubility is reached in approximately 8% acid solution. The use of 8% hydrochloric acid waa objectionable, however, because of its corrosive action on the process equipment, and also because it created numerous di5culties in drying the final product. Figure 2 presents the effect of temperature on the solubility of quinacrine hydrochloride in 1% acid. This curve shows that effective precipitation is obtained at 0" to 5' C. I n this temperature range the solubility in 1% hydrochloric acid is less than 0.006 pound per gallon. CRYSTALLIZATION
%ACE7ONC
e ut,
--
aqueoua hydroohlor$ add at !2Ta C. aqueous hydroohlorro acid a t 0' C. 2.54% aqueoau h y h h l o r i o acrid a t Oo C.
5
The solubility of quinacrine hydrochloride is greatly decreased
in the presence of hydrochloric acid. Usually, enough concentrated hydrochloric acid has been added t o the filtered quinacrine hydrochloride solution at 50-55" C. so that the solution contained about 5% free acid. Upon cooling this solution, practically all of the quinacrine hydrochloride is precipitated. The solubility characteristics of quinacrine hydrochloride in aqueous hydrochloric acid were carefully studied. In Figure 1 the solubility at 27" C. is plotted as a function of acid concentration. A distilled water solution saturated at 27' C. contains 4.92 grams of quinacrine dihydrochloride per 100 cc. The presence of a vsry small quantity of free hydrochloric acid greatly lowers the
The characteristics of the crystals obtained in the precipitation from acid solution were highly important from the standpoint of both filtration and of the disintegration rate of tablets made from the quinacrine dihydrochloride dihydrate. Agitation during precipitation brought about the formation of extremely small crystals which were difficult to handle. It was found highly important to avoid any agitation until the temperature throughout the entire mixture was below 20" C. Following filtration at 5" C., the wet cake of quinacrine hydrochloride crystals was slurried with acetone to facilitate removal of the remaining hydrochloric acid solution and colored impurities. The solubility of quinacrine hydrochloride in mixtures of acetone and aqueous hydrochloric acid solutions of various concentrations waa investigated. Figure 3 discloses that, in mixtures containing 40 to 45% acetone, the solubility reaches a sharp maximum. To avoid appreciable loss of quinacrine hydrochloride in the acetone slurry stage, it was therefore advantageous to use sufficient a c e tone so that the resulting solution contained more than 80% acetone. A second acetone slurry a t 30" to 35" C. removed any residual water-insoluble impurities. The product was dried to the dihydrate (formula 1) in a hot air dryer for 13 hours at 50" C. The process outlined here has a number of advantages over the former one. The yields have been 85% of theoretical, or higher, of a product of consistently high purity. Maximum yields by the old procesa were about 77%. A 33% increase in the volume of production has been achieved with only 60% of the original equipment, which was relatively easily adapted to the present process. The consumption of acetone has been reduced by approximately 40%, phenol by 65%, and hydrochloric acid by 55%. The reduction in the quantity of phenol, removed in the present procesa as sodium phenate, simplifies the problem of recovery or disposal of phenol residues. Corrosion of equipment by hydrochloric acid has been reduced to a minimum. Simplification of the process and equipment has reduced labor requirements aa well as maintenance. LITERATURE CITED
(1) Drosdov and Cherntzov, J . Om. Chem. (U.S.S.R), 5, 1576, 1736 (1935); Magidaon and Grigorovski'l, Khim. Farm. Prom., 1933,
187; Jensch and Eisleb, U.S. Patent 1,782,727(1930): Schulemann, Mietzach, and Wingler, U. S. Patent 1,889,704(1932). (2) Mietesch and Mauss, U. 8. Patent 2,113,357(1938).
Empirical Correction for Compressibility Factor and Activity Coefficient CurvesCorrection Two errors in the July, 1945, issue have been called to our attention by Robert M, Trapp. Both occur on page 670 and correctiona are indicated as follows: First column, second line from This bottom, the last figure should be -1.46 instead of -1.61. does not change the correction factors, however, since the nearest whole numbers for T'and PI are 28 and 14, respectively, aa shown in the article. I n the second column, the third line should read
It should be pointed out that these correction factors should not be considered accurate to better than 1%. If these curves approximate actual conditions t o within 1 or 2%, their use will be justified. RALPEA. MORQEN AND J. H.CHILDS
f/p = 1.16 instead of 1.15.
UNrVEasrTY o, Q A I N ~ B V I L L E , FLA.
