VOl. 77
54%
NOTES .-
-
Ionic Radii of the Histadyl and Pyrilamine Cations BY A. C. ASDREWS, H. B . JOHKSOS~ A N D T. D. LYONS RECEIVEDJUNE 22, 1955
Recent studies of the physical chemistry of the antihistamines* have been valuable in the correlation of the pharmacological properties of such compounds with certain of their physical properties. I t is thought that the ionic radius of an antihistamine may be important in its biological efficiency. This paper describes two techniques which were used to determine the ionic radius of the Histadyl and Pyrilamine cations. The radii obtained by the two methods for Histadyl are in close agreement; however no satisfactory radius could be obtained by the apparent molal volume method for Pyrilamine.
centrations of Histadyl. The densities shown were determined with a Weld pycnometer.
TABLE I APPARENTMOLALVOLUMES OF HISTADYL C
Density
d (ml.1
0 13198 ,23003 30377 ,40761
1.00426 1 00972 1 01397 1 01966
243.7 233 7 242 8 242 9
Using tlie value 243 ml. for the apparent molal volume and the crystallographic radius of the chloride ion as 1.81 X the value for the ionic radius of Histadyl is 3.84 X cm. which agrees closely with the value obtained from ionic conductances.
Acknowledgment.-This investigation was supported in part by funds from grant No. G 3920 from the National Institutes of Health, Public Health Service.
Experimental Materials.-Histadyl (S,N-dimcthyl-N',2-thenyl-~'-a- DEPARTMENT O F CHEMISTRY pyridylethylenediamirie hydrochloride), which was furnished KANSASSTATE COLLEGE by Eli Lilly and Co., carried the manufacturers specificaMAXHATTAS, KANSAS tions of HCl: 12.1-12.4%, Histadyl base: 87.0-87.5%. Pyrilamine (,N-p-methoxybenzyl-r\",N'-dimethyl-N-a-pyridylethylened~aniine maleate), rvliicli was furnished by The Chemical State of FIB from the Fast Neutron Merck and C o . , carried tlie manufacturers ultraviolet -4ssay Irradiation of Fluorobenzene of 99.8% Pyrilamine. The materials were used rvithout further purification since conductance studies3 of recrys- BY A. H. W.ATEN,JR., BEATRIXKOCHA N D J. KOMMANDEUR tallized products showed no deviation from the original RECEIVEDMAY7, 1955 niaterial received. Methods. I. Ionic Radii from Ionic Conductances.-An Experimental equation based on Stokes l a d permits the calculation of We have irradiated fluvrobenzene with fast neutrons obionic radii from a knowledge of the limiting ionic conductained by bombardment of beryllium with 26 Mev. deuterons tance, I " , viscosity of solvelit, 7, and tlie valence of ttie ion, in the Philips synchrocyclotron, The fluorobenzene was Z . The simplified equation has the forrii prepared from CsHbN2BF4 and had been purified by simple 0.8147 x 121 distillation. Before the start of the experiment the liquid 107 = r had been treated with a concentrated solution of hydrowhere r is the ionic radius in centimeters. The values for fluoric acid to introduce a carrier for the inorganic radioI" for the Histadyl and Pyrilamine cations have been pre- fluorine. (The quantity of hydrofluoric acid dissolved in viously r e p ~ r t e d . ~The viscosity of water was taken as this way amounts t o much less than 1% of the organic 8.949 millipoises at 2 5 O . j Substituting these values into the fluorine. ) The fluorobenzene was irradiated in a brass cylinder, which cm. and 3.75 X cquation gives 3.96 X cm. as the was gold-plated on the inside. I t was closed by means of a radii of tlie Histadyl arid Pyrilamine catious, respectively. disc of polyvinyl chloride with a screwed-on top on the out11. Ionic Radii from Apparent Molal Volumes.-The apparent molal volumes of cesium arid rubidium chlorides, side and a thin gold foil on the inside. To separate the inbromides and iodides niny be represented to a close ap- organic radiofluorine from the organic fraction the contents proximation by the equation,G + = 6.47 ( r 3 + r 3 - ) where of the cylinder were poured into a brass tube which was goldon the inside and mixed with a solution of sodium + is the apparent molal volume and r is the crystallographic plated radius. I t was assumed that this equation might be ap- hydroxide and sodium fluoride. The mixing was done by means of a gold-plated silver vibrating stirrer. The liquid plied to Histadyl since large ions are involved in both cases. was then separated in a separating funnel and the two fracThe apparent molal volume for Histadyl was evaluated from tions collected in glass tubes. The original cylinder was tlie relation7 rinsed with hydrogen fluoride and this liquid collected in the gold-plated tube which had served for the first separation. All fractions were measured in their glass or brass tubes \vhere .I1 is the molecular weight of the solute, d' and d are in a Philips hollow liquid -/-counter (KO. 18508), which is emiiiently suitable for this purpose. IVe made sure that the densities of the solvent and solution, respectively, and c the sensitivity for the radiation of F I 8 was the same for all is the concentration of solute in moles per liter. Table I gives the apparent molal volumes of various con- tubes. The activity found in tlie wash liquid and on the xvall of the gold-plated tube, which at most amounted to about 10% of the total, was added to that of the inorganic (1) Abstracted in part from thc 1'h.D. Thesis of H. I3. Johnson, fraction. The correct half-life for F18 was observed in all Kansas State College, 1952. cases. Lye found 0.64 of ttie activity in the inorganic ( 2 ) A . V. Tolstoouhov, I'i.oizs. .Y.Y.Acnrl. Sci., 14, 260 (1952). fraction with a probable error of a few per cent. ( I n the (3) A . C. Xndrews and H. B . Johnson, T v o ~ z s .Knns. A c u d Sci., 6 6 , final series individual experiments gave the figures: 0.68, 4-19 (19.53) 0.64, 0.62, 0.67, 0.59 and 0.63.) ( 4 ) H . S. IIarned and B. E. Owen, "The Phyiical Chemistry of The main uncertainty lay in the dangcr that the radioElectrolytic Solutions," Reinhold Puhl. Corp., S e w I'ork, S . Y , 1950. fluorine atoms might react with the gold-plated walls. IVe (.j) "International Critical Tables," T'ol 3, hIcGraw-Hill Book C u . , were unable to prove that this complication did not occur, New York, S. Y . , 1929, p. 10. as the brass cylindcr became so active that me woulcl not ( 6 ) R. H. Stokes and R . A . Robinson, TIIIS J O U K N A L , 70, 1870 have been able t o recognize the F'8 in its decay curve. IVe (1948). did, however, carry out some irradiatiims in which a very ( 7 ) E. M. Baker, tbid., 71, 3380 (IiJLS).
+
