March 20, 1953
1471
NOTES Synthesis of l,J-Diphenyl-1,2,4-triazole BY M. R. ATKISSOS~ A N D J. B. POLYA RECEIVED AUGUST 12, 1952
Anal.'" Calcd. for C14HllXz: C, 76.99; H, 5.01; N, 18.99. Found: C, 76.31; H , 5.33; S,19.18. The triazole and its picrate depress the m.p.'s of authentic I1 and its p i ~ r a t erespectively. ,~
(10) hlicroanalyses by Dr. W. Zimmermann, Commonwealth Einhorn, Bischkopff and Szelinski2 reported the Scientific and Industrial Research Organization, Melbourne. preparation of 1,3-diphenyl-1,2,4-triazole (I) from CHEMISTRY DEPARTMENT phenylhydrazine and N-formylbenzamide in 30% UNIVERSITY O F TASMASIA aqueous acetic acid. Thompson3 showed that this HOBART, AUSTRALIA reaction affords 1,5-diphenyl-l,2,4triazole(11) identical with the preparations of Young4 and C1eve.j We were able to confirm the work of The High Field Conductance of an Aqueous Solution of Cadmium Chloride at 25'' Thompson and showed that I1 is obtained, although in inferior yield, when pyridine containing pyri- BY FREDERICK EUGENEBAILEY,JR., AND ANDREW PATTERdinium hydrochloride is used instead of dilute SON,JR. acetic acid.6 RECEIVED SOVEMBER 7 , 1952 It was necessary to synthesize I in order to assess The unusual behavior of cadmium halides in the work of Einhorn and his collaborators as the physical data characterizing their triazole differ aqueous solution has been the basis for much disfrom those which apply to I1 by the agreement cussion in the past.2 Harned and Fitzgerald of other authors. The synthesis of I was accom- found that the behavior of aqueous solutions of plished by the method of Ponzio7 which has been cadmium chloride in electrolytic cells might be adefound useful in other triazole Benz- quately explained3in terms of an equilibrium amide phenylhydrazone heated with formic acid CdCl+ I_ C d + + + C1-; K ( 0 ) = 0.011 a t 25" (1) affords I in a yield of 36y0, I, its hydrochloride i t being assumed that the dissociation of CdClz into CdC1+ and C1- is complete. To investigate iSH2 HCOzH + P h l H N = C ( + H-cHN\C-Ph this electrolyte from another point of view, we have Ph determined the high field conductance of an aqueI /I ous solution of cadmium chloride, 1.697 X 2H20 Ph-IT-K molar, a t 25" relative to potassium chloride. and picrate differ from the corresponding products The procedure employed was identical with that described by Einhorn and collaborators. of Gledhill and P a t t e r ~ o n . ~Baker and Adamson C.P. cadmium chloride was recrystallized once from Experimental conductivity water; the resulting hydrate was Benzamide phenylhydrazone \vas prepared by the method dried for four days in a vacuum oven a t SO", of Voswinkelg and purified through its picrate, m.p. 196198'. Benzamide phenylhydrazone (7.20 g.) was refluxed ground in an agate mortar, and again dried for four with 99% formic acid (8.0 ml.) on the water-bath for 90 days in a vacuum oven a t SO". The resulting salt, minutes. The product was adjusted to @H8 with aqueous assumed to be anhydrous, was then stored for use. 10% sodium carbonate and extracted with ether (3 X 50 Both the cadmium chloride and reference electromi.). Distillation of the dried ether extract between 160220" (2 mm.) afforded oily crystals (4.5 g.) which were dis- lyte, potassium chloride, were prepared by weighing solved in dry ether (150 ml.) and treated with dry hydrogen in the form of strong stock solutions and then weight chloride to precipitate the hydrochloride of I as a white, diluted to the desired concentrations in the conmicrocrystalline powder, m.p. 192-191' (Einhorn, et al., ductance cells. The concentrations were : cad176") in a yield of 5.73 g. Anal. Calcd. for C14H11Na.HCl: mium chloride, 1.697 X molar; potassium C1, 13.76. Found: C1, 13.70. molar. The temperature The hydrochloride was decomposed with aqueous 10% chloride, 2.889 X sodium carbonate (100 ml.) and extracted with ether (3 X was25 =t0.015'. 50 ml.) to afford on removing the solvent colorless prisThe results are shown in Fig. 1 for two determinmatic crystals of I, m.p. 79-81' (2.71 g., 36%). Purificaations on the same solution. At 200 kv./cm. the tion through the picrate, yellow needles from ethanol, m.p. 161-161.5' (Anal. Calcd. for C14Hl1iS3.C~H307N3: C, fractional high field conductance quotient, AA/Ao, 53.33; H , 3.11; N, 18.67. Found: C, 53.35; H, 3.24; has the value 1.0770; this value may be compared N, 17.67) (Einhorn, et al., 148") and two recrystallization: with those for potassium chloride, approximately from petroleum ether (60-80") raised the m.p. to 82.5-83 O.4yO,and magnesium sulfate, approximately 3.370, (Einhorn, et al., 96-97'). a t the same field. No theory is currently available (1) Imperial Chemical Industries of Australia and New Zealand to permit computation of values for non-symmetriResearch Fellow. cal valence-type electrolytes, although as a rough (2) A. Einhorn, E . Bischkopff and B. Szelinski, A n n . , 343, 227
+
(1905). (3) Q.E. Thompson, THISJOURNAL, 'IS, 5914 (1951). (4) G. Young, J . Chem. Soc., 61, 1069 (1895). ( 5 ) A. Cleve, Be?., 29, 2679 (1896). (6) (7) (8) (9)
M. R. Atkinson and J. B. Polya, J . Chem. S o c . , in press, (1952). G . Ponzio, Gaze. chim. ital., 40 i , 85 (1910). D . Jerchel and R. Kuhn, A n n . , 668, 185 (1950). H. Voswinkel, Ber., 36, 2484 (1903).
(1) Contribution No. 1133 from the Department of Chemistry, Yale University. (2) N. V. Sidgwick, "The Chemical Elements and Their Compounds," Oxford University Press, New York, N. Y . , 1950, p. 274. (3) H . S . Harned and B. B. Owen, "The Physical Chemistry of Electrolytic Solutions," 2nd ed., Reinhold Publ. Corp., New York, N. Y., 1950 pp. 418-421. (4) J. A. Gledhill and A. Patterson, J . P h y s . Cheiii., 66, 999 (1952).
1472
NOTES
1.5
Vol. 75
quinolines for screening against tumors in mice. The series have been extended by synthesis of the salts of 2-chloropyridine and 3-bromopyridine listed in Table I and the salts of 3-bromoquinoline, 6chloroquinoline and 4,7-dichloroquinoline listed in Table 11. Results of screening tests a t the National Cancer Institute are to be published elsewhere. 4,7-Dichloroquinoline was particularly unreactive and was recovered unchanged from mixtures with several halogen compounds although a small quantity of quaternary salt was obtained in a few cases. Attempts to prepare quaternary salts of 8chloroquinoline by reaction of the base with substituted phenacyl bromides a t 45" produced the hydrobromide as the chief crystalline product instead of the expected quaternary salt.
I,O
0.5
TABLE I SALTSOF SUBSTITUTED PYRIDINES Salt from 2Chloropyridine and:
0
0
100
200
FIELD, KV./CM. Fig. 1.-The high field conductance of an aqueous solution of cadmium chloride, 1.697 X 10-4 molar, relative to potassium chloride at 25".
approximation the increase in equivalent conductance has been found3 to be proportional t o ( Z + Z - ) ~ ; thus, ( Z + Z - ) ~ = 4, and 4 X 0.4 (for potassium chloride) = 1.6%. The curve has a shape something like that of a strong electrolyte, but fails to bend over a t so low a field or in so pronounced a manner as does magnesium sulfate, for example. Determinations on similar valence-type, but stronger, electrolytes, e.g., calcium chloride, are now under way. When completed, these will offer more information on the influence on the high field behavior of the weak ionization referred to in equation 1, above. Acknowledgment.-This work was supported by the Office of Naval Research. STERLING CHEMISTRY LABORATORY YALEUNIVERSITY XEW HAVEN,CONS.
Quaternary Salts of Halogenated Heterocyclic Nitrogen Compounds1 BY CARLTABBBAHNER,WILLIAMK. EASLEY,GEORGEE. BIGGERSTAFF, EMMABROWN,MARGUERITE CLOSE,MARY MARGUERITEISENBERG,HAROLDD. LYONS, LILBURN NORTOS, EMOGENESTEPHEN, BILLY STUMP,BETTYGAY WALDEN BLANCAND MARYWATKINS RECEIVED NOVEMBER 22, 1952
A previous article2 has reported the preparation of quaternary salts of halogenated pyridines and (1) This research was supported in part by a research grant from the National Institutes of Health, U. S. Public Health Service, and in part by a grant from the Damon Runyon Memorisl Fund for Cancer ReSeRrch. (2) C. T. Bahner, W. K. Easley, M. D. Pickens. H. D. Lyons. L. I.. Norton, B. G. Walden and G E. Biggerstaff, Tms J O U R N A L , 73, 3499 (1951).
0-Methoxyphenacyl bromide B-Naphthacyl bromide 5,6,7,8-Tetrahydro8-naphthacyl bromide 4,4'-Bis-(bromoacetyl)-phenyl ether 3-Brornopyridine and: 6-Phenylethyl iodide Iodoacetone Glycerol-u-monochlorohydrin Iodoacetonitrile 4 ,4'-Bis- (bromoacetyl)-phenyl ether 0
Empirical formula
hl.p., OC.
Ionic halogen, % ' Calcd. Found"
Ci,Hi8BrClNOy
171
23.32
23.04
CiiHisBrClNO
175
22.04
22.00
Ci~HuBrClNO
190
21.79
21.69
CmHzoBrzClzNzOa
210
25.01
24.79
CiaHidBrIN CsHsBrIXO
152-154 180
32.45 32.29 37.10 37.29
CiHiiBrClNOz ClHeBrIN
216 177-178
13.20 39.06
13.07 38.83
220
21.95
21.52
C~sIl~oBraNzO8
Average of two analyses. T A B L E 11 QUATERSARY SALTSOF HALOGENATED QUINOLINES
Salt from 3-Brornoqdnoline and: GI ycerol-u, y-dibromohydrin 3,4-Dihydroxyphenacyl chloride 0-Met hoxyphenacyl bromide fi-Chlorophenacyl bromide p-Bromophenacyl bromide 6-Bromoquinoline and : Glycerol-a. y-dibromohydrin Allyl bromide
Empirical formula
M.P., 'C.
Ionic halogen, % Calcd. Found"
CizHizBraNO
251
18.76
18.91
CiiHi3BrCINOa
245
'
CisHisBrzNOz
241
18.28
18.30
CijHnBrzClNOz
240
18.10
18.15
Cl~KnBr3NO
237
16.45
16.63
CIZHIZB~~NO CnHiiBrzN
241 171
18.76 24.29
19.05 24.07
186-187
36.50
36.54
Ci~HzaDrClINO
230
16.3G
1G,32
CiaHirBrClzNO
163
20.12
10.93
CnHzaBrCliNO
185-186
17.68
17.50
6-Chloroquinoline and: Iodoacetone P-Iodophenacyl bromide 4.7- Dichloroquinoline and: Pheaacyl bromide 9-f-Butylphenacyl bromide
CizIIiICIINO
Average of two analyses. Found: C, 51.58; H, 3.49.
* Calcd.:
C, 51.73; H, 3.32.
8-Chloroquinoline Hydrobromide.-Prepared by direct reaction of eauimolecular auantities of the base and concentrated hydro6rornic acid 0; as the principal crystalline prod-
