370
VOI. 71
NOTES
amine was steam distilled. The crude product m. p. 6669 ', was isolated by ether extraction and converted t o the corresponding chloride (for separation from possible traces of butanephosphooic acid) by warming with 51.5g. of phosphorus pentachloride followed by distillation ; 1). p. 156-157' at 28 mm. Hydrolysis of the chloride with warm water and crystallization from hexane gave the pure acid in the form of long silky colorless needles. This acid was previously reported by Plets3 who prepared i t by hydrolysis of either KaPCls or RaPOCl, which were, in turn, derived from dibutylchlorophosphine; he gave in. p. 31-32' for the acid. The higher melting point of the present preparation indicates either higher purity or, possibly, an isomeric form.
best in the presence of an alkaline agent. TritonB was found to be an effective catalyst; sodium and potassium hydroxides serve also. Worth emphasizing is the fact that strongly basic amines such as aliphatic amines, phenethylamine, etc., add readily to the double bond of butadiene sulfone but less basic amines, aniline and benzylamine for example, do not react to give any appreciable yield under similar conditions. Through the courtesy of the Division of Chemotherapy for Tropical Diseases, National Research Council, the products described herein were tested (3) Plets, dissertation, Kazan, IJ S. S. R . , 1938 for activity against a variety of tropical diseases. THERoss CHEXICALLABORATORY None was found to have any significant activity ALABAMA POLYTBCHNIC INSTITUTE in amebiasis, filariasis, schistosomiasis or IeischRECEIVEDSEPTEEEER 21, 1948 AUBURN,ALABAMA maniasis. We are indebted to Mr. E. F. Shelberg of the Preparation and Properties of Tetramethylene Microanalytical Department for the microchemiSulfones cal analyses. BY MARLINT. LEFFLERAND W. D. KRUEGER
Tn the course of a search for new types of chemotherapeutic agents, several cyclotetramethylene sulfones were prepared and studied. These were synthesized by the addition of amines, alcohols ari tl mercaptans to 2,5-dihydrothiophene-1-&oxide (butadiene sulfone) in a manner similar to that described by Delfs.' The general formula, I, illusCH*-CHI
I
(X)-R
trates the types prepared and listed in Table I, where (XIis either -NH-, -0- or -S-, and R is an alkyl or substituted alkyl group.
Experimental The sample of 2,5-dihydrothiophene-l-dioxide(butadiene sulfone) used in this work was furnished by the Shell Development Company under the trade name "Sulfolene. " The tetrahydrothiophene-1-dioxideslisted in Table I were prepared by the following general procedures: 3-Amino Derivatives.-A mixture of 0.5 mole of butadiene sulfone and 2 moles of the primary or secondary amine was stirred and heated at 70-80' for twenty-four hours. The excess amine was then removed by distillation in vacuo and the residue was dissolved in 300 mi. of anhydrous ether, which solution was treated with excess d v , gaseous hydrogen chloride to form the salt. The solid salts were removed by filtration and recrystallized t o constant melting point from absolute alcohol. 3-Substituted Ethers.-A mixture of 0.6 mole of butadiene sulfone, 1.0 mole of the desired alcohol and 2 t o 4 ml. of Triton-B was heated at 70-80" for twenty-four hours. At the end of this time the Triton-B was neutralized with concentrated sulfuric acid and the excess of the
TABLE I
CYCLOTETRAMETHYLBNE SULFONES, CHn-CH-(X)-R
I
1
CHa CHz
\s/ 0 2
Yield,
%
M. p., OC.
148-149 188-189 176-177' 218-219
Amine Hydrochlorides 73 (base) 41
-Analyses, Calcd.
N, %-
Found
76 (base)
CsH&lNOzS C12Hi&lN02S CnH&lzNzOzS GHl&lNO~S
6.15 5.08 8.72 5.84
6.14 5.00 8.49 5.86
62
CI~~NOTPS
4.20
4.31
.7-
,i
Ethers Phosphate: 132-133 Base: B. p. 175-181 (4mm.) 61-63
Formula
C: 54.62 54.48 H: 5.82 5.53 4.22 4.27 HBr: 122-123 48 C1@HaBrN028 0 Dihydrochloride pnCipit&ed by addition of excess alcoholic hydrogen chloride to an acetone solution of the base. Recrystallized from absolute dcohol. -SCH&H'
It is of interest t o note that while the addition of amines to butadiene sulf&e does not require a alcohols and mercaptans (1) Della, U. $. Prtent 2,218,006 (1840); 2,281,796 (1942).
51
CiiH140zS2
alcohol used was removed by distillation in vacilo. The residue was'then distilled under reduced pressure. I n the case of the 3-diethylaminoethoxy derivative, the product was converted t o the phosphate by the addition of a slight excess of phosphoric acid j1(670) t o an alcoholic solution of
Jan., 1949
NOTES
371
the base. The phosphate was purified by recrystalliza- f i n the zinc chelate. In all other cases, the pyrition from a mixture of acetone and methanol (1:4). dine exchange solutions were 0.01 f in the acetate 3-Substituted Thio-ethers.-To a mixture of 0.2 mole of butadiene sulfone, 0.2 mole of the desired mercaptan and 0.01 f in the complex compound. The acetyland 75 ml of water was added slowly and with good agi- acetone exchange was also run a t 0' without tation 0.4 mole of powdered sodium hydroxide. During any apparent difference. Thus, it appears either this addition, the temperature rose to and was held a t 70that rapid exchange was induced by the separation 80'. Stirring was continued and the temperature was maintained a t 70-80" for four hours longer. Then the procedure utilized or, more probably, that the reaction was cooled and extracted with two 250-ml. por- above zinc complex compounds are comparations of ether. The combined ether extracts were washed tively unstable with respect to ionization or diswith 150 cc. of water and dried over anhydrous magnesium placement reactions (stability apparently comsulfate. In the case of the benzylthio ether, the product crys- parable with that of copper salicylaldehyde, coptallized directly from the cold ether solution. It was per salicylaldehyde anil, and copper salicylaldepurified further by recrystallization from dry ether. With hyde methylimine in pyridine solution2). If the the diethylaminoethyl thio-ether, the base was converted rapid exchange was not induced, the above zinc to the hydrobromide by treatment of the dry ether solution with gaseous hydrogen bromide. Purification was complex compounds would not be suitable for accomplished by recrystallizing the salt from absolute al- Szilard-Chalmers separations, a t least in pyridine cohol. solution. Experimental ABBOTTRESEARCHLABORATORIES AUGUST16, 1948 Radiozinc Tracer.-Several sections from a discarded NORTH CHICAGO, ILLINOIS RECEIVED copper cyclotron dee were obtained through the courtesy of Professor J. R. Richardson, to whom our thanks are expressed. Since these copper parts had received Thermal Exchange Experiments with Radio- hereby lengthy deuteron and neutron bombardments and had been active Zinc cooling for over a year, the principal activity in them was due to 250-day ZnQ, formed mainly by the reaction Cu65 BY LEONLEVENTHAL~ AND c. s. GARNER (d,?n)Zn@. Chemical separation and purification of the was effected by a procedure similar to that outDuffield and Calvin2have reported an intensive radiozinc lined by Kamen,a giving a zinc fraction with the half-life study of thermal exchange reactions of copper and radiations characteristic of 250-day 2 ~ 6 6 . chelate compounds in pyridine, most of which reProcedure.-Experiments were run in duplicate. All actions proceeded a t measurable rates. Other zinc compounds were synthesized and their identity esexchange experiments of the type considered here tablished by chemical analyses. The pyridine was dried over potassium hydroxide and distilled through a column. include those of Drehmann3 on manganese(I1) Exchange mixtures were synthesized volumett ically from ions with manganese acetylacetone and manga- standardized stock solutions of the complex compounds nese benzoylacetone in methanol (half-times of ex- and of radioactive zinc acetate in pyridine. After varying change less than one hour), Sue and Yuasa4 on lengths of time the exchange mixtures were subjected to a procedure similar to that used by Duffield and vanadyl and vanadate ions with solid vanadium separation Calvin2 and consisting of the addition of water and chloro8-hydroxyquinoline and solid vanadium cupfer- form followed by extraction of the complex compound ronate (relatively slow exchange), and Johnson into the chloroform-pyridine layer and of the acetate into and Hall6 on nickel(I1) ions with various nickel the water-pyridine layer, re-extraction from each layer, then precipitation of zinc sulfide from the resulting exchelate compounds in acetone, methyl or ethyl tracts buffered with acetic acid-acetate mixtures. Since cellosolve (rapid to slow exchanges). the zinc sulfide precipitates were found after drying to be We have examined the thermal exchange reac- of varying composition they were ignited to the oxide for tions of zinc ions with some zinc complex com- weighing and subsequently mounted on filter paper discs. Both fractions from each experiment were counted in a pounds of the kind referred to above, partly to reproducible geometry with a Geiger-Mueller counter and find conditions under which the kinetics of such scale-of-64, the 0.45- to 1.14-Mev. gamma radiation assoreactions might be studied and partly to learn ciated with the decay of Zno6being counted through a which of these zinc compounds, if any, might be compound absorber. The total activity in each experiment was of the order of 1000 counts per minute, and corsuitable for use in the Szilard-Chalmers method of rections for decay and changes in counter efficiency (by concentrating radioisotopes. use of a standard Znasaliquot) and for background were apComplete exchange of radioactive zinc was plied. The extent of exchange was calculated in the usual found between dipyridine zinc acetate and the fol- manner from the specific activities of the two fractions.
lowing zinc complex compounds in pyridine solution a t 25' after exchange times as short as thirty seconds in each case: zinc acetylacetone, zinc acetylacetone ethylenediimine, zinc benzoylacetone ammoniate, zinc nicotinylacetone and dipyridine zinc thiocyanate. In the case of the nicotinylacetone, the exchange solution in pyridine was 0.0034 f i n dipyridine zinc acetate and 0.0034
(6) M. D. Kamen, "Radioactive Tracers in Biology," Academic Press, Inc., New York, N. Y.,1947, p. 246.
DEPARTMENT OF CHEMISTRY OF CALIFORNIA UNIVERSITY Los ANGELES24, CALIFORNIA RECEIVED SEPTEMBER 25, 1948
( 1 ) Present address: Naval Radiological Defense Laboratory,
Thermal Exchange Experiments with Radioactive Chromium
San Francisco Naval Shipyard, San Francisco 24, California. (2) R. B. Duffield and M. Calvin, THISJOURNAL, 68, 667 (1946). (8) U. Drehmann, Z. physrk. Chcm., B18, 227 (1943). (4) P. Sue and T. Yuana. J . chim. plys., 41, 160 (1944). (6) J. E. Johnson and N. F. Hall, THISJOUBNAL, TO, 2844 (1948).
The only published work on exchange reactions of chromium compounds is the observation of
BY H. E. MENKERAND C. S. GARNER
