I N D U S T R I A I, A N D E N GI N E E 11 I N G C H E M I S T R Y
June, 1932
Hatta, J . Soc. Chem. Ind. (Japan), 31, 869 (1928); 32, 809 (1929). Ledig and STeaver, J . -4m. Chem. Soc., 46, 650 (1924); Ledig, ISD.ESG. CHEM.,16, 1231 (1924). Lewis and TThitman, Ibid., 16,1215 (1924). McBain, J . ('hem. Soc., 101,814 (1912). (15) McCoy, d m .Chem. J . , 29, 437 (1903). 116) hlitsukuri. Science Revts. Tohoku Imp. Cnm., 18,245(1929). i17) Kiou, Conipt. rend., 174, 1017, 1463 (1922); 184 325 (1927); 186, 1543, 1727 (1928).
637
(18) Saal, Rec. trav.chim., 47,264 (1928). (19) Weber and Nilsson, ISD.ENG.CHEN.,18,1070 (1926). (20) Whitman, Chem. M e t . Eng., 29, 147 (1923). (21) Whitman and Davis, IND. ENG.CHEM.,18,264 (19%). (22) Whitman, Long, and Wang, Ibzd, 18,363 (1926). (23) Williamson and Mathews, Ibid., 16, 1157 (1924).
RECEIVED March 3, 1932. T h e present address of J . K. Payne is t h e Vacuum Oil Co., Paulaboro, K.J.
Fluorine Derivatives of Chloroform HAROLD SIJIMONS BOOTHAKD E. R ~ A YBIXBY,Western Reserve University, Cleveland, Ohio
A
containing pea-size p o t a 5 s i u in The preparation and properties of fluorine h y d r o x i d e and barium oxide ties of 166 known gases derivatices qf chloroform are discussed, including (3). Gases mere obtained from suggested that the best a new noninflammable nontoxic gas, monoc y l i n d e r s w h i c h w e r e fitted p o s s i b i l i t y of finding a new chlorodifluoromethane (CHClF2), freezing at with Ohio unit parts (1) and n o n c o m b u s t i ki 1e a n e s t h e t i c -147" io --146" C. and boiling at -39.8" C. a t t a c h e d t o t h e t u b e C' i n gas lay in the field of organic place of tube C. The m i d d l e fluoride compounds. Fluorine I n this series toxicity diminishes as the number horizontal line was c o n n e c t e d substitution for other halogens of Jluorine atoms substituted for chlorine is to the vacuum pumps and also lowers t h e b o i l i n g point, inincreased. ."either the mono- nor the difluoro to the apparatus for making gas creases stability, and generally derimtie\e proced of Ltalue as a n anesthetic, but mixtures and administering the decreases toxicitv. Sayers and the monochlorodifluoromethane should have value gas. co-workers ( I O ) have shown that dichlorodifluoromethane is subas a refrigerant. Fluoroform could not be preSTUDYOF TOSICITY stantially nontoxic, a l t h o u g h pared in sufficient quantity f o r testing its toricity. I n order to conserve the gases, n r o d u c i n n m i l d to m a r k e d the volume of this part i f the tremors in guinea pigs; while carbon tetrachloride is known to be quite toxic, irritating the apparatus was as small as consistent with satisfactory results. broncheal and tracheal membranes, and possessing a very The gas mixtures were synthesized in the 12-liter mixing narrow anesthetic-lethal range. Moreover, there is indica- globe, &, by making u p to definite partial pressures read on tion that, like chlorine, fluorine substitution for hydrogen in the manometer, G. The circulating pump, T', moved the organic compounds lessens the inflammability; for example, gases from this mixing globe through the soda lime tube, X, fluoroforni burns with difficulty, while methane forms explosive and either directly back to the mixing globe or through the mixtures with air. T o narrow the field further for an ap- testing chamber, W, the gas entering through Z and leaving proach to this subject, it ivas logical to study those organic through 2'. The testing chamber, W , consisted of a cylinfluorides which are derivatives of the best of the known drical glass jar with flat ground rim held by a screw clamp anesthetics. The present article discusses the fluorine deriva- against a flat steel plate a t Z' and sealed with stopcock tires of chloroform. grease. Thus the animal undergoing treatment could be continually observed. It was also possible to wash out the toxic gas with air rapidly if necessary through the air connecGESERATION AND P U R I F I C l T I O S O F GASES tion a t 9. The apparatus for this study was made of fused glass and I n performing an experiment for toxicity, the mixing globe the new standard interchangeable conical ground-glass joints !vas filled with gases a t such pressures that the required conto obtain flexibility and easy transition from one set-up to centrations would be reached when the pump and cage volumes another. Figure 1 shows the complete apparatus. On the of air were included. The animal was t h m sealed in the cage. left is the removable generating flask, A , with a refluxing For one minute the gases circulated through the pump, bycondenser above. The gases from the generator passed passing the cage. Stopcock 12 was closed t o pass all of the through a condensing trap, C', in which the gases were usually gas through the pump, mixing it thoroughly. S e x t , the time completely condensed using liquid air, while nonc indensable being noted, stopcock 12 was first opened full; then stopcocks gases passed on. The gas was then boiled into the purifying 9 and 10 were opened simultaneously, stopcock 11 closed, and section of the apparatus and condensed with a suitable finally stopcock 12 adjusted to give the proper rate of circularefrigerant in either tube J or K . Tube J was fitted with a tion, which would avoid too great a vacuuin in the cage. This toluene thermometer that permitted the determination of the usually ranged from 0 to 4 cm. The depth of the mercury approximate boiling point of the liquefied gas. in the manometer was such that any accident of back pressure I n some cases it was convenient to wash the gases before could never cause a pressure greater than 5 cm. above atmosfractionation. This was accomplished by inserting a t D the pheric in the cage. tube H , partly filled with wash-liquid, followed by the drying Blank experiments showed that guinea pigs suffered no ill tube L. The gases were purified by fractional distillation in effects when kept in the apparatus for 3 hours, while ordinary the usual way (2, 7 ) and stored until needed in five &liter air, not replenished with oxygen, was circulated. The longest globes. period of administration in actual tests was 2 hours 30 Dry air, free of carbon dioxide, could be admitted to the minutes. The percentage of oxygen was always initially 20 apparatus for rinsing purposes through the drying tubes, .V, per cent.
SURVEY of the proper-
-
638
INDUSTRIAL AND ENGINEERING CHEMISTRY
Vol. 24, No. 6
U
DICHLORObIONOFLUOROJlETHB?r'E
Fluorochloroform was first prepared by PREPARATION. Swarts (11) in large yields by the action of antimony trifluoride and bromine on chloroform. He noted that it boils a t 14.5' C., has a specific gravity of 1.426, and is insoluble in water but soluble in alcohol, ether, and chloroform; that it is not combustible, but colors the flame green and decomposes when strongly heated. Since bromine vapors tend to cause side reactions and are difficult to remove, the product used in this research was prepared by Swarts' other general method (12) for introducing fluorine-namely, by the use of antimony trifluoride and small amounts of antimony pentachloride. Since it had been found that pure chloroform is not as reactive as the less pure substance, some carbon disulfide was added to catalyze the reaction. One hundred and sixty-eight grams of dry antimony trifluoride were placed in the reaction flask surmounted by a condenser containing broken glass, and cooled with carbon dioxide snow or with calcium chlorideice mixture. After the apparatus was rinsed thoroughly with dry air, free of carbon dioxide, 14 cc. of antimony pentachloride were added by means of the separatory funnel, and after a few minutes were followed by 213 cc. of dry chloroform containing 1 cc. of carbon disulfide. When antimony pentachloride was added with the chloroform, much charring took place. It was necessary first to form the antimony trifluoride-antimony pentachloride complex, probably SbFaC12. The line mas open to the air successively through soda lime, barium oxide, a liquid air trap, and a protecting barium oxide tube. There was slow steady evolution of gas a t room temperature. If gentle heat was applied, the reaction proceeded much faster. Most of the product distilled over in the first 2 hours, but refluxing was continued for 5 to 7 hours. Very large yields of fairly pure gas were obtained, easily separated from chloroform by fractionation. It mas best
separated from a persistent, white, volatile solid contaminating it, by fractionation a t low pressures (6 cm.) and a t the corresponding boiling point of the dichloromonofluoromethane. At higher pressures the solid melted and distilled over. Large amounts of the contaminating substance were formed when attempts were made to dry the gas by passing it over soda lime and barium oxide. These became hot, and the latter pink. Xo fluorine or chlorine could be detected in them. The white substance contained no antimony. It was found that, whereas the pure gas hemolyzed blood, the impure gas also caused it to turn purple, and this fact was used to determine the purity of the gas. For this test it was bubbled through about 5 cc. of a 0.9 per cent saline solution containing a very small amount of blood. The gas was purified by washing it in water, then passing it through a tube of moist potassium hydroxide to remove hydrogen fluoride and silicon fluoride and finally through a calcium chloride drying tube, with subsequent fractional distillation. PROPERTIES. Dichloromonofluoromethane is readily condensed by carbon dioxide-ether mixture and can be held by refrigeration with liquid ammonia or ice water. I t s boiling point, observed in the special fractionating bulb, was found to be between 13.5" and 15.5' C. M. J. Bahnsen of this laboratory carefully determined its melting point as -127" C. by means of melting curves obtained with a multiple thermocouple. The presence of fluorine and chlorine was established by qualitative tests. When a sample of the gas was heated to red heat in a closed tube, there was considerable etching of the tube; and, on adding acidified silver nitrate solution, a heavy precipitate of silver chloride formed. The gas had a sweet chloroform-like, but musty, odor. It was noncombustible but decomposed in a soot flame, forming hydrogen fluoride and hydrogen chloride. When it was condensed onto ice containing methyl orange and thereafter
June, 1932
I ND U S T R I A L A N D E N G I N E E R I N G C H E M I S T R Y
kept 18 days in a sealed tube, the methyl orange remained yellow, showing t h a t no hydrolysis had taken place. When bubbled through water a t 0" C., the gas formed a crystalline froth, apparently a hydrate analogous to t h a t formed b y chloroform. On warming to room temperature, this settled in the water in a transparent colloidal condition and slowly disappeared as the gas escaped. PHYSIOLOGICAL PROPERTIES. Preliminary experiments with mice indicated that dichloromonofluoromethane mould not serve as a n anesthetic. One per cent caused the animal to continuously, vigorously, and frantically scratch and bite itself during 1 hour and 45 minutes. =Inother mouse acted similarly during 30 minutes. Ai4 per cent mixture of the gas with air, during 13minutes, caused a small guinea pig (85 grams) to lengthen its body, to kick spasmodically, and to suffer violent tremors. I t s left side was temporarily paralyzed, but it finally recovered in a few hours. There was no sign of anesthesia. h 6 per cent mixture containing 18.8 per cent oxygen caused guinea pigs in two experiments to become dyspnoic and nearly unconscious during 5 minutes, but recovery was immediate on removing into the fresh air. The muscles were not sufficiently relaxed and the state of unconsciousness not deep enough for surgical anesthesia. One of these guinea pigs died in 5 minutes when exposed to a 20 per cent mixture containing 16 per cent oxygen, while another, not used before, died in 11 minutes. Both breathed with difficulty, suffered violent tremors, and kicked spasmodically. Postmortem examination showed an increase in serous fluid in the abdominal cavity. The other organs were not markedly different from the normal, though the lungs were slightly inflated and the right side of the heart slightly dilated. A 40 per cent mixture, fortified with oxygen to 18 per cent, caused the death of a guinea pig in 6 minutes without signs of anesthesia. There was difficulty in breathing, lengthening of the body, tn-itching from side to side, tremors, and violent kicking. At postmortem examination, the heart was definitely enlarged, and there was excess fluid in the abdominal cavity and congestion of the upper gut. Otherwise the organs were normal. Death was due to respiratory failure. These experiments showed that dichloromonofluoromethane does not produce a proper anesthesia; that in large doses it is fatal; and that its effects are cumulative and dependent on concentration. The dichloromonofluoromethane curve in Figure 2 shows the variation of lethal time with concentration. Similar curves for chloroform and monochlorodifluoroniethane, shown for comparison, indicate t h a t toxicity is decreased on substituting fluorine for chlorine. It must be remembered that such curves can only be approximations, a t b i d .
MONOCHLORODIFLUOROMETHAXE The only mention of monochlorodifluoromethane found in the literature was in a chart in an article by Midgley and Henne (9) who predicted a boiling point of -48" C. for the hypothetical gas. PREPARATION. It was prepared in large quantities for this study by the Ohio Chemical and Manufacturing Company: 2520 grams of antimony trifluoride and 1650 grams of chloroform with 70 cc. of antimony pentachloride were placed in a D cylinder vhich was sealed by a steel pipe surmounted with a gage and placed in a bath of water maintained
