e
e
SYNTHESIS OF CYCLOPROPANE‘ H. B. HASS, E. T. McBEE, G. E. HINDS,* AND E. W. GLUESENKAMPZ Department of Chemistry, Purdue University and Purdue Research Foundation, Lafayette, Ind.
LTHOUGH cyclopropane has been known since 1882 (Z), commercial interest in this conipound dates from the announceiiient by Henderson and Lucas: ( 7 ) in 1930 that they had used it successfully to anesthetize a dog. I t was first applied in human anesthesia by R. Sf. Katers in December. 1930. Pince then it has been rather widely adopted, in spite of its evcessive cost (about tnTenty dollars a pound, June, 1936). Its present status among anesthetists who have used it is summarized by Galasso (3): “The safest anesthetic agent-the one which presents all the good qualities and none of the objectional side effects of the agents we hare on hand-cyclopropane.” This drug has: until recently been manufactured exclusively by the following reaction sequence:
+
HO,CH,,CH?,CH?,OH 2HRr ---+ Rr,CH2CH2.CH2.Rr 2H20 (1) I3r.CH2.CH2.CH2.Rr Zn (or Mg) + (CH,), ZnBr? (or MgBr,) ( 2 )
+
+
+
The 1,3-propaiiediol (triniethylelie glycol) is obtained as a by-product of the soap industry where it esi+ as a iiiiiior
inipurity in the glycerol. Both 1.3-propaiiediol and hydrobromic acid are relatively expensive compared to propane and chlorine, the reagents used in the procedure here described.
Chlorination of Propane The n e w r process is founded upon the discovery announced in the second paper of this series: (5) that every possible nionochloride and polychloride derivable without carbon-skeleton rearrangenlent is always formed when a paraffin is chlorinated under conditions which avoid excessive pyrolysis. It is 1 This paper, which contains material abstracted froin the Pi1.D. theses of G. E. Hinds and of E , iT-. Gluesenkamp, is the fifth in a series on the subject of syntheses from natural gas hydrocarbons. T h e others appeared in I N D . EXG.C H E M23, . , 352 (1931); 27, 1190 (19353; 28, 3 3 3 , 839 (1936). 2 Present addrees, Pbarples Solvents Corporation, Wyandotte, Mich 3 Present addre-s, Thoinas and Hochwalt Laboratories, Dayton. Ohin.
7 178
o c n m i ~1936 .
INDUSTRIAL ASD ESGIXEERISG CHEhlISTKY
evident from this geiiera1iz:ition that the chlorination of propane to the dichloride stage occurs according to the following diagram where for the sake of clarity the hydrogen atoms are omitted: C11
c-e-c
/ (propane, b. p.
\
c12
4c-e-c Cl
CI
(1-chloropropane, I?. p. 46.6" C..) (2-chloropropane,
c1-c-c-c ,
dl (1,l-dichloropropane b. p. 87O C.)
chloride is removed. The moist gases from the hydrochloric acid qcrubber must be dried in order to prevent corrosion in other parts of the plant. This is accomplished in two sulfuric acid scrubbing towers which also remove olefins and chloroolefins which are formed in t'races in the chlorinator. The gas holder serves as a guide to the rate of flow of the make-up propane which is adjusted to keep the gas holder about half full.
-42 6 2 C.)
c-c-c4
.I2/
1179
e
c1-c-c-c--c1'\ !C*l
el2!
c1-c-c-c
I
61 (1,3-dichloropropane b. €1. 120.4" C.)
p. 34.8" C.)
cI1 c-e-c I
JCI?
61
(1,2-dichloro- (2,2-dichloropropane, b. p. propane, b. p. 96.8" C.) 69.7" C.)
In view of the boiling points and of the well-known tendency of mixtures of chloroparaffins to adhere to Raoult's law, it is evident that little difficulty is to be expected in separating 1,3-dichloropropane from its isomers. The experimental verification of these deductions is expressed in Figure 1, a rectification curve which constitutes clear evidence of the presence of all four of these compounds in the dichloride fraction obtained in the vapor-phase thermal chlorination of propane a t 400' C. with recycling of nionochlorides. The relative proportions of the different isomers are, in order of boiling point: 2,2-dichloropropanej 25.5 per cent; 1,l-dichloropropane, 19.6; 1,2-dichloropropane, 35.6; 1,3-dichloropropane. 19.3. Thus, only about one-fifth of the dichloride fraction obtained under these conditions consists of the 1,3-isoiner, n-hich is the only one capable of yielding cyclopropane upon dehalogenation by metali. The ease of the chlorination and of the subsequent separation of the desired compound, the lov cost of propane and chlorine, and the value of the by-products combine to make this proce.. an economical source of 1,3-dichlorogropane in spite of thi, low yield.
1 0
5 0
I
I /ou
M,I/
I
1 /50
I
I
I
200
I 2.50
I
I 300
D , s f / / / d te
FIGURE 1. RECTIFICATIOS CCRVE
FOR
DICHLOROPROPAXES
The crude dichlorides are fractionat,ed in the batch rectifying column in n-hich 1,3-dichloropropane is separated from all other chlorinated products except 1,2,2-trichloropropane. This trichloride (boiling at 123" C.) boils only 1.6" C. higher than the 1,3-dichloride, and its removal bv distillation is therefore impract,ical. Since only about S p& cent of t,he crude dichloride mixture consists of trichlorides, and the 1,2,2- is the only one of the fire isomers present, which is difficultly separable, it occurs in only ininor amounts in the rectified 1,3-dichloropropane. The final elimination of t,his impurity occurs in the ring-clomre reaction where it is converted to 2-chloro-1-propene (boiling at 22.65" e.) ivhicli is removed in the rectification of the crude cyclopropane.
The by-products of the procebs thus consist essentially of hydrochloric acid Cy c 1o p r o p a n e has reand 1,2-dichloropropaiie (propylene c e n t l y a t t r a c t e d much chloride) which are well knonm coinmercially, and of 1,l-dichloropropane paratus shown diagrammatically in favorable attention as a and 2,3-dichloropropane which are Figure 2 : general anesthetic. Its exindustrially new. It is obvious that By means of flon-meters F a molar cessive cost has heretofore removal of 2-chloropropane from the excess of material to be chlorinat'ed hindered its wide adoption (propane and monochlorides) over chlorecycle gas would improve the yieltl rine, of approximately 10:l is maintained by the medical profession. of 1,3-dichloropropane based on chloin the gases flowing to the chlorinator. rine, but a t the present scale of operaA simple, two-step syntheThis excess, in combination n.it,h comtions the complications necessitated plete removal of dichlorides from the resis from the propane of cycled gas by means of the continuous by this step are not justified. n a t u r a l gas is described rectifying column, ensures a low conThe plant shown in the acconipaiiycentration of trichlorides in the crude here. T h i s p r o c e d u r e ing photographs was erected a t dichloride mixture. The chlorine is alPurdue and, after several nioiiths of should make cyclopropane lowed t o react completely in the chlorinator, and the material flowing to the successful operation upon this campus, available at a reasonable condenser and hence t o the continuous wa5 renioved t o the Mallinckrodt price. rectifying column consists essentially of Cheinical Works a t St. Louis where propane, both monochloropropanes, all it is operating a t present. Its cafour dichloropropanes, and hydrogen chloride. The effluent from the base pacity corresponds to about one of the continuous column consists of dichloropropanes n-itll thousand anesthesias daily, minor amounts of more highly chlorinated material. The hydrogen chloride, propane, and monochloride. pas> up through The Ring Closure the column in Tvhich a sufficient monochloride reflux is maintained to remove the dichlorides efficiently from the overhead product. The make-up propane is introduced immediately after the conhlthough Gustavson (4)reported in 1887 that he had obtained cJ'clopropane from 1,3-dichloropropane by the action tinuous column and assists in preventing condensation of monochlorides in the hydrochloric acid scrubber, in which the hydrogen of zinc dust suspended in aqueous alcohol, he stated that the
Description of Chlorination Apparatus Propane is chlorinated in the ap-
VOL. 28, XO. 10 conceive of the ring-closure reaction as proceeding through a Grignard synthesis.
X CH: CHZ.CH?X+ Mg +
(X.CH?.CH*.CH2.MgX)+ (CHz), nfgxz (6)
+
FIGURE 2. FLOWSHEET
O F CHLORINATIOX
yield was low. The writers hare never been able to obtaiii a reasonably rapid conversion rate by Gustavson's procedure, and attempts to force the reaction by the use of elevated temperature result in an evolution of large proportions of hydrogen and propane. This is presumably caused by hydrolysis of zinc chloride and the action of the resulting hydrochloric acid upon the zinc dust. Of the three competing reactions,
+
+
(CHz),Cl, Zn ---f ZnClz (CHZ)~ 2HC1 Zn +ZnCh H, (CH&C12 2Zn 2HC1+ C3H8 2ZnCll
+
+
+
+
+
(3) (4) (5)
(4) and (5) occur to a troublesome extent. If water is eliminated, the reaction rate becomes too low to be of iniportance. The situation in 1930 was well expressed by Lott and Christianson (8) in an article on the synthesis of cyclopropane in which they state: "All of the practical methods are based on the reduction of trimethylene dibromide with metallic zinc in an alcoholic solution." By using a large excess of zinc dust and by raising the temperature of the reaction mixture with high-boiling solvents, the rate of conversion can be increased materially. Thus a 57 per cent yield of cyclopropane was obtained from 1,3-dichloropropane in an apparatus substantially similar to that which Lott and Christianson (8) used with the dibromide, but substituting diphenyl ether as solvent in place of aqueous ethanol and carrying out the reaction a t 210" C. 'L'nder the same conditions, except that sodium was used as reagent and fused biphenyl as solvent, a 64 per cent yield of crude cyclopropane was obtained. With a mixed solvent of dibutyl ether (1-butoxybutane) and xylene, a small quantity of iodide catalyst, and a temperature of 140' C.. magnesium turnings gave a yield of 70 per cent of crude cyclopropane which, upon Podbielniak rectification, proved to be about 86 per cent pure (i. e., a 60 per cent yield of pure cyclopropane). I n the absence of iodide no appreciable reaction with magnesium occurred. The peculiar inertness of 1,3-dichloropropane is well exemplified by an experiment in which it was sealed in a glass tube and heated overnight with butyl ether and magnesium powder a t 150" and again at 200' C. The metal was not even corroded, although such an unreactive compound as chlorobenzene is rapidly attacked by magnesium a t these temperatures. These facts led to an investigation of the catalytic role of iodine in the reaction. It is customary t o start the formation of a Grignard reagent by adding iodine or some organic iodide. It is possible t o
and with the dibromide there is good evidence that this is the actual mechanism. It was not surprising, therefore, to find that free iodine, ethyl iodide, or ethyl magnesium iodide has a powerful positive catalytic effect upon the synthesis of Ho/der cyclopropane from 1,3-dichloropropane. On the other hand, it was more than AiPP.IR.\.I.l-S surprising t o find that, when the iodide ions are removed from the solution, even after the reaction is well started. the liberation of gas ceases and recommences only in the presence of additional iodide ions. This happened through the formation of insoluble cuprous iodide when copper turnings were added to the reaction mixture during tests made in preparation for plant-scale operation. The elucidation of this phenomenon was indicated when 1chloro-3-iodopropane and 1,3-diiodopropane were synthesized from 1,3-dichloropropane by metathesis with sodium iodide and proved t o give cyclopropane rapidly and in good yield4 a t the temperature of refluxing ethanol:
Q
+
2C1CH&H2CH2,I 2Zn (or Mg) + ~ ( C H Z ) ~ZnCh ZnIz (or MgCL MgL) (9) I.CH2.CH2.CH2.1 Zn (or Mg)+(CH& ZnIz (or MgIz) (10)
+
+
+
+
+
When sodium iodide is added to a refluxing mixture of zinc dust, ethanol, and 1,3-dichloropropane, a marked acceleration of the reaction rate occurs. This effect is only temporary, however, since the iodide ions are rapidly converted to zinc iodide by Equations 7 and 9. A separate experiment showed that zinc iodide does not exert any significant catalytic action under these conditions, presumably because of an insufficient degree of ionization. The opposite is true with magnesium iodide under the conditions employed with that metal. At this point it became evident that, if iodide ions were to be used in the synthesis with zinc as intermediate-cornpound-formation catalysts in the heme described in the first article of this series ( 6 ) ,some means must be used for regenerating them from zinc iodide. Two types of reagents have been found which are capable of perforniing this function. The first is exemplified by sodium carbonate, which reacts with zinc iodide in the presence of ethanol t o yield a basic zinc carbonate, sodium iodide, and carbon dioxide. Acetamide is an example of the other type; it is believed to react as follon-s (where subscript xis presumably 4) : Zn12
+ XCHs.C0.NH2 --+- Zn++(CHVCO.NHZ)~ + 21- (11)
Using the same apparatus as before, a solvent consisting of -i o per cent ethanol and 25 per cent water, a mole of anhydrous sodium carbonate for each mole of 1,3-dichloropropane, a 100 * The new processes descrlbed in thls paper are corered by pendlng uatents awpned t o t h e Purdue Research Foundation
U. S
OCTOBER, 1936
I\DUSTRIA4L AND ESC;J\EEl-II\G
per cent excess of zinc dust. and I, 6 mole of sodium iodide, a 95 per cent yield of crude cyclopropane was obtained in 12 hours. When anydrous acetamide is used as a solvent and the temperature is maintained a t about 125' C., cyclopropane can be readily obtained in the absence of sodium carbonate, but better yields and a purer product are obtained if both sodium carbonate and acetamide aie employed. By this procedure, yields in excess of 80 per cent of theory of c. P. cyclopropane have been consistently obtained within 3 or 4 hours using only a 10 per cent excess of zinc dust and 1 / 6 0 m ~ of l e iodide.
Purification of Cyclopropane There has been some question in the literature (10) a!: to whether pure cyclopropane has ever been obtained and even as to whether there is a dependable means of knowing when it is pure. Roginski and Rathmann (9) used selective ahsorption of propene in a saturated, aqueous, iodine tribrornide solution to determine the percentage of propene in cyclopropane samples. This method is not sufficiently precise for the present purposes since even the crude product obtained in the synthesis described here always tests more than 100 per cent pure, because the evaporation of bromine from the solation into the gas sample causes the volume of the latter to increase. The excellent method of Ashdown, Harris, and Armstrong ( I ) , involving the molecular exJinction coefficient of ultraviolet light of wave length 1975 A.. involves equipment not usually available. In the process here described, cyclopropane is always accompanied by traces of propene and propane and somewhat larger amounts of 2-chloro-1-propene and 1,3-dichloropropane. The boiling points are as follows Propene Propane Cyclopropane
-47 67' C. -42 59 -32.89
2-Chloro-1-propene 1,3-Dichloropropane
- 2 2 A-5" C 120 4
+
The routine control of the purity of the final product \\ab devised by J. C. Ballantyne of the Mallinckrodt Chemical Works. The purification is by liquefaction and rectification Since propane has a boiling point between that of propene and of cyclopropane, it is obviow that, if ~ u h ~ t a r i t i a l all l y ot the propane had been removed from the cyclopropane, the removal of propene must have been even more c o m p l e t e Since both cyclopropane and propene (but not propane) are rapidly absorbed by cold, concentrated sulfuric acid, the absence of any significant quantity of nonabsorbed gas indicates the substantial absence of propane, and, under this procedure, of propene also. The combined quantity of 2-chloro1-propene and 1,3-dichloropropane present can be approximated by the combustion of a sample in purified air followed by a halogen analysis on the sodium carbonate s o 1u t i o n used to scrub the gaseous combustion products. A question has been raised concerning the possible presence in traces of arsine derived from the zinc dust. J. C. Ballantyne reports that careful work has failed t o detect any of this poisonous substance. This fact may be attributed to the
CHE~lISTH~
1181
substantially neutral and anhydrous conditions maintained during the synthesis with the accompanying absence of liberation of hydrogen, which reaction would be expected to cause the formation of arsine.
Acknowledgment The authors wish to thank the hfallinckrodt Chemical Works for providing the funds for these researches as Purdue Research Foundation Fellowships 35 and 36. Thanks are also due the Purdue School of Chemical Engineering for generously furnishing the space for the erection of the chlorination unit.
Literature Cited (1) Ashdoan, Harris, and Armst,rong, J . Ani. C h e m . S o c . , 58, 850 (1936). (2) Freund, J . p r a k f . Chem., 26,367 (1882). (3) Galasso, Anesthesia and Analgesia, 15, 32 (19361. 14) Gustavson, J . prakt. Chem., 2 , 3 6 , 300 (1887). ( 5 ) Hass, H. B., McBee, E. T., and Weber, Paul. IND.EHQ.CHEM,. 27, 1190 (1935). (6) Hass, H. B., and Marshall, J. R.. Ibid., 23, 352 (1931). (7) Henderson and Lucas. Anesthesia and Analgesia, 9, 1-6 (1930). (8) Lott and Christianson, J . Am. Pharm. Assoc., 19, 341-4 (1930). (9) Roginski and Rathniann, J. Am. Chem. Soc., 55,2800 (1933). (10) Wolkow and Menschutkin, J . Russ. P/iys.-Chem. Soc., 32, 126 (1900); Cenfralblatt, 1900, II,43; Ber., 31,3067 (1898).
RECEIVED July 21, 1936. Presented before the Division of Orgenio Chemistry at the 92nd Meeting o f the ;\rnerirali ChPtiiiral Society. Pittsburgh, Pa., 3epternber 7 t o 1 1 , 1936
