Chemistry of L (Lewisite) 

Lewisite (L, 2Çchlorovinyldichloroarsine, 2-chlorovinylarsonous dichloride) has the chemical name (2Çchloroethenyl)arsonous dichloride, molecular formula C ₂H ₂AsCl ₃, and formula weight 207.32. Its Chemical Abstracts Service registry number is 541-25-3.

General Information

Lewisite was discovered near the end of World War I by a team of Americans headed by Capt. W. Lee Lewis working at Catholic University in Washington DC. ^1,2 Lewisite was never used because of the armistice; a shipload of Lewisite-filled munitions was crossing the Atlantic at the cessation of hostilities. ² In an interesting footnote, the Germans had been searching for a non-persistent vesicant in early 1918, but rejected Lewisite in favor of ethyldichloroarsine. ³ Production took place in the United States, Great Britain, France, Italy, the Soviet Union, and Japan in the immediate post war years. ⁴ During World War II, the American, British, Soviet, German, and Japanese armies had considerable stocks of Lewisite available. ^4,5 Following World War II, Lewisite was considered obsolete by the major powers because of the discovery that 2,3-dimercaptopropanol ("British anti-Lewisite") was an inexpensive and effective antidote to Lewisite exposure. ⁶ However, it may have been used recently by the Iraqis in addition to mustard agent. ⁷ Industrially-produced Lewisite has a strong penetrating geranium odor; the pure compound is odorless.

Lewisite is actually a complex mixture of several compounds, all of which occur as cis- and trans-isomers. In chemical agent grade Lewisite, the L-1 isomer generally predominates. The three homologues (L-1, L-2, and L-3 in the table below) form because Lewisite is produced by the catalyzed reaction of arsenic trichloride and acetylene. L-1 forms initially, but it will react with some of the acetylene to form L-2, which will in turn react to form L-3. Proper choice of the catalyst and reaction conditions are necessary for a reasonable yield of L-1. L-1 is the vesicant agent; it reacts with the active sites of certain enzymes. L-2 and L-3 are also toxic, but considerably less so than L-1.

Structure	Designation	Chemical Name
	L-1	2-Chlorovinylarsonous dichloride ( trans- isomer shown, also occurs as the cis- isomer)
	L-2	Bis(2-chlorovinyl)arsinous chloride ( trans,trans- isomer shown, also occurs as the cis,trans- and cis,cis- isomers)
	L-3	Tris(2-chlorovinyl)arsine ( trans,trans,trans- isomer shown, also occurs as three other isomers)

References:
1. Paxman, J.; Harris, R., A Higher Form of Killing : The Secret Story of Chemical and Biological Warfare, Hill and Wang, New York:1982, p. 32
2. Stockholm International Peace Research Institute, The Problem of Chemical and Biological Warfare. A Study of the Historical Technical, Military, Legal, and Political Aspects of CBW and Possible Disarmament Measures. Vol. 1. The Rise of CB Weapons, Humanities Press: New York, 1971, pp. 50,62.
3. Stockholm International Peace Research Institute, The Problem of Chemical and Biological Warfare. A Study of the Historical Technical Military, Legal, and Political Aspects of CBW and Possible Disarmament Measures. Vol. 1. The Rise of CB Weapons, Humanities Press: New York, 1971, p. 50.
4. Compton, J. A. F., Military Chemical and Biological Agents: Chemical and Toxicological Properties, Telford Press: Caldwell, NJ, 1988, pp. 37-38.
5. Franke, S., Manual of Military Chemistry, Volume 1. Chemistry of Chemical Warfare Agents, Deutscher Militîrverlag: Berlin (East), 1967. Translated from German by U.S Department of Commerce, National Bureau of Standards, Institute for Applied Technology, NTIS no. AD-849 866, pp. 157-8.
6. Waters, L. I.; Stock, C., BAL (British Anti-Lewisite), Science, 1945, 102, 601. Peters, R. A.; Stocken, L. A., Thompson, R. H. S., British Anti-Lewisite (BAL), Nature, 1945, 156, 616.
7. Perera, J., New Scientist, 4 April 1985, 107, 8.

Physical Properties of Lewisite

Data taken from Franke, S., Manual of Military Chemistry, Volume 1. Chemistry of Chemical Warfare Agents, Deutscher Militîrverlag: Berlin (East), 1967. Translated from German by U.S. Department of Commerce, National Bureau of Standards, Institute for Applied Technology, NTIS no. AD-849 866, pp. 247, 252 .

melting point	-18ÉC
boiling point	190ÉC
vapor pressure (20ÉC)	0.35 mm Hg
density (20ÉC)	1.89 g cm -3
aqueous solubility	0.5 g L -1
estimated log K ow 1	2-3
estimated log K d for arsenic 2	2.30

The U.S. Army Center for Health Promotion and Preventive Medicine has prepared a fact sheet about blister agent Lewisite (L). (pdf)

Hydrolysis

The hydrolysis of Lewisite proceeds according to the following scheme:

The hydrolysis product mixture has a reported log K _{benzene-water} 0.15. ¹ The initial hydrolysis reaction is rapid relative to formation of the 2Çchlorovinylarsenous acid/Lewisite oxide equilibrium mixture. L is relatively rapidly hydrolyzed compared to H. ¹ The literature indicates that production of two equivalents of chloride occurs within three minutes at 20ÉC. At 5ÉC, 90 percent reaction occurs within 2 minutes; the completion of the reaction requires several hours. ² The titration methodology used in reference 2 does not allow the determination of precise rate constants, because over 80 percent reaction occurs before the first measurement can be obtained. Nevertheless, these data indicate that the hydrolysis rate constant at 20ÉC is on the order of 1 min ^-1.

The immediate hydrolysis products 2Çchlorovinylarsenous acid and Lewisite oxide are also vesicants. ¹ There is no appreciable difference in toxicity between Lewisite and the 2Çchlorovinylarsonous acid/Lewisite oxide equilibrium mixture. Given the rapidity of hydrolysis it is possible that these species are responsible in vivo for the effects of Lewisite. The vesicant properties of the mixture are reported to remain unchanged after storage for 10 weeks in sea water. ³

Over time, the hydrolysis products will be transformed into both other organic and inorganic forms of arsenic. Waters and Williams observed that cold alkali decomposes 2Çchlorovinylarsonous acid into arsonous acid, acetylene, and chloride: ¹

At 17ÉC, this reaction shows no detectable acetylene product after 24 hours at pH 8.5, shows a slight amount of product after 24 hours at pH 9.5, and shows substantial amounts of product after 2 hours at pH 10.5. This is roughly consistent with the observation of continued vesicant properties after 10 weeks at 0ÉC in sea water. The arsonous acid produced by this reaction will subsequently undergo the expected transformations of arsenic in the environment.

Hydrolysis Product from L
Compound	FW	Solubility, g L -1	Estimated log  K ow
2-chlorovinylarsonous acid	170.43	20 4	1.4 to 2.4 5
Lewisite oxide	152.41	20 4	-1.4 to -0.4 6
Arsenic	74.92	-	-

References:
1. Waters, W. A.; Williams, J. H., Hydrolyses and derivatives of some vesicant arsenicals, J. Chem. Soc. 1950, 18-22.
2. Rovida, G., Richerche sperimentali con la Lewisite. I. Storia e generalit› della Lewisite. Il comportamento delle clorovinilcloroarsine con l'aqua, Sperimentale, 1926, 80, 5-24.
3. Epstein, J.; Rosenblatt, D. H.; Gallacio, A.; McTeague, W. F., Summary report on a data base for predicting consequences of chemical disposal operations, EASP 1200-12, January 1973, AD-B955399 (distribution limited to U.S. Government).
4. The hydrolysis mixture has a solubility greater than 2 percent in sea water; see reference 4.
5. ClCH=CHP(OH) ₂ has an estimated value of 1.94 using Syracuse Research Corporation, LOGKOW version 1.50; (see Meylan, W. M.; Howard, P. H., J. Pharm. Sci. 1995, 84(1): 83-92); no fragment descriptions were available for arsenic.
6. ClCH=CHP=O has an estimated value of -0.94 using Syracuse Research Corporation, LOGKOW version 1.50; (see Meylan, W. M.; Howard, P. H., J. Pharm. Sci. 1995, 84(1): 83-92); no fragment descriptions were available for arsenic.

Oxidation

Lewisite does not oxidize significantly. However, the oxide produced by hydrolysis can be slowly oxidized in air to 2-chlorovinylarsonic acid:

Photolysis

Lewisite and its hydrolysis products exhibit no significant phototransformations in sunlight.

Thermolysis

Lewisite and its hydrolysis products are thermally stable at temperatures less than 49ÉC.

Decontamination

The effect of Lewisite can be prevented by rapid topical application of 2,3-dimercaptopropanol, known as British anti-Lewisite (BAL). BAL reacts with Lewisite to form a stable non-toxic cyclic product:

Hydrolysis alone provides less than optimal decontamination, because the L-3 isomers do not hydrolyze. However, oxidation of the Lewisite hydrolysate, e.g., with hydrogen peroxide, converts the arsenic(III) to arsenic(V):

2-chlorovinylarsonic acid	bis(2-chlorovinyl)arsinic acid	tris(2-chlorovinyl)arsine oxide

These three products all react with aqueous sodium hydroxide at elevated temperature to form acetylene, sodium chloride, and sodium arsenate. Thus, the combination of oxidation and hydrolysis is effective at destroying all Lewisite isomers.

Reference:

Goldman, M.,; Dacre, J. C., Lewisite: Its Chemistry, Toxicology, and Biological Effects, Rev. Environ. Contam. Toxicol., 1989, 110, 75-115.