Chemistry of H (Mustard)

Mustard "gas", (also known as H, yperite, sulfur mustard, Kampfstoff Lost) is actually a viscous liquid with the chemical name 1,1'Çthiobis[2Çchloroethane], molecular formula C₄H₈Cl₂S, and formula weight 159.08. Its Chemical Abstracts Service registry number is 505-60-2.

General Information

Mustard was first used by the Germans on the night of 12-13 July 1917 near Ypres in Flanders.¹ The French introduced mustard into their arsenal in June 1918, the British in September 1918. ² In one of the supreme ironies of the history of chemical warfare, the British had tested mustard during the summer of 1916, but the developers had been unable to convince the military of its utility. Meanwhile, the Germans began developing mustard in September 1916, and first filled shells with mustard in the spring of 1917. The Germans waited to introduce mustard to the battlefield until they had accumulated a large supply, knowing that it would be difficult for the Allies to catch up; indeed it took the French 11 months and the British 14 months before they were able to use the agent on the battlefield.²

Subsequent documented uses of mustard include use in Morocco in 1925, ³ during 1935 in Ethiopia,³ in China between 1934 and 1944,³ and in the Iran-Iraq war by both sides. Large quantities were prepared by both the Allies and the Axis during World War II. Although no chemical warfare agents were used in Europe or in the Pacific,⁴ there was a release of mustard into Bari harbor in Italy in 1943.³ Mustard was stockpiled by the Soviet Union and the United States through the Cold War.

Mustard was first synthesized by Meyer in 1886,⁵ although it had been produced in very poor yield by Guthrie some 25 years previously⁶ (had Guthrie's preparation produced a higher yield, he likely would have been severely injured⁷). When pure, H is a colorless and odorless liquid. Agent grade material is typically yellow to dark brown;^4,8 the odor is variously described as "similar to that of burning garlic,"³ "a characteristic sweetish odor,"⁴ and "a weak, sweet, agreeable odor."⁸ It is a strong vesicant.⁹

References

A Higher Form of Killing: The Secret Story of Chemical and Biological Warfare

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

Military Chemical and Biological Agents: Chemical and Toxicological Properties

Manual of Military Chemistry, Volume 1. Chemistry of Chemical Warfare Agents

Uber Thiodiglykolverbindungen

Ber.

1886

On Some Derivatives from the Olefins

Qly. J. Chem. Soc.,

1860

1860-1

The Poisonous Cloud. Chemical Warfare in the First World War

The Merck Index, 11 ed

Physical Properties of H.

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, unless otherwise noted.

melting point	13-14ÉC
boiling point	215-217ÉC
vapor pressure (20ÉC)	0.11 mm Hg
density (20ÉC)	1.27 g cm^-3
aqueous solubility (20ÉC)	0.8 g L^-1
aqueous solubility (10ÉC)¹	0.7 g L^-1
aqueous solubility (0ÉC)²	0.3 g L^-1
estimated log K_oc³	2.12
estimated log K_ow³	1.37
estimated log K_ow⁴	2.41

Additional data on properties, health hazards, and handling is given in the material safety data sheet (MSDS) for mustard.

References

Syracuse Research Corporation, LOGKOW version 1.50

J. Pharm. Sci

1995

Hydrolysis

The Reaction

The first step in the hydrolysis of H is neighboring group nucleophilic attack of the sulfide S on the bÇcarbon to form an intermediate sulfonium ion:¹

This is considered to be an SN1 reaction with anchimeric ("neighboring group") assistance. The reactant and the ion pair are in equilibrium, so that the observed reaction rate will decrease with increasing chloride concentration. Water attacks the sulfonium ion at one of the ring carbons, opening the ring to give hemimustard and hydrogen chloride:

Hemimustard is also a vesicant. It then reacts in a similar fashion with water to give thiodiglycol and an additional molecule of hydrogen chloride:

The cyclic intermediate formed from hemimustard also reacts via an internal displacement to give 1,4-thioxane and an additional molecule of hydrogen chloride:

The hemimustard hydrolysis reaction gives roughly 4:1 thiodiglycol:thioxane; 1,4Çdithiane and 2-(vinylthio)ethanol are produced from hydrolysis at high concentrations of H (> 2 mole L^-1) at high temperature (100C) but appear unlikely to form at lower temperatures.²

H Hydrolysis Products
Compound	FW	Solubility,³ g L^-1	Estimated log K_ow⁴	product produced from 1 kg H, g
TDG	122.19	6900	-0.62	648
1,4-Thioxane	104.17	286	0.53	120

Reaction Rates

Ogston, et al., measured values at 25ÉC of k₁ = 0.174 min^-1 for mustard and k'₁ = 0.223 min^-1 for hemimustard.¹³ Independently, Bartlett and Swain established values at 25ÉC of k₁ = 0.155 min^-1 for mustard and k'₁ = 0.260 min^-1 for hemimustard.¹ Thus hemimustard is thus a relatively short-lived hydrolysis intermediate.

Hydrolysis Rate Constants of H at Various Temperatures
T (ÉC)	k₁, min^-1	Reference
0.0	0.0068	5
0.6	[0.0044]⁶	7
5	0.0124	5
10	0.0224	5
10	[0.0131]⁶	7
12.5	0.0215	8
14.5	0.028	9
15	0.0390	5
20	0.0696	5
20	0.044	8
20	[0.046]⁶	7
24.6	0.097	9
25	0.118	5
25	0.155 >	1
25	0.174	13
30	0.188	8
30	[0.20]⁶	7
36.8	0.385	9
37.5	[0.28]⁶	7
40	0.924	9
40	0.261	8
50	0.646	8

The accuracy of the rate constants in reference 7 have been questioned because of the experimental technique used by Hopkins.⁶ More recently, another group has questioned the validity of the rate constants in references 5, 8, and 9 because they were calculated assuming a single first-order reaction rather than consecutive first-order reactions.¹⁰ However, the activation energy, H^‡ = 18.5 kcal mole^-1, has been determined for H hydrolysis.¹¹ Using this value and the accepted rate constant at 25ÉC (0.155 min^Ç1) gives a calculated value of k₁ = 0.0089 min^Ç1 at 0ÉC, which is in reasonable accord with the experimental value of 0.0068 min^-1.

Hydrolysis in Sea Water

A group of U.S. Army researchers has also measured the half-life of H in sea water at several different temperatures.¹² these values are given in the accompanying table along with the corresponding rate constants.

Half-lives of H in sea water
T (ÉC)	sea water t_á (min)	k₁, calculated (min^-1)
5	175	0.0040
15	49	0.0141
25	15	0.046

These rates are considerably slower than the reaction rates discussed in the previous section because aqueous chloride ion affects the equilibrium between mustard and the intermediate sulfonium ion. The effect of chloride is to slow the observed rate of mustard hydrolysis by a factor equal to:

where F varies with the ionic strength according to the Bronsted-Bjerrum rate equation with a limiting value of F⁰_Cl- = 32.2 L mole^-1 at zero ionic strength:¹

which uses the constant from the Debye-H½ckel equation:

At 25ÉC, the value of the Debye-H½ckel A term is calculated as 0.50. The charges (z_R3S+ and z_Cl-) are +1 and -1, and the ionic strength of sea water, = 0.70, which gives a value of F_Cl- = 4.8 for sea water at 25ÉC. If the hydrolysis rate constant in fresh water is 0.155 min^-1 at 25ÉC and [Cl^-] = 0.55 mole L^-1 this gives a hydrolysis rate constant k₁ = 0.043 min^-1 in sea water. Although the ionic strength of sea water is above the level at which deviations from the Debye-H½ckel law are typically observed, the calculated rate constant corresponds to a half-life of 16.2 min, in close agreement with the measured value from reference 12.

References

Kinetics of Hydrolysis and Displacement reactions of b,b'-Dichlorodiethyl Sulfide (Mustard Gas) and of b-Chloro-b-hydroxydiethyl Sulfide (Mustard Chlorohydrin)

J. Am. Chem. Soc

1949

The identification of compounds in mustard hydrolysate (U)

Syracuse Research Corporation, LOGKOW version 1.50

J. Pharm. Sci

1995

The kinetics of hydrolysis of vesicants. Part II. 2,2'-dichlorodiethylsulphide (H)

Reactions of the chlorine atoms of mustard gas in aqueous media

On dichlorethylsulphide (mustard gas). III. Solubility and hydrolysis of dichlorethylsulphide with a new method for estimating small amounts of the same

J. Pharmacol

1919

Chemische Kampfstoffe XXIII. Hydrolyse von b,b'-Dichlor-diîthyl-sulfid

Helv. Chim. Acta

1941

Rate of liberation of Acid by b,b'-dichlorodiethyl sulfide and its analogues and its relation to the "acid" theory of skin vesication

Biochem. J.

1923

On the activation energy for the hydrolysis of bis(2-chloroethyl) sulfide

Thermochim. Acta

1984

On the activation energy for the hydrolysis of bis(2-chloroethyl) sulfide. II

Thermochim. Acta

1987

114

Summary report on a data base for predicting consequences of chemical disposal operations

Trans. Faraday Soc.

1948

Dissolution of Mustard

Despite the relative rapidity of the hydrolysis reaction, H has been found to persist in soil or even under water for periods of decades. In such incidents of long-term persistence, the common thread is the presence of bulk H. While the hydrolysis of dissolved H is relatively fast, the dissolution of H does not occur rapidly. A likely sequence for the fate of bulk H introduced into quiescent water would be the following:

H that initially dissolves from the droplet is hydrolyzed to TDG.
At the interface where little water is present, the intermediate sulfonium ion forms and then react with another molecule of H (rather than with water) to form 1,2-bis[(2-chloroethyl)thio]ethane (Q) and 1,2-dichloroethane:

In addition, Q is a byproduct of several methods of mustard agent manufacturing, including the Levinstein process used by the United States. Thus, under long term storage conditions of H, significant additional amounts of Q can accumulate in the container. Note that the presence of a certain level of Q was considered desirable because it is a powerful vesicant in its own right and depresses the freezing point of H. The solubility of Q is 0.3 g L^Ç1.¹

Due to lack of appreciable motion, a concentrated TDG layer builds up at the H droplet-water interface. The TDG at the interface also reacts with the intermediate sulfonium ion to form stable sulfonium salts of the type:²

In time, non-reactive sulfonium salts such as these and higher homologues (e.g., from the analogous reactions of Q) build up at the interface between the H droplet and the bulk aqueous phase. The sulfonium salts create a thicker boundary layer.
Dissolution of H slows, because the driving force for diffusion of H into the bulk aqueous phase decreases. Similarly, diffusion of water into the H droplet slows, which lowers the observed rate of hydrolysis. However, if the water is subject to disturbance, such as a heavy rain, or is rapidly flowing, it is less likely that H droplets would persist for significant periods.

Brookfield et al. first established the rate () at which H dissolves in quiescent water as a function of temperature:³

More recently, Demek et al. measured the rate of H dissolution as = 3.4 x 10^-7 gm cm^-2 sec^-1 at 4C, 0.15 knot current.⁴ Epstein et al. estimate that a one ton block of H would require 5 years to dissolve.⁵ If a cylinder of solid H with surface area of 4 x 10⁴ cm² is placed in a 0.15 knot current, H concentration drops within 1 foot to 0.3 ppm.⁶ Thus, in order to perform environmental fate assessments of H, both the hydrolysis and dissolution rate must be considered.

References

Manual of Military Chemistry, Volume 1. Chemistry of Chemical Warfare Agents

Kinetics and mechanism of the hydrolysis of 2Çchloroethyl sulfides

J. Org. Chem.

1988

53(14)

The rate of dissolution of 2,2'-dichlorodiethylsulphide (H) in distilled and natural waters

Behavior of chemical agents in seawater

Summary report on a data base for predicting consequences of chemical disposal operations

Results of the chemical survey at DWD Area A in 1972

Environmental Condition Report for Deep Water Dump Area A

Oxidation

H and a number of its hydrolysis products are oxidized to give the sulfoxide and sulfone analogs:

Noteworthy oxidants include oxygen (in air, significant in environmental degradation) and hypochlorite anion (significant in bleach-based decontamination); other oxidants include hydrogen peroxide, nitric acid, potassium permanganate, and chromic acid. The rates of these reactions increase as pH increases.¹ The sulfoxide and sulfone analogs of H are less toxic than the parent compound. H sulfone and H sulfoxide easily eliminates HCl to give divinylsulfone and divinylsulfoxide, respectively. With excess oxidant and heat, the sulfoxide and sulfone are further oxidized to CO₂, H₂O, chloride, and SO₂. Intermediates such as 2-chloroethanesulfonic acid have been isolated,² but the specific reaction mechanism for further oxidant is not readily apparent.

References

Final report on chemical lists for analyte selection

Manual of Military Chemistry, Volume 1. Chemistry of Chemical Warfare Agents

Photolysis

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

Thermolysis

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

Decontamination

Dissolved mustard is rapidly hydrolyzed, but dissolution into water is slow. The primary means of detoxification in aqueous solution is via oxidation. Hypochlorite bleaches were the earliest decontaminants used to detoxify mustard.¹ During World War II both common bleach (NaOCl^-) and superchlorinated bleaches (Ca(OCl^-)₂) were used. More stable N-chloro compounds such as chloramine have been used in more modern personal decontamination systems. In the 1950s a non-aqueous equipment decontamination solution "DS2" (2% NaOH, 70% diethylenetriamine, 28% ethylene glycol monomethyl ether) was developed in which the conjugate base of the glycol ether reacts rapidly with mustard via double elimination.

Reference

1. Yang, Y.-C.; Baker, J. A.; Ward, J. R., Decontamination of chemical warfare agents, Chem. Rev., 1992, 92, 1729-1743.