Chemistry of Other Lethal Chemical Agents 

Here are presented a number of lethal chemical agents for which only basic physical properties and relatively general information. These are chemicals which are either obsolete for chemical warfare or are used widely in medicine or industry, and are thus amply reviewed elsewhere.

Chlorine

Although it was the first lethal chemical used in modern chemical warfare, chlorine is now considered obsolete as a chemical warfare agent (chlorine is not listed as a scheduled chemical in the Chemical Weapons Convention). It is a major chemical feeds stock, produced predominantly by the electrolysis of brine in the chloralkali industry, Chlorine is used in bleaching, water disinfection, and in the manufacture of chlorinated hydrocarbons, synthetic rubbers, and plastics. More information on the industrial uses of chlorine can be found at http://www.cl2.com/ and http://www.c3.org/. Information on the toxicity, handling, and safety of chlorine can be found at the New Jersey Department of Health and Senior Services site (document in .pdf format requires Adobe Acrobat reader).

CyanogenChloride

Cyanogen chloride hydrolyzes, initially to hydrogen chloride and unstable cyanic acid; the cyanic acid decomposes to carbon dioxide and ammonia. Cyanogen chloride is used in specialty chemical synthesis; it is listed on Schedule 3 of the Chemical Weapons Convention. Noblis recently published a review of melting point, boiling point, vapor pressure, density, water solubility, hydrolysis rates, and partitioning data for cyanogen chloride.

HN-1

HN-1 is listed on Schedule 1 of the Chemical Weapons Convention. HN-1 undergoes dimerization five times more slowly than HN-2.

All nitrogen mustards react initially via cyclization to the corresponding iminium ion. The rate of this reaction is pH dependant because the protonated form of the amine cannot cyclize. The iminium ion then reacts with water in a slower reaction. At pH 8, the nitrogen mustards are essentially quantitatively converted to the iminium ion for subsequent slow reaction with water. In contrast, at pH 4 cyclization and hydrolysis show the classic form of reactions in series.

The U.S. Army Center for Health Promotion and Preventive Medicine has prepared a fact sheet about nitrogen mustard HN-1 (document in .pdf format requires Adobe Acrobat reader). Noblis recently published a review of data for melting point, boiling point, vapor pressure, density, water solubility, Henry’s Law constant, and hydrolysis rates for HN-1.

HN-2 

HN-2 combines with acid to form the corresponding ammonium salt. The hydrochloride salt of HN-2 is used therapeutically as an antineoplastic; a search of Medline produced 2,756 citations for HN-2.

All nitrogen mustards react initially via cyclization to the corresponding iminium ion. The rate of this reaction is pH dependant because the protonated form of the amine cannot cyclize. The iminium ion then reacts with water in a slower reaction. At pH 8, the nitrogen mustards are essentially quantitatively converted to the iminium ion for subsequent slow reaction with water. In contrast, at pH 4 cyclization and hydrolysis show the classic form of reactions in series.

The U.S. Army Center for Health Promotion and Preventive Medicine has prepared a fact sheet about nitrogen mustard HN-2 (document in .pdf format requires Adobe Acrobat reader).

Although HN-2 is listed on Schedule 1 of the Chemical Weapons Convention, it is less suited to use as a chemical agent than is HN-1 or HN-3 because HN-2 tends to dimerize upon storage. HN-1 undergoes the analogous reaction five times more slowly than HN-2, and HN-3 is very much slower than HN-2; HN-1 and HN-3 are thus sufficiently stable towards dimerization for use in chemical weapons.

HN-3

The hydrolysis of HN-3 is reviewed in the following references:

• Crane, C. W.; Rydon, H. N., The Chemistry of 2-Chloroalkylamines. Part III. The Dimerisation and Hydrolysis of 2:2':2''-Trichlorotriethylamine, J. Chem. Soc., 1947, 527-530.
• Golumbic, C.; Stahmann, M. A.; Bergmann, M., Chemical Reactions of the Nitrogen Mustard Gases. IV. The Transformations of Tris(ß-Chloroethyl)-Amine in Water, J. Org Chem., 1946, 11, 550.
• Sartori, M. F., New Developments in the Chemistry of War Gases, Chem. Rev., 1951, 48, 225–257.

All nitrogen mustards react initially via cyclization to the corresponding iminium ion. The rate of this reaction is pH dependant because the protonated form of the amine cannot cyclize. The iminium ion then reacts with water in a slower reaction. At pH 8, the nitrogen mustards are essentially quantitatively converted to the iminium ion for subsequent slow reaction with water. In contrast, at pH 4 cyclization and hydrolysis show the classic form of reactions in series.

HN-3 undergoes dimerization to give a tetrachloroethylpiperazine salt very much more slowly than HN-2 undergoes the analogous reaction.

HN-3 combines with acid to form the corresponding ammonium salt. HN-3 hydrochloride is used therapeutically as an antineoplastic. Some relevant leading references include:

• Trichlormethine(trimustine hydrochloride), IARC Monogr. Eval. Carcinog .Risks Hum.,1990, 50, 143-149.
• Einhorn, J., Nitrogen mustard: the origin of chemotherapy for cancer, Int. J. Radiat. Oncol. Biol. Phys., 1985, 11(7), 1375-1378.
• Goodman, L. S.; Wintrobe, M. M.; Dameshek, W.; Goodman, M. J.; Gilman, A.; McLennan, M. T., Landmark article Sept. 21, 1946: Nitrogen mustard therapy. Use of methyl-bis(beta-chloroethyl)amine hydrochloride and tris(beta-chloroethyl)amine hydrochloride for Hodgkin's disease, lymphosarcoma, leukemia and certain allied and miscellaneous disorders. J. Am. Med. Assoc., 1984, 251(17), 2255-2261.
• Trichlorotriethylaminehydrochloride, IARC Monogr. Eval. Carcinog Risk Chem.Man., 1975, 9, 229-234.

HN-3 is listed on Schedule 1 of the Chemical Weapons Convention.

The U.S. Army Center for Health Promotion and Preventive Medicine has prepared a fact sheet about nitrogen mustard HN-3 (document in .pdf format requires Adobe Acrobat reader).

Hydrogen Cyanide

Hydrogen cyanide hydrolyzes, initially to formamide, and subsequently to ammonium formate. Upon prolonged standing, it can polymerize explosively. Hydrogen cyanide is used commercially as a rodenticide and insecticide for fumigating enclosed spaces. Hydrogen cyanide is used in the manufacture of the following:

• adiponitrile (for nylon plastics)
• sodium cyanide (for extracting gold from ore, silver from use film, and other chemical manufacturing)
• ferrocyanides
• pharmaceuticals, and specialty chemicals

Phosgene

Phosgene hydrolyzes rapidly; the half-life in water is 0.4-1 s at 2 deg C and 0.1-0.2 s at 25 deg C. Phosgene is used as a chemical intermediate, notably in the production of the following:

• compact discs, lightweight eyeglasses, and shatterproof glass are made from polycarbonate resins in which phosgene is a monomer
• foams, paints, fibers, adhesives, and spandex are made from polyurethanes, in which the diisocyanate monomers are made using phosgene
• isocyanate intermediates for manufacture of pharmaceuticals and agricultural chemicals

Information on the toxicity, handling, and safety of phosgene can be found at the New Jersey Department of Health and Senior Services, the U.S. Army Center for Health Promotion and Preventive Medicine, and the eMedicine web sites (both documents in .pdf format requires Adobe Acrobat reader). Phosgene is listed on Schedule 3 of the Chemical Weapons Convention. Noblis recently published a review of melting point, boiling point, vapor pressure, density, Henry’s Law constant, hydrolysis rates, and partitioning data for phosgene.

Diphosgene

Diphosgene undergoes slow hydrolysis.

Triphosgene

Triphosgene undergoes hydrolysis more slowly than diphosgene.

Phosgene Oxime

Phosgene oxime has been the subject of German and Russian interest prior to and during World War II. It is slowly hydrolyzed by water, and is rapidly hydrolyzed in basic solution. The U.S. Army Center for Health Promotion and Preventive Medicine has prepared a fact sheet about phosgene oxime (document in .pdf format requires Adobe Acrobat reader).

Perfluoroisobutylene

Mixtures

In addition to filling weapons with individual chemical agents, the United States has filled weapons with mixtures of the following of agents:

• PD - lethal agent phosgene (CG) and irritant diphenylcyanoarsine (DC)
• PG - lethal agent phosgene (CG) and tear gas chloropicrin (PS)
• CNS - tear gases chloroaceophenone (CN) and chloropicrin (PS) with chloroform as a solvent and diluent
• NC - tear gas chloropicrin (PS) and smoke tin tetrachloride (KF)

The weapons that contained these mixtures are no longer part of the US chemical weapons stockpile.

Tin Tetrachloride

References

1. The Merck Index, 11 ed., Budavari, S.; O'Niel, M. J.; Smith, A.; Heckelmanm, P. E., Eds., Merck & Co.: Rahway, 1989.
   
2. Francke, 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.
3. Cohen, B., Kinetics of reactions of sulfur and nitrogen mustards, in Chemical warfare agents and related chemical problems, parts III-VI, Vol. II, Summary Technical Report of the National Defense Research Committee Division 9, Office of Scientific Research and Development: Washington, DC, 1946, p. 418. NTIC no. AD-234249.
4. Bizzigotti, G. O.; Castelly, H.; Hafez, A. M.; Smith, W. H. B.; Whitmire, M. T., Parameters for Evaluation of the Fate, Transport, and Environmental Impacts of Chemical Agents in Marine Environments, Chem. Rev., 2009, in press.