Organoarsenic chemistry

Organoarsenic chemistry is the chemistry of compounds containing a chemical bond between arsenic and carbon. A few organoarsenic compounds, also called "organoarsenicals," are produced industrially with uses as insecticides, herbicides, and fungicides. In general these applications are declining in step with growing concerns about their impact on the environment and human health. The parent compounds are arsane and arsenic acid. Despite the toxicity of arsenic, organoarsenic natural products are well known.

History

file:Cacodyl Structural Formula V.3.svg|140px|thumb|right|Cacodyl was one of the first organoarsenic compounds.
Surprising for an area now considered of minor importance, organoarsenic chemistry played a prominent role in chemistry's history. The oldest known organoarsenic compound, the foul smelling cacodyl was reported in "cacodyl" and is sometimes classified as the first synthetic organometallic compound. The compound Salvarsan was one of the first pharmaceuticals, earning a Nobel prize for Paul Ehrlich. Various other organoarsenic compounds formerly found use as antibiotics or other medical uses.

Synthesis and classification

Arsenic typically occurs in the oxidation states and, illustrated by the halides AsX₃ and AsF₅. Correspondingly, organoarsenic compounds are commonly found in these two oxidation states.
The hydroxyarsenic compounds are known:

arsonous acids, rare
arsinous acids, rare
arsinic acids, common, illustrated by cacodylic acid
arsonic acids, common, illustrated by phenylarsonic acid

Organoarsenic(V) compounds and uses

Arsenic compounds typically feature the functional groups RAsO₂ or R₂AsO. Cacodylic acid, central to arsenic chemistry, arises from the methylation of arsenic oxide. Phenylarsonic acids can be accessed by the reaction of arsenic acid with anilines, the so-called Bechamp reaction.
The monomethylated acid, methanearsonic acid, is a precursor to fungicides in the cultivation of rice and cotton. Derivatives of phenylarsonic acid are used as feed additives for livestock, including 4-hydroxy-3-nitrobenzenearsonic acid, ureidophenylarsonic acid and p-arsanilic acid. These applications are controversial as they introduce soluble forms of arsenic into the environment.
Compounds of arsenic containing only organic ligands are rare, the pre-eminent member being the pentaphenyl derivative As₅.

Organoarsenic(III) compounds and uses

Many organoarsenic compounds are prepared by alkylation of AsCl₃ and its derivatives using organolithium and Grignard reagents. For example, the series trimethylarsine, dimethylarsenic chloride, and methylarsenic dichloride is known. Reduction of the chloride derivatives with hydride reducing reagents affords the corresponding hydrides, such as dimethylarsine and methylarsine. Similar manipulations apply to other organoarsenic chloride compounds.
Akin to the Direct process in organosilicon chemistry, methyl halides react with elemental As, as illustrated in the following idealized equation:
Such reactions require copper catalysts, are conducted near 360 °C.
Another route to dimethylarsenic compounds begins with reduction of the As^V compound cacodylic acid:
A variety of heterocycles containing arsenic are known. These include arsole, the arsenic analogue of pyrrole, and arsabenzene, the arsenic analogue of pyridine.
Symmetrical organoarsenic compounds, e.g. trimethylarsine and triphenylarsine, are commonly used as ligands in coordination chemistry. They behave like phosphine ligands, but are less basic. The diarsine C₆H₄₂, known as diars, is a chelating ligand. Thorin is an indicator for several metals.

Lower-order organoarsenic compounds and uses

Per the double bond rule, compounds with As=As, As=C, and As≡C bonds are rare. They are observed in the gas phase but considerable steric protection is required to inhibit their conversion to oligomers as liquids or solids.
Oligomers with As-As bonds include the anti-syphylic drugs Salvarsan and Neosalvarsan. They are typically tricoordinate at As and have formal oxidation state As^I. Small substituents, such as in , equilibrate between three-, four-, and five-membered rings, but bulkier substituents usually settle on a four-membered configuration. Synthesis is typically by reductive dehalogenation with a metal.

Reactions

Protic arsines oxidize to oligomers. For example, methylarsine oxidizes first to cyclo-methylarsine:
These compounds have structures similar to the phosphorus sulfides.
Arsenic-arsenic bonds are very weak, and oligomeric arsenic compounds are even more liable to oxidize than their hydrogenated precursors. The following reaction can, however, be prepared through electrochemical reduction in a zinc-sulfate cell. Oxidation first forms polymeric arsinoxides, e.g.:
Further oxidation then depolymerizes them to arsinous acids.
Arsine compounds add to multiple bonds as nucleophiles, but arsine rings may instead insert the bond into the ring. In general, arsines are less Brønsted basic than phosphines.
Arsine ylides are generally less stable than phosphine ylides, decomposing spontaneously in the absence of a vicinal carbonyl. Stabilized ylides olefinate to a mixture of stereoisomers, whereas unstabilized ylides tend to epoxidate. With enones, they either olefinate or cyclopropanate. With nitroso compounds, they either form imines or nitrones.

Chemical warfare

Organoarsenic compounds, especially those featuring As-Cl bonds, have been used as chemical weapons, especially during World War I. Infamous examples include "Lewisite" and "Clark I". "phenyl dick" is another one.

In nature

As arsenic is toxic to most life forms and it occurs in elevated concentration in some areas several detoxification strategies have evolved. Inorganic arsenic and its compounds, upon entering the food chain, are progressively metabolized to a less toxic form of arsenic through a process of methylation. Organoarsenic compounds arise via biomethylation of inorganic arsenic compounds, via processes mediated by enzymes related to vitamin B₁₂. For example, the mold Scopulariopsis brevicaulis produces significant amounts of trimethylarsine if inorganic arsenic is present. Biomethylation of arsenic compounds starts with the formation of methanearsonates. Thus, trivalent inorganic arsenic compounds are methylated to give methanearsonate. S-adenosylmethionine is the methyl donor. The methanearsonates are the precursors to dimethylarsonates, again by the cycle of reduction followed by a second methylation. This dimethyl compound is cacodylic acid
The organic compound arsenobetaine, a betaine, is found in some marine foods such as fish and algae, and also in mushrooms in larger concentrations. The average person's intake is about 10-50 μg/day. Values about 1000 μg are not unusual following consumption of fish or mushrooms. But there is little danger in eating fish because this arsenic compound is nearly non-toxic. Arsenobetaine was first identified in the Western rock lobster
So-called arsenosugars have been isolated from seaweeds. Arsenic containing lipids are also known. Although arsenic and its compounds are toxic for humans, one of the first synthetic antibiotics was Salvarsan, the use of which has long been discontinued.
The only polyarsenic compound isolated from a natural source is arsenicin A, found in the New Caledonian marine sponge Echinochalina bargibanti.
Organoarsenic compounds may pose significant health hazards, depending on their speciation. Arsenous acid has an LD50 of 34.5 mg/kg whereas for the betaine ₃As⁺CH₂CO₂⁻ the LD50 exceeds 10 g/kg.

Representative compounds

Some illustrative organoarsenic compound are listed in the table below:

Name	Substituents	Structure	Molar mass	CAS number	Properties	Use
10,10'-oxybis-10H-Phenoxarsine	Aryl		502.2318	58-36-6		obsolete plastic additive
Triphenylarsine	Phenyl		306.23	603-32-7	Melts 58-61 °C	Ligand in coordination chemistry, reagent in organic synthesis
Phenyldichloroarsine	Phenyl, chlorine		222.93	696-28-6		Chemical weapon
Roxarsone	Phenyl, oxygen		263.04	121-19-7		Animal medicine and feed additive along with nitarsone, arsanilic acid, and carbarsone.
Arsenobetaine	Methyl			64436-13-1		Natural product, most common form of arsenic in fish, low toxicity
Arsenicin A	Methyl, oxygen		389.76	925705-41-5	Melts	Cytotoxic natural product