Organomercury chemistry

Synthesis

Reflecting the strength of the C−Hg bond, organomercury compounds are generated by many methods. Indeed, mercury adsorbs onto laboratory glassware, such that laboratories performing mercury experiments may have difficulty avoiding C−Hg bond formation. In some regards, organomercury chemistry more closely resembles organopalladium chemistry and contrasts with organocadmium compounds.

Synthesis from elemental mercury

Metallic mercury reacts only slowly with methyl iodide to give dimethylmercury. With more electrophilic alkylating agents, the reaction is more efficient. Also, sodium amalgams react with organic halides to give diorganomercury compounds.

Mercuration of aromatic rings

Electron-rich arenes, such as phenol, undergo mercuration upon treatment with Hg(O₂CCH₃)₂. The one acetate group that remains on the mercury atom can be displaced by chloride:

C₆H₅OH + Hg(O₂CCH₃)₂ → C₆H₄(OH)–HgO₂CCH₃ + CH₃CO₂H

C₆H₄(OH)–HgO₂CCH₃ + NaCl → C₆H₄(OH)–HgCl + NaO₂CCH₃

The first such reaction, including a mercuration of benzene itself, was first reported by Otto Dimroth in 1898.

Addition to alkenes and alkynes

The Hg²⁺ center binds to alkenes, inducing the addition of hydroxide and alkoxide. For example, treatment of methyl acrylate with mercuric acetate in methanol gives an α-mercuri ester:

Hg(O₂CCH₃)₂ + CH₂=CHCO₂CH₃ → CH₃OCH₂CH(HgO₂CCH₃)CO₂CH₃

The resulting Hg−C bond can be cleaved with bromine to give the corresponding alkyl bromide:

CH₃OCH₂CH(HgO₂CCH₃)CO₂CH₃ + Br₂ → CH₃OCH₂CHBrCO₂CH₃ + BrHgO₂CCH₃

This reaction is called the Hofmann–Sand reaction.

Internal alkynes undergo mercuration with incorporation of solvent:

RC≡CR + Hg(OAc)₂ + ROH → R(AcOHg)C=CR(OR) + HOAc

Reaction of Hg(II) compounds with C-heteroatom bonds

A general synthetic route to organomercury compounds entails alkylation with Grignard reagents and organolithium compounds. Diethylmercury results from the reaction of mercury chloride with two equivalents of ethylmagnesium bromide, a conversion typically conducted in diethyl ether solution.

Similarly, diphenylmercury can be prepared by reaction of mercury chloride and phenylmagnesium bromide. A related preparation entails formation of phenylsodium in the presence of mercury(II) salts.

Hg(II) can be alkylated by treatment with diazonium salts in the presence of copper metal. In this way 2-chloromercuri-naphthalene has been prepared.

4-Chloromercuritoluene is obtained by the chloromercuration of sodium toluenesulfinite:

CH₃C₆H₄SO₂Na + HgCl₂ → CH₃C₆H₄HgCl + SO₂ + NaCl

Reactions

Organomercury compounds are versatile synthetic intermediates due to the well-controlled conditions under which Hg−C bonds cleave. The bond is remarkably resilient, as when potassium permanganate oxidizes 4‑chloro­mercuri­toluene to 4‑chloro­mercuri­benzoic acid.

Nevertheless, organomercurials are used in transmetalation reactions. For example diphenylmercury reacts with aluminium to give triphenyl aluminium:

3 (C₆H₅)₂Hg + 2 Al → Al(C₆H₅)₃ + 3 Hg

Organomercury compounds react with halogens to give the corresponding organic halide, and palladium catalyzes cross-coupling between organomercurials and organic halides. This approach usually forms C−C bonds with low selectivity, but selectivity increases in the presence of halide salts. Carbonylation of lactones has been shown to employ Hg(II) reagents under palladium catalyzed conditions. (C−C bond formation and cis ester formation).

Phenylmercuric chloride reversibly stores dichlorocarbene as phenyl(trichloromethyl)mercury. A convenient carbene source is sodium trichloroacetate:

C₆H₅HgCl + CCl₂ → C₆H₅HgCCl₃,

reversed with heat.

Organomercury halides react with hydride sources to give organomercury hydrides. Those compounds have an exceptionally weak C−Hg bond, and readily cleave to alkyl radicals.

Applications

The toxicity of organomercury compounds notwithstanding, organomercury compounds have often proved useful catalysts.

Hydration and related reactions of acetylene

Several Hg-catalyzed conversions of acetylene have been commercialized by Hoechst AG, BASF, and Chisso. Acetaldehyde is produced by Hg-catalyzed hydration of acetylene:

C₂H₂ + H₂O → CH₃CHO

The mishandling Hg-containing waste stream of the Chisso process led to an environmental catastrophe causing Minamata disease.

Ethylidene diacetate, a precursor to acetaldehyde and vinyl acetate, was also produced by a similar process. Some of these routes, once dominant, have been significantly displaced by the Pd-catalyzed Wacker process, a greener process that starts with ethylene. In general oxymercuration reactions of alkenes and alkynes using mercuric compounds proceed via organomercury intermediates. A related reaction forming phenols is the Wolffenstein–Böters reaction.

Production of chlorocarbons

Mercury-based catalysis is woven throughout the history of chlorinated ethanes and ethylenes. Vinyl chloride is produced by the addition of HCl to acetylene using a mercury-carbon catalyst. Considerable effort is required to limit the contamination of the product with mercury.

Medicinal

The toxicity is useful when applied at ultra-low concentrations, such in antiseptics like thiomersal and merbromin, and fungicides such as ethylmercury chloride and phenylmercury acetate.

Mercurial diuretics such as mersalyl acid were once in common use, but have been superseded by the thiazides and loop diuretics, which are safer and longer-acting, as well as being orally active.

Thiol affinity chromatography

Thiols are also known as mercaptans due to their propensity for mercury capture. Thiolates (R-S⁻) and thioketones (R₂C=S), being soft nucleophiles, form strong coordination complexes with mercury(II), a soft electrophile. This mode of action makes them useful for affinity chromatography to separate thiol-containing compounds from complex mixtures. For example, organomercurial agarose gel or gel beads are used to isolate thiolated compounds (such as thiouridine) in a biological sample.

Toxicity

The toxicity of organomercury compounds presents both dangers and benefits. Dimethylmercury in particular is notoriously toxic, but found use as an antifungal agent and insecticide. Merbromin and phenylmercuric borate are used as topical antiseptics, while thimerosal is safely used as a preservative for vaccines and antitoxins.