Organomercury chemistry

Structure and bonding

Most organomercury compounds feature diamagnetic Hg(II) and adopt a linear C-Hg-X structure. Indeed, no organic derivatives of Hg are known, as Hg requires electronegative subtituents for condensed-phase stability.

Hg(II) derivatives are neither Lewis basic or Lewis acidic. They are stable to oxygen and water, indicating the low polarity of the Hg-C bond.

Mercury forms a compound with two cyclopentadiene ligands, but the resulting complex may not be a metallocene. When made in the 1950s, it was too sensitive for structural determination.

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.

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.

From Hg

Metallic Hg reacts only slowly with methyl iodide to give dimethylmercury. With more electrophilic alkylating agents, the reaction is more efficient. Also, sodium amalgam 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: :

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: :

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 4chloro­mercuri­toluene to 4chloro­mercuri­benzoic acid.

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

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. is produced by Hg-catalyzed hydration of acetylene: : 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 in antiseptics such as thiomersal and merbromin, and fungicides such as ethylmercury chloride and phenylmercury acetate.

thumb|right|220px|Thiomersal (Merthiolate) is a well-established [[antiseptic]] and [[antifungal agent]].

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.

References

References

1. {{Greenwood&Earnshaw2nd
2. Thayer, John S.. (2010). "Relativistic Methods for Chemists". Springer Science+Business Media B.V..
3. (1956). "Cyclo­pentadienyl-triethyl­phosphine-copper(I) and bis-cyclopentadienyyl­mercury(II)". Journal of Inorganic and Nuclear Chemistry.
4. Hintermann, H.. (2010). "Organomercurials. Their Formation and Pathways in the Environment". RSC publishing.
5. Aschner, M.. (2010). "Toxicology of Alkylmercury Compounds". RSC publishing.
6. (August 25, 2020). "Thimerosal and Vaccines".
7. (1974). "Tetrakis(trifluoroacetoxymercuri)methane and Tetrakis(acetoxymercuri)methane as the Reaction Products of Hofmann's Base with the Corresponding Acid: X-ray Crystallographic Evidence". J. Chem. Soc., Chem. Commun..
8. Richard C. Larock. (1985). "Organomercury Compounds in Organic Synthesis". Springer.
9. {{cite encyclopedia. Robert H.. Crabtree. Wiley
10. (1925). "o-Chloromercuriphenol".
11. [[Otto Dimroth]]. (1898). "Directe Einführung von Quecksilber in aromatische Verbindungen". [[Berichte der deutschen chemischen Gesellschaft]].
12. (1955). "dl-Serine".
13. (January–April 1900). "Ueber das Verhalten von Mercurisalzen gegen Olefine". [[Berichte der deutschen chemischen Gesellschaft]].
14. (1980). "A re-investigation of o-phenylenemercurials(V) [1]: The crystal and molecular structure of monoclinic tribenzo[b,e,h] [1,4,7] trimercuronin". Inorganica Chimica Acta.
15. (1996). "Synthetic Methods of Organometallic and Inorganic Chemistry Volume 5, Copper, Silver, Gold, Zinc, Cadmium, and Mercury". Georg Thieme Verlag.
16. Calvery, H. O.. (1941). "Diphenylmercury".
17. Nesmajanow, A. N.. (1943). "β-Naphthylmercuric Chloride".
18. (1923). "''p''-Tolyl Chloride". Organic Syntheses.
19. (1927). "P-Chloromercuribenzoic ACID". Organic Syntheses.
20. "Reactivity control in palladium-catalyzed reactions: a personal account" Pavel Kocovsky J. Organometallic Chemistry 687 (2003) 256-268. {{doi. 10.1016/j.jorganchem.2003.07.008
21. Logan, T. J.. (1973). "Phenyl(trichloromethyl)mercury".
22. (1984). "Reactivity of the 5-hexenyl radical toward the anion of 2-nitropropane and borohydride anion". Pergamon.
23. (2006). "Ullmann's Encyclopedia of Industrial Chemistry".
24. (2000). "Ullmann's Encyclopedia of Industrial Chemistry".
25. GB Patent 238825A 'Process of Manufacture of Acetic Anhydride and Aldehyde'
26. (2011). "Ullmann's Encyclopedia of Industrial Chemistry".
27. (2012-03-15). "Organic Chemistry". OUP Oxford.
28. (1977). "Separation of Newly-Synthesized RNA by Organomercurial Agarose Affinity Chromatography". [[J. Biochem.]].