Organomercury chemistry

Organomercury compounds contain at least one carbon bonded to a mercury atom, shown here.

Organomercury chemistry refers to the study of organometallic compounds that contain mercury. Typically the Hg–C bond is stable toward air and moisture but sensitive to light. Important organomercury compounds are the methylmercury(II) cation, CH₃Hg⁺; ethylmercury(II) cation, C₂H₅Hg⁺; dimethylmercury, (CH₃)₂Hg, diethylmercury and merbromin ("Mercurochrome"). Thiomersal is used as a preservative for vaccines and intravenous drugs.

The toxicity of organomercury compounds^[1]^[2] 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.^[3]

Synthesis

Organomercury compounds are generated by many methods, including the direct reaction of hydrocarbons and mercury(II) salts. In this regard, organomercury chemistry more closely resembles organopalladium chemistry and contrasts with organocadmium 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:^[4]

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 reported by Otto Dimroth between 1898 and 1902.^[5]^[6]^[7]

Addition to alkenes

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:^[8]

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.^[9]

Reaction of Hg(II) compounds with carbanion equivalents

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 that would typically be conducted in diethyl ether solution.^[10] The resulting (CH₃CH₂)₂Hg is a dense liquid (2.466 g/cm³) that boils at 57 °C at 16 torr. The compound is slightly soluble in ethanol and soluble in ether.

Similarly, diphenylmercury (melting point 121–123 °C) 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.^[11]

Other methods

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.^[12]

Phenyl(trichloromethyl)mercury can be prepared by generating dichlorocarbene in the presence of phenylmercuric chloride. A convenient carbene source is sodium trichloroacetate.^[13] This compound on heating releases dichlorocarbene:

C₆H₅HgCCl₃ → C₆H₅HgCl + CCl₂

Reactions

Organomercury compounds are versatile synthetic intermediates due to the well controlled conditions under which they undergo cleavage of the Hg-C bonds. Diphenylmercury is a source of the phenyl radical in certain syntheses. Treatment with aluminium gives triphenyl aluminium:

3 Ph₂Hg + 2 Al → (AlPh₃)₂ + 3 Hg

As indicated above, organomercury compounds react with halogens to give the corresponding organic halide. Organomercurials are commonly used in transmetalation reactions with lanthanides and alkaline-earth metals.

Cross coupling of organomercurials with organic halides is catalyzed by palladium, which provides a method for C-C bond formation. Usually of low selectivity, but if done in the presence of halides, selectivity increases. Carbonylation of lactones has been shown to employ Hg(II) reagents under palladium catalyzed conditions. (C-C bond formation and Cis ester formation).^[14]

Applications

Due to their toxicity and low nucleophilicity, organomercury compounds find limited use. The oxymercuration reaction of alkenes to alcohols using mercuric acetate proceeds via organomercury intermediates. A related reaction forming phenols is the Wolffenstein–Böters reaction. The toxicity is useful in antiseptics such as thiomersal and merbromin, and fungicides such as ethylmercury chloride and phenylmercury acetate.

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.^[15] 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.^[16]

References

^ Hintermann, H. (2010). Organomercurials. Their Formation and Pathways in the Environment. Metal Ions in Life Sciences. Vol. 7. Cambridge: RSC publishing. pp. 365–401. ISBN 978-1-84755-177-1.
^ Aschner, M.; Onishchenko, N.; Ceccatelli, S. (2010). Toxicology of Alkylmercury Compounds. Metal Ions in Life Sciences. Vol. 7. Cambridge: RSC publishing. pp. 403–434. doi:10.1515/9783110436600-017. ISBN 978-1-84755-177-1. PMID 20877814.
^ "Thimerosal and Vaccines". Centers for Disease Control and Prevention. August 25, 2020. Retrieved April 15, 2024.
^ Whitmore FC, Hanson ER (1925). "o-Chloromercuriphenol". Organic Syntheses. 4: 13. doi:10.15227/orgsyn.004.0013.
^ Otto Dimroth (1898). "Directe Einführung von Quecksilber in aromatische Verbindungen". Berichte der deutschen chemischen Gesellschaft. 31 (2): 2154–2156. doi:10.1002/cber.189803102162.
^ Otto Dimroth (1899). "Ueber die Einwirkung von Quecksilberoxydsalzen auf aromatische Verbindungen". Berichte der deutschen chemischen Gesellschaft. 32 (1): 758–765. doi:10.1002/cber.189903201116.
^ Otto Dimroth (1902). "Ueber die Mercurirung aromatischer Verbindungen". Berichte der deutschen chemischen Gesellschaft. 35 (2): 2032–2045. doi:10.1002/cber.190203502154.
^ Carter HE, West HD (1955). "dl-Serine". Organic Syntheses; Collected Volumes, vol. 3, p. 774.
^ Hofmann, K. A.; Sand, J. (January–April 1900). "Ueber das Verhalten von Mercurisalzen gegen Olefine". Berichte der deutschen chemischen Gesellschaft. 33 (1): 1340–1353. doi:10.1002/cber.190003301231.
^ W.A. Herrmann, ed. (1996). Synthetic Methods of Organometallic and Inorganic Chemistry Volume 5, Copper, Silver, Gold, Zinc, Cadmium, and Mercury. Georg Thieme Verlag. ISBN 3-13-103061-5.
^ Calvery, H. O. (1941). "Diphenylmercury". Organic Syntheses; Collected Volumes, vol. 1, p. 228.
^ Nesmajanow, A. N. (1943). "β-Naphthylmercuric Chloride". Organic Syntheses; Collected Volumes, vol. 2, p. 432.
^ Logan, T. J. (1973). "Phenyl(trichloromethyl)mercury". Organic Syntheses; Collected Volumes, vol. 5, p. 969.
^ "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
^ Jonathan Clayden; Nick Greeves; Stuart Warren (2012-03-15). Organic Chemistry. OUP Oxford. p. 658. ISBN 978-0-19-927029-3.
^ Masao Ono & Masaya Kawakami (1977). "Separation of Newly-Synthesized RNA by Organomercurial Agarose Affinity Chromatography". J. Biochem. 81 (5): 1247–1252. PMID 19428.

External links

"1967 Evaluations of some Pesticide Residues in Food: Organomercury compounds". International Programme on Chemical Safety.
"Organomercury Compounds". Comparative Toxicogenomics Database. Mount Desert Island Biological Laboratory.
Safety data for a typical organomercury compound: "Safety data sheet for phenylmercuric acetate". Merck. 2022-07-22. Retrieved 2022-08-19.

[1] Hintermann, H. (2010). Organomercurials. Their Formation and Pathways in the Environment. Metal Ions in Life Sciences. Vol. 7. Cambridge: RSC publishing. pp. 365–401. ISBN 978-1-84755-177-1.

[2] Aschner, M.; Onishchenko, N.; Ceccatelli, S. (2010). Toxicology of Alkylmercury Compounds. Metal Ions in Life Sciences. Vol. 7. Cambridge: RSC publishing. pp. 403–434. doi:10.1515/9783110436600-017. ISBN 978-1-84755-177-1. PMID 20877814.

[3] "Thimerosal and Vaccines". Centers for Disease Control and Prevention. August 25, 2020. Retrieved April 15, 2024.

[4] Whitmore FC, Hanson ER (1925). "o-Chloromercuriphenol". Organic Syntheses. 4: 13. doi:10.15227/orgsyn.004.0013.

[5] Otto Dimroth (1898). "Directe Einführung von Quecksilber in aromatische Verbindungen". Berichte der deutschen chemischen Gesellschaft. 31 (2): 2154–2156. doi:10.1002/cber.189803102162.

[6] Otto Dimroth (1899). "Ueber die Einwirkung von Quecksilberoxydsalzen auf aromatische Verbindungen". Berichte der deutschen chemischen Gesellschaft. 32 (1): 758–765. doi:10.1002/cber.189903201116.

[7] Otto Dimroth (1902). "Ueber die Mercurirung aromatischer Verbindungen". Berichte der deutschen chemischen Gesellschaft. 35 (2): 2032–2045. doi:10.1002/cber.190203502154.

[8] Carter HE, West HD (1955). "dl-Serine". Organic Syntheses; Collected Volumes, vol. 3, p. 774.

[9] Hofmann, K. A.; Sand, J. (January–April 1900). "Ueber das Verhalten von Mercurisalzen gegen Olefine". Berichte der deutschen chemischen Gesellschaft. 33 (1): 1340–1353. doi:10.1002/cber.190003301231.

[10] W.A. Herrmann, ed. (1996). Synthetic Methods of Organometallic and Inorganic Chemistry Volume 5, Copper, Silver, Gold, Zinc, Cadmium, and Mercury. Georg Thieme Verlag. ISBN 3-13-103061-5.

[11] Calvery, H. O. (1941). "Diphenylmercury". Organic Syntheses; Collected Volumes, vol. 1, p. 228.

[12] Nesmajanow, A. N. (1943). "β-Naphthylmercuric Chloride". Organic Syntheses; Collected Volumes, vol. 2, p. 432.

[13] Logan, T. J. (1973). "Phenyl(trichloromethyl)mercury". Organic Syntheses; Collected Volumes, vol. 5, p. 969.

[14] "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

[15] Jonathan Clayden; Nick Greeves; Stuart Warren (2012-03-15). Organic Chemistry. OUP Oxford. p. 658. ISBN 978-0-19-927029-3.

[16] Masao Ono & Masaya Kawakami (1977). "Separation of Newly-Synthesized RNA by Organomercurial Agarose Affinity Chromatography". J. Biochem. 81 (5): 1247–1252. PMID 19428.

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