Organomercury chemistry

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Organomercury compounds contain at least one carbon bonded to a mercury atom, shown here. Organomercury-Logo.svg
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. Many organomercury compounds are highly toxic, but some are used in medicine, e.g., merbromin ("Mercurochrome") and the vaccine preservative thiomersal. [1]

Contents

Structure and bonding

Most organomercury compounds feature Hg(II), which is diamagnetic. They almost all adopt a linear C-Hg-X structure. They are neither Lewis basic or Lewis acidic. They are stable to oxygen and water, indicating the low polarity of the Hg-C bond.

Toxicity

The toxicity of organomercury compounds [2] [3] 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. [4]

Synthesis

Tetrakis(acetoxymercurio)methane C(HgOAc)4.svg
Tetrakis(acetoxymercurio)methane

In part reflecting the strength of the C-Hg bond, organomercury compounds are generated by many methods. [6] Indeed, mercury may adsorb onto laboratory glassware, such that laboratories performing mercury experiments may have difficulty avoiding C–Hg bond formation. [7]

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. [6]

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: [8]

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. [9]

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: [10]

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. [11]

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

(C6H4Hg)3, a planar molecule, is the product of the reaction of sodium amalgam and 1,2-dihalobenzenes. CSD CIF TBTMER01.png
(C6H4Hg)3, a planar molecule, is the product of the reaction of sodium amalgam and 1,2-dihalobenzenes.

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. [13] The resulting (CH3CH2)2Hg is a dense liquid (2.466 g/cm3) that boils at 57 °C at 16 torr. This extremely toxic 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. [14]

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. [15]

4-Chloromercuritoluene is obtained by the chloromercuration of sodium toluenesulfinite: [16]

CH3C6H4SO2Na + HgCl2 → CH3C6H4HgCl + SO2 + NaCl

Reactions

Organomercury compounds are versatile synthetic intermediates due to the well-controlled conditions under which Hg-C bonds undergo cleave.

Organomercurials are used in transmetalation reactions. For example diphenylmercury reacts with aluminium gives triphenyl aluminium:

3 (C6H5)2Hg + 2 Al → Al(C6H5)3)2 + 3 Hg

As indicated above, organomercury compounds react with halogens to give the corresponding organic halide. Phenyl(trichloromethyl)mercury can be prepared by generating dichlorocarbene in the presence of phenylmercuric chloride. A convenient carbene source is sodium trichloroacetate. [17] This compound on heating releases dichlorocarbene:

C6H5HgCCl3 → C6H5HgCl + CCl2

Cross coupling of organomercurials with organic halides is catalyzed by palladium. This approach 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). [18]

One remarkable feature of organomercury compounds is the resilience of the C-Hg bond. This property is illustrated by the preparation of 4-chloromercuribenzoic acid by oxidation of 4-chloromercuritoluene using potassium permanganate. [19]

Organomercury halides react with hydride sources to give organomercury hydrides. Exceptionally, those compounds have a weak C–Hg bond, and readily cleave to alkyl radicals. [20]

Applications

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

Several Hg-catalyzed conversions of acetylene have been commercialized by Hoechst AG, BASF, and Chisso. Acetaldehyde is produced by hydration of acetylene: [21]

C2H2 + H2O → CH3CHO

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

Ethylidene diacetate, a precursor to acetaldehyde, was also produced by a similar process. 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. [22]

Medicinal

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. Thiomersal.svg
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. [23] 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. [24]

See also

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References

  1. ↑ Greenwood, Norman N.; Earnshaw, Alan (1997). Chemistry of the Elements (2nd ed.). Butterworth-Heinemann. ISBN   978-0-08-037941-8.
  2. ↑ 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.
  3. ↑ 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.
  4. ↑ "Thimerosal and Vaccines". Centers for Disease Control and Prevention. August 25, 2020. Retrieved April 15, 2024.
  5. ↑ Grdenić, Drago; Kamenar, Boris; Korpar-Čolig, Branka; Sikirca, Milan; Jovanovski, Gligor (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. (16): 646–647. doi:10.1039/C39740000646.
  6. 1 2 Richard C. Larock (1985). Organomercury Compounds in Organic Synthesis. Springer. doi:10.1007/978-3-642-70004-0.
  7. ↑ Crabtree, Robert H. "Mercury". Encyclopedia of Reagents for Organic Synthesis. Wiley. doi:10.1002/047084289X.rm027.pub2.
  8. ↑ Whitmore FC, Hanson ER (1925). "o-Chloromercuriphenol". Organic Syntheses . 4: 13. doi:10.15227/orgsyn.004.0013 .
  9. ↑ Otto Dimroth (1898). "Directe Einführung von Quecksilber in aromatische Verbindungen". Berichte der deutschen chemischen Gesellschaft . 31 (2): 2154–2156. doi:10.1002/cber.189803102162.
  10. ↑ Carter HE, West HD (1955). "dl-Serine". Organic Syntheses ; Collected Volumes, vol. 3, p. 774.
  11. ↑ 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.
  12. ↑ Brown, David S.; Massey, Alan G.; Wickens, Denys A. (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. 44: L193 –L194. doi:10.1016/S0020-1693(00)91002-8.
  13. ↑ 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.
  14. ↑ Calvery, H. O. (1941). "Diphenylmercury". Organic Syntheses ; Collected Volumes, vol. 1, p. 228.
  15. ↑ Nesmajanow, A. N. (1943). "β-Naphthylmercuric Chloride". Organic Syntheses ; Collected Volumes, vol. 2, p. 432.
  16. ↑ Whitmore, Frank C.; Hamilton, Frances H.; Thurman, N. (1923). "p-Tolyl Chloride". Organic Syntheses. 3: 99. doi:10.15227/orgsyn.003.0099.
  17. ↑ Logan, T. J. (1973). "Phenyl(trichloromethyl)mercury". Organic Syntheses ; Collected Volumes, vol. 5, p. 969.
  18. ↑ "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
  19. ↑ Whitmore, Frank C.; Hamilton, Frances H.; Thurman, N. (1927). "P-Chloromercuribenzoic ACID". Organic Syntheses. 7: 18. doi:10.15227/orgsyn.007.0018.
  20. ↑ Russell, Glen A.; Guo Deliang (1984) [9 May 1984]. "Reactivity of the 5-hexenyl radical toward the anion of 2-nitropropane and borohydride anion". Tetrahedron Letters. 25 (46). Great Britain: Pergamon: 5239–5242. doi:10.1016/S0040-4039(01)81573-2.
  21. ↑ Eckert, Marc; Fleischmann, Gerald; Jira, Reinhard; Bolt, Hermann M.; Golka, Klaus (2006). "Acetaldehyde". Ullmann's Encyclopedia of Industrial Chemistry. doi:10.1002/14356007.a01_031.pub2. ISBN   978-3-527-30385-4.
  22. ↑ Dreher, Eberhard-Ludwig; Torkelson, Theodore R.; Beutel, Klaus K. (2011). "Chlorethanes and Chloroethylenes". Ullmann's Encyclopedia of Industrial Chemistry. doi:10.1002/14356007.o06_o01. ISBN   978-3-527-30385-4.
  23. ↑ Jonathan Clayden; Nick Greeves; Stuart Warren (2012-03-15). Organic Chemistry. OUP Oxford. p. 658. ISBN   978-0-19-927029-3.
  24. ↑ 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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