Organomercury chemistry

{{Short description|Group of chemical compounds containing mercury}} 150px|thumb|right|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-, or have once been, used in medicine, e.g., merbromin ("Mercurochrome") and the vaccine preservative thiomersal.<ref>{{Greenwood&Earnshaw2nd}}</ref>

==Structure and bonding== Most organomercury compounds feature diamagnetic Hg(II) and adopt a linear C-Hg-X structure.<ref>{{cite book|title=Organometallics|author=C. Elschenbroich|publisher=VCH|year=2006|isbn= 978-3-527-29390-2}}</ref> Indeed, no organic derivatives of Hg{{su|b=2|p=2+}} are known, as Hg{{su|b=2|p=2+}} requires electronegative subtituents for condensed-phase stability.<ref>{{cite book|chapter=Relativistic effects and the chemistry of the heavier main group elements|first=John&nbsp;S.|last=Thayer|editor-first1=M.|editor-last1=Barysz|editor2=Ishikawa Y.|title=Relativistic Methods for Chemists|series=Challenges and Advances in Computational Chemistry and Physics|volume=10|doi=10.1007/978-1-4020-9975-5_2|publisher=Springer Science+Business Media B.V.|year=2010|page=71|via=CiteSeerX}}</ref>

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.

The structure of "mercurocene" is instructive. When made in the 1950s, it was too sensitive for structural determination.<ref>{{cite journal|pages=34,36|doi=10.1016/0022-1902(56)80101-2|journal=Journal of Inorganic and Nuclear Chemistry|year=1956|volume=2|title=Cyclo&shy;pentadienyl-triethyl&shy;phosphine-copper(I) and bis-cyclopentadienyyl&shy;mercury(II)|first1=G.|last1=Wilkinson|first2=T.&nbsp;S.|last2=Piper|orig-date=3 May 1955}}</ref> Later analysis determined that the products have the mercury σ-bonded to just one carbon of each ring, rather than a metallocene with the metal bonded to the rings' π systems.<ref name=Carmona/>

==Toxicity== The toxicity of organomercury compounds<ref>{{cite book|last=Hintermann|first=H.|title=Organomercurials. Their Formation and Pathways in the Environment|publisher=RSC publishing| location=Cambridge|year=2010|series=Metal Ions in Life Sciences|volume=7|pages=365–401|isbn=978-1-84755-177-1}}</ref><ref>{{cite book|last=Aschner|first=M.|author2=Onishchenko, N. |author3=Ceccatelli, S. |title=Toxicology of Alkylmercury Compounds|publisher=RSC publishing|location=Cambridge|year=2010|series=Metal Ions in Life Sciences|volume=7|pages=403–434|doi=10.1515/9783110436600-017|pmid=20877814|isbn=978-1-84755-177-1}}</ref> 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.<ref>{{cite web|website=Centers for Disease Control and Prevention |url=https://www.cdc.gov/vaccinesafety/concerns/thimerosal/index.html |title=Thimerosal and Vaccines |date=August 25, 2020 |access-date=April 15, 2024}}</ref>

==Synthesis== [[File:C(HgOAc)4.svg|thumb|Tetrakis(acetoxymercurio)methane<ref>{{cite journal |doi=10.1039/C39740000646 |title=Tetrakis(trifluoroacetoxymercuri)methane and Tetrakis(acetoxymercuri)methane as the Reaction Products of Hofmann's Base with the Corresponding Acid: X-ray Crystallographic Evidence |date=1974 |last1=Grdenić |first1=Drago |last2=Kamenar |first2=Boris |last3=Korpar-Čolig |first3=Branka |last4=Sikirca |first4=Milan |last5=Jovanovski |first5=Gligor |journal=J. Chem. Soc., Chem. Commun. |issue=16 |pages=646–647 }}</ref>]] Reflecting the strength of the C-Hg bond, organomercury compounds are generated by many methods.<ref name="Larock">{{cite book|title=Organomercury Compounds in Organic Synthesis|author=Richard C. Larock|doi=10.1007/978-3-642-70004-0|publisher=Springer|year=1985}}</ref> Indeed, mercury adsorbs onto laboratory glassware, such that laboratories performing mercury experiments may have difficulty ''avoiding'' C&ndash;Hg bond formation.<ref>{{cite encyclopedia|doi=10.1002/047084289X.rm027.pub2|entry=Mercury|first=Robert&nbsp;H.|last=Crabtree|author-link=Robert Crabtree|encyclopedia=Encyclopedia of Reagents for Organic Synthesis|publisher=Wiley}}</ref> 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.<ref name="Larock"/>

===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:<ref>{{OrgSynth | vauthors = Whitmore FC, Hanson ER | title = o-Chloromercuriphenol | volume = 4 | pages = 13 | year = 1925 | doi = 10.15227/orgsyn.004.0013}}</ref> :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.<ref>{{cite journal | title = Directe Einführung von Quecksilber in aromatische Verbindungen | journal = Berichte der deutschen chemischen Gesellschaft | volume = 31 | issue = 2 | year = 1898 | pages = 2154–2156 | author = Otto Dimroth | doi = 10.1002/cber.189803102162| url = https://zenodo.org/record/1425906}}</ref>

===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:<ref>{{OrgSynth|vauthors=Carter HE, West HD |title=dl-Serine |collvol=3 |collvolpages=774 |year=1955 |prep = cv3p0774}}</ref>

: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'''.<ref>{{cite journal|first1=K. A. |last1=Hofmann |first2=J. |last2=Sand |journal=Berichte der deutschen chemischen Gesellschaft |title=Ueber das Verhalten von Mercurisalzen gegen Olefine |volume=33 |issue=1 |pages=1340–1353 |date=January–April 1900 |doi=10.1002/cber.190003301231|url=https://zenodo.org/record/1425962}}</ref>

Internal alkynes undergo mercuration with incorporation of solvent: :{{chem2|RC\tCR + Hg(OAc)2 + ROH -> R(AcOHg)C\dCR(OR) + HOAc}}

===Reaction of Hg(II) compounds with C-heteroatom bonds=== [[File:CSD CIF TBTMER01.png|thumb|{{chem2|(C6H4Hg)3}}, a planar molecule, is the product of the reaction of sodium amalgam and 1,2-dihalobenzenes.<ref>{{cite journal |doi=10.1016/S0020-1693(00)91002-8 |title=A re-investigation of o-phenylenemercurials(V) [1]: The crystal and molecular structure of monoclinic tribenzo[b,e,h] [1,4,7] trimercuronin |date=1980 |last1=Brown |first1=David S. |last2=Massey |first2=Alan G. |last3=Wickens |first3=Denys A. |journal=Inorganica Chimica Acta |volume=44 |pages=L193–L194 }}</ref>]] 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.<ref>{{cite book | title = Synthetic Methods of Organometallic and Inorganic Chemistry Volume 5, Copper, Silver, Gold, Zinc, Cadmium, and Mercury | editor = W.A. Herrmann | isbn = 3-13-103061-5| year = 1996| publisher = Georg Thieme Verlag }}</ref>

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.<ref>{{OrgSynth | author = Calvery, H. O. | title = Diphenylmercury | collvol = 1 | collvolpages = 228 | year = 1941 | prep = CV1P0228}}</ref>

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.<ref>{{OrgSynth | author = Nesmajanow, A. N. | title = β-Naphthylmercuric Chloride | collvol = 2 | collvolpages = 432 | year = 1943 | prep = CV2P0432}}</ref>

4-Chloromercuritoluene is obtained by the chloromercuration of sodium toluenesulfinite:<ref>{{cite journal |doi=10.15227/orgsyn.003.0099 |title=''p''-Tolyl Chloride |journal=Organic Syntheses |date=1923 |volume=3 |page=99|first1=Frank C.|last1=Whitmore|first2=Frances H. |last2=Hamilton|first3=N.|last3=Thurman }}</ref> :{{chem2|CH3C6H4SO2Na + HgCl2 -> CH3C6H4HgCl + SO2 + NaCl}}

===Salt-forming reactions=== Organomercury compounds can also be prepared by traditional salt metathesis routes involving organolithium and Grignard reagents. Illustrative is the preparation of Hg(C5H5)2, which features σ-bonded alkyls rather than a metallocene.<ref name=Carmona>{{cite journal |last1= Grirrane |first1= Abdessamad |last2= Resa |first2= Irene |last3= Del Río |first3= Diego |last4= Rodríguez |first4= Amor |last5= Álvarez |first5= Eleuterio |last6= Mereiter |first6= Kurt |last7= Carmona |first7= Ernesto |title= Solid-State Structures and Solution Studies of Novel Cyclopentadienyl Mercury Compounds |journal= Inorganic Chemistry |date= 2007 |volume= 46 |issue= 11 |pages= 4667–4676 |doi= 10.1021/ic0624672 |pmid= 17461576 }}</ref>

==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{{nbh}}chloro&shy;mercuri&shy;toluene to 4{{nbh}}chloro&shy;mercuri&shy;benzoic acid.<ref>{{cite journal |doi=10.15227/orgsyn.007.0018 |title=P-Chloromercuribenzoic ACID |journal=Organic Syntheses |date=1927 |volume=7 |page=18|first1=Frank C.|last1=Whitmore|first2= Frances H. |last2= Hamilton|first3=N.|last3=Thurman}}</ref>

Nevertheless, organomercurials are used in transmetalation reactions. For example diphenylmercury reacts with aluminium to give triphenyl aluminium: :{{chem2|3 (C6H5)2Hg + 2 Al → Al(C6H5)3)2 + 3 Hg}}

Organomercury compounds react with halogens to give the corresponding organic halide,{{cn|date=May 2025}} 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).<ref>"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}}</ref>

Phenylmercuric chloride reversibly stores dichlorocarbene as phenyl(trichloromethyl)mercury. A convenient carbene source is sodium trichloroacetate:<ref>{{OrgSynth | author = Logan, T. J. | title = Phenyl(trichloromethyl)mercury | collvol = 5 | collvolpages = 969 | year = 1973 | prep = cv5p0969}}</ref> :C₆H₅HgCl&nbsp;+ CCl₂&nbsp;→ C₆H₅HgCCl₃, reversed with heat.

Organomercury halides react with hydride sources to give organomercury hydrides. Those compounds have an exceptionally weak C&ndash;Hg bond, and readily cleave to alkyl radicals.<ref>{{cite journal|doi=10.1016/S0040-4039(01)81573-2|journal=Tetrahedron Letters|volume=25|issue=46|pages=5239–5242|location=Great Britain|year=1984|publisher=Pergamon|title=Reactivity of the 5-hexenyl radical toward the anion of 2-nitropropane and borohydride anion|first1=Glen&nbsp;A.|last1=Russell|author2=Guo Deliang|orig-date=9 May 1984}}</ref>

==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:<ref>{{cite book |doi=10.1002/14356007.a01_031.pub2 |chapter=Acetaldehyde |title=Ullmann's Encyclopedia of Industrial Chemistry |date=2006 |last1=Eckert |first1=Marc |last2=Fleischmann |first2=Gerald |last3=Jira |first3=Reinhard |last4=Bolt |first4=Hermann M. |last5=Golka |first5=Klaus |isbn=978-3-527-30385-4 }}</ref> :{{chem2|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.<ref>{{cite book|doi=10.1002/14356007.a27_419 |chapter=Vinyl Esters |title=Ullmann's Encyclopedia of Industrial Chemistry |date=2000 |last1=Roscher |first1=Günter |isbn=978-3-527-30385-4 }}</ref><ref>GB Patent 238825A 'Process of Manufacture of Acetic Anhydride and Aldehyde'</ref> 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.<ref>{{cite book |doi=10.1002/14356007.o06_o01 |chapter=Chlorethanes and Chloroethylenes |title=Ullmann's Encyclopedia of Industrial Chemistry |date=2011 |last1=Dreher |first1=Eberhard-Ludwig |last2=Torkelson |first2=Theodore R. |last3=Beutel |first3=Klaus K. |isbn=978-3-527-30385-4 }}</ref>

===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.

[[file:Thiomersal.svg|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 ''mer''cury ''capt''ure. Thiolates (R-S⁻) and thioketones (R₂C=S), being soft nucleophiles, form strong coordination complexes with mercury(II), a soft electrophile.<ref>{{cite book|author1=Jonathan Clayden|author2=Nick Greeves|author3=Stuart Warren|title=Organic Chemistry|url=https://books.google.com/books?id=kQgu2j_ber0C&pg=PA658|date=2012-03-15|publisher=OUP Oxford|isbn=978-0-19-927029-3|pages=658}}</ref> 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.<ref>{{cite journal |author1=Masao Ono |author2=Masaya Kawakami |name-list-style=amp | title = Separation of Newly-Synthesized RNA by Organomercurial Agarose Affinity Chromatography | journal = J. Biochem. | year = 1977 | volume = 81 | issue = 5 | pages = 1247–1252 | pmid = 19428}}</ref>

==See also== *Heavy metal poisoning *Mercury poisoning *Minamata disease

==References== {{Reflist}}

==External links== * {{cite web | publisher = International Programme on Chemical Safety | title = 1967 Evaluations of some Pesticide Residues in Food: Organomercury compounds | url = http://www.inchem.org/documents/jmpr/jmpmono/v067pr27.htm}} * {{cite web |title= Organomercury Compounds |work= Comparative Toxicogenomics Database | url = http://ctdbase.org/detail.go?type=chem&acc=D009941 | publisher = Mount Desert Island Biological Laboratory}} * Safety data for a typical organomercury compound: {{cite web |url=https://www.sigmaaldrich.com/GB/en/sds/aldrich/p27127 |title=Safety data sheet for phenylmercuric acetate |publisher=Merck |date=2022-07-22 |access-date=2022-08-19 }}

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Category:Organomercury compounds Category:Obsolete pesticides