Sulfonyl halide

File:Sulfonyl chloride.png

Sulfonic acid chlorides, or sulfonyl chlorides, are a sulfonyl halide with the general formula {{chem2|RSO2Cl}}.

Arylsulfonyl chlorides are made industrially in a two-step, one-pot reaction from an arene (in this case, benzene) and chlorosulfuric acid:{{Ullmann|first1=Otto |last1=Lindner |first2=Lars |last2=Rodefeld |title=Benzenesulfonic Acids and Their Derivatives |doi=10.1002/14356007.a03_507}}

:{{chem2|C6H6 + HOSO2Cl -> C6H5SO3H + HCl}}

:{{chem2|C6H5SO3H + HOSO2Cl -> C6H5SO2Cl + H2SO4}}

The intermediate benzenesulfonic acid can be chlorinated with thionyl chloride as well. Benzenesulfonyl chloride, the most important sulfonyl halide, can also be produced by treating sodium benzenesulfonate with phosphorus pentachlorides.{{OrgSynth|first1=Roger |last1=Adams|first2=C. S. |last2=Marvel|first3=H. T. |last3=Clarke|first4=G. S. |last4=Babcock|first5=T. F. |last5=Murray|year=1921|title=Benzenesulfonyl chloride|volume=1|pages=21|collvol=1|collvolpages=84|prep=CV1P0084}}

Benzenediazonium chloride reacts with sulfur dioxide and copper(I) chloride to give the sulfonyl chloride:

:{{chem2|[C6H5N2]Cl + SO2 -> C6H5SO2Cl + N2}}

For alkylsulfonyl chlorides, one synthetic procedure is the Reed reaction:

:{{chem2|RH + SO2 + Cl2 -> RSO2Cl + HCl}}

Sulfonyl chlorides react with water to give the corresponding sulfonic acid:

:{{chem2|RSO2Cl + H2O -> RSO3H + HCl}}

These compounds react readily with many other nucleophiles as well, most notably alcohols and amines (see Hinsberg reaction). If the nucleophile is an alcohol, the product is a sulfonate ester; if it is an amine, the product is a sulfonamide:{{citation needed|date=November 2024}}

:{{chem2|RSO2Cl + R'2NH -> RSO2NR'2 + HCl}}

However, sulfonyl chlorides also react frequently as a source of RSO{{su|b=2|p=−}} and Cl⁺.{{cite journal|url=https://www.researchgate.net/publication/264675433|doi=10.1002/anie.201309399|title=Sulfur(VI) fluoride exchange (SuFEx)|author1=Dong Jiajia|first2=Larissa|last2=Krasnova|first3=M. G.|last3=Finn|first4=K. Barry|last4=Sharpless|journal= Angewandte Chemie International Edition in English|year=2014|publisher=Wiley-VCH|volume=53|issue=36 |page=9433|pmid=25112519 }} For example benzenesulfonyl chloride chlorinates ketene acetals{{cite journal|doi=10.1002/cber.19821150138|pages=399–401|journal=Chemische Berichte|volume=115|year=1982|title=Darstellung von (2,2-Dimethyl-1-methylenpropyl)-methansulfonat und trifluoracetat|language=de|first1=Elisabeth|last1=Hirsch|first2=Siegfried|last2=Hünig|first3=Hans-Ulrich|last3=Reißig|issue=1 |orig-date=21 April 1981}} and mesyl chloride chlorinates para-xylene under Friedel-Crafts conditions.{{cite journal|journal=Synthesis|year=1984|issue=3|pages=214–217|doi=10.1055/s-1984-30774|publisher=Thieme|title=Synthesis of aryl alkyl and aryl vinyl sulfones via Friedel-Crafts reactions of sulfonyl fluorides|first1=John A.|last1=Hyatt|first2=Alan W.|last2=White}} Using sodium sulfite as the nucleophilic reagent, p-toluenesulfonyl chloride is converted to its sulfinate salt, {{chem2|CH3C6H4SO2Na}}.{{cite journal |last1=Field |first1=L |last2=Clark |first2=R.D. |title=Methyl p-Tolyl Sulfone |journal=Organic Syntheses |date=1958 |volume=38 |page=62 |doi=10.15227/orgsyn.038.0062 |url=http://orgsyn.org/demo.aspx?prep=CV4P0674 |access-date=9 July 2023|url-access=subscription }} Chlorosulfonated alkanes are susceptible to crosslinking via reactions with various nucleophiles.

Sulfonyl chlorides readily undergo Friedel–Crafts reactions with arenes giving sulfones, for example:{{citation needed|date=November 2024}}{{dubious|reason=Contradicted by cited statement above|date=November 2024}}

:{{chem2|RSO2Cl + C6H6 -> RSO2C6H5 + HCl}}

A readily available arylsulfonyl chloride source is tosyl chloride.Organic Syntheses, Coll. Vol. 5, p.39 (1973); Vol. 48, p.8 (1968) [http://www.orgsynth.org/orgsyn/prep.asp?prep=cv5p0039 Online Article] The desulfonation of arylsulfonyl chlorides provides a route to aryl chlorides:

:{{chem2|ArSO2Cl -> ArCl + SO2}}

1,2,4-Trichlorobenzene is made industrially in this way.

Treatment of alkanesulfonyl chlorides having α-hydrogens with amine bases can give sulfenes, highly unstable species that can be trapped:

:{{chem2|RCH2SO2Cl -> RCH\dSO2 + HCl}}

Reduction with tetrathiotungstate ions ({{chem2|WS4(2-)}}) induces dimerization to the disulfide.{{cite journal|journal=Journal of Organic Chemistry|year=1990|volume=55|pages=3728–3729|title=Chemistry of Tetrathiotungstates: A Novel Synthesis of Disulfides from Sulfonyl Derivative|first1=Preeti|last1=Dhar|first2=Rajeev|last2=Ranjan|first3=Srinivasan|last3=Chandrasekaran|issue=12 |orig-date=8 Sep 1989|publisher=American Chemical Society|doi=10.1021/jo00299a010}}

Chlorosulfonated polyethylene (CSPE) is produced industrially by chlorosulfonation of polyethylene. CSPE is noted for its toughness, hence its use for roofing shingles.{{Ullmann|doi=10.1002/14356007.o23_o05|isbn=978-3527306732|title=Rubber, 8. Synthesis by Polymer Modification|year=2011|last1=Happ|first1=Michael|last2=Duffy|first2=John|last3=Wilson|first3=G. J.|last4=Pask|first4=Stephen D.|last5=Buding|first5=Hartmuth|last6=Ostrowicki|first6=Andreas}}

An industrially important derivative is benzenesulfonyl chloride. In the laboratory, useful reagents include tosyl chloride, brosyl chloride, nosyl chloride and mesyl chloride.

Sulfonyl fluorides have the general formula RSO₂F. They can be produced by treating sulfonic acids with sulfur tetrafluoride:{{cite book |doi=10.1002/0471264180.or021.01 |chapter=Fluorination by Sulfur Tetrafluoride |title=Organic Reactions |date=2011 |last1=Boswell |first1=G. A. |last2=Ripka |first2=W. C. |last3=Scribner |first3=R. M. |last4=Tullock |first4=C. W. |pages=1–124 |isbn=978-0-471-26418-7 }}

:{{chem2|SF4 + RSO3H → SOF2 + RSO2F + HF}}

Perfluorooctanesulfonyl derivatives, such as PFOS, are produced from their sulfonyl fluoride, which are produced by electrofluorination{{cite journal |last=Lehmler |first=H. J. |title=Synthesis of Environmentally Relevant Fluorinated Surfactants—a review |journal=Chemosphere |volume=58 |issue=11 |pages=1471–1496 |year=2005 |pmid=15694468 |doi=10.1016/j.chemosphere.2004.11.078 |bibcode=2005Chmsp..58.1471L}}

In the molecular biology, sulfonyl fluorides are used to label proteins. They specifically react with serine, threonine, tyrosine, lysine, cysteine, and histidine residues. The fluorides are more resistant than the corresponding chlorides and are therefore better suited to this task.{{cite journal | last1 = Narayanan | first1 = Arjun | last2 = Jones | first2 = Lyn H. | year = 2015 | title = Sulfonyl fluorides as privileged warheads in chemical biology | journal = Chemical Science | volume = 6 | issue = 5| pages = 2650–2659 | doi = 10.1039/C5SC00408J | pmid = 28706662 | pmc = 5489032}}

Some sulfonyl fluorides can also be used as deoxyfluorinating reagents, such as 2-pyridinesulfonyl fluoride (PyFluor) and N-tosyl-4-chlorobenzenesulfonimidoyl fluoride (SulfoxFluor).{{cite journal |last1=Nielsen |first1=Matthew K. |last2=Ugaz |first2=Christian R. |last3=Li |first3=Wenping |last4=Doyle |first4=Abigail G. |title=PyFluor: A Low-Cost, Stable, and Selective Deoxyfluorination Reagent |journal=Journal of the American Chemical Society |date=5 August 2015 |volume=137 |issue=30 |pages=9571–9574 |doi=10.1021/jacs.5b06307|doi-access=free |pmid=26177230 |bibcode=2015JAChS.137.9571N }}{{cite journal |last1=Guo |first1=Junkai |last2=Kuang |first2=Cuiwen |last3=Rong |first3=Jian |last4=Li |first4=Lingchun |last5=Ni |first5=Chuanfa |last6=Hu |first6=Jinbo |title=Rapid Deoxyfluorination of Alcohols with N-Tosyl-4-chlorobenzenesulfonimidoyl Fluoride (SulfoxFluor) at Room Temperature |journal=Chemistry – A European Journal |date=28 May 2019 |volume=25 |issue=30 |pages=7259–7264 |doi=10.1002/chem.201901176|pmid=30869818 |s2cid=76667829 }}

Sulfonyl bromides have the general formula RSO₂Br. In contrast to sulfonyl chlorides, sulfonyl bromides readily undergo light-induced homolysis affording sulfonyl radicals, which can add to alkenes, as illustrated by the use of bromomethanesulfonyl bromide, BrCH₂SO₂Br in Ramberg–Bäcklund reaction syntheses.{{OrgSynth|author1=Block |first1=E.|author2= Aslam |first2=M.|title=A General Synthetic Method for the Preparation of Conjugated Dienes from Olefins using Bromomethanesulfonyl Bromide: 1,2-Dimethylenecyclohexane|collvol=Coll. Vol. 8|collvolpages=212 |prep=cv8p0212 |year=1993}}{{cite journal |last1=Block |first1=E.|last2=Aslam |first2=M. |last3=Eswarakrishnan |first3=V. |last4=Gebreyes |first4=K. |last5=Hutchinson |first5=J. |last6=Iyer |first6=R. |last7=Laffitte |first7=J.-A. |last8= Wall |first8=A. |title=α-Haloalkanesulfonyl Bromides in Organic Synthesis. 5. Versatile Reagents for the Synthesis of Conjugated Polyenes, Enones and 1,3-Oxathiole 1,1-Dioxides|journal=J. Am. Chem. Soc.|volume=108|issue=15|pages=4568–4580|year=1986|doi=10.1021/ja00275a051|bibcode=1986JAChS.108.4568B }}

Sulfonyl iodides, having the general formula RSO₂I, are quite light-sensitive. Methanesulfonyl iodide evolves iodine in vacuum and branched-alkyl sulfonyl iodides are worse.{{cite book|title=Sulfur in Organic and Inorganic Chemistry|volume=1|editor-first=Alexander|editor-last=Senning|year=1971|publisher=Marcel Dekker|location=New York|lccn=70-154612|isbn=0-8247-1615-9|first=James P.|last=Danehy|chapter=The Sulfur–Iodine Bond|pages=336–337}} Perfluoroalkanesulfonyl iodides, prepared by reaction between silver perfluoroalkanesulfinates and iodine in dichloromethane at −30 °C, react with alkenes to form the normal adducts, RFSO₂CH₂CHIR and the adducts resulting from loss of SO₂, RFCH₂CHIR.{{cite journal |last1=Huang |first1=W.-Y. |first2=Hu |last2=L.-Q. |title=The chemistry of perfluoroalkanesulfonyl iodides |journal=Journal of Fluorine Chemistry |volume=44 |issue=1 |pages=25–44 |year=1989|doi=10.1016/S0022-1139(00)84369-9|bibcode=1989JFluC..44...25H }}

Arenesulfonyl iodides, prepared from reaction of arenesulfinates or arenehydrazides with iodine, are much more stable and can initiate the synthesis of poly(methyl methacrylate) containing C–I, C–Br and C–Cl chain ends.{{cite journal |last1=Percec |first1=V. |last2=Grigoras |first2=C. |title=Arenesulfonyl iodides: The third universal class of functional initiators for the metal-catalyzed living radical polymerization of methacrylates and styrenes. |journal=Journal of Polymer Science Part A: Polymer Chemistry |volume=43 |issue=17 |pages=3920–3931 |year=2005|doi=10.1002/pola.20860|bibcode = 2005JPoSA..43.3920P}} Their reduction with silver gives the disulfone:

:2 ArSO₂I + 2Ag → (ArSO₂)₂ + 2 AgI

In the episode "Encyclopedia Galactica" of his TV series Cosmos: A Personal Voyage, Carl Sagan speculates that some intelligent extraterrestrial beings might have a genetic code based on polyaromatic sulfonyl halides instead of DNA.

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