Chlorocarbonylsulfenyl chloride

Chlorocarbonylsulfenyl chloride
Identifiers
CAS Number	2757-23-5 ;
3D model (JSmol)	Interactive image;
ChemSpider	68489;
EC Number	220-415-2;
PubChem CID	75990;
CompTox Dashboard (EPA)	DTXSID10181970 ;
	InChI InChI=1S/CCl2OS/c2-1(4)5-3 Key: MNOALXGAYUJNKX-UHFFFAOYSA-N;
	SMILES C(=O)(SCl)Cl;
Properties
Chemical formula	Cl−C(=O)−S−Cl
Molar mass	130.97 g·mol−1
Appearance	colorless liquid
Density	1.552 g/cm3
Boiling point	98 °C (208 °F; 371 K)
Hazards
	GHS labelling:
Pictograms
Signal word	Danger
Hazard statements	H314
Precautionary statements	P260, P264, P280, P301+P330+P331, P302+P361+P354, P304+P340, P305+P354+P338, P316, P321, P363, P405, P501
	Except where otherwise noted, data are given for materials in their standard state (at 25 °C [77 °F], 100 kPa). Infobox references

Chlorocarbonylsulfenyl chloride is the chemical compound with the formula Cl−C(=O)−S−Cl. It is a colorless, distillable liquid that is related to phosgene. It features two reactive functional groups, an acyl chloride and a sulfenyl chloride. According to X-ray crystallography, the molecule is planar.^[1]

Preparation and reactions

Chlorocarbonylsulfenyl chloride is prepared by hydrolysis of trichloromethane sulfenyl chloride in sulfuric acid as solvent:^[2]

Cl₃C−S−Cl + H₂O → Cl−S−C(=O)−Cl + 2 HCl

The compound, being bifunctional, has been used for the preparation of several heterocycles including oxathiazol-2-ones, oxathialones, and oxathiazoles.^[3]

Treatment with formamides gives dithiazolidinediones (also known as dithiasuccinoyl, or DTS).^[4]

Relevant to amino acid chemistry, ethylthionocarbamates react with chlorocarbonylsulfenyl chloride to give DTS derivatives:^[5]^[6]

Cl−S−C(=O)−Cl + CH₃CH₂−O−C(=S)−NH−R → S₂(CO)₂NR + HCl + CH₃CH₂Cl

Alcohols and amines react at the acyl chloride position to form alkoxycarbonylsulfenyl chlorides and carbamoylsulfenyl chlorides. Thiols selectively react at the sulfenyl chloride position to form S-alkylchlorocarbonyl disulfides:^[2]

ROH + Cl–S–C(=O)–Cl → Cl–S–C(=O)–OR + HCl

RNH₂ + Cl–S–C(=O)–Cl → Cl–S–C(=O)–NHR + HCl
RSH + Cl–S–C(=O)–Cl → RS–S–C(=O)–Cl + HCl

These reagents are useful for the derivatization of biological thiols. Methoxycarbonylsulfenyl chloride, a related reagent derived from the above chemistry, is used in solid-phase peptide synthesis for selective disulfide bond formation via conversion of the acetamidomethyl (Acm) cysteine protecting group to thiol-labile S-alkylsulfenyl thiocarbonate (carbomethylsulfenyl, Scm) protecting group.^[7]

References

↑ Romano, Rosana M.; Della Védova, Carlos O.; Downs, Anthony J.; Parsons, Simon; Smith, Caroline (2003). "Structural and vibrational properties of CLC(O)SY compounds with y = Cl and CH3". New Journal of Chemistry. 27 (3): 514–519. doi:10.1039/B209005H.
1 2 Zumach, G.; Kühle, E. (1970). "Chlorosulfenylated Carbonic Acid Derivatives". Angewandte Chemie International Edition in English. 9: 54–63. doi:10.1002/anie.197000541.
↑ Lin, Gang; Li, Dongyang; De Carvalho, Luiz Pedro Sorio; Deng, Haiteng; Tao, Hui; Vogt, Guillaume; Wu, Kangyun; Schneider, Jean; Chidawanyika, Tamutenda; Warren, J. David; Li, Huilin; Nathan, Carl (2009). "Inhibitors selective for mycobacterial versus human proteasomes". Nature. 461 (7264): 621–626. Bibcode:2009Natur.461..621L. doi:10.1038/nature08357. PMC 3172082. PMID 19759536.
↑ Martinez, Ana; Alonso, Mercedes; Castro, Ana; Dorronsoro, Isabel; Gelpí, J. Luis; Luque, F. Javier; Pérez, Concepción; Moreno, Francisco J. (2005). "SAR and 3D-QSAR Studies on Thiadiazolidinone Derivatives: Exploration of Structural Requirements for Glycogen Synthase Kinase 3 Inhibitors". Journal of Medicinal Chemistry. 48 (23): 7103–7112. doi:10.1021/jm040895g. hdl:10261/419122. PMID 16279768.
↑ Barany, George; Merrifield, R. B. (1977). "A new amino protecting group removable by reduction. Chemistry of the function". Journal of the American Chemical Society. 99 (22): 7363–7365. Bibcode:1977JAChS..99.7363B. doi:10.1021/ja00464a050. PMID 915158.
↑ Wood, Mark E. (2007). "1,2,4-Dithiazolidine-3,5-dione". Encyclopedia of Reagents for Organic Synthesis. doi:10.1002/9780470842898.rn00717. ISBN 978-0-471-93623-7.
↑ Spears, Richard J.; McMahon, Clíona; Chudasama, Vijay (2021). "Cysteine protecting groups: applications in peptide and protein science". Chemical Society Reviews. 50 (19): 11098–11155. doi:10.1039/D1CS00271F. ISSN 0306-0012.

[1] Romano, Rosana M.; Della Védova, Carlos O.; Downs, Anthony J.; Parsons, Simon; Smith, Caroline (2003). "Structural and vibrational properties of CLC(O)SY compounds with y = Cl and CH3". New Journal of Chemistry. 27 (3): 514–519. doi:10.1039/B209005H.

[:0-2] 1 2 Zumach, G.; Kühle, E. (1970). "Chlorosulfenylated Carbonic Acid Derivatives". Angewandte Chemie International Edition in English. 9: 54–63. doi:10.1002/anie.197000541.

[3] Lin, Gang; Li, Dongyang; De Carvalho, Luiz Pedro Sorio; Deng, Haiteng; Tao, Hui; Vogt, Guillaume; Wu, Kangyun; Schneider, Jean; Chidawanyika, Tamutenda; Warren, J. David; Li, Huilin; Nathan, Carl (2009). "Inhibitors selective for mycobacterial versus human proteasomes". Nature. 461 (7264): 621–626. Bibcode:2009Natur.461..621L. doi:10.1038/nature08357. PMC 3172082. PMID 19759536.

[4] Martinez, Ana; Alonso, Mercedes; Castro, Ana; Dorronsoro, Isabel; Gelpí, J. Luis; Luque, F. Javier; Pérez, Concepción; Moreno, Francisco J. (2005). "SAR and 3D-QSAR Studies on Thiadiazolidinone Derivatives: Exploration of Structural Requirements for Glycogen Synthase Kinase 3 Inhibitors". Journal of Medicinal Chemistry. 48 (23): 7103–7112. doi:10.1021/jm040895g. hdl:10261/419122. PMID 16279768.

[5] Barany, George; Merrifield, R. B. (1977). "A new amino protecting group removable by reduction. Chemistry of the function". Journal of the American Chemical Society. 99 (22): 7363–7365. Bibcode:1977JAChS..99.7363B. doi:10.1021/ja00464a050. PMID 915158.

[6] Wood, Mark E. (2007). "1,2,4-Dithiazolidine-3,5-dione". Encyclopedia of Reagents for Organic Synthesis. doi:10.1002/9780470842898.rn00717. ISBN 978-0-471-93623-7.

[7] Spears, Richard J.; McMahon, Clíona; Chudasama, Vijay (2021). "Cysteine protecting groups: applications in peptide and protein science". Chemical Society Reviews. 50 (19): 11098–11155. doi:10.1039/D1CS00271F. ISSN 0306-0012.

[1]

[2]

[3]

[4]

[5]

[6]

[7]