Chlorosulfonyl isocyanate explained

Chlorosulfonyl isocyanate is the chemical compound ClSO₂NCO, known as CSI. This compound is a versatile reagent in organic synthesis.

Preparation, structure, handling

CSI is prepared by treating cyanogen chloride with sulfur trioxide, the product being distilled directly from the reaction mixture.^[1]

SO₃ + ClCN → ClSO₂NCOIn this transformation, both the carbon and the nitrogen termini of CN are functionalized.

The structure of CSI is represented as ClS(O)₂-N=C=O. It consists of two electron-withdrawing components, the chlorosulfonyl group (SO₂Cl) and the isocyanate group (-N=C=O). Because of its resulting electrophilicity, the use of CSI in chemical synthesis requires relatively inert solvents such as chlorocarbons, acetonitrile, and ethers.^[2]

Uses

The molecule has two electrophilic sites, the carbon and the S(VI) center.^[3]

CSI has been employed for the preparation of β-lactams,^[4] some of which are medicinally important. Thus, alkenes undergo a [2+2]-cycloaddition to give the sulfonamide. The SO₂Cl group can be removed simply by hydrolysis, leaving the secondary amide.^[5] Other reactions of CSI:

• Cycloaddition to alkynes to give 1,2,3-oxathiazine-2,2-dioxide-6-chlorides.
• Conversion of primary alcohols to carbamates.^[6]
• Conversion of carboxylic acids and the acid chlorides into nitriles.
• Preparation of N,N-disubstituted sulfamides, R₂NSO₂NH₂
• Preparation of Burgess reagent

Safety considerations

CSI is toxic, corrosive and reacts violently with water.

References

1. Graf, R. "Chlorosulfonyl Isocyanate" Organic Syntheses, Collected Volume 5, pages 226ff.
2. Miller, M. J.; Ghosh, M.; Guzzo, P. R.; Vogt, P. F.; Hu, J.; Filzen, G. F.; Geyer, A. G. "Chlorosulfonyl Isocyanate" in "Encyclopedia of Reagents for Organic Synthesis" 2005 John Wiley & Sons: New York.
3. D. N. Dhar, K. S. K. Murthy "Recent Advances in the Chemistry of Chlorosulfonyl Isocyanate" Synthesis 1986; pages 437-449.
4. Kaur. Rajneesh. Singh. Raman. Kumar. Antresh. Kaur. Satvinder. Priyadarshi. Nitesh. Singhal. Nitin Kumar. Singh. Kuldeep. June 2020. 1,2,3-Triazole β-lactam conjugates as antimicrobial agents. Heliyon. en. 6. 6. e04241. 10.1016/j.heliyon.2020.e04241. free . 7327255. 32637684.
5. Cremlyn, R. J. “An Introduction to Organosulfur Chemistry” John Wiley and Sons: Chichester (1996).
6. Burgess, E. M.; Penton, Jr., H. R.; Taylor, E. A.; Williams, W. M. "Conversion of Primary Alcohols to Urethanes via the Inner Salt of Triethylammonium Hydroxide: Methyl (Carboxylsulfamoyl) Triethylammonium Hydroxide Methyl n-Hexylcarbamate" Organic Syntheses, Coll. Vol. 6, p.788