Benzenesulfonyl Isocyanate

[2845-62-7]  · C7H5NO3S  · Benzenesulfonyl Isocyanate  · (MW 183.18)

(derivatizing agent for alcohols and phenols;1 used to convert (thio)carbonyl compounds to imino derivatives;2,3 used in the preparation of b-lactams4 and a wide variety of heterocycles via cycloaddition reactions)

Physical Data: bp 130 °C/9 mmHg; d 1.369 g cm-3.

Solubility: sol chlorinated, aromatic, and ethereal solvents; reacts violently with H2O, basic and protic solvents.

Form Supplied in: colorless liquid; widely available; more expensive than p-toluenesulfonyl isocyanate.

Handling, Storage, and Precautions: lachrymator; corrosive; use only in a fume hood; wear protective gloves and preferably a NIOSH-approved respirator. All transfers and reactions should be carried out under anhydrous conditions. Store in a cool dry place, taking care to avoid contamination with protic, basic, or organometallic materials, as these may induce polymerization. Toxicity data for isocyanates are available.5

Hydroxy Derivatization.

First prepared by Billetter in 1904, benzenesulfonyl isocyanate has been found to be an excellent reagent for the preparation of highly crystalline carbamates from hindered primary and secondary alcohols and polynitrophenols in very high yield (eq 1).1 Indeed, the sulfonyl group not only activates the isocyanate moiety relative to alkyl or aryl substituents,1,6 but these derivatives are also very easily purified (typically by aqueous extraction). Surprisingly, no reports have been made of amine derivatizations, despite a great potential for this purpose.

(Thio)carbonyl to Imide Conversion.

This transformation appears quite general, occurring for ketone, amide, oxamate,2 and thioamide3 groups. Heating the (thio)carbonyl derivative with benzenesulfonyl isocyanate leads to a formal [2 + 2] cycloaddition, followed by fragmentation, to give the N-protected imine derivative and CO2 or COS (eq 2). Although this conversion represents an interesting and general method of preparing imines, (thio)imino esters, amidines, etc., note that removal of the benzenesulfonyl group generally requires vigorous reaction conditions that may, in certain circumstances, destroy the imino derivative.

[2 + 2] and [2 + 3] Cycloadditions.

All isocyanates undergo these reactions to some extent, but benzenesulfonyl isocyanate is several orders of magnitude more reactive for some types of cycloaddition.6,7 Perhaps the most useful reaction involving this isocyanate is [2 + 2] cycloaddition with enol ethers,4 ketenes, and thioketenes8 to afford b-(thio)lactams. This is a very useful entry into N-protected b-lactams, despite the relative difficulty of removing the benzenesulfonyl group without cleaving the b-lactam (eq 3).

Interestingly, the analogous N,O-ketene acetals give only acyclic products.9 A number of [2 + 3] cycloadditions have been reported, including the syntheses of indolin-2-ones,10 dehydroazepinones,11 and tetrazolones.7

Miscellaneous Uses.

The patent literature contains numerous examples of N-benzenesulfonyl carbamate and urea compounds (derived respectively from alcohols and amines) exhibiting pharmaceutically12 and agriculturally useful properties (e.g. imparting H2O solubility and functioning as a pharmacophore). Benzenesulfonyl isocyanate itself has also been reported in the patent literature to be of use in polymer chemistry as a dehydrating, stabilizing, and crosslinking agent, and as a catalyst or reagent in the preparation of carbodiimides and other isocyanates. See also p-Toluenesulfonyl Isocyanate.

1. McFarland, J. W.; Howard, J. B. JOC 1965, 30, 957.
2. (a) Tamura, H.; Iwakawa, T.; Hayase, Y. CPB 1990, 38, 1069. (b) Burger, V. K.; Hoess, E. CZ 1988, 112, 349. (c) Gompper, R.; Studeneer, A.; Elser, W. TL 1968, 1019.
3. L'abbé, G.; Sannen, I.; Vandendriessche, A. JHC 1992, 29, 69.
4. Effenberger, F.; Gerlach, O. CB 1974, 107, 278.
5. (a) Karol, M. H. CRC Crit. Rev. Toxicol. 1986, 16, 349. (b) Henderson, R. ACS Symp. Ser. 1981, 172, 87.
6. (a) The Chemistry of Cyanates and Their Thio Derivatives; Patai, S.; Ed., Wiley: New York, 1977, Part 2, pp 742-755. (b) MOC 1983, E4, 738.
7. (a) Vandensavel, J.-M.; Smets, G.; L'abbé, G. JOC 1973, 38, 675. (b) Denecker, G.; Smets, G.; L'abbé, G. T 1975, 31, 765.
8. Schaumann, E.; Moeller, M.; Adiwidjaja, G. CB 1988, 121, 689.
9. Schaumann, E.; Sieveking, S.; Walter, W. CB 1974, 107, 3589.
10. Kagabu, S.; Saito, K.; Watanabe, H.; Takahashi, K.; Wada, K. BCJ 1991, 64, 106.
11. Sarel, S.; Felzenstein, A. M.; Weisz, M. Isr. J. Chem. 1982, 22, 64.
12. Vicini, P.; Amoretti, L.; Caretta, A. FES 1992, 47, 265 (CA 1992, 117, 69 772e).

Erik P. Johnson

Ciba-Geigy Corporation, Summit, NJ, USA

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