p-Toluenesulfonyl Isocyanate1

[4083-64-1]  · C8H7NO3S  · p-Toluenesulfonyl Isocyanate  · (MW 197.23)

(converts oxiranes to 2-oxazolinones;2 undergoes many [2 + x] cycloadditions; useful for (thio)carbonyl to imine functional group interchange; introduces the Tac protecting group to amino acids3)

Alternate Name: tosyl isocyanate.

Physical Data: bp 144 °C/10 mmHg; d 1.295 g cm-3.

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

Form Supplied in: colorless liquid; widely available.

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. See Karol4a and Henderson4b for toxicity data of isocyanates.

Conversion of Oxiranes to 2-Oxazolinones.

Tosyl isocyanate can be considered either as a heteroatom ring-expanding reagent, or as an NH3 synthetic equivalent. A prime example might be its Lewis or p-acid catalyzed reaction with epoxides to give N-tosylated 2-oxazolinones directly,2,5 or 1,2-amino alcohols after hydrolysis. An elegant and powerful variation utilizing chiral, nonracemic Pd-phosphine complexes, which exploits the greater reactivity of sulfonylated isocyanates, has also been developed, giving access to optically active cyclic 1,2-amino alcohols (eq 1).6 In a related sequence, allylic amines are converted to N,N-cyclic ureas with I2 catalysis.7

[2 + x] Cycloadditions.

Highly reactive tosyl isocyanate readily undergoes a wide variety of [2 + 2] cycloadditions.8 Much effort has been expended upon the preparation of N-tosylated b-lactams. Despite the difficulty of removal of the sulfonyl group without cleaving the b-lactam,9 novel variations continue to appear (eq 2).10

Other [2 + 2] cycloadditions have been reported with hydrazones,11 and imino ethers.12 [2 + 3] Cycloadditions that afford pyrrolidinone derivatives from transition metal complexes have recently been reported (eq 3).13 Higher-order cycloadditions also appear in the literature.14

(Thio)carbonyl to Imide Reactions.

Desulfur- and deoxygenations of (thio)lactams, glyoxaldehydes, and phosphine oxides induced by tosyl isocyanate liberate CO2 or COS. The product N-sulfonyl amidines, which give novel stereochemistry in aldol reactions,15 glyoximines, which may be used directly in aza-Diels-Alder reactions,16 and phosphinimines17 are obtained in high yields.

Miscellaneous Reactions.

Reaction (20-80%) with amino acids introduces the N-Tac group, which, while stable to cold TFA, dilute base, HBr/acetic acid, and catalytic hydrogenation, may be removed by hot primary alcohols.3 Tosyl isocyanate is an efficient dehydrating agent for tertiary (especially allylic) alcohols.18 The N-tosyl group is a pharmacophore.19 Novel ring expansions of medium- and large-ring keto esters triggered by tosyl isocyanate afford macrolactams.20

Related Reagents.

Benzenesulfonyl Isocyanate; Chlorosulfonyl Isocyanate.

1. Ulrich, H. CRV 1965, 65, 369.
2. McFarland, J.; Beaulieu, J. J.; Arrey, L. N.; Frey, L. M. JHC 1988, 25, 1431.
3. Weinstein, B.; Ho, T. N. S.; Fukura, R. T.; Angell, G. C. SC 1976, 6, 17.
4. (a) Karol, M. H. CRC Crit. Rev. Toxicol. 1986, 16, 349. (b) Henderson, R. ACS Symp. Ser. 1981, 172, 87.
5. Trost, B. M.; Sudhakar, A. R. JACS 1988, 110, 7933.
6. Trost, B. M.; Van Vranken, D. L. AG(E) 1992, 31, 228.
7. Cardillo, G.; Orena, M.; Penna, M.; Sandri, S.; Tomasini, C. T 1991, 47, 2263.
8. (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.
9. Barrett, A. G. M.; Betts, M. J.; Fenwick, A. JOC 1985, 50, 169.
10. (a) Kaluza, Z.; Fodony, W.; Belzeki, C; Chmielewski, M. TL 1989, 30, 5171. (b) Mostowicz, D.; Zegrocka, O.; Chmielewski, M. Carbohydr. Res. 1991, 212, 283.
11. Brehme, R.; Klemann, A. T 1987, 43, 4113.
12. Aue, D. H.; Thomas, D. JOC 1975, 40, 2356.
13. (a) Shuchart, C. E.; Willis, R. R.; Wojcicki, A. JOM 1992, 424, 185. (b) Giering, W. P.; Raghu, S.; Rozenblum, M.; Cutler, A.; Elntholt, D.; Fisl, R. N. JACS 1972, 94, 8251. (c) Takai, K.; Kataoka, Y.; Yoshizumi, K.; Oguchi, Y.; Utimoto, K. CL 1991, 1479.
14. (a) Ito, K.; Saito, K.; Takguchi, S.; Takahashi, K. H 1992, 34, 1415. (b) Gibbard, A. C.; Moody, C. J.; Rees, C. W. JCS(P1) 1986, 145.
15. Magnus, P.; Moursounidis, J. JOC 1991, 56, 1529.
16. Harmley, P.; Holmes, A. B.; Kee, A.; Ladduwahetly, T.; Smith, D. F. SL 1991, 29.
17. Hall, R. C.; Smith, D. J. H. JCS(P2) 1977, 1373.
18. (a) Roach, L. C.; Daly, W. H. CC 1970, 606. (b) Kakushima, M.; Scott, D. G. CJC 1979, 57, 1399.
19. Howbert, J. J.; Grossman, C. S.; Crowell, T. A.; Rieder, B. J.; Harper, R. W.; Kramer, K. E.; Tao, E. U.; Aikins, J.; Poure, G. A. Rinzel, S. M.; Grindey, G. B.; Shaw, W. N.; Todd, G. C. JMC 1990, 33, 2393.
20. Ognyanov, V. I.; Hesse, M. HCA 1989, 72, 1522.

Erik P. Johnson

Ciba-Geigy Corporation, Summit, NJ, USA

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