Trichloroacetyl Isocyanate1

[3019-71-4]  · C3Cl3NO2  · Trichloroacetyl Isocyanate  · (MW 188.39)

(derivatization of alcohols to the trichloroacetyl2 and unsubstituted3 carbamates (urethanes); reacts also with phenols, amines, and thiols;2 [4 + 2] cycloadditions with strained4 and electron-rich5 alkenes)

Physical Data: bp 80-85 °C/20 mmHg; d 1.581 g cm-3.

Solubility: sol CH2Cl2, ether, THF; reacts with H2O and protic solvents.

Form Supplied in: colorless oil; widely available.

Handling, Storage, and Precautions: should be stored in the absence of moisture and be handled in a fume hood; lachrymator.

Carbamates.

The strong electrophilic properties of this reagent allow ready reaction to occur with alcohols and phenols (O-acylation) to form trichloroacetyl carbamates (urethanes),2,3 with amines to give trichloroacetyl ureas,2d and with thiols to give trichloroacetyl thiocarbamates.2b These in situ derivatizations are useful for the expeditious classification of alcohols as well as amines and thiols by NMR spectroscopy.2 However, C-acylation sometimes takes place if a pyrrole or furan nucleus is present in the molecule.6 Selective removal of the trichloroacetyl group is readily achieved by mild hydrolysis under neutral to weakly basic conditions (aq Potassium Carbonate3a,b,d or aq NaHCO33f in MeOH or EtOH; Ammonia in MeOH;3g Alumina;3e SiO2 in MeOH3c) to give unsubstituted carbamates (eq 1).3d,7 This procedure has been often used for the synthesis of carbamates in the field of antibiotics.3c,f,g This method is complementary to the use of Chlorosulfonyl Isocyanate to prepare unsubstituted carbamates from alcohols.7 Carbamates are useful for stereoselective alkene functionalization. Iodonium ion mediates cyclization of allylic and homoallylic carbamates to give cyclic carbonates.3b Base-catalyzed intramolecular conjugate addition to activated alkenes afforded oxazolidinones and perhydrooxazinones (eq 1).7

Trichloroacetyl isocyanate is an effective dehydrating reagent in the preparation of 1,2-benzisoxazoles from salicylaldoximes (eq 2).8

Cycloaddition with Alkenes.

This isocyanate reacts preferably as a 4p component with strained (eq 3)4b and electron-rich alkenes (eq 4)5b to give [4 + 2] cycloaddition products, in contrast to the [2 + 2] reactions of sulfonyl isocyanates.4,5 Various other heterocycles have been synthesized similarly via cycloadditions5,10 and also via O-8 and N-acylation.9

Oxidation of 4-phenylurazole to triazolinedione is more effectively achieved by use of a DMSO-CCl3CONCO combination compared with other Pfitzner-Moffatt-type systems.11

Related Reagents.

Chloroacetyl Isocyanate; Chlorosulfonyl Isocyanate.


1. (a) Speziale, A. J.; Smith, L. R. JOC 1962, 27, 3742. (b) Deng, M.-Z.; Caubere, P.; Senet, J. P.; Lecolier, S. T 1988, 44, 6079.
2. (a) Goodlett, V. W. Anal. Chem. 1965, 37, 431. (b) Butler, P. E.; Mueller, W. H. Anal. Chem. 1966, 38, 1407. (c) Trehan, I. R.; Monder, C.; Bose, A. K. TL 1968, 67. (d) Bose, A. K.; Srinivasan, P. R. T 1975, 31, 3025.
3. (a) Minami, N.; Ko, S. S.; Kishi, Y. JACS 1982, 104, 1109. (b) Hirama, M.; Uei, M. TL 1982, 23, 5307. (c) Perrone, E.; Alpegiani, M.; Bedeschi, A.; Giudici, F.; Foglio, M.; Franceschi, G. TL 1983, 24, 3283. (d) Hirama, M.; Shigemoto, T.; Yamazaki, Y.; Itô, S. JACS 1985, 107, 1797. (e) Koc&ocaron;vský, P. TL 1986, 27, 5521. (f) Pattenden, G.; Stapleton, A.; Humber, D. C.; Roberts, S. M. JCS(P1) 1988, 1685. (g) Fukuyama, T.; Yang, L. JACS 1989, 111, 8303.
4. (a) Smith, L. R.; Speziale, A. J.; Fedder, J. E. JOC 1969, 34, 633. (b) Byrne, B.; Wilson, II, C. A.; Agosta, W. C. TL 1976, 2189. (c) Byrne, B.; Wilson, II, C. A.; Wolff, S.; Agosta, W. C. JCS(P1) 1978, 1550.
5. (a) Chmielewski, M.; Kaluza, Z.; Abramski, W.; Grodner, J.; Belzecki, C.; Sedmera, P. T 1989, 45, 227. (b) Kaluza, Z.; Fudong, W.; Belzecki, C.; Chmielewski, M. TL 1989, 5171. (c) Kawamura, S.; Sanemitsu, Y. JOC 1993, 58, 414. (d) Roedig, A.; Ritschel, W.; Fouré, M. CB 1980, 113, 811. (e) Schweizer, E. E.; Lee, K.-J. JOC 1987, 52, 3681.
6. (a) Samek, Z.; Novotný, L. TL 1972, 5167. (b) Lösel, W.; Pook, K.-H. CB 1986, 119, 2553.
7. (a) Hirama, M.; Shigemoto, T.; Itô, S. JOC 1987, 52, 3342. (b) Hirama, M.; Itô, S. H 1989, 28, 1229.
8. Stokker, G. JOC 1983, 48, 2613.
9. Buchanan, J. G.; Harrison, M.; Wightman, R. H.; Harnden, M. R. JCS(P1) 1989, 925.
10. Vandensavel, J.-M.; Smets, G.; L'abbé, G. JOC 1973, 38, 675.
11. Moore, J. A.; Muth, R.; Sorace, R. JOC 1974, 39, 3799.

Masahiro Hirama & Tohru Oishi

Tohoku University, Sendai, Japan



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