Chloroacetyl Isocyanate

[4461-30-7]  · C3H2ClNO2  · Chloroacetyl Isocyanate  · (MW 119.51)

(preparation of primary amides from Grignard reagents,11 monosubstituted ureas from primary amines12 and from b-lactams13)

Physical Data: fp 61 °C; bp 50-55 °C/20 mmHg, 68-79 °C/70 mmHg; d 1.403 g cm-3.

Solubility: sol benzene, THF, etc.

Form Supplied in: colorless-yellow oil, commercially available; can also be prepared in the laboratory.1

Handling, Storage, and Precautions: toxic, lachrymator, corrosive, reacts with moisture; refrigerate and store under nitrogen; should be handled in a fume hood.

Addition Reactions.

Chloroacetyl isocyanate (1) undergoes a variety of reactions, typical of the isocyanate class, including addition reactions with alcohols,2 amines,3 organic peroxides,4 ketene silyl acetals,5 hydrazines,6 2-pyrazolines,7 and triazoline-3,5-diones.8 In addition, the bifunctionality of this reagent endows it with specialized uses including the synthesis of heterocyclic rings9,10 and polymers.3,4

Addition-Cleavage Reactions: N-Unsubstituted Amides and Ureas.

Grignard reagents add to reagent (1) to afford mixed imides.11 These compounds may then be cleaved either reductively or hydrolytically at the chloromethyl-substituted carbonyl to give primary amides (eq 1).

Likewise, chloroacetyl ureas derived from (1) and primary amines are subject to regioselective cleavage by nucleophiles to give N-monosubstituted ureas.12

Condensation of (1) with photopyridones (b-lactams, eq 2)13 gave N-chloracetylcarbamoyl derivatives. Treatment of these compounds with Triethylamine in methanol gave the all-cis-1,2,3-trisubstituted cyclobutanes, whereas treatment with sodium methoxide in methanol afforded the trans,trans-cyclobutanes. The latter class of compounds provides an intermediate for the synthesis of oxetanosyl N-glycosides.

Related Reagents.

Chlorosulfonyl Isocyanate; Trichloroacetyl Isocyanate.

1. Speziale, A. J.; Smith, L. R. OSC 1973, 5, 204.
2. Müller, E.; Dinges, K. Angew. Makromol. Chem. 1972, 27, 99.
3. Endo, T.; Noguchi, S.; Mukaiyama, T. BCJ 1971, 44, 3424.
4. Höft, E.; Ganschow, S. JPR 1974, 316, 569.
5. Cambie, R. C.; Davis, P. F.; Rutledge, P. S.; Woodgate, P. D. AJC 1984, 37, 2073.
6. Nuribzhanyan, K. A.; Kuznetsova, G. B. ZOR 1973, 1171.
7. Zobova, N. N.; Nazyrova, A. Z.; Litvinov, I. A.; Aganov, A. V.; Naumov, V. A. J. Gen. Chem. USSR 1991, 61, 1329.
8. Capuano, L.; Müller, K. CB 1977, 110, 1691.
9. Zara-Kacziàn, E.; Deàk, G. Acta Chim. Hung. 1989, 126, 723.
10. Anjaneyulu, B.; Nagarajan, K. IJC(B) 1991, 30B, 399.
11. Parker, K. A.; Gibbons, E. G. TL 1975, 981.
12. Marui, S.; Kishimoto, S. CPB 1992, 40, 575.
13. Katagiri, N.; Sato, H.; Kaneko, C. CPB 1990, 38, 288.

Kathlyn A. Parker & David Taveras

Brown University, Providence, RI, USA

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