[65095-13-8]  · C7H4ClN3O  · 1-Chlorocarbonylbenzotriazole  · (MW 181.58)

(formation of carbamates from alcohols;1,2 peptide synthesis3,4)

Physical Data: mp 54-55 °C.

Preparative Methods: by bubbling phosgene through a suspension of benzotriazole in toluene at 60 °C until a clear solution is obtained. Evaporation at reduced pressure gives (1) (99% yield); this crude material has mp 52-54 °C. Alternatively, an ethereal solution of benzotriazole may be added dropwise over 20 min to a 20% solution of phosgene in toluene (4 equiv); stirring until a clear solution is obtained followed by evaporation at reduced pressure gives 98% yield of (1) with mp 52 °C.1

Purification: recrystallization from light petroleum.

Preparation of Carbamates from Alcohols.

Reaction of 1-chlorocarbonylbenzotriazole (1) with an alcohol results in formation of the 1-alkoxycarbonylbenzotriazole (2). These compounds are stable to water or alcohols, but react with amines (or hydrazines) to give the carbamates (3) (eq 1).1,2 Similarly, unsymmetrical ureas can be prepared if an amine is used rather than an alcohol in the first step.5

Peptide Synthesis.

(1) reacts with two equivalents of an amino acid in dioxane to give the N-(1-benzotriazolylcarbonyl) (Btc) amino acid (4) (eq 2), which separates almost quantitatively from the hydrochloride salt of the second equivalent of amino acid employed.6

These Btc-amino acids can be used for peptide synthesis in two ways. Reaction of (4) with an amine or amino acid in acetonitrile or in aqueous acetone effects amide bond formation without racemization (eq 3).3 Benzotriazole and CO2 are the coproducts.

N-Activation can also be achieved. Treatment of the ester (5), derived from (4), with a Cbz-protected amino acid again results in loss of CO2 and benzotriazole to form an amide bond (eq 4).4 This procedure seems to offer little advantage over other methods of peptide synthesis, however.

1. Butula, I.; Prostenik, M. V.; Vela, V. Croat. Chem. Acta 1977, 49, 837 (CA 1979, 90, 38 755w).
2. Butula, I.; Curkovic, Lj.; Prostenik, M. V.; Vela, V.; Zorko, F. S 1977, 704 (CA 1978, 88, 37 582j).
3. Butula, I.; Zorc, B.; Ljubic, M.; Karlovic, G. S 1983, 327 (CA 1983, 99, 22 912v).
4. Zorc, B.; Karlovic, G.; Butula, I. Croat. Chem. Acta 1990, 63, 565 (CA 1991, 115, 183 860r).
5. Butula, I.; Vela, V.; Ivezic, B. Croat. Chem. Acta 1978, 51, 339 (CA 1979, 90, 203 522c).
6. Butula, I.; Zorc, B.; Vela, V. Croat. Chem. Acta 1981, 54, 435 (CA 1982, 97, 24 189x).

Alan Armstrong

University of Bath, UK

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