1-N-(t-Butoxycarbonyl)-1H-benzotriazole 3-N-Oxide

[111615-82-8]  · C11H13N3O3  · 1-N-(t-Butoxycarbonyl)-1H-benzotriazole 3-N-Oxide  · (MW 235.27)

(a reagent for protection of amines with the t-butoxycarbonyl group1)

Physical Data: mp 105 °C.

Solubility: sol DMF, CH2Cl2, and dioxane, among others.

Form Supplied in: the reagent is a white solid; however, it is not commercially available.

Handling, Storage, and Precautions: anhydrous conditions are not necessary for reactions, and the reagent can be stored at rt.

Introduction.

The subject of this review was believed initially to be 1-N-(t-butoxycarbonyloxy)benzotriazole. However, a single-crystal X-ray analysis established the structure unequivocally as 1-N-(t-butoxycarbonyl)-1H-benzotriazole 3-N-oxide (1). It is likely that initially the carbonate, i.e. 1-N-(t-butoxycarbonyloxy)benzotriazole, is formed, and it then rearranges to the more stable carbamate (1). Two syntheses for (1), which actually had been originally targeted for 1-N-(t-butoxycarbonyloxy)benzotriazole, are reported. In the first synthesis, 1-Hydroxybenzotriazole is converted to its chloroformate, which in turn is allowed to react with t-butanol to give 1-N-(t-butoxycarbonyloxy)benzotriazole (eq 1).1 In the second synthesis, 1-hydroxybenzotriazole is deprotonated by Triethylamine, and subsequent mixing with Di-t-butyl Dicarbonate affords the carbonate which rearranges to (1) (eq 2).2

t-Butoxycarbonylation.

Reagent (1) is exceptionally effective in N-protection of amino acids. For example, when 1 equiv of the reagent was added to a solution of L-proline and triethylamine in aqueous dioxane, an essentially quantitative conversion to the corresponding N-Boc amino acid took place in under 1 min.1 The reaction in aqueous DMF proceeds somewhat more sluggishly; however, the reaction reaches completion within 30 min. The speed of these reactions is in sharp contrast to the more commonly used reagents for N-t-butoxycarbonylation, such as Di-t-butyl Dicarbonate, 2-(t-Butoxycarbonyloxyimino)-2-phenylacetonitrile (Boc-ON), 1,2,2,2-tetrachloroethyl t-butyl carbonate, or t-Butyl Azidoformate, which usually require from a few hours to overnight reaction duration. The isolated yields for the products of the reactions of several typical amino acids with (1) have been reported in the range of 80-99% (eq 3).

The reaction of (1) with simple amines, such as Piperidine or benzylamine, or even less reactive amines, such as aniline (eq 4) or Imidazole, have been reported.1 In contrast to the reactions with amino acids, simpler amines appear to require somewhat longer reaction times.


1. Kim, S.; Chang, H. CC 1983, 1357. Kim, S.; Chang, H. Bull. Korean Chem. Soc. 1986, 7, 70.
2. Singh, J.; Fox, R.; Wong, M.; Kissick, T.; Moniot, J.; Gougoutas, J.; Malley, M.; Kocy, O. JOC 1988, 53, 205.

Ioannis Grapsas & Shahriar Mobashery

Wayne State University, Detroit, MI, USA



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