https://doi.org/10.15255/KUI.2006.034
Published: Kem. Ind. 56 (3) (2007) 123–134
Paper reference number: KUI-34/2006
Paper type: Conference paper
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The Curious Molecule Benzotriazole

I. Butula+ and B. Zorc

Abstract

In this paper, a review of reactions with benzotriazole as synthetic auxiliary is given. In contrast to most other azoles, benzotriazole reacts with phosgene in molar ratio 1:1 yielding carboxylic acid chloride (BtcCl, 1), which readily reacts with nucleophiles giving reactive compounds. These products can be easily transformed into carbamates, ureas, semicarbazides, carbazides, sulfonylureas, sulfonylcarbazides, nitroalkanic acid esters, etc. In addition, benzotriazole was used in the synthesis of various heterocyclic compounds: benzoxazine, kinazoline, triazinetrione, hydantoin and oxadiazine derivatives. The reaction of chloride 1 with amino acids enabled the use of benzotriazole in peptide chemistry, with triple role of benzotriazolecarbonyl group as N-protecting, N-activating, and both N-protecting/C-activating group. N-(1-benzotriazolecarbonyl)-amino acids 25 are starting compounds in the synthesis of various amino acid, di- and tripeptide derivatives, hydantoic acids and hydroxyureas. Benzotriazole was also applied in the preparation of polymer-drug and thiomer-drug conjugates, polymeric prodrugs with drugs covalently bound to the polymeric carriers. Such macromolecular prodrugs may offer many advantages compared to other drug delivery systems such as increased drug solubility, prolonged drug release, increased stability. It is also possible to accumulate the drug at the site of the pathological process and to minimize its toxicity. In this paper, the binding of drugs from various therapeutic groups (mostly nonsteroidal, anti-inflammatory drugs) to polymers of polyaspartamide type by the benzotriazolide method is described.

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Keywords

azole, benzotriazole, 1-benzotriazole carboxilic acid chloride, organic synthesis