Hydroxybenzotriazole

Hydroxybenzotriazole
IUPAC name 1-Hydroxybenzotriazole
Other names N-Hydroxybenzotriazole HOBt
Identifiers
CAS number	2592-95-2 Y,  123333-53-9 (hydrate)
ChemSpider	68282 Y
Jmol-3D images	Image 1
SMILES n1nn(O)c2ccccc12
InChI InChI=1S/C6H5N3O/c10-9-6-4-2-1-3-5(6)7-8-9/h1-4,10H Y Key: ASOKPJOREAFHNY-UHFFFAOYSA-N Y InChI=1/C6H5N3O/c10-9-6-4-2-1-3-5(6)7-8-9/h1-4,10H Key: ASOKPJOREAFHNY-UHFFFAOYAP
Properties
Molecular formula	C6H5N3O
Molar mass	135.12 g mol−1
Melting point	156-159 °C (decomp.)
Y (verify) (what is: Y/N?) Except where noted otherwise, data are given for materials in their standard state (at 25 °C, 100 kPa)
Infobox references

Hydroxybenzotriazole (abbreviated HOBt) is an organic compound that is a derivative of benzotriazole. It is mainly used to suppress racemization and improve the efficiency of peptide synthesis. It is a white crystalline powder. Commercial HOBt always contains some water (~11.7% wt as the HOBt monohydrate crystal) because anhydrous HOBt is explosive.

Use in peptide synthesis

Automated peptide synthesis involves the condensation of the amino group of protected amino acids with the activated ester. HOBt is used to produce such activated esters. These esters are insoluble (like the N-hydroxysuccinimide esters) and react with amines at ambient temperature to give amides.^[1]

HOBt is also used for the synthesis of amides from carboxylic acids aside from amino acids. These substrates may not be convertable to the acyl chlorides.^[2] For instance amide derivatives of ionophoric antibiotics have been prepared in this way.^[3]

Example of a coupling reaction with HOBt

Together with laccase, HOBt is also used for bleaching pulps. The method is still on the experimental stage and have yet not been commercialized.

Safety

Due to reclassification as UN0508, a class 1.3C explosive, hydroxybenzotriazole and its monohydrate crystal are no longer allowed to be transported by sea or air as per 49CFR (USDOT hazardous materials regulations). However, UNECE draft proposal ECE/TRANS/WP.15/AC.1/HAR/2009/1 has been circulated to UN delegates and, if implemented, would amend current regulations thus allowing for the monohydrate crystal to be shipped under the less-stringent code of UN3474 as a class 4.1 desensitized explosive.

References

1. ^ W. König, R. Geiger (1970). "Eine neue Methode zur Synthese von Peptiden: Aktivierung der Carboxylgruppe mit Dicyclohexylcarbodiimid unter Zusatz von 1-Hydroxy-benzotriazolen". Chem. Ber. 103 (3): 788–798. doi:10.1002/cber.19701030319. 
2. ^ Andrew G. Myers, Bryant H. Yang, and Hou Chen TRANSFORMATION OF PSEUDOEPHEDRINE AMIDES INTO HIGHLY ENANTIOMERICALLY ENRICHED ALDEHYDES, ALCOHOLS, AND KETONES Organic Syntheses, Vol. 77, p. 29 (2000); Coll. Vol. 10, p.509 (2004).
3. ^ Łowicki, Daniel; A. Huczyński, M. Ratajczak-Sitarz, A. Katrusiak, J. Stefańska, B. Brzezinski, F. Bartl (2009). "Structural and antimicrobial studies of a new N-phenylamide of monensin A complex with sodium chloride". Journal of Molecular Structure 923 (1–3): 53–59. doi:10.1016/j.molstruc.2009.01.056.