3-Hydroxy-1,2,3-benzotriazin-4(3H)-one

[28230-32-2]  · C7H5N3O2  · 3-Hydroxy-1,2,3-benzotriazin-4(3H)-one  · (MW 163.15)

(additive to improve yields and decrease racemization in DCC-promoted peptide synthesis1)

Alternate Names: Dhbt-OH; 3-hydroxy-4-keto-3,4-dihydro-1,2,3-benzotriazine.

Physical Data: mp 180-181 °C (dec).

Preparative Method: reaction of Sodium Nitrite with o-aminobenzhydroxamic acid.2

Solubility: sol most organic solvents.

Handling, Storage, and Precautions: regarded as an irritant rather than toxic. Possible explosive hazard.

Peptide Synthesis.

An appreciable amount of racemization (up to 70%) is often found to accompany the DCC-promoted synthesis of peptides (see 1,3-Dicyclohexylcarbodiimide). The use of Dhbt-OH as an additive improves yields (by up to 15%) and decreases racemization to almost undetectable levels in all the solvents tried (DMF, THF, CH2Cl2, DMSO).1 Undesirable side-products resulting from attack on the triazine-ring carbonyl have meant that this reagent has been little used, 1-Hydroxybenzotriazole being preferred. Recently, Dhbt-amino esters have shown promise in solid-phase peptide synthesis.3,4 By premixing the N-protected amino acid and DCC before addition of Dhdt-OH, side-reactions are eliminated. Dhbt-amino esters have a useful self indication property in peptide synthesis, the liberated Dhbt-O- anion giving a transient yellow color to the reaction until all the reacting amino groups have been consumed.

Miscellaneous.

Oligodeoxynucleoside phosphorodithiolates have been been efficiently synthesized using a Dhbt-OH-based phosphorus reagent.5 Reductive decarboxylation of cinnamic acid with Tri-n-butylstannane was accomplished in excellent yield via the Dhbt-ester (eq 1).6


1. König, W.; Gieger, R. CB 1970, 103, 2034.
2. Harrison, D.; Smith, A. C. B. JCS 1960, 2157.
3. Atherton, E.; Cameron, L.; Meldal, M.; Sheppard, R. C. CC 1986, 1763.
4. Atherton, E.; Holder, J.; Meldel, M.; Sheppard, R. C.; Valerio, R. M. JCS(P1) 1988, 2887.
5. Dahl, B. H.; Bjergarde, K.; Nielson, J.; Dahl, O. TL 1990, 31, 3489.
6. Barton, D. H. R.; Blundell, P.; Jaszberenyi, J. Cs. TL 1989, 30, 2341.

Stephen C. Moratti

University of Cambridge, UK



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