HBTU

HBTU (Hexafluorophosphate Benzotriazole Tetramethyl Uronium) is a coupling reagent used in solid phase peptide synthesis.

[7][8] HBTU activates carboxylic acids by forming a stabilized HOBt (Hydroxybenzotriazole) leaving group.

To create the HOBt ester, the carboxyl group of the acid attacks the imide carbonyl carbon of HBTU.

Subsequently, the displaced anionic benzotriazole N-oxide attacks of the acid carbonyl, giving the tetramethyl urea byproduct and the activated ester.

[11] Thermal hazard analysis by differential scanning calorimetry (DSC) shows HBTU is potentially explosive.

HBTU Structural Formula
This scheme depicts the general mechanistic steps of HBTU creating an activated ester out of the carboxylate anion of the acid substrate. The deprotination of the carboxylic acid and the aminolysis of the activated ester are not shown.