HBTU (Hexafluorophosphate Benzotriazole Tetramethyl Uronium) is a
coupling
A coupling is a device used to connect two shafts together at their ends for the purpose of transmitting power. The primary purpose of couplings is to join two pieces of rotating equipment while permitting some degree of misalignment or end mo ...
reagent
In chemistry, a reagent ( ) or analytical reagent is a substance or compound added to a system to cause a chemical reaction, or test if one occurs. The terms ''reactant'' and ''reagent'' are often used interchangeably, but reactant specifies a ...
used in solid phase
peptide synthesis
In organic chemistry, peptide synthesis is the production of peptides, compounds where multiple amino acids are linked via amide bonds, also known as peptide bonds. Peptides are chemically synthesized by the condensation reaction of the carboxyl ...
. It was introduced in 1978 and shows resistance against racemization. It is used because of its mild activating properties.
HBTU is prepared by reaction of HOBt with
TCFH under basic conditions and was assigned to a
uronium type structure, presumably by analogy with the corresponding phosphonium salts, which bear a positive carbon atom instead of the phosphonium residue. Later, it was shown by X-ray analysis that salts crystallize as
guanidinium rather than the corresponding uronium salts.
Mechanism
HBTU activates carboxylic acids by forming a stabilized HOBt (Hydroxybenzotriazole) leaving group. The activated intermediate species attacked by the amine during aminolysis is the HOBt ester.
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. Aminolysis displaces the benzotriazole N-oxide to form the desired amide.
Safety
''In vivo'' dermal sensitization studies according to
OECD
The Organisation for Economic Co-operation and Development (OECD; , OCDE) is an international organization, intergovernmental organization with 38 member countries, founded in 1961 to stimulate economic progress and international trade, wor ...
429 confirmed HBTU is a moderate skin
sensitizer, showing a response at 0.9 wt% in the
Local Lymph Node Assay (LLNA) placing it in
Globally Harmonized System of Classification and Labelling of Chemicals (GHS) Dermal Sensitization Category 1A. Thermal hazard analysis by
differential scanning calorimetry (DSC) shows HBTU is potentially explosive.
See also
*
EDC
*
HATU
*
BOP reagent
*
PyBOP
*
PyAOP reagent
References
{{reflist
Hexafluorophosphates
Peptide coupling reagents
Benzotriazoles
Dimethylamino compounds
Guanidinium compounds