Chemistry:HBTU
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| IUPAC name
[benzotriazol-1-yloxy(dimethylamino)methylidene]-dimethylazanium;hexafluorophosphate[1]
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Other names
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| Identifiers | |
3D model (JSmol)
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PubChem CID
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| Properties | |
| C11H16F6N5OP | |
| Molar mass | 379.247 g·mol−1 |
| Appearance | White crystals |
| Melting point | 200 °C (392 °F; 473 K) |
| Hazards[2] | |
| Main hazards | Irritant |
| GHS pictograms | 
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| GHS Signal word | Warning |
| H315, H319, H335 | |
| P210, P240, P241, P261, P264, P271, P280, P302+352, P304+340, P305+351+338, P312, P332+313, P337+313, P362, P370+378, P403+233, P405, P501 | |
Except where otherwise noted, data are given for materials in their standard state (at 25 °C [77 °F], 100 kPa). | |
| Infobox references | |
HBTU (Hexafluorophosphate Benzotriazole Tetramethyl Uronium) is a coupling reagent used in solid phase peptide synthesis. It was introduced in 1978 and shows resistance against racemization.[3][4] It is used because of its mild activating properties.[5]
The product obtained by reaction of HOBt with tetramethyl chloro uronium salt (TMUCl) 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 aminium rather than the corresponding uronium salts.[6][7]
Mechanism
File:Mechanism tiff.tif 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.[8]
See also
References
- ↑ CID 2733084 from PubChem
- ↑ "2-(1h-Benzotriazole-1-yl)-1,1,3,3-tetramethyluronium hexafluorophosphate" (in en). https://pubchem.ncbi.nlm.nih.gov/compound/2733084#section=Safety-and-Hazards.
- ↑ Dourtoglou, Vassilis. (April 1978). "L'hexafluorophosphate de O-benzotriazolyl-N,N-tetramethyluronium: Un reactif de couplage peptidique nouveau et efficace". Tetrahedron Letters 19 (15): 1269–1272. doi:10.1016/0040-4039(78)80103-8.
- ↑ Knorr, R.; Trzeciak, A.; Bannwarth, W.; Gillessen, D. (1989). "New coupling reagents in peptide chemistry". Tetrahedron Letters 30 (15): 1927–1930. doi:10.1016/S0040-4039(00)99616-3.
- ↑ Solange, A. (1992). "HBTU: a mild activating agent of muramic acid". Bioorganic & Medicinal Chemistry Letters 2 (6): 571–574. doi:10.1016/S0960-894X(01)81199-9.
- ↑ Carpino, L.; Imazumi, H.; El-Faham, A.; Ferrer, F.; Zhang, C.; Lee, Y.; Foxman, B.; Henklein, P. et al. (2002). "The uronium/guanidinium peptide coupling reagents: Finally the true uronium salts". Angewandte Chemie International Edition 41 (3): 441–445. doi:10.1002/1521-3773(20020201)41:3<441::AID-ANIE441>3.0.CO;2-N. PMID 12491372.
- ↑ Abdelmoty, I.; Albericio, F.; Carpino, L.; Foxman, B.; Kates, S. (1994). "Structural studies of reagents for peptide bond formation: Crystal and molecular structures of HBTU and HATU". Letters in Peptide Science 1 (2): 57–67. doi:10.1007/BF00126274.
- ↑ Bradley, Mark; Valeur, Eric (2009-01-26). "Amide bond formation: beyond the myth of coupling reagents" (in en). Chemical Society Reviews 38 (2): 606–631. doi:10.1039/B701677H. ISSN 1460-4744. PMID 19169468.
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