HCTU
HCTU
Names
IUPAC name
O -(1H -6-Chlorobenzotriazole-1-yl)-1,1,3,3-tetramethyluronium hexafluorophosphate
Other names
2-(6-Chloro-1H -benzotriazole-1-yl)-1,1,3,3-tetramethylaminium hexafluorophosphate
Identifiers
ChemSpider
ECHA InfoCard
100.116.975
EC Number
InChI=1S/C11H15ClN5O.F6P/c1-15(2)11(16(3)4)18-17-10-7-8(12)5-6-9(10)13-14-17;1-7(2,3,4,5)6/h5-7H,1-4H3;/q+1;-1
Key: ZHHGTMQHUWDEJF-UHFFFAOYSA-N
CN(C)C(=[N+](C)C)ON1C2=C(C=CC(=C2)Cl)N=N1.F[P-](F)(F)(F)(F)F
Properties
C 11 H 15 Cl F 6 N 5 O P
Molar mass
413.69 g·mol−1
Appearance
White to off white powder
Melting point
>185 °C
Hazards
GHS labelling :
Warning
H228 , H302 , H315 , H319 , H335
P210 , P240 , P241 , P261 , P264 , P270 , P271 , P280 , P301+P312 , P302+P352 , P304+P340 , P305+P351+P338 , P312 , P321 , P330 , P332+P313 , P337+P313 , P362 , P370+P378 , P403+P233 , P405 , P501
Except where otherwise noted, data are given for materials in their
standard state (at 25 °C [77 °F], 100 kPa).
Chemical compound
HCTU is an amidinium coupling reagent used in peptide synthesis . It is analogous to HBTU .[ 1] The HOBt moiety has a chlorine in the 6 position which improves reaction rates and the synthesis of difficult couplings[ 2] [ 3] HCTU and related reagents containing the 6-chloro-1-hydroxybenzotriazole moiety can be prepared by reaction with TCFH under basic conditions.[ 4] It can exist in an N-form (guanidinium ) or an O-form (uronium ), but the N-form is generally considered to be more stable for this class of reagent.[ 5] In vivo dermal sensitization studies according to OECD 429 confirmed HCTU is a strong skin sensitizer , showing a response at 0.50 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.[ 6]
References
^ Marder, Oleg; Shvo, Youval; Albericio, Fernando (2003-08-12). "HCTU and TCTU: New Coupling Reagents — Development and Industrial Aspects". ChemInform . 34 (32). doi :10.1002/chin.200332258 . ISSN 1522-2667 .
^ Hood, Christina A.; Fuentes, German; Patel, Hirendra; Page, Karen; Menakuru, Mahendra; Park, Jae H. (2008-01-01). "Fast conventional Fmoc solid-phase peptide synthesis with HCTU". Journal of Peptide Science . 14 (1): 97–101. CiteSeerX 10.1.1.595.917 . doi :10.1002/psc.921 . ISSN 1099-1387 . PMID 17890639 . S2CID 24163278 .
^ Sabatino, Giuseppina; Mulinacci, Barbara; Alcaro, Maria C.; Chelli, Mario; Rovero, Paolo; Papini, Anna M. (2002-03-01). "Assessment of new 6-Cl-HOBt based coupling reagents for peptide synthesis. Part 1: Coupling efficiency study". Letters in Peptide Science . 9 (2–3): 119–123. doi :10.1007/bf02576873 . ISSN 0929-5666 . S2CID 29545816 .
^ El-Faham, Ayman; Albericio, Fernando (2008-04-01). "Morpholine-Based Immonium and Halogenoamidinium Salts as Coupling Reagents in Peptide Synthesis 1" . The Journal of Organic Chemistry . 73 (7): 2731–2737. doi :10.1021/jo702622c . ISSN 0022-3263 .
^ Carpino, Louis A.; Imazumi, Hideko; El-Faham, Ayman; Ferrer, Fernando J.; Zhang, Chongwu; Lee, Yunsub; Foxman, Bruce M.; Henklein, Peter; Hanay, Christiane; Mügge, Clemens; Wenschuh, Holger; Klose, Jana; Beyermann, Michael; Bienert, Michael (2002-02-01). "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 .
^ Graham, Jessica C.; Trejo-Martin, Alejandra; Chilton, Martyn L.; Kostal, Jakub; Bercu, Joel; Beutner, Gregory L.; Bruen, Uma S.; Dolan, David G.; Gomez, Stephen; Hillegass, Jedd; Nicolette, John; Schmitz, Matthew (2022-06-20). "An Evaluation of the Occupational Health Hazards of Peptide Couplers" . Chemical Research in Toxicology . 35 (6): 1011–1022. doi :10.1021/acs.chemrestox.2c00031 . ISSN 0893-228X . PMC 9214767 . PMID 35532537 .