[Skip to Content](https://www.sigmaaldrich.com#main-content) [](https://www.sigmaaldrich.com/US/en) Products Cart0 USEN Products [Login / Register](https://www.sigmaaldrich.com/oidc-sign-in) [Order Lookup](https://www.sigmaaldrich.com/US/en/order-lookup) [Quick Order](https://www.sigmaaldrich.com/US/en/quick-order) Cart0 [Home](https://www.sigmaaldrich.com/US/en)[Fluorination](https://www.sigmaaldrich.com/US/en/applications/chemistry-and-synthesis/synthetic-methods/fluorination)Acid Halogenation Reagents # Acid Halogenation Reagents The generation of an acid chloride is an obvious way to activate the carboxy group for amide bond formation. However, practical application of acid chlorides in peptide synthesis is restricted, because they are prone to side reactions and racemization. In spite of this disadvantage, acid chlorides are frequently recommended to link extremely hindered or achiral amino acids. 1-Chloro-*N,N*,2- trimethyl-1-propenylamine, developed by Ghosez, enables the conversion of carboxylic acids into the corresponding chlorides under strictly neutral conditions.1 This method was successfully applied by Fürstner in the total synthesis of Caloporoside and Roseophilin.2 The most notable advance in acid halogenation has been the introduction of fluoroamidinium salts by Carpino.3 Compared to the chlorides, the acid fluorides show greater stability toward water and a relative lack of conversion to the corresponding oxazolones upon treatment with organic bases. TFFH (fluoro- *N,N,N’,N’*-tetramethylformamidinium hexafluorophosphate) and BTFFH (fluoro-*N,N,N’,N’*-bis(tetramethylene)formamidinium hexafluorophosphate) are stable, non-hygroscopic salts. These reagents act *in situ* as fluorinating reagents and are suitable both for solution syntheses and for solid-phase peptide synthesis (SPPS). ## Materials Sorry, an unexpected error has occurred Response not successful: Received status code 500 ### References 1\. 1979\. a-CHLORO ENAMINES, REACTIVE INTERMEDIATES FOR SYNTHESIS: 1-CHLORO-N,N,2-TRIMETHYLPROPENYLAMINE. Org. Synth.. 5926. [https://doi.org/10.15227/orgsyn.059.0026](https://doi.org/10.15227/orgsyn.059.0026) 2\. Fürstner A, Konetzki I. 1998. Total Synthesis of Caloporoside. J. Org. Chem.. 63(9):3072-3080. [https://doi.org/10.1021/jo9800098](https://doi.org/10.1021/jo9800098) 3\. Carpino LA, El-Faham A. 1995. Tetramethylfluoroformamidinium Hexafluorophosphate: A Rapid-Acting Peptide Coupling Reagent for Solution and Solid Phase Peptide Synthesis. J. Am. Chem. Soc.. 117(19):5401-5402. [https://doi.org/10.1021/ja00124a040](https://doi.org/10.1021/ja00124a040) __Related Articles__ - [AlPhos and \[(AlPhosPd)2•COD\] for Pd-Catalyzed Fluorination](https://www.sigmaaldrich.com/US/en/technical-documents/technical-article/chemistry-and-synthesis/fluorination/alphos) - [Deoxyfluorination with 2-Pyridinesulfonyl Fluoride (PyFluor)](https://www.sigmaaldrich.com/US/en/technical-documents/technical-article/chemistry-and-synthesis/fluorination/deoxyfluorination-with-pyfluor) - [Diethylaminosulfur Trifluoride (DAST)](https://www.sigmaaldrich.com/US/en/technical-documents/technical-article/chemistry-and-synthesis/fluorination/diethylaminosulfur) - [Fluoroalkylation: Expansion of Togni Reagents](https://www.sigmaaldrich.com/US/en/technical-documents/technical-article/chemistry-and-synthesis/fluorination/fluoralkylation) - [Fluorinated Azides: Click Chemistry Meets Fluorine](https://www.sigmaaldrich.com/US/en/technical-documents/technical-article/chemistry-and-synthesis/fluorination/fluorinated-azides) - [PhenoFluor™ Deoxyfluorination Solution](https://www.sigmaaldrich.com/US/en/technical-documents/technical-article/chemistry-and-synthesis/fluorination/phenofluor) - [Selectfluor™](https://www.sigmaaldrich.com/US/en/technical-documents/technical-article/chemistry-and-synthesis/fluorination/selectfluor) - [AISF: A Solid Alternative to Sulfuryl Fluoride Gas](https://www.sigmaaldrich.com/US/en/technical-documents/technical-article/chemistry-and-synthesis/fluorination/stable-alternative-aisf) - [View More](https://www.sigmaaldrich.com/US/en/search/facet-search?focus=sitecontent&term=facet-search) __Related Product Categories__ - [Click Chemistry Reagents Overview](https://www.sigmaaldrich.com/US/en/products/chemistry-and-biochemicals/chemical-biology/click-chemistry-reagents) - [Amino Acids, Resins & Reagents for Peptide Synthesis](https://www.sigmaaldrich.com/US/en/products/chemistry-and-biochemicals/amino-acids-resins-and-reagents-for-peptide-synthesis) - [Organic Building Blocks](https://www.sigmaaldrich.com/US/en/products/chemistry-and-biochemicals/building-blocks/organic-building-blocks) Top __Sign In To Continue__ To continue reading please sign in or create an account. Sign In__Don't Have An Account?__Register An unknown error has occured. - English - EN - Español - ES [Learn More](https://www.sigmaaldrich.com)