1,1,3,3-Tetramethylfluoroformamidinium Hexafluorophosphate

Abstract

[164298-23-1] C5H12F7N2P (MW 264.125) InChI = 1S/C5H12FN2.F6P/c1-7(2)5(6)8(3)4;1-7(2,3,4,5)6/h1-4H3;/q+1;-1 InChIKey = ZAVXOOLKAGPJPI-UHFFFAOYSA-N (acyl fluoride formation, coupling reagent for amide preparation, and both solution and solid phase peptide synthesis, preparation of isothiocyanates and acylhydrazides)1, 2 Alternate Names: fluoro-N,N,N′,N′-tetramethylformamidinium hexafluorophosphate, TFFH. Physical data: m.p. 110 °C. Solubility: soluble in DMSO, DMF, CH3CN, and CH2Cl2. Form supplied in: white crystalline solid, commercially available. Analysis of Reagent Purity: 1H NMR, elemental analysis. Preparative Methods: The title reagent, and its analog. bis(tetramethylene)fluoroformamidinium hexafluorophosphate (BTFFH), are readily obtained by reaction of tetramethylchloroformamidinium hexafluorophosphate (TCFH) with excess anhydrous KF (eq 1).1, 3 An improved large scale synthesis of this reagent was achieved using a one pot process starting from oxalyl chloride and tetramethylurea.4 In another synthesis,2 using POCl3 and hexafluorophosphoric acid, TCFH could be obtained efficiently from tetramethylurea. This avoids the use of phosgene, which is difficult to handle, and of the more expensive ammonium hexafluorophosphate. (1) Purification: recrystallization from a mixture of MeCN and ether or from CH2Cl2 and ether. Handling, Storage and Precautions: TFFH is not hygroscopic and can be stored indefinitely at 0 °C. A TFFH solution in DMF is sensitive to moisture and cannot be stored, which makes TFFH less stable relative to other uronium salts such as HATU or HBTU.5 The synthesis of peptides should be carried out with a freshly prepared solution.