Benzotriazol-1-yloxytris(dimethylamino) phosphonium Hexafluorophosphate

Abstract

[56602-33-6] C12H22F6N6OP2 (MW 442.29) InChI = 1/C12H22N6OP.F6P/c1-15(2)20(16(3)4,17(5)6)19-18-12-10-8-7-9-11(12)13-14-18;1-7(2,3,4,5)6/h7-10H,1-6H3;/q+1;-1 InChIKey = MGEVGECQZUIPSV-UHFFFAOYAP (peptide coupling agent providing high yield and low racemization levels;1 promotes peptide cyclization19 and other lactamization,23 especially β-lactam formation;24 used to effect various amidification reactions25-29 and selective esterification;31 reagent for nucleotidic coupling32) Alternate Name: BOP; Castro's reagent. Physical Data: mp 138 °C (dec.). Solubility: insol H2O; sol THF, CH2Cl2, MeCN, acetone, DMF, NMP, DMSO. Form Supplied in: white solid; commercially available. Purity 97–98%. Analysis of Reagent Purity: 1H NMR (acetone-d6): 3.0 (d, 18H, JH–P = 10 Hz, NMe2), 7.9 (m, 4H, arom.). 31P NMR (CH2Cl2): + 43.7 (s, P+), −144.2 (septet, PF6−). IR (KBr): 1010 (P–N), 840, 770, 560 (PF6−). Preparative Methods: BOP reagent was initially obtained2a by reaction of Hexamethylphosphorous Triamide (tris (dimethylamino)phosphine, TDAP) with CCl4 in the presence of HOBt (1‐Hydroxybenzotriazole) followed by precipitation of the phosphonium salt by anion exchange with aqueous KPF6 solution. It was then prepared2b,c by reaction of cheaper (Me2N)3PO (HMPA) with COCl2 (phosgene) to generate the chlorophosphonium chloride intermediate, with treatment of the latter with HOBt and base, and precipitation as below. COCl2 was further replaced by POCl3.2d,e Triphosgene can also be employed and a resin-bound version of BOP is known. The crude final product can, if necessary, be purified by recrystallization from a mixture of acetone–ether or CH2Cl2 (DCM)–ether. Handling, Storage, and Precautions: irritant and harmful. Light sensitive. Incompatibility: strong oxidizing agents. Avoid breathing dust; avoid contact with eyes, skin, and clothing. Keep container closed and store in the dark. Refrigerate. Although BOP is widely used, it is important to stress that the carcinogenic HMPA is a side product and the reagent must be handled with caution. All operations should be carried out in a fume hood.