PyBOP

Benzotriazol- 1-yl oxytripyrrolidinophosphoniumhexafluorophosphat

Colorless crystals

Solid, crystalline

156-157 ° C

Soluble in dichloromethane

Attention

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PyBOP (benzotriazol -1 -yl - oxytripyrrolidinophosphonium hexafluorophosphate ) is one of the organic phosphonium salts and is used as a coupling reagent in peptide synthesis. This introduced in 1990 by the group of Castro connection constitutes a development of the phosphonium salt BOP, which as the latter does not release a highly toxic HMPA after coupling.

Representation

The original synthesis of PyBOP is based Tripyrrolidinophosphinoxid, which is converted by means of phosgene, in the Chlorophosphoniumsalz. Subsequently is reacted with the triethylammonium salt of the 1- hydroxybenzotriazole (HOBt ), which is accessible from HOBt, and triethylamine ( Et3N ) to give a chloride to OBT is substituted. The last step is the replacement of the chloride anion with a weakly coordinating hexafluorophosphate anion. Instead of gaseous phosgene can also solid triphosgene, or phosphoryl chloride are used.

The structurally related BOP can be represented equally in this way. The BOP is only the pyrrolidino - or pyrrolidin-1- id - substituted by Dimethylamidgruppen.

Use

Coupling reagent

PyBOP is employed in the peptide synthesis as a coupling reagent. Here, the activation via the phosphonium salt 2 or OBt active ester 3 is realized. The latter is known to suppress racemization, but also reacts slowly with an amine 4 to the peptide or generally to the amide. A driving force of the reaction is the formation of stable phosphoric triamide 5 dar.

B is in this scheme for base. PyBOP usually used in conjunction with DIPEA.

Other reactions

Agent PyBOP can also Thiolsäureester 6 link with amines, but in addition to the amide 8, the thionamide 7 is formed, so that a simple access to this class is created. The typical synthesis of runs under thionamides reaction of an amide with Lawesson's reagent. The reason for the O / S selectivity shown here is the stronger bond of phosphorus to oxygen.

By the reaction of amides with PyBOP / DIPEA to nitriles can be represented. Here, too, the oxygen of the carbonyl group attacks nucleophilically to the phosphorus atom of the PyBOPs. In the presence of base, the hexafluorophosphate anion, HOBt and the phosphoric triamide be cleaved. The abstraction of the imine hydrogen atom can (as shown in the diagram ) done directly by the base by the OBt or anion.