Bis(o-nitrophenyl) Phenylphosphonate

[73404-18-9]  · C18H13N2O7P  · Bis(o-nitrophenyl) Phenylphosphonate  · (MW 400.28)

(coupling reagent for peptide1,2 and carboxamide synthesis3)

Preparative Method: readily prepared from o-nitrophenol and phenylphosphonic dichloride (PhP(O)Cl2).1

Peptide and Carboxamide Synthesis.

Condensation of the tetrabutylammonium salt of N-benzoyl-L-leucine with glycine ethyl ester, the components in the Young's test,4 in DMF in the presence of bis(o-nitrophenyl) phenylphosphonate proceeds to give the corresponding dipeptide in 82-93% yield without racemization.1 Employment of quarternary ammonium salts5 enables the reaction to proceed smoothly because of increased solubility6 and nucleophilicity of the carboxyl component. The coproducts are o-nitrophenol and the phosphonate ammonium salt, which means that no free base such as tertiary amines need to be utilized, which often cause serious problems such as racemization during condensation (eq 1).4 This method has been efficiently applied to more complex hexaglycine and leucine-enkephalin (L-Tyr-Gly-Gly-L-Phe-L-Leu) peptides.2

Preparation of both peptides and carboxamides have been simplified by the use of phase-transfer conditions in which the tetrabutylammonium carboxylic acid salts are formed in situ.3 Thus treatment of free acids and amines in aqueous CH2Cl2 (or aqueous THF) with bis(o-nitrophenyl) phenylphosphonate in the presence of n-Bn4N+HSO4- (or n-Bn4N+Br-) gave corresponding carboxamides and peptides. An example of the method3 is the preparation of an arylamide in quantative yield (eq 2).

Related Reagents.

Bis(p-nitrophenyl) Phenylphosphonate.

1. Mukaiyama, T.; Morito, N.; Watanabe, Y. CL 1979, 11, 1305.
2. Watanabe, Y.; Morito, N.; Kamekawa, K.; Mukaiyama, T. CL 1981, 1, 65.
3. Watanabe, Y.; Mukaiyama, T. CL 1981, 3, 285.
4. Williams, M. W.; Young, G. T. JCS 1963, 881.
5. Wakselman, M.; Acher, F. TL 1980, 21, 2705.
6. Luisi, P. L.; Bonner, F. J.; Pellegrini, A.; Wiget, P.; Wolf, R. HCA 1979, 62, 740.

Harjinder S. Bansal

Zeneca Agrochemicals, Bracknell, UK

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