Phosphonylation partial

Pentavalent phosphorus derivatives can be converted to phosphonyl halides or phosphine oxides by partial hydrolysis or by other oxygen donors. 

Standard conditions for these reactions were chosen on the basis of preliminary test reactions from which several generalizations were derived (a) reactions occur more rapidly in MeOH than EtOH and with triethyl phosphite than with trimethyl phosphite (b) where the solvent alcohol is not identical with the alcohol from which the P(III) ester is derived, partial ester exchange results in a mixed P(V) ester and (c) reactions in phenol are cleaner and result in higher yields with only minor or no contamination by products from ester exchange. It has been demonstrated that when phenol is used as the proton source, crotonaldehyde undergoes hydrophosphonylation, even at 0°C, to selectively furnish the phosphonate as its diphenyl acetal. The yield of phosphonylated crotonaldehyde diphenyl acetal in phenol at lOO C was 82% against 59% of diethyl acetal in refluxing EtOH for the same time. ... 

Diphenyl H-phosphonate represents an inexpensive, commercially available reagent suitable for the convenient and efficient conversion of partially protected deoxyribo- and ribonucleotides into the corresponding 3 -phosphonate monoesters. The reagent is stable, easy to handle, and affords H-phosphonate monoesters of purity usually better than 95% even without column chromatography. Considering that phosphonylation with diphenyl phosphonate occurred effectively in rather mild conditions, it could be expected that this procedure will find applications outside the nucleotide field, for example, peptides, carbohydrates, etc. 

Partial phosphonylation. 2-3 moles of pentamethylene glycol warmed 48 hrs. at 100° with 1 mole of phenylphosphonyl oxide 5-hydroxybutyl phenylphos-phonate. Y 77%. F. e. s. E. Cherbuliez, F. Hunkeler, and J. Rabinowitz, Helv. 44, 1824 (1961) and other papers of this series. 

---