Phosphorus(V) Oxide-Phosphoric Acid

P2O5-H3PO4
(P2O5)

[1314-56-3]  · O5P2  · Phosphorus(V) Oxide-Phosphoric Acid  · (MW 141.94) (H3PO4)

[7664-38-2]  · H3O4P  · Phosphorus(V) Oxide-Phosphoric Acid  · (MW 98.00)

(moderately strong mineral acid with a range of dehydrating properties; used for cyclizations and phosphorylations)

Physical Data: hygroscopic; viscous to highly viscous; colorless or light amber; specific gravity is dependent upon the concentration of the reagent, 2.060 at 83% phosphorus pentoxide content (see below).

Solubility: dissolution in any protic solvent will result in violent solvolysis of the reagent; dissolution in polar aprotic solvents can result in dehydration or destruction of the solvent; these reagents are not soluble in and do not react with nonpolar organics such as toluene or hexane.

Preparative Methods: best carried out by heating P2O5 with 85% H3PO4. A solution which is theoretically 76% P2O5 (see below) is obtained when 3x g of Phosphorus(V) Oxide is mixed with 4x g of 85% orthophosphoric acid. This mixture is heated and stirred until complete dissolution occurs.1 When concentrations over 83% are desired, polyphosphoric acid (PPA) is used to dissolve the P2O5. A concentration of 86% P2O5 (super polyphosphoric acid) is reported to be useful in reactions which fail when PPA is used.2 Preparation of super polyphosphoric acid is accomplished by mechanically stirring x g of P2O5 and 5x g of PPA while heating to 170-180 °C for 1 h. The reagent is kept warm while the substrate is added to avoid the extremely viscous mixture which results upon cooling to rt. Workup is accomplished by pouring the hot mixture onto ice.

Handling, Storage, and Precautions: when diluting P2O5 or any partially hydrolyzed derivative, care must be taken to avoid spattering caused by the exothermic hydrolysis. PPA has the ability to burn mucous membranes immediately and unprotected skin with time. Other than its corrosive nature, it has low inherent toxicity. Use in a fume hood.

Description of the Reagent.

P2O5/H3PO4 is not a discrete molecular entity, but can be considered to be any mixture which results from partial hydration of P2O5. The resulting solution is a complex mixture of phosphoric acids, which consists of orthophosphoric acid and linear phosphoric acid chains. In order to avoid discussion of this complicated equilibrium, these mixtures are described empirically by stating the weight percent of the solution as if it were simply a solution of P2O5 in water. When the theoretical weight percent of P2O5 reaches 83%, the resulting mixture is commonly known as Polyphosphoric Acid (PPA). As the weight percent of P2O5 goes above 83%, longer chain phosphoric acids begin to predominate until at 89% P2O5 the mixture is 87% hypolyphosphoric acid (greater than 14 phosphoric acid units).

Cyclizations.

In work directed toward the synthesis of jasmone, the utility of a PPA/P2O5 (86% P2O5) mixture was first evidenced when a lactone was converted into a cyclic ketone (eq 1).3

The term super polyphosphoric acid was first coined when 86% P2O5 successfully effected the Pomeranz-Fritsch cyclization even though the resulting isoquinoline is sterically congested (eq 2).2 Super PPA was also used to effect a Bischler-Napieralski cyclization to obtain isoquinolines in higher than normal yields (eq 3).2 Some confusion exists about this report since N-formylphenethylamines should yield dihydroisoquinolines and not the tetrahydroisoquinolines reported.4 It would appear that reduction of the intermediate dihydroisoquinoline was inadvertently omitted. In an efficient synthesis of a benzindolone (6-methoxy-Uhle's ketone), use of super PPA improved the low yield route which utilized normal PPA (eq 4).5 In an attempt to develop methodology to convert methylcyclohexenones into indolones and pyrroloazepinediones, cyclization of a pyrrolo acid was found to proceed in 85% yield using super PPA while normal PPA gave poor yields (eq 5).6

Phosphorylations.

A mixture of P2O5 and H3PO4 (78% P2O5) was used to phosphorylate proteins in the first reported use of this reagent.1 This methodology was applied to small molecules in the synthesis of pyridoxal phosphate (eq 6).7


1. Ferrel, R. E.; Olcott, H. S.; Fraenkel-Conrat, H. JACS 1948, 70, 2101.
2. Bailey, D. M.; DeGrazia, C. G.; Lape, H. E.; Frering, R.; Fort, D.; Skulan, T. JMC 1973, 16, 151.
3. Ficini, J.; Maujean, A. BSF(2) 1972, 11, 4392.
4. Meece, C. O.; Ebner, T. J. Labelled Compd. Radiopharm. 1988, 25, 335.
5. Meyer, M. D.; Kruse, L. I. JOC 1984, 49, 3195.
6. Kasum, B.; Prager, R. H.; Tsopelas, C. AJC 1990, 43, 355.
7. Wilson, A. N.; Harris, S. A. JACS 1951, 73, 4693.

John H. Dodd

The R. W. Johnson Pharmaceutical Research Institute, Raritan, NJ, USA



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