Phosphorus(V) Oxide

P2O5
(P2O5)

[1314-56-3]  · O5P2  · Phosphorus(V) Oxide  · (MW 141.94) (P4O10)

[16752-60-6]  · O10P4  · Phosphorus(V) Oxide  · (MW 283.88)

(dehydrating agent for acids and amides;1 cyclization catalyst)

Alternate Names: phosphorus pentoxide; phosphoric anhydride.

Physical Data: mp 569 °C; sublimes at 250 °C under vacuum.

Solubility: sol H2SO4, MeSO3H.

Form Supplied in: white powder; commercially available from many sources.

Preparative Method: prepared by combustion of phosphorus in dry air.

Purification: generally used without further purification; can be sublimed under vacuum.

Handling, Storage, and Precautions: corrosive! Reacts violently with water, releasing H3PO4 and heat.

Dehydration of Amides to Nitriles.

Dehydration of amides with P2O5 is one of many methods for the synthesis of nitriles.2 Distillation of an unsubstituted amide from an excess of P2O5 leads to good yields of the nitrile (eq 1).3,4 In many cases the reaction is carried out in the absence of solvents, although suitably high-boiling solvents can be used. These conditions are not compatible with many common functional groups, and this transformation can be achieved by other reagents,5 including Thionyl Chloride and Phosphorus Oxychloride.

Amides can be made by treatment of silyl esters with P2O5, followed by treatment with Hexamethyldisilazane.6 Some N-substituted amides convert to ketene imines upon treatment with P2O5 (eq 2).7

Formation of Anhydrides.

Dehydration of carboxylic acids with P2O5 is an effective method for the preparation of carboxylic anhydrides (eq 3). Acids have been converted to anhydrides with silica gel-supported P2O5, marketed as Sicapent by Merck.8 Similar results are obtained by heating a suspension of a carboxylic acid with a powdered mixture of P2O5, CuSO4, and Na2SO4 in a primary alcohol. This gives the ester in 60-80% yields.9

Cyclization Catalyst.

A 10% by weight (approximately saturated) solution of P2O5 in Methanesulfonic Acid (Eaton's reagent) has been used as an effective replacement for Polyphosphoric Acid (PPA) as an acid cyclization catalyst. Advantages to this reagent include the ease of stirring MeSO3H solutions relative to PPA and the greater solubility of many organic compounds in MeSO3H relative to PPA. Yields are comparable to or better than those obtained with PPA in Beckmann rearrangements (eq 4).10 The combination of P2O5 and methanesulfonic acid is an efficient catalyst for acid/alkene cycloadditions (eq 5).11 See also Phosphorus(V) Oxide-Methanesulfonic Acid.

This mixture is a particularly useful catalyst in the synthesis of 2-substituted indole derivatives via the Fischer indole reaction of asymmetrical ketones (eq 6).12 Other catalysts (PPA, H2SO4/MeOH, PPSE, Amberlyst 15) give lower regioselectivity. Decomposition of the starting material can be minimized by dilution of the P2O5/MeSO3H mixture with CH2Cl2. Treatment of (1) with P2O5 at high temperature results in cyclization to produce 7-deazahypoxanthines (eq 7).13

Condensing Agent.

Heating a mixture of P2O5, a primary or secondary amine (often using the amine as solvent), and a heterocyclic ketone or alcohol is a general route to substituted adenines (eq 8),14,15 purines,16,17 and pyrimidines.18 Cyclization and ketone/amine condensations can often be combined in the one-pot transformations of 4,5-disubstituted imidazoles to substituted adenines (eqs 9 and 10).19

Cyclodehydrations.

The Pictet-Gams modification of the Bischler-Napieralski reaction is an important method for the preparation of isoquinolines.19 This reaction relies on the dehydration of molecules such as (2) with P2O5 at high temperature (eq 11).20 Lower temperatures lead to oxazoles, which can be converted to the isoquinolines by heating to 196 °C.

Trimethylsilyl Polyphosphate.

Heating a mixture of P2O5 with Hexamethyldisiloxane results in the formation of Trimethylsilyl Polyphosphate (PPSE), an organic soluble, aprotic alternative to PPE or PPA.21 This reagent has proven useful for Beckmann rearrangements (eq 12),21-23 and for generation and cyclization of nitrilium ions.24

Formamidines.

Condensation of formanilides with secondary amines in the presence of P2O5 produces formamidines in good yield (eq 13).25 The reaction is compatible with electron-rich and electron-deficient arenes, but is limited to secondary amines.

Related Reagents.

Dimethyl Sulfoxide-Phosphorus Pentoxide; Phosphorus(V) Oxide-Methanesulfonic Acid; Phosphorus(V) Oxide-Phosphoric Acid.


1. FF 1967, 1, 871.
2. Mowry, D. T. CR 1948, 42, 189.
3. Reisner, D. B.; Hornung, E. C. OSC 1963, 4, 144.
4. Rickborn, B.; Jensen, F. R. JOC 1962, 27, 4608.
5. Larock, R. C. Comprehensive Organic Transformations; VCH: New York, 1989; pp 991-992.
6. Rao, C. S., Rambabu, M.; Srinirasan, P. S. IJC(B) 1987, 26B, 407.
7. Stevens, C. L.; Singhal, G. H. JOC 1964, 29, 34.
8. Burton, S. G.; Kaye, P. T. SC 1989, 19, 3331.
9. Banerjee, A.; Sengupta, S.; Adak, M. M.; Banerjee, G. C. JOC 1983, 48, 3106.
10. Jeffs, P. W.; Molina, G.; Cortese, N. A.; Hauck, P. R.; Wolfram, J. JOC 1982, 47, 3876.
11. Eaton, P. E.; Carlson, G. R.; Lee, J. T. JOC 1973, 38, 4071.
12. Zhao, D.; Hughes, D. L.; Bender, D. R.; DeMarco, A. M.; Reider, P. J. JOC 1991, 56, 3001.
13. Girgis, N. S.; Jørgensen, A.; Pedersen, E. B. S 1985, 101.
14. Girgis, N. S.; Pedersen, E. B. S 1982, 480.
15. Nielsen, F. E.; Pedersen, E. B. T 1982, 38, 1435.
16. El-Bayouki, K. A. M.; Nielsen, F. E.; Pedersen, E. B. S 1985, 104.
17. Nielsen, F. E.; Nielsen, K. E.; Pedersen, E. B. CS 1984, 24, 208.
18. Hilmy, K. M. H.; Mogensen, J.; Jorgensen, A.; Pedersen, E. B. H 1990, 31, 367.
19. Kametani, T.; Fukumoto, K. In Isoquinolines; Grethe, G., Ed.; Wiley: New York, 1981; Vol. 31, Part 1, pp 142-160.
20. Fitton, A. O.; Frost, J. R.; Zakaria, M. M.; Andrew, G. CC 1973, 889.
21. Imamoto, T.; Yokoyama, H.; Yokoyama, M. TL 1981, 22, 1803.
22. Donaruma, L. G.; Heldt, W. Z. OR 1960, 11, 1.
23. Gawley, R. E. OR 1988, 35, 1.
24. Gawley, R. E.; Chemburkar, S. R. H 1989, 29, 1283.
25. Hansen, B. W.; Pedersen, E. B. ACS 1980, 5, 369.

Mark S. Meier

University of Kentucky, Lexington, KY, USA



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