Phosphoric Acid

H3PO4

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

(acid catalyst; dehydrating agent; phosphorylating agent1)

Physical Data: mp 41 °C; bp 158 °C.

Solubility: sol water, formic acid, acetic acid.

Form Supplied in: commercially available; low melting white solid or colorless liquid.

Analysis of Reagent Purity: titration.

Preparative Method: anhydrous H3PO4 can be prepared by dissolving P2O5 in 85% H3PO4.

Purification: dry at 150 °C. At temperatures above 200 °C, monomeric H3PO4 changes to oligomeric metaphosphoric acid.

Handling, Storage, and Precautions: corrosive.

Introduction.

Phosphoric acid is a strong, nonoxidizing acid that is available in a number of different forms. Anhydrous, monomeric H3PO4 (orthophosphoric acid) is a low melting solid that can be purchased commercially or prepared by adding P2O5 to commercial 85% aqueous H3PO4. This combination has been used to iodinate alcohols, cleave ethers, and hydroiodinate alkenes, in addition to a variety of uses listed below.2 Metaphosphoric acid [37267-86-0] is an oligomeric form, also commercially available.3

Hydrolysis of Imines, Amides, and Nitriles.

The hydrolysis of imines,4 amides, and nitriles to carboxylic acids (eq 1) using H3PO4 is a time-honored technique.5 There are numerous methods for accomplishing this transformation.6

Preparation of Phosphates.1

Phosphate mono- and dialkyl esters have been prepared from phosphoric acid (see also Phosphorus Oxychloride). Treatment of (1) with H3PO4 at rt provides the corresponding phosphate in good yield (eq 2).7 At high temperatures, diesterification can occur (eq 3).8

An effective, large-scale synthesis of diammonium acetylphosphate has been developed, and involves direct acylation of H3PO4. Either ketene9 or acetic anhydride10 (eq 4) can be used in this process.

Acid Cyclization Catalyst.

A common use for H3PO4, as a solution in water, a liquid acid, or in anhydrous form, is as an acid cyclization catalyst. Cyclization of cross-conjugated ketones in H3PO4/formic acid leads to 2,3-dialkylcyclopentenones (eq 5) rather than the 3,4-dialkyl products expected of the Nazarov cyclization.11 This result is obtained when either the ketone or the corresponding ethylene acetal is used as starting material. Similar results are obtained using HBr/HOAc, although, in these examples, some of the 3,4-dialkyl products are obtained as well.

An intermolecular example of an alkene-cation addition reaction provides access to chromenes through isoprenylation of a phenol (eq 6).12

Cyclization of (2) in phosphoric acid results in an azabicyclononane (eq 7).13

Phosphoric acid-mediated condensation of indole derivatives with ketones provides access to 3-substituted indoles (eq 8).14

Cyclization of enol acetates (eq 9), d,ε-unsaturated aldehydes,15 and ketene dithioacetals (eq 10) can also be accomplished by heating in H3PO4. The cyclization of (3) results in dithiopyridines by way of an intramolecular Ritter reaction followed by a 1,3-methylthio shift. Lewis acids, Boron Trifluoride Etherate in particular, lead to simple dehydration.16

Debenzylation.

Treatment of (4), an N-benzyl derivative of biotin, with anhydrous H3PO4 and phenol at elevated temperature leads to debenzylation (eq 11).17 This reaction provides a nonreductive route to deprotection of the urea while not attacking the unsaturated ester.

Related Reagents.

Phosphorus(V) Oxide-Phosphoric Acid; Phosphorus Oxychloride; Polyphosphoric Acid; Sulfuric Acid.


1. MOC 1982, E2, 491.
2. FF 1967, 1, 872.
3. Kirk-Othmer Encyclopedia of Chemical Technology; Wiley: New York, 1978; Vol. 17, pp 428, 448-452.
4. Mislow, K.; McGinn, F. A. JACS 1958, 80, 6036.
5. Berger, G.; Olivier, S. C. J. RTC 1927, 46, 600.
6. Haslam, E. T 1980, 36, 2409.
7. Wilson, A. N.; Harris, S. A. JACS 1951, 73, 4693.
8. Inamoto, Y.; Aigami, K.; Kadono, T.; Nakayama, H.; Takatsuki, A.; Tamura, G. JMC 1977, 20, 1371.
9. Whitesides, G. M.; Siegel, M.; Garrett, P. JOC 1975, 40, 2516.
10. Lewis, J. M.; Haynie, S. L.; Whitesides, G. M. JOC 1979, 44, 864.
11. Hirano, S.; Hiyama, T.; Nozaki, H. TL 1974, 1429.
12. Ahluwalia, V. K.; Arora, K. K. T 1981, 37, 1437.
13. Beretta, M. G.; Rindone, B.; Scolastico, C. S 1975, 440.
14. Freter, K. JOC 1975, 40, 2525.
15. Saucy, G.; Ireland, R. E.; Bordner, J.; Dickerson, R. E. JOC 1971, 36, 1195.
16. Gupta, A. K.; Ila, H.; Junjappa, H. TL 1988, 29, 6633.
17. Field, G. F.; Zally, W. J.; Sternbach, L. H.; Blount, J. F. JOC 1976, 41, 3853.

Mark S. Meier

University of Kentucky, Lexington, KY, USA



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