Sodium Hypophosphite

NaH2PO2

[7681-53-0]  · H2NaO2P  · Sodium Hypophosphite  · (MW 87.98)

(source of hydrogen in heterogeneous catalytic transfer reductions;1-10 synthesis of phosphonous acids via hydrophosphorylation of terminal alkenes11)

Physical Data: decomposes upon strong heating with release of phosphine, which is highly flammable in air.

Solubility: sol water, alcohol; insol ether.

Form Supplied in: monohydrate, white solid.

Handling, Storage, and Precautions: explodes when triturated with chlorates or other oxidizing agents.

Functional Group Reductions.

Sodium hypophosphite is a very effective and mild hydrogen-transfer reagent capable of reducing a wide range of functional groups when utilized with the appropriate catalyst. The reductions of aldehydes to alcohols,1 alkynes to alkenes,2 azides to amines,1 benzoquinones to dihydrobenzoquinones,3 epoxides to alcohols,1 alkyl or aryl halides to alkanes or arenes,1,4 ketones to alcohols,1 nitriles to aldehydes,5 nitroalkenes to oximes,6 nitroarenes to aryl amines,7 N-oxides to amines,1 alkenes to alkanes,8 oximes to ketones,1,9 and phenols to arenes,10 as well as the hydrogenolysis of benzylic ethers,1 have all been effected. Reactions have been carried out in solvent systems ranging from aqueous to anhydrous organic solvents, typically at elevated temperatures (50-75 °C), with excess sodium hypophosphite and most often Palladium on Carbon as the catalyst. Reaction workup generally involves filtration of the catalyst, extraction if appropriate, and removal of solvent.

Studies on polyfunctional molecules have shown the reduction to be tunable; while treatment of cinnamonitrile (1) with sodium hypophosphite and 5% Pd/C yields 87% of dihydrocinnamonitrile (2),1 reduction with sodium hypophosphite and Raney Nickel gives only cinnamaldehyde (3)5 (eq 1). A more profound demonstration of selectivity is seen in the conversion of (4) to (5) (eq 2), intermediates in the synthesis of (+)-pilocarpine.5b

Hydrophosphorylation of Alkenes.

Terminal alkenes (6), when treated with sodium hypophosphite in the presence of Azobisisobutyronitrile, yield phosphonous acids (7) (eq 3).11


1. Boyer, S. K.; Bach, J.; McKenna, J.; Jagdmann, E., Jr. JOC 1985, 50, 3408.
2. (a) Johnstone, R. A.; Wilby, A. H. T 1981, 37, 3667. (b) Brienne, M.-J.; Varech, D.; Leclercq, M.; Jacques, J.; Radembino, N.; Dessalles, M.-C.; Mahuzier, G.; Gueyouche, C.; Bories, C.; Loiseau, P.; Gayval, P. JMC 1987, 30, 2232.
3. Entwistle, I. D.; Johnstone, R. A. W.; Telford, R. P. JCR(S) 1977, 117.
4. Sauer, G.; Heindl, J.; Wachtel, H. TL 1988, 29, 6425.
5. (a) Backeberg, O. G.; Staskun, B. JCS 1962, 3961. (b) Compagnone, R. S.; Rapoport, H. JOC 1986, 51, 1713.
6. (a) Davey, D. D.; Lumma, W. C., Jr. JOC 1989, 54, 3211. (b) Varma, R. S.; Varma, M.; Kabalka, G. W. SC 1986, 16, 91.
7. (a) Entwistle, I. D.; Jackson, A. E.; Johnstone, R. A. W.; Telford, R. P. JCS(P1) 1977, 443. (b) Best, W. M.; Wege, D. AJC 1986, 39, 647. (c) Entwistle, I. D. TL 1979, 555.
8. Sala, R.; Doria, G.; Passcarotti, C. TL 1984, 4565.
9. Monti, D.; Gramatica, P.; Speranza, G.; Taglapietra, S.; Manitto, P. SC 1986, 16, 803.
10. (a) Entwistle, I. D.; Hussey, B. J.; Johnstone, R. A. W. TL 1980, 21, 4747. (b) Brigas, A. F.; Johnstone, R. A. W. TL 1990, 31, 5789.
11. (a) Karanewsky, D. S.; Badia, M. C.; Cushman, D. W.; DeForrest, J. M.; Dejenka, T.; Loots, M. J.; Perri, M. J.; Petrillo, E. W., Jr.; Powell, J. R. JMC 1988, 31, 204. (b) Nifant'ev, E. E., Magdeeva, R. K.; Shchepet'eva, N. P. JGU 1980, 50, 1416. (c) Nifante'ev, É. E.; Korateev, M. P. JGU 1967, 37, 1293.

Jeffrey O. Saunders

Vertex Pharmaceuticals, Cambridge, MA, USA



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