[7440-23-5]  · Na  · Sodium-Alcohol  · (MW 22.99)

(reducing agent for esters, amides, ketones, oximes, nitriles, sulfonamides, aromatic hydrocarbons, certain alkenes, ethers, and carbon-halogen bonds; moderately strong base)

Physical Data: Na: mp 97.5 °C; bp 880 °C; d 0.97 g cm-3. EtOH: mp -117.3 °C; bp 78.5 °C; d 0.7893 g cm-3.

Form Supplied in: Na: silvery white, soft metal. EtOH and other alcohols: liquid. Drying: absolute ethanol can usually be employed without further drying. Most other common alcohols can be dried by storing over anhydrous calcium sulfate followed by distillation.

Handling, Storage, and Precautions: Sodium metal is a water-reactive, flammable solid. In case of contact with water, the heat of the reaction is usually sufficient to ignite the product hydrogen. Ethanol and other alcohols likely to be encountered in these reductions are flammable liquids. Use in a fume hood.

Reduction of Esters and Carboxamides.

Though often replaced by the use of more modern hydride reagents, the Bouveault-Blanc reduction has long been known to convert esters to alcohols by refluxing the former reagents with sodium in alcohols.2 For example, ethyl hydrocinnamate is converted to hydrocinnamyl alcohol in good yields (eq 1).2 Numerous examples of reductions of mono-3 and diesters4 can be found in the literature. The major improvement in the procedure over the years has been the use of stoichiometric amounts of ester, alcohol, and toluene or xylene added to sodium in xylene.5 Treatment of unsaturated esters with sodium in alcohols reduces conjugated double bonds2 but not unconjugated alkenes (eq 2).6 Less common have been reductions of carboxamides to amines by sodium in alcohols. For example, a number of primary, secondary, and tertiary amides have been reduced to their corresponding amines in good yields by sodium in propanol.7

Reduction of Ketones and Derivatives.

Aliphatic ketones and phenones are readily converted to alcohols by sodium in alcohols,8 as illustrated by the thermodynamically controlled reduction shown in eq 3, which forms part of a recently described synthesis of taxol and its analogs.8d

Reduction by sodium in alcohols of a,b-unsaturated ketones affords saturated alcohols (eq 4),9 while similar reductions of diaryl ketones give methylene derivatives (eq 5).10

Oximes are conveniently converted to amines by sodium in alcohols.11 For example, the oxime of 2-phenylcyclohexanone is reduced by sodium in ethanol to the corresponding amine in quantitative yield (eq 6).11b The use of higher molecular weight alcohols has been reported to afford better yields of products.11d

Reduction of Nitriles.

Aliphatic nitriles are also reduced to amines in satisfactory yields by sodium in n-butyl alcohol12a or ethanol and toluene (eq 7).12b

Reduction of Sulfonamides.

Both aliphatic and aromatic sulfonamides are converted to sulfinic acids and amines by sodium in isopentyl alcohol.13 This reduction has been employed in the preparation of azetidine (eq 8).13b

Reduction of Aromatic Hydrocarbons.

Naphthalene and higher aromatic hydrocarbons, as well as certain amino, ether, and carboxyl derivatives, are reduced to more saturated derivatives by sodium in numerous alcohols.1a,14 Thus while naphthalene itself is converted by sodium in ethanol and benzene to the 1,4-dihydro derivative,14b b-naphthylamine and b-alkoxynaphthalenes are reduced to tetrahydro-b-naphthylamine (eq 9)14a and b-tetralone (eq 10),14c,d respectively.

Interestingly, sodium/isopentyl alcohol reduction of salicylic acid gives pimelic acid (eq 11).14e In the case of biphenyl substituted with a carboxyl group on one ring and a methoxy group on the other, the ring bearing the carboxyl group is converted to its hexahydro derivative (eq 12).14f

Pyridine derivatives are also reduced by sodium in ethanol15 or in pentyl alcohol.11b For example, benzo[f]quinoline is converted to the trans-amine (eq 13).11b

Reduction of Alkenes.

Perhaps surprisingly, numerous examples of alkenes conjugated with aromatic rings have been converted to alkanes by sodium in alcohols.1a For example, cinnamyl alcohol is conveniently reduced by this method (eq 14).16

Cleavage of Ethers.

4-Phenyl-m-dioxane has been reduced to 3-phenyl-1-propanol by sodium in isobutyl alcohol.17 Similar examples include demethoxylations of methyl aryl ethers (eq 15)18a,b and debenzylations of benzyl derivatives of certain sugars.18c

Reduction of Carbon-Halogen Bonds.

gem-Dibromides are reduced by sodium in wet methanol to the parent hydrocarbons (eqs 16 and 17).19 Both vinylic and allylic chlorides, but not methyl ether moieties, are similarly reduced by sodium in t-butyl alcohol and THF (eq 18).20

1. (a) Campbell, K. N.; Campbell, B. K. CRV 1942, 31, 77. (b) House, H. O. Modern Synthetic Reactions, 2nd ed.; Benjamin: Menlo Park, CA, 1972; Chapter 3. (c) Hudlicky, M Reductions in Organic Chemistry; Horwood: Chichester, 1984.
2. (a) Bouveault, L; Blanc, G CR(C) 1903, 136, 1676. (b) Bouveault, L; Blanc, G BSF 1904, 31, 666.
3. (a) Ford, S. G.; Marvel, C. S. OSC 1943, 2, 372. (b) Reid, E. E.; Cockerille, F. O.; Meyer, J. D.; Cox, W. M., Jr.; Ruhoff, J. R. OSC 1943, 2, 468.
4. Manske, R. H. F. OSC 1943, 2, 154.
5. Hansley, V. L. CA 1947, 41, 1202.
6. Adkins, H; Gillespie, R. H. OSC 1955, 3, 671.
7. Bhandari, K; Sharma, V. L.; Chatterjee, S. K. CI(L) 1990, 547.
8. (a) Whitmore, F. C.; Otterbacher, T. J. OSC 1943, 2, 317. (b) Jones, D. N.; Lewis, J. R.; Shoppee, C. W.; Summers, G. H. R. JCS 1955, 2876. (c) House, H. O.; Müller, H. C.; Pitt, C. G.; Wickham, P. P. JOC 1963, 28, 2407. (d) Wender, P. A.; Mucciaro, T. P. JACS 1992, 114, 5878.
9. Pinder, A. R.; Robinson, R. JCS 1955, 3341.
10. Klages, A.; Allendorf, P. CB 1898, 31, 998.
11. (a) Lycan, W. H.; Puntambeker, S. V.; Marvel, C. S. OSC 1943, 2, 318. (b) Masamune, T.; Ohno, M.; Koshi, M.; Ohuchi, S.; Iwadare, T. JOC 1964, 29, 1419. (c) Rausser, R.; Weber, L.; Hershberg, E. B.; Oliveto, E. P. JOC 1966, 31, 1342. (d) Sugden, J. K.; Patel, J. J. B. CI(L) 1972, 683.
12. (a) Suter, C. M.; Moffett, E. W. JACS 1934, 56, 487. (b) Walter, L. A.; McElvain, S. M. JACS 1934, 56, 1614.
13. (a) Klamann, D.; Hofbauer, G. CB 1953, 86, 1246. (b) Schaefer, F. C. JACS 1955, 77, 5928.
14. (a) Waser, E. B. H.; Möllering, H. OSC 1932, 1, 489. (b) Cook, E. S.; Hill, A. J. JACS 1940, 62, 1995. (c) Cornforth, J. W.; Cornforth, R. H.; Robinson, R. JCS 1942, 689. (d) Soffer, M. D.; Bellis, M. P.; Gellerson, H. E.; Stewart, R. A. OSC 1963, 4, 903. (e) Muller, A. OSC 1943, 2, 535. (f) Johnson, W. S.; Gutsche, C. D.; Offenhauer, R. D. JACS 1946, 68, 1648. (g) Bass, K. C. OSC 1973, 5, 398.
15. (a) Marvel, C. S.; Lazier, W. A. OSC 1932, 1, 99. (b) Profft, E.; Linke, H.-W. CB 1960, 93, 2591.
16. Gray, W. H. JCS 1925, 127, 1150.
17. Shriner, R. L.; Ruby, P. R. OSC 1963, 4, 798.
18. (a) Clayson, D. B. JCS 1949, 2016. (b) Thomas, H.; Siebeling, W. CB 1911, 44, 2134. (c) Prentice, N.; Cuendet, L. S.; Smith, F. JACS 1956, 78, 4439.
19. (a) Doering, W. V. E.; Hoffmann, A. K. JACS 1954, 76, 6162. (b) Winstein, S.; Sonnenberg, J. JACS 1961, 83, 3235.
20. Gassman, P. G.; Marshall, J. L. OSC 1973, 5, 424.

Edwin M. Kaiser

University of Missouri-Columbia, MO, USA

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