SODIUM ALCOHOL 1
Sodium Alcohol1
Na
EtOH, Et2O
0 °C
Na ROH
60%
TBDMSO
O
OH
(Na)
[7440-23-5] Na (MW 22.99)
InChI = 1/Na
(3)
InChIKey = KEAYESYHFKHZAL-UHFFFAOYAO
TBDMSO
OH
OH
(reducing agent for esters, amides, ketones, oximes, nitriles, sul-
fonamides, aromatic hydrocarbons, certain alkenes, ethers, and
Reduction by sodium in alcohols of Ä…,²-unsaturated ketones af-
carbon halogen bonds; moderately strong base)
fords saturated alcohols (eq 4),9 while similar reductions of diaryl
ć% ć%
Physical Data: Na: mp 97.5 C; bp 880 C; d 0.97 g cm-3. EtOH:
ketones give methylene derivatives (eq 5).10
ć% ć%
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.
Na
Drying: absolute ethanol can usually be employed without fur-
(4)
O i-C5H11OH OH
ther drying. Most other common alcohols can be dried by stor-
ing 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
Na
heat of the reaction is usually sufficient to ignite the product
Ph2CO Ph2CH2 (5)
EtOH
hydrogen. Ethanol and other alcohols likely to be encountered
in these reductions are flammable liquids. Use in a fume hood.
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
Reduction of Esters and Carboxamides. Though often
quantitative yield (eq 6).11b The use of higher molecular weight
replaced by the use of more modern hydride reagents, the
alcohols has been reported to afford better yields of products.11d
Bouveault Blanc reduction has long been known to convert
esters to alcohols by refluxing the former reagents with sodium
Ph Ph
in alcohols.2 For example, ethyl hydrocinnamate is converted to
Na
(6)
hydrocinnamyl alcohol in good yields (eq 1).2 Numerous exam-
EtOH
NOH NH2
ples 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 unsat- Reduction of Nitriles. Aliphatic nitriles are also reduced to
urated esters with sodium in alcohols reduces conjugated double amines in satisfactory yields by sodium in n-butyl alcohol12a or
bonds2 but not unconjugated alkenes (eq 2).6 Less common have ethanol and toluene (eq 7).12b
been reductions of carboxamides to amines by sodium in alcohols.
Na
For example, a number of primary, secondary, and tertiary amides
BuOH
NH2 (7)
have been reduced to their corresponding amines in good yields
N 86%
by sodium in propanol.7
Reduction of Sulfonamides. Both aliphatic and aromatic sul-
Na
CO2Et
(1)
fonamides are converted to sulfinic acids and amines by sodium
Ph OH
Ph
EtOH
in isopentyl alcohol.13 This reduction has been employed in the
preparation of azetidine (eq 8).13b
Na
Na, EtOH
(8)
N N
OH
(2)
i-C5H11OH
CO2Et
7 Ts H
57% 7
7
7
Reduction of Aromatic Hydrocarbons. Naphthalene and
Reduction of Ketones and Derivatives. Aliphatic ketones higher aromatic hydrocarbons, as well as certain amino, ether, and
and phenones are readily converted to alcohols by sodium in carboxyl derivatives, are reduced to more saturated derivatives by
alcohols,8 as illustrated by the thermodynamically controlled re- sodium in numerous alcohols.1a,14 Thus while naphthalene itself
duction shown in eq 3, which forms part of a recently described is converted by sodium in ethanol and benzene to the 1,4-dihydro
synthesis of taxol and its analogs.8d derivative,14b ²-naphthylamine and ²-alkoxynaphthalenes are
Avoid Skin Contact with All Reagents
2 SODIUM ALCOHOL
reduced to tetrahydro-²-naphthylamine (eq 9)14a and ²-tetralone (eqs 16 and 17).19 Both vinylic and allylic chlorides, but not
(eq 10),14c,d respectively. methyl ether moieties, are similarly reduced by sodium in t-butyl
alcohol and THF (eq 18).20
Na
NH2 C5H11OH NH2
(9)
Br Na
51 57% (16)
Br wet MeOH
Na
OEt O
EtOH
(10)
Br Na
40 50%
(17)
Br wet MeOH
Interestingly, sodium/isopentyl alcohol reduction of salicylic
acid gives pimelic acid (eq 11).14e In the case of biphenyl substi-
OMe OMe
MeO MeO
tuted with a carboxyl group on one ring and a methoxy group on
Cl
Na
Cl
(18)
the other, the ring bearing the carboxyl group is converted to its
t-BuOH, THF
hexahydro derivative (eq 12).14f
Cl
Cl
CO2H
Na
(11)
HO2CCO2H
i-C5H11OH
OH
1. (a) Campbell, K. N.; Campbell, B. K., Chem. Rev. 1942, 31, 77.
(b) House, H. O. Modern Synthetic Reactions, 2nd ed.; Benjamin: Menlo
Na
Park, CA, 1972; Chapter 3. (c) Hudlicky, M Reductions in Organic
i-C5H11OH
Chemistry; Horwood: Chichester, 1984.
HO2C OMe
92%
2. (a) Bouveault, L; Blanc, G., C. R. Hebd. Seances Acad. Sci., Ser. C 1903,
136, 1676. (b) Bouveault, L; Blanc, G., Bull. Soc. Chem. Fr. 1904, 31,
666.
(12)
HO2C OMe
3. (a) Ford, S. G.; Marvel, C. S., Org. Synth., Coll. Vol. 1943, 2, 372.
(b) Reid, E. E.; Cockerille, F. O.; Meyer, J. D.; Cox, W. M. Jr., Ruhoff,
J. R., Org. Synth., Coll. Vol. 1943, 2, 468.
Pyridine derivatives are also reduced by sodium in ethanol15 or
4. Manske, R. H. F., Org. Synth., Coll. Vol. 1943, 2, 154.
in pentyl alcohol.11b For example, benzo[f]quinoline is converted
5. Hansley, V. L., Chem. Abstr. 1947, 41, 1202.
to the trans-amine (eq 13).11b
6. Adkins, H; Gillespie, R. H., Org. Synth., Coll. Vol. 1955, 3, 671.
7. Bhandari, K; Sharma, V. L.; Chatterjee, S. K., Chem. Ind. (London) 1990,
Na 547.
N NH
(13)
C5H11OH
8. (a) Whitmore, F. C.; Otterbacher, T. J., Org. Synth., Coll. Vol. 1943, 2,
317. (b) Jones, D. N.; Lewis, J. R.; Shoppee, C. W.; Summers, G. H.
R., J. Chem. Soc. 1955, 2876. (c) House, H. O.; Müller, H. C.; Pitt, C.
G.; Wickham, P. P., J. Org. Chem. 1963, 28, 2407. (d) Wender, P. A.;
Mucciaro, T. P., J. Am. Chem. Soc. 1992, 114, 5878.
Reduction of Alkenes. Perhaps surprisingly, numerous ex-
9. Pinder, A. R.; Robinson, R., J. Chem. Soc. 1955, 3341.
amples of alkenes conjugated with aromatic rings have been
10. Klages, A.; Allendorf, P., Chem. Ber. 1898, 31, 998.
converted to alkanes by sodium in alcohols.1a For example, cin-
namyl alcohol is conveniently reduced by this method (eq 14).16 11. (a) Lycan, W. H.; Puntambeker, S. V.; Marvel, C. S., Org. Synth., Coll.
Vol. 1943, 2, 318. (b) Masamune, T.; Ohno, M.; Koshi, M.; Ohuchi,
S.; Iwadare, T., J. Org. Chem. 1964, 29, 1419. (c) Rausser, R.; Weber,
Na
(14)
Ph OH L.; Hershberg, E. B.; Oliveto, E. P., J. Org. Chem. 1966, 31, 1342.
Ph OH
C5H11OH
(d) Sugden, J. K.; Patel, J. J. B., Chem. Ind. (London) 1972, 683.
12. (a) Suter, C. M.; Moffett, E. W., J. Am. Chem. Soc. 1934, 56, 487.
(b) Walter, L. A.; McElvain, S. M., J. Am. Chem. Soc. 1934, 56, 1614.
Cleavage of Ethers. 4-Phenyl-m-dioxane has been reduced
13. (a) Klamann, D.; Hofbauer, G., Chem. Ber. 1953, 86, 1246. (b) Schaefer,
to 3-phenyl-1-propanol by sodium in isobutyl alcohol.17 Sim-
F. C., J. Am. Chem. Soc. 1955, 77, 5928.
ilar examples include demethoxylations of methyl aryl ethers
14. (a) Waser, E. B. H.; Möllering, H., Org. Synth., Coll. Vol. 1932, 1, 489.
(eq 15)18a,b and debenzylations of benzyl derivatives of certain
(b) Cook, E. S.; Hill, A. J., J. Am. Chem. Soc. 1940, 62,
sugars.18c
1995. (c) Cornforth, J. W.; Cornforth, R. H.; Robinson, R.,
J. Chem. Soc. 1942, 689. (d) Soffer, M. D.; Bellis, M. P.;
Na
Gellerson, H. E.; Stewart, R. A., Org. Synth., Coll. Vol. 1963,
O O
i-C5H11OH
4, 903. (e) Muller, A., Org. Synth., Coll. Vol. 1943, 2, 535.
(15)
N xylene N
O O (f) Johnson, W. S.; Gutsche, C. D.; Offenhauer, R. D., J. Am. Chem.
Me Me
Soc. 1946, 68, 1648. (g) Bass, K. C., Org. Synth., Coll. Vol. 1973, 5, 398.
OMe
15. (a) Marvel, C. S.; Lazier, W. A., Org. Synth., Coll. Vol. 1932, 1, 99.
(b) Profft, E.; Linke, H.-W., Chem. Ber. 1960, 93, 2591.
16. Gray, W. H., J. Chem. Soc. 1925, 127, 1150.
Reduction of Carbon Halogen Bonds. gem-Dibromides are
reduced by sodium in wet methanol to the parent hydrocarbons 17. Shriner, R. L.; Ruby, P. R., Org. Synth., Coll. Vol. 1963, 4, 798.
A list of General Abbreviations appears on the front Endpapers
SODIUM ALCOHOL 3
18. (a) Clayson, D. B., J. Chem. Soc. 1949, 2016. (b) Thomas, H.; Siebeling, 20. Gassman, P. G.; Marshall, J. L., Org. Synth., Coll. Vol. 1973, 5,
W., Chem. Ber. 1911, 44, 2134. (c) Prentice, N.; Cuendet, L. S.; Smith, 424.
F., J. Am. Chem. Soc. 1956, 78, 4439.
19. (a) Doering, W. V. E.; Hoffmann, A. K., J. Am. Chem. Soc. 1954, 76,
Edwin M. Kaiser
6162. (b) Winstein, S.; Sonnenberg, J., J. Am. Chem. Soc. 1961, 83, 3235.
University of Missouri, Columbia, MO, USA
Avoid Skin Contact with All Reagents