Sodium Hydride1

NaH

[7646-69-7]  · HNa  · Sodium Hydride  · (MW 24.00)

(used as a base for the deprotonation of alcohols, phenols, amides (NH), ketones, esters, and stannanes; used as a reducing agent for disulfides, disilanes, azides, and isoquinolines)

Physical Data: mp 800 °C (dec); d 1.396 g cm-3.

Solubility: decomposes in water; insol all organic solvents; insol liq NH3; sol molten sodium.

Form Supplied in: free-flowing gray powder (95% dry hydride); gray powder dispersed in mineral oil.

Handling, Storage, and Precautions: the dispersion is a solid and may be handled in the air. The mineral oil may be removed from the dispersion by stirring with pentane, then allowing the hydride to settle. The pentane/mineral oil supernatant may be pipetted off, but care should be exercised to quench carefully any hydride in the supernatant with a small amount of an alcohol before disposal. The dry powder should only be handled in an inert atmosphere.

Sodium hydride dust is a severe irritant and all operations should be done in a fume hood, under a dry atmosphere. Sodium hydride is stable in dry air at temperatures of up to 230 °C before ignition occurs; in moist air, however, the hydride rapidly decomposes, and if the material is a very fine powder, spontaneous ignition can occur as a result of the heat evolved from the hydrolysis reaction. Sodium hydride reacts more violently with water than sodium metal (eq 1); the heat of reaction usually causes hydrogen ignition.

Introduction.

The following is arranged by reaction type: NaH acting as a base on oxygen, nitrogen, germanium/silicon, and carbon acids, and as a reducing agent.

Oxygen Acids (Alcohol Deprotonation).

Sodium hydride may be used as a base in the Williamson ether synthesis in neat benzyl chloride,2 in DMSO,3 or in THF (eq 2).4 Phenols may also be deprotonated and alkylated in THF.4b

Curiously, tertiary propargylic alcohols may be alkylated in preference to either axial or equatorial secondary alcohols, using sodium hydride in DMF (eq 3).5

Sodium hydride in DMF is also used to deprotonate carbohydrate derivatives, for methylation or benzylation (eq 4).6

Unstable benzyl tosylates may be made by deprotonation of benzyl alcohols and acylation with p-Toluenesulfonyl Chloride (eq 5).7

An interesting conformational effect is seen when p-t-butylcalix[4]arene is tetraethylated. When Potassium Hydride is used as the base, the partial cone conformation predominates (i.e. one of the aryl groups is inverted), whereas with sodium hydride, the cone is produced exclusively (eq 6).8

Deprotonation of vinylsilane-allylic alcohols using sodium hydride in HMPA is followed by an essentially quantitative C -> O silicon migration (eq 7).9

Nitrogen Acids.

Sodium hydride in DMSO, HMPA, NMP, or DMA assists the transamination of esters (eq 8).10

Acyl amino acids and peptides may be alkylated on nitrogen using sodium hydride, with no racemization (eq 9).11 A slight change of reaction conditions allows simultaneous esterification.12

A similar intramolecular alkylation has been used to make b-lactams (eq 10).13

Germanium/Silicon Acids.

Germanium-hydrogen and silicon-hydrogen bonds are quantitatively cleaved with sodium hydride in ethereal solvents (eq 11).14

Carbon Acids.

Active methylene compounds, such as malonates and b-keto esters, can be deprotonated with sodium hydride and alkylated on carbon (eqs 12 and 13).15 Alkylation of Reissert anions is also facile with sodium hydride (eq 14).16

Normally, sodium enolates of ketones alkylate on oxygen. A superactive form of sodium hydride is formed when butylsodium is reduced with hydrogen; superactive sodium hydride is an excellent base for essentially quantitative deprotonation of ketones, trapped as their silyl ethers.17 For example, cyclododecanone is converted to its enol ether (containing a hyperstable double bond) in 92% yield (eq 15).

More commonly, sodium hydride is used as a base for carbonyl condensation reactions. For example, Claisen condensations of ethyl acetate18 and ethyl isovalerate19 are effected by sodium hydride. Condensations of cyclohexanone with methyl benzoate19 and ethyl formate (eq 16)20 are also facile.21 Sodium hydride can also doubly deprotonate b-diketones, allowing acylation at the less acidic site (eq 17).22

An undergraduate experiment using sodium hydride involves the crossed condensation of ethyl acetate and dimethyl phthalate (eq 18).23 Sodium hydride is also effective as a base in the Stobbe condensation24 and the Darzens condensation.25 It is also effective in a stereoselective intramolecular Michael reaction (eq 19).26

The Dieckmann condensation of esters27 and thioesters28 is mediated by sodium hydride (eq 20). Conditions for the latter are significantly more mild than for the former, and the yields are higher.

Sodium hydride may be used to cleave formate esters and formanilides (eqs 21 and 22).29 The mechanism apparently involves removal of the formyl proton and loss of carbon monoxide.

Dehydrohalogenation with sodium hydride is a means of making methylenecyclopropanes (eq 23).30

Enolate formation apparently accelerates the Diels-Alder cycloaddition/cycloreversion, shown in eq 24, which occurs at room temperature.31

An unusual cyclization of N-allyl-a,b-unsaturated amides is mediated by sodium hydride in refluxing xylene (eq 25).32 The reaction is thought to proceed by intramolecular 1,4-addition of the dianion shown.

Reductions.

The sodium salt of trimethylsilane is produced quantitatively by reduction of hexamethyldisilane with sodium hydride (eq 26).33

Sodium hydride in DMSO is an effective medium for the reduction of disulfide bonds in proteins under aprotic conditions.34 When the molar ratio of hydride to 1/2 cystine residues exceeds 2:1, essentially complete reduction of the disulfide bonds of bovine serum albumin is achieved.

Azides are reduced to amines by sodium hydride, although the yields are moderate (eq 27).35 Sodium hydride also reduces isoquinoline to 1,2-dihydroisoquinoline in good yield (eq 28).36

Related Reagents.

Calcium Hydride; Iron(III) Chloride-Sodium Hydride; Lithium Aluminum Hydride; Potassium Hydride; Potassium Hydride-s-Butyllithium-N,N,N,N-Tetramethylethylenediamine; Potassium Hydride-Hexamethylphosphoric Triamide; Sodium Borohydride; Sodium Hydride-Copper(II) Acetate-Sodium t-Pentoxide; Sodium Hydride-Nickel(II) Acetate-Sodium t-Pentoxide; Sodium Hydride-Palladium(II) Acetate-Sodium t-Pentoxide; Tris(cyclopentadienyl)lanthanum-Sodium Hydride.


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2. Tate, M. E.; Bishop, C. T. CJC 1963, 41, 1801.
3. Doornbos, T.; Strating, J. SC 1971, 1, 175.
4. (a) Stoochnoff, B. A.; Benoiton, N. L. TL 1973, 21. (b) Brown, C. A.; Barton, D.; Sivaram, S. S 1974, 434.
5. Hajos, Z. G.; Duncan, G. R. CJC 1975, 53, 2971.
6. (a) Brimacombe, J. S.; Jones, B. D.; Stacey, M.; Willard, J. J. Carbohydr. Res. 1966, 2, 167. (b) Brimacombe, J. S.; Ching, O. A.; Stacey, M. JCS(C) 1969, 197.
7. Kochi, J. K.; Hammond, G. S. JACS 1953, 75, 3443.
8. Groenen, L. C.; Ruël, B. H. M.; Casnati, A.; Timmerman, P.; Verboom, W.; Harkema, S.; Pochini, A.; Ungaro, R.; Reinhoudt, D. N. TL 1991, 32, 2675.
9. Sato, F.; Tanaka, Y.; Sato, M. CC 1983, 165.
10. Singh, B. TL 1971, 321.
11. Coggins, J. R.; Benoiton, N. L. CJC 1971, 49, 1968.
12. McDermott, J. R.; Benoiton, N. L. CJC 1973, 51, 1915.
13. (a) Baldwin, J. E.; Christie, M. A.; Haber, S. B.; Kruse, L. I. JACS 1976, 98, 3045. (b) Wasserman, H. H.; Hlasta, D. J.; Tremper, A. W.; Wu, J. S. TL 1979, 549. (c) Wasserman, H. H.; Hlasta, D. J. JACS 1978, 100, 6780.
14. Corriu, R. J. P.; Guerin, C. JOM 1980, 197, C19.
15. Zaugg, H. E.; Dunnigan, D. A.; Michaels, R. J.; Swett, L. R.; Wang, T. S.; Sommers, A. H.; DeNet, R. W. JOC 1961, 26, 644.
16. (a) Kershaw, J. R.; Uff, B. C. CC 1966, 331. (b) Uff, B. C.; Kershaw, J. R. JCS(C) 1969, 666.
17. Pi, R.; Friedl, T.; Schleyer, P. v. R.; Klusener, P.; Brandsma, L. JOC 1987, 52, 4299.
18. Hinckley, A. A. Sodium Hydride Dispersions; Metal Hydrides, Inc., 1964 (quoted in: FF 1967, 1, 1075).
19. Swamer, F. W.; Hauser, C. R. JACS 1946, 68, 2647.
20. Ainsworth, C. OSC 1963, 4, 536.
21. (a) Bloomfield, J. J. JOC 1961, 26, 4112. (b) Bloomfield, J. J. JOC 1962, 27, 2742. (c) Anselme, J. P. JOC 1967, 32, 3716.
22. Miles, M. L.; Harris, T. M.; Hauser, C. R. JOC 1965, 30, 1007.
23. Gruen, H.; Norcross, B. E. J. Chem. Educ. 1965, 42, 268.
24. (a) Ref. 18. (b) Daub, G. H.; Johnson, W. S. JACS 1948, 70, 418. (c) Daub, G. H.; Johnson, W. S. JACS 1950, 72, 501.
25. (a) Ref. 18. (b) Della Pergola, R.; DiBattista, P. SC 1984, 14, 121.
26. Stork, G.; Winkler, J. D.; Saccomano, N. A. TL 1983, 24, 465.
27. Pinkney, P. S. OSC 1943, 2, 116.
28. Liu, H.-J.; Lai, H. K. TL 1979, 1193.
29. Powers, J. C.; Seidner, R.; Parsons, T. G. TL 1965, 1713.
30. Carbon, J. A.; Martin, W. B.; Swett, L. R. JACS 1958, 80, 1002.
31. Tamura, Y.; Sasho, M.; Nakagawa, K.; Tsugoshi, T.; Kita, Y. JOC 1984, 49, 473.
32. Bortolussi, M.; Bloch, R.; Conia, J. M. TL 1977, 2289.
33. Corriu, R. J. P.; Guérin, C. CC 1980, 168.
34. Krull, L. H.; Friedman, M. Biochem. Biophys. Res. Commun. 1967, 29, 373.
35. Lee, Y.-J.; Closson, W. D. TL 1974, 381.
36. Natsume, M.; Kumadaki, S.; Kanda, Y.; Kiuchi, K. TL 1973, 2335.

Robert E. Gawley

University of Miami, Coral Gables, FL, USA



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