Sodium Amide

NaNH2

[7782-92-5]  · H2NNa  · Sodium Amide  · (MW 39.02)

(strong base;3 strong nucleophile38)

Alternate Name: sodamide.

Physical Data: mp 210 °C; bp 400 °C/760 mmHg.

Solubility: sol liq ammonia (~1 mol L-1 at -33 °C).1

Form Supplied in: commercially available as a powder; easily prepared in the laboratory.

Preparative Methods: combination of Ammonia, small quantities of an iron(III) salt, and Sodium leads to formation of a black catalyst, whereupon the remainder of the sodium is added. Published procedures differ in details.2

Handling, Storage, and Precautions: flammable; corrosive; when opened to air, decomposes and forms a potentially explosive yellow byproduct.1

Reaction as a Base.

Sodamide often serves as a base to generate reactive anions.3 In DMSO in the presence of various bases, including sodamide, carbohydrates are benzylated in good yield with Benzyl Chloride.3a Reaction of (1) and (2) in the presence3b of sodamide gives (3) (eq 1). Sodamide is effective in generating the acetonitrile anion for reaction with sulfines.4 Deprotonation of phenylacetic esters in the presence of sodamide allows aldol reaction with benzaldehyde derivatives to afford 2,3-diaryl-3-hydroxypropionic acids.5 Similarly, reaction of acetophenone and ethyl chloroacetate (eq 2) gives the Darzens' product (4).6 Treatment of primary anilines and cyanopyridines with sodamide leads to good yields of carboxamidines.7 Oxygenation of hindered 4-alkylphenols in the presence of sodamide provides a convenient source of quinols.8

Sodamide in THF with boric acid neutralization has proven effective for the deconjugation of conjugated unsaturated steroids.9 The presence of sodamide in liquid ammonia at low temperature facilitates interconversion of 1,4- and 1,3-cyclohexadienes.10 Deprotonation of 2-bromothiophenes and 2-halothianaphthalenes affords the 3-halo isomers via a series of complex equilibria.11 Cyclopropenes, which possess an acidity comparable to alkynes, are rapidly metalated by sodamide (and other alkali amides) to produce reactive intermediates for alkylation.12 Selective deprotonation occurs with a wide variety of acidic methyl, methylene, and methine hydrogens adjacent to carbonyls or attached to heterocycles. For example, 2,4-lutidine (5) undergoes deprotonation (eq 3) to (6) followed by reaction with ethyl benzoate to yield (7).13a Deprotonation followed by reaction with electrophiles is a powerful method for generating complex carbon skeletons.13 Examination of the role of bases, including sodamide, on the stereochemistry (including isomerization) of products formed in the Michael reaction has been reported.14 In the racemization of the single stereogenic center in nicotine, sodamide was inferior to Potassium t-Butoxide.15

Dianion Generation.

Numerous early investigations into dianion chemistry16 employed sodamide as the base. Conversion of the simple heterocycle (8) into the corresponding dianion with sodamide in liquid ammonia followed by reaction with benzonitrile (eq 4) led to an interesting rearrangement product (9).17 b-Dicarbonyl dianions are routinely prepared by reaction with sodamide. These strongly nucleophilic species undergo regioselective alkylation (eq 5) by reaction of disodioacetylacetone (10) (much more soluble in liquid ammonia than its dipotassium counterpart16a) with 11-bromoundecanoic acid to give (11)18 and reaction of (10) (eq 6) with diphenyliodonium chloride to yield (12).19

Elimination Reactions.

Sodamide's utility as a reagent for elimination reactions is illustrated by the following selected examples. Methiodide (13) undergoes facile loss of HI and diethylmethylamine to generate methyl vinyl ketone.20 Five isomeric alkenes and a cyclopropane result from treatment of 2-benzyl-3-phenylpropyltrimethylammonium iodide with sodamide.21 Upon reaction with sodamide, various thioamides eliminate hydrogen sulfide to form ynamines in fair yield.22 In the presence of sodamide, cis-1,4-dichloro-2-butene (14) yields mainly trans-1-chloro-1,3-butadiene (15) (eq 7) while trans-1,4-dichloro-2-butene gives a preponderence of cis-1-chloro-1,3-butadiene (16) (eq 8).23 Upon warming a mixture of methallyl chloride (17) and sodamide (eq 9), there is formed methylenecyclopropane (18) and 1-methylcyclopropene (19).24 Sodamide, Sodium Hydride, and Sodium Methoxide all have utility in the Bamford-Stevens reaction for the conversion of tosylhydrazones into alkenes.25

Preparation of Alkynes.

Sodamide-mediated elimination of one or two moles of HX from a suitable substrate is a classical method for the synthesis of alkynes. For example, b-bromostyrene with sodamide in liquid ammonia provides an excellent source of phenylacetylene.26 Cyclohexylpropyne (21) can be generated by reaction (eq 10) of vinyl bromide (20) with 3 equiv (excess) of sodamide.27 Oleic acid (22) can be transformed into stearolic acid (23) by a straightforward sequence (eq 11) involving bromination followed by reaction with excess sodamide.28 Similar methodology has been employed to synthesize many other alkynes.29 Dehydrohalogenation with concomitant ether cleavage provides an efficient route to complex alkynes. For example, reaction of (24) with sodamide (eq 12) provides the hydroxylic terminal pentyne (25).29j Alkyne-allene isomerization has been accomplished with sodamide.30

Aryne Chemistry.

Among the many existing methods for the generation of arynes,31 reaction of a halobenzene derivative with sodamide (as in the example (eq 13) of (26) going to (27)32a) is a commonly employed procedure.32 The highly reactive intermediate arynes can be made to undergo reaction with nucleophiles other than amide anion. Thus bromobenzene (28) is converted (eq 14) into aryl sulfide (29).33a Sodamide-generated arynes have also been reacted with more complex species,34 as illustrated by the transformation (eq 15) of (30) into (31) followed by cyclization to (32).34a Intramolecular benzyne reactions involving sodamide have been used successfully in the synthesis of aporphine alkaloids.35

Generation of Ylides.

Sodamide is a common base for the generation of ylides in the Wittig reaction.36 The commercially available instant ylide consists37a of a 1:1 stoichiometric mixture of Methyltriphenylphosphonium Bromide and sodium amide (eq 16).37b

Reaction as a Nucleophile.

Nucleophilic addition reactions are a major feature of sodamide chemistry. Addition followed by intramolecular attack provides a convenient methodology for the construction of unusual adducts.38 Sodamide, sodamide/potassamide mixtures, and other alkali metal amides have been found to catalyze the amination of alkenes.39 The Chichibabin reaction and its variants40 provide a useful route to numerous substituted heterocycles. The addition-elimination reaction of sodamide on a heterocyclic substrate is nicely illustrated by the transformation (eq 17) of (33) into 6-methylisocytosine (34).41 Nucleophilic addition reactions to nitro-substituted aromatic substrates have been observed.42 Also intriguing are the various reaction pathways observed for heterocycles containing an appended trifluoromethyl group.43 Photochemically assisted additions of sodamide have been reported (eq 18).44 Sodamide is also an effective reagent for accomplishing N-dealkylations (eq 19)45a and N-deacylations.45b

Cleavage and Rearrangement.

Sodamide is involved in many cleavage and rearrangement reactions. Cleavage reactions,46 with specific reference to the Haller-Bauer reaction,47 exemplified by (35) going to (36) (eq 20),47d are a convenient synthetic transform. It is significant that the addition of 1,4-Diazabicyclo[2.2.2]octane (DABCO) permits the Haller-Bauer reaction to be performed with commercial sodamide.47d Rearrangement reactions involving sodamide are well-known,48 with several being common name reactions such as the Truce-Stiles,49 the Sommelet-Hauser,50a and the Stevens50a reactions. A typical Sommelet-Hauser rearrangement is illustrated by (37) going to (38) (eq 21).50b Vinylpyridines undergo polymerization in sodamide/liquid ammonia.51

In recent years, sodamide has been combined with other bases (especially with alkali metal t-butoxides) to create a whole family of so-called complex bases with exceptional properties (see Sodium Amide-Sodium t-Butoxide).52 Typical applications of these bases are in the syn elimination depicted52d by (39) going to (40) and (41) (eq 22) and the carbanion alkylation involving the conversion of (42) to (43) (eq 23).52f

Related Reagents.

Lithium Amide; Potassium Amide; Potassium t-Butoxide; Sodium Amide-Sodium t-Butoxide; Sodium-Ammonia; Sodium Hydride.


1. FF 1967, 1, 1034.
2. (a) Vaughn, T. H.; Vogt, R. R.; Nieuwland, J. A. JACS 1934, 56, 2120. (b) Hauser, C. R.; Adams, J. T.; Levine, R. OSC 1955, 3, 291. (c) Hauser, C. R.; Dunnavant, W. R. OS 1960, 40, 38. (d) Jones, E. R. H.; Eglinton, G.; Whiting, M. C.; Shaw, B. L OSC 1963, 4, 404. (e) Khan, N. A.; Deatherage, F. E.; Brown, J. B. OSC 1963, 4, 851. (f) Greenlee, K. W.; Henne, A. L. Inorg. Synth. 1946, 2, 128.
3. (a) Iwashige, T.; Saeki, H. CPB 1967, 15, 1803. (b) Ireland, R. E.; Kierstead, R. C. JOC 1966, 31, 2543.
4. Loontjes, J. A.; van der Leij, M.; Zwanenberg, B. RTC 1980, 99, 39.
5. Kratchanov, C. G.; Kirtchev, N. A. S 1971, 317.
6. Allen, C. F. H.; VanAllan, J. OSC 1955, 3, 727.
7. Hisano, T.; Tasaki, M.; Tsumoto, K.; Matsuoka, T.; Ichikawa, M. CPB 1983, 31, 2484.
8. Nishinaga, A.; Itahara, T.; Matsuura, T. BCJ 1975, 48, 1683.
9. Shapiro, E. L.; Leggatt, T.; Weber, L.; Olivetto, E. P.; Tanabe, M.; Crowe, D. F. Steroids 1964, 3, 183.
10. Rabideau, P. W.; Huser, D. L. JOC 1983, 48, 4266.
11. (a) Reinecke, M. G.; Hollingworth, T. A. JOC 1972, 37, 4257. (b) Brandsma, L.; de Jong, R. L. P. SC 1990, 20, 1697.
12. (a) Schipperijn, A. J.; Smael, P. RTC 1973, 92, 1121. (b) Schipperijn, A. J.; Smael, P. RTC 1973, 92, 1159.
13. (a) Levine, R.; Dimmig, D. A.; Kadunce, W. M. JOC 1974, 39, 3834. (b) Yamamoto, M.; Sugiyama, N. BCJ 1975, 48, 508. (c) Kaiser, E. M.; Bartling, G. J.; Thomas, W. R.; Nichols, S. B.; Nash, D. R. JOC 1973, 38, 71. (d) Harris, T. M.; Harris, C. M.; Wachter, M. P. T 1968, 24, 6897. (e) Vanderwerf, C. A.; Lemmermann, L. V. OSC 1955, 3, 44. (f) Coffman, D. D. OSC 1955, 3, 320. (g) Hauser, C. R.; Adams, J. T.; Levine, R. OSC 1955, 3, 291. (h) Potts, K. T.; Saxton, J. E. OS 1960, 40, 68. (i) Kaiser, E. M.; Bartling, G. J. JOC 1972, 37, 490. (j) Rash, F. H.; Boatman, S.; Hauser, C. R. JOC 1967, 32, 372.
14. (a) Gospodova, T. S.; Stefanovsky, Y. N. M 1990, 121, 275. (b) Viteva, L. Z.; Stefanovsky, Y. N. M 1982, 113, 181.
15. Tsujino, Y.; Shibata, S.; Katsuyama, A.; Kisaki, T.; Kaneko, H. H 1982, 19, 2151.
16. (a) Harris, T. M.; Harris, C. M. OR 1969, 17, 155. (b) Harris, T. M.; Harris, C. M. JOC 1966, 31, 1032.
17. Kashima, C.; Yammamoto, M.; Kobayashi, S.; Sugiyama, N. BCJ 1974, 47, 1805.
18. Pendarvis, R. O.; Hampton, K. G. JOC 1974, 39, 2289.
19. Hampton, K. G.; Harris, T. M.; Hauser, C. R. OS 1971, 51, 128.
20. (a) duFeu, E. C.; McQuillin, F. J.; Robinson, R. JCS 1937, 53. (b) Cornforth, J. W.; Robinson, R. JCS 1949, 1855.
21. Bumgardner, C. L.; Iwerks, H. JACS 1966, 88, 5518.
22. Halleux, A.; Reimlinger, H.; Viehe, H. G. TL 1970, 3141.
23. Heasley, V. L.; Lais, B. R. JOC 1968, 33, 2571.
24. (a) Fisher, F.; Applequist, D. E. JOC 1965, 30, 2089. (b) Salaun, J. R.; Conia, J. M. CC 1971, 1579. (c) Koster, R.; Arora, S.; Binger, P. S 1971, 322. (d) Arora, S.; Binger, P.; Koster, R. S 1973, 146. (e) Fitjer, L.; Conia, J.-M. AG(E) 1973, 12, 332.
25. Kirmse, W.; von Bullow, B.-G.; Schepp, H. LA 1966, 691, 41.
26. Vaughan, T. H.; Vogt, R. R.; Nieuwland, J. A. JACS 1934, 56, 2120.
27. Lespieau, R.; Bourguel, M. OSC 1941, 1, 191.
28. Khan, N. A.; Deatherage, F. E.; Brown, J. E. OSC 1963, 4, 851.
29. (a) Khan, N. A. OSC 1963, 4, 969. (b) Ashworth, P. J.; Mansfield, G. H.; Whiting, M. C. OSC 1963, 4, 128. (c) Messeguer, A.; Serratosa, F.; Rivera, J. TL. 1973, 2895. (d) Armitage, J. B.; Jones, E. R. H.; Whiting, M. C. JCS 1953, 3317. (e) Bohlmann, F. CB 1951, 84, 545. (f) Jones, E. R. H.; Eglinton, G.; Whiting, M. C. Shaw, B. L. OSC 1963, 4, 404. (g) Wasserman, H. H.; Wharton, P. S. JACS 1960, 82, 661. (h) Newman, M. S.; Geib, J. R.; Stalick, W. M. OPP 1972, 4, 89. (i) Brandsma, L.; Harryvan, E.; Arens, J. F. RTC 1968, 87, 1238. (j) Jones, E. R. H.; Eglinton, G.; Whiting, M. C. OSC 1963, 4, 755.
30. (a) Carr, M. D.; Gan, L. H.; Reid, I. JCS(P2) 1973, 672. (b) Montijn, P. P.; Kupecz, A.; Brandsma, L.; Arens, J. F. RTC 1969, 88, 958.
31. Hoffmann, R. W., Dehydrobenzene and Cycloalkynes; Academic: New York, 1967.
32. (a) Biehl, E. R.; Patrizi, R.; Reeves, P. C. JOC 1971, 36, 3252. (b) Biehl, E. R.; Stewart, W.; Marks, A.; Reeves, P. C. JOC 1979, 44, 3674. (c) Levine, R.; Biehl, E. R. JOC 1975, 40, 1835. (d) Biehl, E. R.; Smith, S. M.; Reeves, P. C. JOC 1971, 36, 1841. (e) Biehl, E. R.; Nieh, E.; Hsu, K. C. JOC 1969, 34, 3595. (f) Biehl, E. R.; Hsu, K. C.; Nieh, E. JOC 1970, 35, 2454. (g) Kraakman, P. A.; Valk, J.-M.; Niederländer, H. A. G.; Brower, D. B. E.; Bickelhaupt, F. M.; de Wolf, W. H.; Bickelhaupt, F.; Stam, C. H. JACS 1990, 112, 6638. (h) Apeloig, Y.; Arad, D.; Halton, B.; Randall, C. J. JACS 1986, 108, 4932.
33. (a) Caubere, P. BSF 1967, 3446, 3451. (b) Carre, M. C.; Ezzinadi, A. S.; Zouaoui, M. A.; Geoffroy, P.; Caubere, P. SC 1989, 19, 3323.
34. (a) Skorcz, J. A.; Kaminski, F. E. OS 1968, 48, 53. (b) Carre, M.-C.; Gregoire, B.; Caubere, P. JOC 1984, 49, 2050. (c) Loubinoux, B.; Caubere, P. S 1974, 201. (d) Buske, G. R.; Ford, W. T. JOC 1976, 41, 1995.
35. Kametani, T.; Fukumoto, K.; Nakano, T. JHC 1972, 9, 1363.
36. (a) Moiseenkov, A. M.; Schaub, B.; Margot, C.; Schlosser, M. TL 1985, 26, 305. (b) Schaub, B.; Blaser, G.; Schlosser, M. TL 1985, 26, 307. (c) Schlosser, M.; Schaub, B.; de Oliveira-Neto, J.; Jeganathan, S. C 1986, 40, 244. (d) Schaub, B.; Jeganathan, S.; Schlosser, M. C 1986, 40, 246. (e) Dauphin, G.; David, L.; Duprat, P.; Kergomard, A.; Veshambre, H. S 1973, 149. (f) Takahashi, H.; Fujiwara, K.; Ohta, M. BCJ 1962, 35, 1498. (g) Yamamoto, Y.; Schimidbaur, H. CC 1975, 668. (h) Quast, H.; Jakobi, H. CB 1991, 124, 1619.
37. (a) Schlosser, M.; Schaub, B. C 1982, 36, 396. (b) Ciana, L. D.; Dressick, W. J.; von Zelewsky, A. JHC 1990, 27, 163.
38. (a) Barnard, I. F.; Elvidge, J. A. JCS(P1) 1983, 1813. (b) Yamagouchi, K. BCJ 1976, 49, 1366.
39. Pez, G. P.; Galle, J. E. PAC 1985, 57, 1917.
40. Vorbruggen, H. Adv. Heterocycl. Chem. 1990, 49, 117.
41. Botta, M.; De Angelis, F.; Finizia, G.; Gambacorta, A.; Nicoletti, R. SC 1985, 15, 27.
42. Gandhi, S. S.; Gibson, M. S.; Kaldas, M. L.; Vines, S. M. JOC 1979, 44, 4705.
43. (a) Kobayashi, Y.; Kumadaki, I.; Taguchi, S.; Hanzawa, Y. TL 1970, 3901. (b) Kobayashi, Y.; Kumadaki, I.; Hanzawa, Y.; Minura, M. CPB 1975, 23, 2044. (c) Kobayashi, Y.; Kumadaki, I.; Hanzawa, Y.; Mimura, M. CPB 1975, 23, 636. (d) Kobayashi, Y.; Kumudaki, I.; Taguchi, S.; Hanzawa, Y. CPB 1972, 20, 1047.
44. Tintel, C.; Rietmeyer, F. J.; Cornelisse, J. RTC 1983, 102, 224.
45. (a) Hirai, Y.; Egawa, H.; Yamada, S.; Yamazaki, T. H 1983, 20, 1243. (b) Fraenkel, G.; Cooper, J. W. JACS 1971, 93, 7228.
46. (a) Furukawa, N.; Tanaka, H.; Oae, S. BCJ 1968, 41, 1463. (b) Shiotani, S.; Kometani, T. CPB 1973, 21, 1160.
47. (a) Hamlin, K. E.; Weston, A. W. OR 1957, 9, 1. (b) Alexander, E. C.; Tom, T. TL 1978, 1741. (c) Paquette, L. A.; Maynard, G. D. JOC 1989, 54, 5054. (d) Kaiser, E. M.; Warner, C. D. S 1975, 395.
48. (a) Mason, J. G.; Youssef, A. K.; Ogliaruso, M. A. JOC 1975, 40, 3015. (b) Youssef, A. K.; Ogliaruso, M. A. JOC 1973, 38, 3998. (c) Sarel, S.; Klug, J. T.; Taube, A. JOC 1970, 35, 1850. (d) Klein, K. P.; Hauser, C. R. JOC 1966, 31, 4275.
49. Crowther, G. P.; Hauser, C. R. JOC 1968, 33, 2228.
50. (a) Pine, S. H. OR 1970, 18, 403. (b) Kantor, S. W.; Hauser, C. R. JACS 1951, 73, 4122. (c) Giumanini, A. G.; Trombini, C.; Lercker, G.; Lepley, A. R. JOC 1976, 41, 2187.
51. Laurin, D.; Parravano, G. J. Polym. Sci. Part A-1, Polym. Chem. Ed. 1968, 6, 1047.
52. (a) Caubere, P. ACR 1974, 7, 301. (b) Caubere, P. Top. Curr. Chem. 1978, 73, 49. (c) Ndebeka, G.; Raynal, S.; Caubere, P. JOC 1980, 45, 5394. (d) Croft, A. P.; Bartsch, R. A. JOC 1983, 48, 876. (e) Croft, A. P.; Bartsch, R. A. TL 1983, 24, 2737. (f) Carre, M. C.; Ndebeka, G.; Riondel, A.; Bourgasser, P.; Caubere, P. TL 1984, 25, 1551. (g) Raynal, S. Eur. Polym. J. 1986, 22, 559.

John L. Belletire & R. Jeffery Rauh

The University of Cincinnati, OH, USA



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