Sodium Amide-Sodium t-Butoxide1


[7782-92-5]  · H2NNa  · Sodium Amide-Sodium t-Butoxide  · (MW 39.02) (R = t-Bu)

[865-48-5]  · C4H9NaO  · Sodium Amide-Sodium t-Butoxide  · (MW 96.12) (R = Et(OCH2CH2)2)

[52382-21-5]  · C6H13NaO3  · Sodium Amide-Sodium Ethoxyethoxyethoxide  · (MW 156.18)

(strong bases, very efficient for syn eliminations of organic halides, useful in aromatic, heteroaromatic, and cycloalkenyl elimination-addition reactions; initiate anionic polymerizations)

Physical Data: sodium amide complex bases have not been characterized structurally. They are generated in situ, or commercial preparations are used as received. They are white or light yellow suspensions in the reaction solvent.

Solubility: poorly sol THF or DME.

Preparative Methods: complex bases NaNH2-RONa (2:1) are conveniently prepared by the reaction of an alcohol (ROH, 1 equiv) with NaNH2 (3 equiv) in ethereal solvents (THF, DME, etc.) or in hydrocarbons; t-BuOH and Et(OCH2CH2)2OH are distilled from sodium. Complex bases (2:1) contain 2 equiv NaNH2 and 1 equiv RONa (activating agent).

Form Supplied in: suspensions in THF: NABUT (~0.8 mol L-1, d 0.915-0.920 g mL-1); NAMEDEG (~0.7 mol L-1, d 0.928-0.933 g mL-1).

Handling, Storage, and Precautions: complex bases must be handled and stored under inert atmosphere (N2 or Ar). Hydrolysis is performed by slow addition of cold water.

Proton Abstractions.

Complex bases NaNH2-RONa (2:1) abstract protons from very weak organic acids. Condensation of the resulting carbanions with electrophiles takes place in excellent yields, as exemplified in eq 1.2

Complex bases strongly favor monoalkylation of activated methylenes, a property used to perform monoalkylation of carboxylic acid derivatives on an industrial scale.3

NaNH2-t-BuONa or NaNH2-Et(OCH2CH2)2ONa (the strongest of the sodium amide-containing complex bases) may conveniently replace organolithium reagents or lithium amides in the synthesis of diazaphospholanes4 as well as in the thiomethylation of ketones (eq 2).5

Elimination Reactions.

Complex bases are efficient in usual elimination reactions and they conveniently replace more expensive and/or less accessible bases. Thus NaNH2-t-BuONa may be used instead of Potassium Amide in the preparation of methylenecyclopropane (eq 3).2b

The complex base NaNH2-t-BuONa (2:1) promotes syn eliminations under mild conditions (eq 4).6

The poorer leaving group is preferentially eliminated in reactions of trans-dihalocyclohexanes with NaNH2-t-BuONa (1:1).7 Advantage may be gained from the strong propensity of NaNH2-t-BuONa (2:1) to effect syn eliminations in the synthesis of linear8 and cyclic alkynes.9

Elimination-Addition Reactions.

Nucleophilic arynic substitutions may be performed in etheral solvents such as THF or DME due to the facile generation of arynes from aryl halides and NaNH2-t-BuONa or NaNH2-Et(OCH2CH2)2ONa. Such reactions are more convenient than condensations usually performed in liquid NH3 and the scope of applications is more extended.

Thus amines and sodium thiolates are condensed with aryl halides (including fluorides) under mild conditions and in very good yields, as exemplified in eq 5.10

Such reactions may be also performed with polyhalogenobenzenes11 and used in the synthesis of nitrogen containing heterocycles (eq 6).11d

Use of the complex base NaNH2-Et(OCH2CH2)2ONa provides a good solution to the difficult monoarylation of nitriles (eq 7).12

Arynic condensations of ketone enolates which cannot be performed in the presence of sodium amide alone, are easily performed with NaNH2-t-BuONa. Thus 1,2-diketone monoacetals are condensed with bromobenzene to give benzocyclobutenol derivatives in good yields (eq 8).5b,13

In the same way, one-step syntheses of naphthalenes, tetralones, indanones, and dihydronaphthocyclobutenols are easily performed via arynic condensation of a,b-unsaturated ketone enolates with aryl halides in the presence of NaNH2-t-BuONa.14

NaNH2-t-BuONa is also an efficient reagent for generating cyclopropabenzynes (eq 9),15 while classical conditions in liquid NH3 are unsuccessful.

NaNH2-t-BuONa easily generates pyrid-3-yne, allowing hetarynic condensations with nucleophiles.16

Finally, strained cycloalkynes and cycloalka-1,2-dienes are generated under mild conditions from the corresponding 1-halocycloalkenes and NaNH2-t-BuONa and condensed with nucleophiles (eq 10).17

Such reactions have found a large number of extensions and applications.1b,d,18

Anionic Polymerizations.

The complex bases NaNH2-t-BuONa and NaNH2-Et(OCH2CH2)2ONa are very efficient in initiating anionic polymerizations of acrylic and methacrylic derivatives as well as styrene and vinylpyridine.1c These reactions can be performed in solution or in the absence of solvent.

1. (a) Caubére, P. ACR 1974, 7, 301. (b) Caubére, P. Top. Curr. Chem. 1978, 73, 50. (c) Caubére, P. In Crown Ethers and Phase Transfer Catalysis in Polymer Science, Mathias, L. J.; Carraher, C. E., Jr., Eds.; Plenum: New York, 1984; p 139. (d) Caubére, P. Rev. Heteroatom Chem. 1991, 4, 78. (e) Caubére, P. CRV 1993, 93, 2317.
2. (a) Caubére, P.; Loubinoux, B. BSF 1969, 2483 (CA 1970, 72, 11 930r). (b) Caubére, P.; Coudert, G. BSF 1971, 2234 (CA 1971, 75, 87 770w); (c) Ndebeka, G.; Caubére, P.; Raynal, S.; Lecolier, S. Polymer 1981, 22, 347.
3. Bouisset, M.; Chignac, M.; Grain, C.; Pigerol, C. Sanofi Fr. Patent 7 930 039, 1979; Eur. Patent 80 870 053.8, 1980 (CA 1981, 95, 168 579f).
4. Savignac, P.; Dreux, M. JOM 1974, 66, 81 (CA 1974, 80, 133 357v).
5. (a) Carré, M. C.; Ndebeka, G.; Riondel, A.; Bourgasser, P.; Caubére, P. TL 1984, 25, 1551. (b) Grégoire, B.; Carré, M. C.; Caubére, P. JOC 1986, 51, 1419.
6. Caubére, P.; Coudert, G. CC 1972, 1289. Guillaumet, G.; Lemmel, V.; Coudert, G.; Caubére P. T 1974, 30, 1289 (CA 1974, 81, 104 232r).
7. Lee, J. G.; Bartsch, R. A. JACS 1979, 101, 228. Lee, J. G.; Bartsch, R. A. TL 1983, 24, 2737. Lee, J. G.; Kang, K. T.; Lee, E. S. J. Korean Chem. Soc. 1984, 28, 20. Bartsch, R. A.; Cho, B. R.; Pugia, M. J. JOC 1987, 57, 5494.
8. Caubére, P.; Coudert, G. T 1972, 28, 5635 (CA 1973, 78, 57 897n).
9. Caubére, P.; Coudert, G. BSF 1973, 3067 (CA 1974, 80, 70 402h).
10. Caubére, P.; Loubinoux, B. BSF 1968, 3857 (CA 1969, 70, 2945f). Caubére, P.; Dérozier, N. BSF 1969, 1737 (CA 1969, 71, 80 831a. Caubére, P.; Hochu, M. F. BSF 1969, 2854 (CA 1969, 71, 112 082a).
11. (a) Caubére, P.; Lalloz, L. BSF 1974, 1983 (CA 1975, 82, 124 359m). (b) Caubére, P.; Lalloz, L. BSF 1974, 1989 (CA 1975, 82, 124 360e). (c) Caubére, P.; Lalloz, L. BSF 1974, 1996 (CA 1975, 83, 9345n). (d) Lalloz, L.; Caubére, P. S 1975, 657; (e) Moreau-Hochu, M. F.; Caubére, P. T 1977, 33, 955.
12. Carré, M. C.; Ezzinadi, A. S.; Zouaoui, M. A.; Geoffroy, P.; Caubére, P. SC 1989, 19, 3323.
13. Carré, M. C.; Jamart-Grégoire, B.; Geoffroy, P.; Caubére, P. T 1988, 44, 127. Carré, M. C.; Aatif, A. A.; Geoffroy, P.; Caubére, P. SC 1989, 19, 2523. Zouaoui, M. A.; Mouaddib, A.; Jamart-Grégoire, B.; Ianelli, S.; Nardelli, M.; Caubére, P. JOC 1991, 56, 4078.
14. Sammes, P. G.; Wallace, T. W. CC 1973, 524. Brunet, J. J.; Essiz, M.; Caubére, P. TL 1974, 15, 871 (CA 1974, 81, 37 195r). Sammes, P. G.; Wallace, T. W. JCS(P1) 1975, 1377. Essiz, M.; Guillaumet, G.; Caubére, P. T 1979, 35, 1167. Essiz, M.; Guillaumet, G.; Brunet, J. J.; Caubére, P. JOC 1980, 45, 240.
15. Halton, B.; Randall, C. J. JACS 1983, 105, 6310. Apeloig, Y.; Arad, D.; Halton, B.; Randall, C. J. JACS 1986, 108, 4932.
16. Jamart-Grégoire, B.; Léger, C.; Caubére, P. TL 1990, 31, 7599.
17. Caubére, P.; Brunet, J. J. TL 1969, 10, 3323 (CA 1969, 71, 123 089j). Caubére, P.; Brunet, J. J.; BSF 1970, 2418 (CA 1970, 73, 108 978w). Caubére, P.; Brunet, J. J. T 1971, 27, 3515 (CA 1971, 75, 98 026j). Brunet, J. J.; Fixari, B.; Caubére, P. CR(C) 1973, 276, 1045 (CA 1973, 78, 147 426n). Brunet, J. J.; Fixari, B.; Caubére P. T 1974, 30, 2931 (CA 1975, 82, 97 738a).
18. Jamart-Grégoire, B.; Brosse, N.; Ianelli, S.; Nardelli, M.; Caubére, P. TL 1991, 32, 3069.

Paul Caubére

University of Nancy I, France

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