Reagent Friday: Sodium Amide (NaNH2) - Master Organic Chemistry

Sodium Amide (Sodamide, NaNH2), A Strong Base For The Deprotonation Of Terminal Alkynes (Among Other Uses)

In a blatant plug for the Reagent Guide, each Friday  I profile a different reagent that is commonly encountered in Org 1/ Org 2. Version 1.2 just got released this week, with a host of corrections and a new page index. 

Note: there should also be another exciting announcement about the Reagent Guide coming up in the next little while or so… more details to come!

NaNH2 (Sodium amide) 

 What it’s used for: NaNH2 is a strong base. In the rare cases when its strong basicity doesn’t cause side reactions, it can be an excellent nucleophile  It’s used for deprotonation of weak acids and also for elimination reactions.

Similar to: LDA (lithium diisopropylamide).

The NH2- anion is the conjugate base of ammonia (NH3). If you’ll recall, the weaker the acid, the stronger the conjugate base – and since NH3 has a pKa of 38, NH2 is a strong base indeed. (Note that although I’m talking about NaNH2 here, the bases LiNH2 and KNH2 essentially behave the same way.)

As a strong base, NaNH2 will deprotonate alkynes, alcohols, and a host of other functional groups with acidic protons such as esters and ketones.

As a base, it’s often used in situations where a strong, small base is required. Like a piranha, NaNH2 is small, fast, and has razor sharp teeth, and can find its way into tight, enclosed spaces.

Sodium Amide (NaNH2) For The Deprotonation Of Terminal Alkynes To Give Acetylide Ions

One common application of NaNH2 is in the deprotonation of alkynes to give so-called “acetylide” ions. These ions are excellent nucleophiles and can go on to react with alkyl halides to form carbon-carbon bonds as well as add to carbonyls in addition reactions

NaNH2 As A Base For The Double Elimination Of Geminal Or Vicinal Dihalides To Give Alkynes

A second application of NaNH2 is in the formation of alkynes from halogens. Treatment of either geminal dihalides (i.e. – two halogens on one carbon) or vicinal dihalides (halogens on adjacent carbons) with NaNH2 (2 equiv) will result in the formation of alkynes.

Since vicinal dihalides are easily made by the reaction of alkenes with halogens such as Br2 or I2, this is a useful way of converting alkenes to alkynes.

Mechanism Of NaNH2 : Double Elimination To Give Alkynes

How it works.

Deprotonation of functional groups such as OH and even alkyne C-H should hopefully be straightforward, but the use of bases to make alkenes may require some explanation. This is what is known as an elimination reaction, in that the elements H and Br (in this example) are removed in order to form the alkene. Specifically, this is an example of an E2 reaction. 

Since the alkene still has a halide attached, this too can be removed to generate a second double bond (π bond). This is another example of the E2 in that the hydrogen has to be anti to the bromine that is eliminated, but is unusual in that it is an sp2 hydrogen that is affected here:

This arrangement is necessary in order for the reaction to occur in that the pair of electrons in the C–H bond that is breaking will simultaneously interact with the antibonding orbital of the C-Br bond, leading to formation of the new π bond and expulsion of the Br(-)

P.S. You can read about the chemistry of NaNH2 and more than 80 other reagents in undergraduate organic chemistry in the “Organic Chemistry Reagent Guide”, available here as a downloadable PDF.

EDIT/UPDATE. @chemistinjapan makes the following observation:

A note of caution on use of NaNH2 as a nucleophile. My trusty copy of March has the following to say:

“The conjugate base of ammonia  is sometimes used as a nucleophile, but in most cases offers no advantage over ammonia, since the latter is basic enough.”

Furthermore, since NaNH2 is a strong base, it has the significant disadvantage of promoting side reactions from elimination (this can occur when attempting an SN2 with NaNH2 as the nucleophile, for example). Therefore, it is generally wise to avoid using NaNH2 as a nucleophile in organic synthesis. Sodium azide (followed by reduction) is the usual substitute.

I suppose one could use NaNH2 as a nucleophile in a case like this one (below) but again it offers no significant advantage over NH3:

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(Advanced) References and Further Reading

1. SODIUM AMIDE F. W. Bergstrom Org. Synth. 1940, 20, 86 DOI: 10.15227/orgsyn.020.0086 How to prepare solid sodium amide, NaNH2, by passing a stream of ammonia through a crucible of molten sodium.  From Organic Syntheses, a compendium of reliable procedures for the preparation of organic compounds.
2. Eliminations from Olefins DR. G. KOBRICH. Angew. Chem. Int. Ed. 1965 4 (1), 49 DOI: 10.1002/anie196500491 A review describing various types of a- and b-elimination reactions of alkenes to give alkynes.
3. Elimination Strategy for Aromatic Acetylenes Orita, H.; Otera, J. Chem. Rev. 2006, 106, 5387 DOI: 10.1021/cr050560m Section 3.3 in this review covers the synthesis of alkynes by double dehydrobromination reactions from vic-dibromoalkanes.
4. Unsaturated eight-membered ring compounds. XI. Synthesis of sym-dibenzo-1,5-cyclooctadiene-3,7-diyne and sym-dibenzo-1,3,5-cyclooctatrien-7-yne, presumably planar conjugated eight-membered ring compounds Henry N. C. Wong, Peter J. Garratt, and Franz SondheimerJournal of the American Chemical Society 1974 96 (17), 5604-5605 DOI: 10.1021/ja00824a066 The reaction used to synthesize the strained cyclooctyne is the double dehydrobromination reaction, using fairly standard conditions (KOtBu in THF).
5. Proton NMR study of two tetradehydrocyclodecabiphenylenes Charles F. Wilcox Jr. and Karl A. Weber The Journal of Organic Chemistry 1986 51 (7), 1088-1094 DOI: 10.1021/jo00357a028 The authors also use a double dehydrobromination reaction to obtain cyclic dialkynes, also using standard conditions (KOtBu in THF). The experimental section has detailed procedures.