Reagent Friday: Hydrazine (NH2NH2)
Last updated: January 29th, 2020 |
Hydrazine (NH2NH2) As A Reagent In Organic Chemistry For The Wolff-Kishner And Gabriel Synthesis
The first time I ever heard about anhydrous hydrazine, it was from my instructor for 3rd year advanced organic chemistry, Walter Szarek. “If ya ever work with this stuff”, he said, in his Rodney Dangerfield-like accent, “lemme know, so I can leave the buildin’ “.
Hydrazine is dangerous. Not only is it toxic, but it is also potentially explosive. As a common component of rocket fuel, it can literally take you to the moon. See, every molecule of hydrazine yearns in its soul to one day shed its hydrogens so that it can become elemental nitrogen, N2, which makes it a powerful reducing agent given the right conditions.
Hydrazine (NH2NH2) In The Wolff-Kishner Reaction
The Wolff Kishner reaction is a means of turning a ketone into an alkane. Note what’s happening here: we’re breaking two C-O bonds and replacing them with two C-H bonds. What happens to hydrazine? It’s converted into elemental nitrogen. This reaction requires quite a bit of heat (~200 deg C) and has been supplanted by milder methods.
Hydrazine In The Second Step Of The Gabriel Synthesis
Hydrazine is also used in the second step of the Gabriel synthesis, for liberating the new amine from the phthalyl group.
Mechanism: NH2NH2 In The Wolff-Kishner Reaction
How it works. Let’s just look at the Wolff-Kishner here. The first step of the Wolff-Kishner is formation of a “hydrazone“, which is what we call an imine with another nitrogen attached. (Here’s a post on how imines form.) In the presence of base, one of the protons on the NH2 group is removed. Once this anion forms, you can hopefully imagine a resonance form where a N=N double bond is formed and the negative charge has been transferred to the carbon. The carbon then is protonated by a molecule of water (it’s also reasonable to use the solvent, ethylene glycol as the acid here). A second round of deprotonation leads to formation of a nitrogen nitrogen triple bond, breakage of the C-N bond (liberating nitrogen!) and then protonation of the carbon with a second molecule of water (or solvent). Result: an alkane.
Real life tips: Hydrazine (stabilized as the hydrate) has its uses and is not leave-the-building worthy so long as you know what you’re doing. Avoid contact with high surface area metals (which catalyze its decomposition) , and (it should go without saying) any contact with skin. I don’t know of anyone who’s worked with unstabilized anhydrous hydrazine (any stories out there?): there’s an example of something you can work with while I go on a “lunch break”.
P.S. You can read about the chemistry of hydrazine and more than 80 other reagents in undergraduate organic chemistry in the “Organic Chemistry Reagent Guide”, available here as a downloadable PDF. The Reagents App is also available for iPhone, click on the icon below!
(Advanced) References And Further Reading
- Ueber eine Darstellungsweise primärer Amine aus den entsprechenden Halogenverbindungen
Gabriel Chem. Ber. 1887, 20 (2), 2224-2236
The original paper by Siegmund Gabriel on the synthesis of primary amines using phthalimide.
- γ-AMINOBUTYRIC ACID
C. DeWitt Org. Synth. 1937, 17, 4
This procedure in Organic Syntheses, a source of reliable and independently tested synthetic organic reactions, is a slight variation of the Gabriel amine synthesis, using acid to hydrolyze the phthalimide and liberate the primary amine.
- An Improved Procedure for the Condensation of Potassium Phthalimide with Organic Halides
John C. Sheehan, William A. Bolhofer
J. Am. Chem. Soc. 1950, 72 (6), 2786-2788
This paper shows that DMF (N,N-dimethylformamide) is a suitable solvent for the first step of the Gabriel amine synthesis.
- Novel Gabriel reagents
Ulf Ragnarsson, Leif Greh
Acc. Chem. Res. 1991, 24 (10), 285-289
This account covers alternatives to phthalimide that can be used in the Gabriel amine synthesis.
- The Gabriel Synthesis of Primary Amines
Gibson, M. S.; Bradshaw R. W. Chem. Int. Ed. 1968, 7 (12), 919-930
An older, but still useful review, on the scope and limitations of the Gabriel amine synthesis.