Jeremy Tervo:

Well Janelle, the most vital component to understanding this reaction process resides in assigning hydrazine and ammonia their appropriate nucleophilicity parameter. Hydrazine, with its unique N-N bond, demonstrates certain electron-repulsive tendencies as a consequence of the proximity of these electronegative atoms.

The tendency for these electrons to dissociate more easily as a result of this electrochemical effect enables Hydrazine to act as a more potent nucleophile. If you observe this photo that I posted for you below, then you may notice that the carbonyl that Hydrazine attacks is not extraordinarily electrophilic, but Janelle don't you worry -- this effect, occurring from the resonance potential with the adjacent Nitrogen, is relatively inconsequential. When Hydrazine is supplied within the reaction the desired acyl transfer may take place through an analogue of a reaction titled the Gabriel Synthesis. Hydrazine selectively incites the acyl transfer at the desired carbonyl for analogous reasons to Ammonia's shortcomings. The right-most carbonyl (in between Nitrogen and Oxygen) is too shielded with electron density from resonance forms to interact with Hydrazine; thus, Hydrazine is chosen for its precise nucleophilicity in carrying out this specific process. WOW!

Hydrazine's nucleophilicity parameter in Acetonitrile is within the realm of 16.45 upon manipulation of the rate equation, and Ammonia's nucleophilicity parameter is 11.39 in the same solvent (Nigst, T. A.; Antipova, A.; Mayr, H. J. Org. Chem. 2012, 77, 8142-8155.). The carbonyl bond in question is not electrophilic enough to react with the lower nucleophilicity inherently associated with Ammonia; therefore, Ammonia is apt to equilibrate with other portions of the molecule. Namely, the -OH portion of the β-hydroxy amide present in towards the center of Molecule 20. Although the Keq lies in sizable favor of the protonated hydroxyl group, a marginal presence of the anionic oxygen upon equilibrium may incite the retro-aldol reaction to occur as the molecule is in an appropriate conformation.

Hydrazine, although acting as a more expedient nucleophile, is realistically less basic than ammonia; this phenomenon is explained through the unstable protonation state of these proximally oriented electronegative atoms. With this in mind, there is no need to worry about whether Hydrazine will also deprotonate that -OH, and hence why the retro-aldol reaction does not occur with its usage!

 

 

Now witness the full power of nucleophilic Hydrazine (via an analogy to the Gabriel Synthesis)!