This question is about reacting aldehydes and ketones with hydrazine.
I would like to prepare an asymmetric azine: I'm thinking about adding aldehyde 1 (eg salicylic aldehyde) to an excess of hydrazine, then to isolate the hydrazone and finally to react the hydrazone with the second aldehyde, eg benzaldehyde.
I just wonder if this might work or if (although there is an excess of hydrazine, eg 10-fold, it's just small scale) still the azine forms preferentially. That because the aldehyde might react faster with the hydrazone than with hydrazine or because there could be an equilibrium that is not in my favor.
The aldehyde reacts with 0.5 equiv of hydrazine at RT in EtOH within a few minutes. But the product precipitates, thus removing itself from a possibly existing equilibrium.
Has anyone some experience with this topic and could give me some advice how to proceed?
Yes this is perfectly possible in mild conditions and in ethanol.
You are facing a problem of level of reactivity (nucleophily) of the formed azine compared to the hydrazine. Indeed, the basicity of the hydrazine is lower than the one of ammoniac but its nucleophily is much higher due to the presence of the two free doublets of electrons on each nitrogen that make repulsion. When the azine is first formed, this phenomenon is reinforced by the further substitution of one nitrogen, which makes it very much more reactive than the hydrazine itself. Any excess of this hydrazine only plays a role of catalytic factor ...
To my opinion, you may anticipate this second reaction only by using "high dilution" conditions, ie, at least 0.001 mmole/l and by letting the aldehyde to be the "restricting factor": it should be added at the diluted state, drop-wise to the diluted solution of hydrazine.
Please let me know if this works.
Agreed with Joseph. The nucleophilicity of hydrazine is much higher than any other amine due to the "alpha-heteroatom effect", or the fact that one heteroatom's doublet fills the anti-bonding orbital of the other one. This effect is also observed to a lesser extend with hydroxylamine, which is why oximes are prepared so easily.
In your case, I think you have 2 options: Use high dilution and high excess of hydrazine or use BOC-hydrazine, which is a lot less nucleophilic due to the electron withdrawing effect of the boc. You jusy have to take it off with diluted HCL in the presence of your second carbonyl. To have the boc-hydrazine would also make it easier to work with I think.
Good luck!
I remember quite well, that it strongly depends on the used ketone/aldehyde. Sometimes we could only observe azines, sometimes a mixture or just hydrazones. So as it is often the case, give it a try and see what will happen.
Of cause azines could be transformed into hydrozones again:
http://onlinelibrary.wiley.com/doi/10.1002/cber.19160490245/abstract;jsessionid=A751E2B84973AAF952ABB1B1650A0518.d02t01
I think in the preparation of azine temperature effect and mild basic condition should be maintained.
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