Let me introduce a new friend to you! This is semicarbazide (1), a member in the family of hydrazine derivatives. Semicarbazides can undergo condensation (addition-elimination) reactions with ketones and aldehydes, through an iminium ion intermediate (2), and subsequently leads to semicarbazones (3) (Figure 1).
Figure 1
Many semicarbazones are known to be crystalline solids. Why? Because these compounds have large relative molecular masses, and their intermolecular attractions are based on hydrogen bonding.
Semicarbazones, like the other known hydrazone derivatives, are really useful for structure identification in organic chemistry before the advent of NMR spectroscopy. These compounds are often used to confirm the supposed identity of the parent aldehydes and ketones in the past. How is it possible?
Consider the 2 ketones (4) and (5), which are very similar in structure (Figure 2). While they can be easily distinguished through the comparison of their 1H NMR spectra, that was not so in the past. Because ketones (4) and (5) have exactly the same boiling point, this is not a good property to distinguish between the 2 brothers.
Figure 2
If we convert (4) and (5) into their corresponding semicarbazones (6a, 7a) and hydrazones (6b,7b), our lives become easier (Figure 2, cont.). Because the two resulting semicarbazones (6a, 7a) and hydrazones (6b, 7b) have very different melting points, it will not be hard to tell which is which. Thus, through a comparison of the melting point of the ‘-zone’ derivative to literature data, one can likely deduce the parent aldehyde or ketone that it is derived from.
I have got a further example from a recent research article (Figure 3). All the hydrazone derivatives (8-10) are stable and they all have different colors, too! (PCAIJ, 2016, 11, 24-34.)
Figure 3
So, how is the iminium ion (2) formed in the first place? We can understand it through the following mechanism (Figure 4).
Figure 4
Those who wants to play devil's advocate may ask, 'oh, well, why doesn't the other nitrogen atom in (1) react instead?' Well, the reason is because the 2 nitrogen centers have quite distinct electron density. The terminal amine group is more nucleophilic and it can react with the carbonyl group. Yet, for the nitrogen center on the amide group, the electron pair on the nitrogen center is participating in resonance with the nearby C=O group, therefore becomes less electron-donating, and less nucleophilic as a result.
This article is based on a question from the HKALE Chemistry paper in 2012, with some further information from me.
by Ed Law
