Addition of ammonia, amines and derivs. to aldehydes and ketones
If the oxygen of an alcohol can donate electrons to a C=O group, the nitrogen of ammonia and amines will do so even more easily, because it is less electronegative than oxygen.
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Ammonia, primary amines and anilines
Aldehydes and ketones condense with ammonia, primary alkylamines or primary anilines to give imines. The term condensation means that a water molecule is lost in the process. Imines contain a C=N double bond and are generally stable compounds, especially when the C=N is conjugated with an aromatic ring. The C=N double bond can undergo nucleophilic attack in the same way as the C=O.
Imine formation is usually combined with an in situ reduction, so that a new amine is obtained; the overall process is called reductive amination of aldehydes and ketones. Look at a couple of examples with two different reducing agents:
In these two examples the "main character" is the aldehyde and the "supporting actor" is ammonia or methylamine. However, the idea can also be used the other way around: the smallest aldehyde, formaldehyde, can act as the "supporting actor" to methylate an amine (now the "main character"). Look at an example:
If you need to introduce one methyl group (and only one!) on an amine, reductive amination is undoubtedly the method of choice.
Click here to review the problems of the alkylation of amines with alkyl halides by SN.
Secondary amines
With a secondary amine, the addition product (hemiaminal) has no hydrogen on nitrogen that it can lose. Water is then lost with the participation of a hydrogen α to the original carbonyl group. The result is an enamine, i.e. an amine attached to a C=C double bond. Isn't an enamine very much like a trapped enolate?
Hydroxylamine
The reaction is completely analogous to that of primary amines, except that the final product, which has an OH group on the nitrogen, receives the special name of oxime.
Hydrazines
The reaction is completely analogous to that of primary amines, except that the final product, which has an amino group on the nitrogen, receives the special name of hydrazone.
When hydrazones are treated with hydroxide, nitrogen bubbles off and the double bond disappears.
The overall process aldehyde/ketone + hydrazine + basic medium is a method for the complete reduction of the C=O group to CH2: the Wolff-Kishner reduction.
It is named after Ludwig Wolff and Nikolai Kishner, who discovered it independently: Kishner published it in 1911 and Wolff in 1912.
