In this section, we will learn about the various methods for the preparation of amines and tips to remember those using mnemonics.
A way to remember all the preparation methods is by memorizing this statement,
‘In search of amines, two brothers, Schmidt-Hofmann-Gabriel-Hofmann, wanted to reduce ANI-ANO. ’ in which, ANI stands for Amide, Nitrile, and Imine and ANO for Azide, Nitro and Oxime.
The names of the two brothers are for four name reaction for the preparation of amines, namely:
1) Schmidt Reaction
2) Hofmann degradation of primary amides
3) Gabriel Phthalimide reaction
4) Hofmann Ammonolysis
From the statement, we learn that the two brothers want to Reduce ANI-ANO. It means that all the methods are for functional group reduction specifically, nitrogen-containing functional groups.
The amide, in general, is represented as carbonyl attached to N, nitrile also known as cyano is written as C triple bond N, imine is a functional group containing Carbon-nitrogen double bond. Azide functional group is shown as N3; Nitro is shown as NO2, and oxime is similar to imine in having carbon-nitrogen double bond with nitrogen attached to hydroxyl group shown as C=N-OH.
The Most commonly used reducing agents for amine preparation are H2 gas in Raney Ni and LAH.
The first A of the ANI-ANO stands for Amide, and the reaction is the reduction of the amide functional group to an amine.
What we observe is that primary, secondary and tertiary amides are reduced to the respective amines using LAH in solvent diethyl ether. In the second step, water is added to end the reaction and to isolate the product.
From the general reaction scheme, we can see that the change is from CO of the amide to the CH2 of the amine. This change is brought about by reducing agent LAH that is the best reducing agent for the reduction of carbonyls such as amides, esters, aldehydes, ketones etc. It reduces amide by donating hydride, i.e., H-. that is an anion of hydrogen.
All the four hydrides of LAH can be used in the reduction, and the method can be best explained by showing you the example of a reduction of primary alkyl amide to the primary alkyl amine.
The hydride of the LAH adds to the carbonyl of the amide to give an intermediate imine, with one hydrogen coming from LAH. This imine is highly reactive due to the positive charge on electronegative nitrogen. It then undergoes further addition of the hydrogen from LAH to give primary alkyl amine as the final product. This method can be used for the synthesis of alkyl amine and aryl amine from alkyl or aryl amides.
Let’s look at a few examples;
When acetamide is treated with LAH, it gives ethyl amine.
Similarly, secondary alkyl amide, N-methyl acetamide undergoes reduction to give ethyl methyl amine.
The third example is of tertiary alkyl amide, N,N-Dimethylacetamide that gets reduced to form ethyl dimethyl amine.
Benzamide is the case of aromatic amide that gives benzylamine on treatment with LAH.
Test your knowledge by attempting this quiz.
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