What is the right way to get reduced amines? Here is a more universal method for producing amines, which does not lead to excessive alkylation. This method is quite simple and transparent even for beginners in chemistry. Just a few simple reactions. However, you will need some reagents that are hard to find on the market. Using this method, for example, reductive amination of amino acids can be carried out.
Start
Starting with an aldehyde or ketone, form an imine (an analog of nitrogen aldehyde or ketone). Reduce imine with a reducing agent such as sodium cyanoborohydride (NaBH3CN), sodium borohydride (NaBH4) or sodium acetoxyborohydride (NaBH (OAC) 3). It turns out a new amine. There is no need to isolate the intermediate imine (which may be somewhat unstable anyway). The reduction can be performed in place (i.e., in the same reaction flask), after which give the imine sufficient time to form.
This process is called reductive amination. The name "reductive amination" is also found. Here is a specific example: hydro-methylbenzylamine.
Say you have a primary amine, such as benzylamine, and you want to make hydro-methylbenzylamine. How do you do this? Immediately treating benzylamine with an alkene agent (e.g. methyl iodide) will result in significant formation of an undesired tertiary amine (i.e., dealkylation).
Yes, you can try to separate the secondary amine, which is formed from a tertiary amine, but we are not going to agree on a 10-30% concentration that this method gives. Separating mixtures is good on paper, but it can be a real pain in practice. Is there any other way to do this? Try reductive amination. This is a much more controlled way to form nitrogen-carbon bonds.
After the imine is formed, it must be reduced to the amine. A familiar sodium borohydride (NaBH4) reducing agent can be used for this process. You may recall that NaBH4 is used to reduce aldehydes and ketones. There are two other commonly used reductive amination reducing agents: sodium cyanoborohydride (NaBH3CN) and sodium acetoxyborohydride (NaBH (OAC) 3). For our purposes, they can be considered the same. In practice, NaBH3CN is slightly better than NaBH4.
Application
Reductive amination is very versatile and can be used to establish a wide variety of different alkyl groups on amines. The best part is that the bands just go once.
Ketones also work
What about ketones? They work too! Use a ketone, which will lead us to branched alkyl substituents on the amine. For example, the use of acetone in the next reductive amination gives an isopropyl group. The rest is simple.
Sequential amination is another useful feature of the reductive amination reaction. The peculiarity is that two (or three, if one starts with ammonia) processes can be used in a certain sequence. For example, see the synthesis of a tertiary amine. It is important to note that the sequence of reactions is not critical. We could do the first reductive amination with the first benzaldehyde and acetone secondly, and still the same product is obtained.
Intramolecular reductive amination
Finally, there is an intramolecular case that always brings students a headache. If the molecule contains both amine and carbonyl groups, it can give a cyclic amine. When pulling the product of ring formation, we strongly recommend that you count and number your angles. Many students make mistakes when redrawing, which is worth the time spent.
Work in the opposite direction: planning for reductive amination
This may take some time, but reductive amination is an extremely powerful way to get amines. It is very useful to be able to think in the opposite direction from the amine product to how the starting materials look.
In general, reductive amination is a very powerful and useful protocol for the formation of amines. Every student can understand it. If you want to repeat these reactions at home, then for a beginner it is easiest to carry out reductive amination of glutamic acid.