Reductive Amination: Study with Video Lessons, Practice Problems & Examples

Reductive amination is a key reaction involving the conversion of carbonyl compounds, such as aldehydes or ketones, into amines. The process begins with the formation of an iminium cation through the reaction of a carbonyl with a primary amine in an acidic environment. Instead of forming an imine, a reducing agent like sodium cyanoborohydride (NaBH₃CN) is used to add hydrogen, resulting in a primary amine. This method is efficient for synthesizing amines, highlighting the importance of understanding reaction mechanisms and the role of intermediates in organic synthesis.

Reductive Amination

Hey guys. In this video, we're going to cook up a really important reaction called reductive amination. So guys, recall back to your ketones and aldehydes section of the text that ketones and aldehydes when reacted with a primary amine in an acidic environment, what would you get? You would get the functional group called an imine. Now what was an imine? Well, remember that an imine is just a carbonyl carbon but instead of the O being attached to the C, you're going to replace that O with an N. That N could be attached to up to 1 R groups. The reason that it can't be 2 R groups is because that would be called an enamine and the double bond would be in a different spot. We're not going to be talking about enamines here. We're only talking about imines. Well, guys, this mechanism was a reversible reaction. Remember that you have your double-sided equilibrium arrows showing that you can go from the carbonyl to the imine and then back to the carbonyl. But regardless of which direction y

Provide the Major Product

Alright, guys. So you might not have noticed, but this is one of the most famous applications of reductive amination. This is the Walter White special. This is how he made his millions. Remember that he didn't want to be making meth from pseudoephedrine anymore and he was looking for a more efficient type of cook. He really needed to find methylamine. Methylamine was his limiting reagent. Well, that's because he needed to do a reductive amination of methylamine, a primary amine source, with phenylacetone, which is a precursor for methamphetamine. Then all we need is methylamine at the top in an acidic environment. And then we need a mild reducing agent such as our sodium borohydride with the cyano group. That would work perfectly. Now he might have used some kind of H₂ gas with a catalyst, whatever. As long as you have some kind of mild reducing agent, you can reduce the iminium cation to the amine. So let's go ahead and draw both steps. I'm not going t

Here’s what students ask on this topic:

What is reductive amination in organic chemistry?

Reductive amination is a chemical reaction that converts carbonyl compounds, such as aldehydes or ketones, into amines. The process involves the formation of an iminium cation intermediate through the reaction of a carbonyl compound with a primary amine in an acidic environment. Instead of forming an imine, a reducing agent like sodium cyanoborohydride (NaBH₃CN) is used to add hydrogen, resulting in a primary amine. This method is efficient for synthesizing amines and is widely used in organic synthesis.

What reagents are commonly used in reductive amination?

In reductive amination, the common reagents used include a carbonyl compound (such as an aldehyde or ketone), a primary amine, and a reducing agent. The most frequently used reducing agent is sodium cyanoborohydride (NaBH₃CN). This reagent is preferred because it is mildly reducing, which helps to avoid unwanted side reactions and ensures the selective reduction of the iminium cation to form the desired amine.

What is the role of sodium cyanoborohydride (NaBH₃CN) in reductive amination?

Sodium cyanoborohydride (NaBH₃CN) plays a crucial role in reductive amination as the reducing agent. It selectively reduces the iminium cation intermediate to form the desired amine. The presence of the cyano group (CN) makes NaBH₃CN a mildly reducing agent, which helps to prevent over-reduction and unwanted side reactions. This selectivity ensures that the reaction proceeds efficiently, yielding the primary amine as the final product.

What is the difference between an imine and an iminium cation?

An imine is a functional group characterized by a carbon-nitrogen double bond (C=N), formed by the reaction of a carbonyl compound with a primary amine. An iminium cation, on the other hand, is an intermediate in the formation of an imine. It has a positively charged nitrogen atom (N⁺) and is formed when the nitrogen of the amine reacts with the carbonyl carbon, resulting in a positively charged intermediate. The iminium cation is then reduced to form the final amine product in reductive amination.

Why is reductive amination considered a convenient method for synthesizing amines?

Reductive amination is considered a convenient method for synthesizing amines because it allows for the direct conversion of carbonyl compounds (aldehydes or ketones) into amines in a single reaction sequence. The process involves the formation of an iminium cation intermediate, which is then selectively reduced to form the desired amine. The use of a mild reducing agent like sodium cyanoborohydride (NaBH₃CN) ensures high selectivity and minimizes side reactions, making the method efficient and straightforward for producing a wide range of amines.