Organic Chemistry: Concepts and Applications - Headley Allan D. 2020
Reduction Reactions in Organic Chemistry
10.4 Reduction of Imines
Close inspection of the imine functionality reveals that it should undergo similar reactions as those of the carbonyl functionality since they are both polarized double bonds. As a result, imines can be reduced in a similar manner as carbon—oxygen double bonds to form the corresponding amine.
10.4.1 Reduction Using NaBH4 and LiAlH4
The reduction of compounds that have C=N─R functionality by LiAlH4 gives amide salts. A condensed mechanism for the reaction is shown in Reaction (10-38).
(10-38)
In the presence of an acidic aqueous solution, amide salts, which are strongly basic, are neutralized by an acid—base reaction to give secondary amines if R is an alkyl group. In the case where R is hydrogen, the product is a primary amine. These reactions are shown in Reactions (10-39) and (10-40).
(10-39)
(10-40)
The overall reaction showing the two-reaction sequence, which includes the acidic workup, is shown in Reaction (10-41).
(10-41)
A similar type of reaction is expected using NaBH4, as shown in Reaction (10-42).
(10-42)
Reaction (10-43) shows an example of the reduction of the N-methyl-2-butaneimine.
(10-43)
You will readily notice that different secondary amines result from these reduction reactions depending on the structure of the starting imine compound. Thus, the imines shown below will result in different amines upon reduction.
Reactions (10-44) through (10-46) show the reduction of different imines with lithium aluminum hydride, followed by hydrolysis.
(10-44)
(10-45)
(10-46)
Problem 10.8
i. Give the major organic products of the reaction of each of the following compounds with LiAlH4, followed by hydrolysis.
ii. Complete the following reactions by supplying an appropriate reactant or the major organic products.
10.4.2 Reduction Using Hydrogen with a Catalyst
The reduction of imines as discussed in the previous section can be accomplished using hydrogen, an appropriate catalyst and under the right reaction conditions, such as elevated temperature and pressure. Reaction (10-47) shows the reduction of an imine to form the amine in the presence of hydrogen and a catalyst.
(10-47)
Problem 10.9
Give the reactant or the organic product to complete the reactions shown below.
Using reactions that we have already covered thus far, we can transform a carbonyl-containing compound into an amine with strategic selection of appropriate reactions. Reactions (10-48) and (10-49) show how benzaldehyde can be transformed into benzylamine. You will recall from Section 9.8 that the addition of ammonia and primary amines to ketones and aldehydes results in imines as the products as shown in Reaction (10-48).
(10-48)
In another reaction, the imine can be reduced to form a primary amine, as shown in Reaction (10-49).
(10-49)
Reaction (10-48) shows the formation of the imine from the corresponding benzaldehyde, and Reaction (10-49) shows the reduction reaction. This combination of reactions, which essentially converts a carbonyl compound to an amine, is called reductive amination. Thus, the above two reactions are used to accomplish the transformation shown in Reaction (10-50).
(10-50)
Students should be able to examine the transformation shown in Reaction (10-50) and critically think through the type of reactions and specific reactions that could be used to accomplish the transformation shown. Problem 10.10 is designed to get students to apply that critical thinking process to carry out the transformations.
Problem 10.10
Starting with any carbonyl-containing compound, show how reductive amination can be used to synthesize the following compounds.
