CHEM F311 Lecture 24 Amine Synthesis.pptx

Notes

1. CHEM F311 Organic Chemistry – III Lecture 24 – 14 th Oct. 2024

2. Recap Chemoselectivity : Guidelines One of two identical groups may react if the product is less reactive than the starting material. When one functional group can react twice, reaction will be successful only if the first product is less reactive than the starting material. Use of protecting groups can resolve problems pertaining to selectivity With two functional groups of unequal reactivity, the more reactive can always be made to react alone. One of two identical functional group may react with one equivalent of reagent using the statistical effect. A more reliable method with two identical functional groups is to use a derivative which can react once only. When two groups are nearly but not quite identical, avoid attempts to make only one of them react. Preview Amine synthesis

3. Amine synthesis Amines cannot be prepared by S N 2 reaction   on an alkyl halide with NH 3 or a primary amine. The problem is that the  amine formed by nucleophilic substitution still has a lone pair of electrons, thus it can serve as a nucleophile or a base reacting with the alkyl halide.  This gives a mixture of 1°, 2°, and 3° amines which limits its application.

4. Reduction of alkylazides Reduction of nitriles LiAlH 4 , Catalytic hydrogenation or Na in EtOH LiAlH 4 or catalytic hydrogenation can be used

5. Reduction of amides Amides yield 1 ° amines on reduction by LiAlH 4 , while N‐substituted and N, N‐ disubstituted amides produce 2 ° and 3 ° amines, respectively.

6. Reduction of nitro compounds Aromatic / aliphatic amines are normally prepared by reduction of the corresponding nitro compound using Sn or Fe / HCl or catalytic hydrogenation. Reduction of oximes Branched 1 ° amines can be prepared by reducing oximes with LiAlH 4 , or catalytic hydrogenation

7. Reductive amination of aldehydes and ketones Carbonyl compounds react with NH 3 or amines forming imines are reduced using catalytic hydrogenation or NaCNBH 3 to amines.

8. Gabriel Synthesis (for preparation of 1  amines) Hoffmann bromamide reaction

9. Fenfluramine