Amide reduction with strong reducing agents like lithium aluminum hydride proceeds through a nucleophilic acyl substitution to form amines. Primary, secondary, and tertiary amides yield primary, secondary, and tertiary amines, respectively.
Amide reduction requires two equivalents of the reducing agent, acting as a source of hydride ions. As shown in the figure, the reaction is initiated with a nucleophilic attack by the hydride ion at the carbonyl carbon to form a tetrahedral intermediate. Subsequently, thecarbonyl oxygen atom reacts with aluminum hydride to formanoxygen–aluminum bond. This is followed by the rearrangement of electron pairs with the expulsion of the aluminate anion as a leaving group to give an iminium ion intermediate. A second nucleophilic attack on the iminium ion by the hydride yields amine as a final product.
Cyclic amides often called lactams, are also reduced with lithium aluminum hydride to give cyclic amines.
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