14.13:
Acid Halides to Alcohols: LiAlH4 Reduction
Acid halides react with strong reducing agents like lithium aluminum hydride to form primary alcohols.
This is a nucleophilic substitution reaction in which the acid halide is first converted into an aldehyde and then into a primary alcohol. So, the reaction requires two equivalents of the reducing agent.
The mechanism begins with a nucleophilic attack by the hydride ion at the carbonyl carbon, forming a tetrahedral intermediate.
The second step involves the reconstruction of the carbon-oxygen π bond with the departure of the halide ion to give an aldehyde.
Next, the aldehyde is attacked by another equivalent of the hydride, generating an alkoxide intermediate.
Lastly, protonation of the alkoxide yields a primary alcohol as the final product.
Unlike lithium aluminum hydride, a milder reducing agent like lithium tri(tert-butoxy) aluminum hydride selectively reduces acid halides to aldehydes.
Here, the bulky tert-butoxy groups transform the reagent into a sterically hindered hydride donor, reducing its reactivity and preventing further reduction of the aldehyde to alcohol.
14.13:
Acid Halides to Alcohols: LiAlH4 Reduction
Acid halides are reduced to alcohols in the presence of a strong reducing agent like lithium aluminum hydride.
The mechanism proceeds in three steps. First, the nucleophilic hydride ion attacks the carbonyl carbon of the acid halide to form a tetrahedral intermediate. Next, the carbonyl group is re-formed, and the halide ion departs as a leaving group, generating an aldehyde. A second nucleophilic attack by the hydride yields an alkoxide ion, which, upon protonation, gives a primary alcohol as the final product.
However, it is possible to stop the reaction at the aldehyde by using a milder reducing agent like diisobutylaluminum hydride or lithium tri(t-butoxy)aluminum hydride.