Lithium Aluminium hydride reduction

Session Objectives

By the end of this session, students will be able to:

• Structure of lithium Aluminium hydride

• Properties of lithium Aluminium hydride

• Reactions of lithium Aluminium hydride

Lithium aluminium hydride

• Lithium aluminium hydride, LiAlH4, also abbreviated as LAH, is a reducing agent commonly employed in modern organic synthesis.

• It is a nucleophilic reducing agent, best used to reduce polar multiple bonds like C=O.

• LiAlH4 can reduce aldehydes to primary alcohols, ketones to secondary alcohols, carboxylic acids and esters to primary alcohols, amides and nitriles to amines, epoxides to alcohols and lactones to diols.

• Lithium aluminium hydride cannot reduce an isolated non-polar multiple bond like C=C. However, the double or triple bonds in conjugation with the polar multiple bonds can be reduced.

• LiAlH4 is a powerful reducing agent compared to sodium borohydride, NaBH4, since the Al-H bond is weaker and thus less stable than B-H bond.

Structure of Lithium aluminium hydride - LiAlH₄

• There is a tetrahedral arrangement of hydrogens around aluminium in aluminium hydride, AlH₄^- ion. 

• It is formed by coordination of hydride, H^- ions to aluminium, Al³⁺ ion.

• The hybridization in central aluminium is sp³.

Preparation of Lithium aluminium hydride

• LiAlH₄ is prepared by the reaction between lithium hydride and aluminium chloride.

Properties of Lithium aluminium hydride

• The reaction must be carried out in anhydrous non protic solvents like diethyl ether, THF etc.

• It is highly soluble in diethyl ether.

• However it may spontaneously decompose in it due to presence of catalytic impurities.

• Therefore the preferred solvent for LAH is THF despite the low solubility.

• The reactions are usually performed with excess of LiAlH4.

• White solid but the commercial samples are usually gray due to presence of impurities.

• *It reacts violently with water by producing hydrogen gas.

• Hence it should not be exposed to moisture and the reactions are performed in inert and dry atmosphere.

Workup:

• During the workup, the reaction mixture is initially chilled in an ice bath and then the Lithium aluminium hydride is quenched by careful and very slow addition of ethyl acetate followed by the addition of methanol and then cold water.

• Sometimes, the reagent is decomposed by adding undried solvent slowly and then dilute sulphuric acid to the reaction mixture.

Mechanism of Reduction By Lithium Aluminium Hydride

• The reduction of a carbonyl group by LiAlH₄ is initiated by the attack of nucleophilic hydride ion on the carbonyl carbon to give a tetrahedral intermediate.

• * LiAlH₄ is a nucleophilic reducing agent since the hydride transfer to the carbonyl carbon occurs prior to the coordination to the carbonyl oxygen.

• It reacts faster with electron deficient carbonyl groups.

• The reactivity of carbonyl compounds with this reagent follows the order:

Aldehydes > Ketones > ester > amide > carboxylic acid

Reduction of Aldehydes or Ketones to 1⁰ or 2⁰ alcohols: Initially, a hydride ion is transferred onto the carbonyl carbon and the oxygen atom coordinates to the remaining aluminium hydride species to furnish an alkoxytrihydroaluminate ion, which can reduce the next carbonyl molecule. Thus three of the hydride ions are used up in reduction.

Reduction of Esters to 1⁰ alcohols: The ester is first converted to aldehyde which is further reduced to primary alcohol.

Reduction of Amides to amines:

• Amides are converted to amines.

• The mechanism is slightly different from that depicted for esters.

• In iminium ion is formed during the reaction since nitrogen atom is relatively a good donor than oxygen atom. 

Reduction of nitriles to primary amines:

Synthesis of Salmefamol

Summary

• It is a nucleophilic reducing agent, best used to reduce polar multiple bonds like C=O.

• LiAlH4 can reduce aldehydes to primary alcohols, ketones to secondary alcohols, carboxylic acids and esters to primary alcohols, amides and nitriles to amines, epoxides to alcohols and lactones to diols.

• Lithium aluminium hydride cannot reduce an isolated non-polar multiple bond like C=C.

• However, the double or triple bonds in conjugation with the polar multiple bonds can be reduced.