Reduction of Carbonyls to Alcohols Using Metal Hydrides

Hydrogen can be used as a nucleophile if it’s bonded to a metal in such a way that the electron density balance favors the hydrogen side. A hydrogen atom that carries a net negative charge and bears a pair of unshared electrons is called a hydride ion. How much negative charge density resides on hydrogen depends on the difference in electronegativity between hydrogen and the metal it’s bonded to.

metal hydrides can be ionic or covalent.svg
(M = metal)

The most common sources of the hydride anion (:H) are lithium aluminum hydride (LiAlH4) and sodium borohydride (NaBH4). Note! these reagents serve as a source of hydride due to the presence of a polar metal-hydrogen bond. Because aluminum is less electronegative than boron, the Al-H bond in LiAlH4 is more polar, thereby, making LiAlH4 a stronger reducing agent.

examples of covalent metal hydrides (sodium borohydride and lithium aluminum hydride) versus hydride nucleophile, H-.svg

General Reaction

Nucleophilic addition of a hydride anion (:H) to an aldehyde or a ketone gives a tetrahedral alkoxide anion intermediate, which on protonation yields the corresponding alcohol. Aldehydes produce 1o-alcohols and ketones produce 2o-alcohols. Both LiAlH4 and NaBH4 are capable of reducing aldehydes and ketones to the corresponding alcohol.

general example of hydride reduction of an aldehyde to give a primary alcohol.svg
general example of hydride reduction of a ketone to give a secondary alcohol.svg

Predicting the Product of a Hydride Addition to a Carbonyl

During the reduction, the C=O double bond in the reactant becomes a C-O single bond in the product. The breaking of the C=O double bond allows for the formation of two new single bonds in the product. One will be attached to the oxygen (O-H) and one to the carbon (C-H).

predicting the products of a hydride reduction.svg


reduction of benzaldehyde with sodium borohydride in methanol to give benzyl alcohol.svg
reduction of 2-butanone with 1. lithium aluminum hydride, followed by 2. water to give 2-butanol.svg

Mechanism for the Reduction of Carbonyls using LiAlH4

Step 1. Nucleophilic attack to form a tetrahedral alkoxide intermediate

hydride reduction mechanism step 1.svg

Step 2. Protonation to form an alcohol

hydride reduction mechanism step 2.svg
ReagentPreferred SolventsFunctions Reduced
Sodium Borohydride
ethanol; aqueous ethanol
15% NaOH;
aldehydes to 1º-alcohols
ketones to 2º-alcohols
Lithium Aluminum Hydride
ether;aldehydes to 1º-alcohols
ketones to 2º-alcohols
carboxylic acids to 1º-alcohols
esters to alcohols
nitriles & amides to amines

Mechanism for the Addition of Grignard Reagents

The mechanism starts with the formation of a acid-base complex between +MgX and the carbonyl oxygen. The +MgBr of the Grignard reagent acts as a Lewis acid and accepts a lone pair of electrons from the carbonyl oxygen. This gives the oxygen a positive charge which correspondingly increases the partial positive charge on the carbonyl carbon increasing it susceptibility to nucleophilic attack. The carbanion nucleophile from the Grignard reagent adds to the electrophilic carbon of the acid-base complex forming a C-C bond. The two electrons of the C=O are pushed toward the carbonyl oxygen atom forming a tetrahedral magnesium alkoxide intermediate. The alkoxide intermediate is converted to an alcohol through addition of a acidic aqueous solution. The +MgX ion is also converted to HOMgX.

Step 1. Lewis acid-base formation

Mechanism, grignard step 1.svg

step 2. Nucleophilic attack

Mechanism, grignard step 2.svg

Step 3. Protonation

grignard mechanism step 2.svg

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