Course Hero Logo


Preparation of Alcohols via Substitution and Addition

Alcohols are prepared by substitution reactions or via the hydration of alkenes using three different reagents that produce different regiochemistry and stereochemistry.
A substitution reaction (or displacement reaction) is a chemical reaction where one functional group is replaced with another functional group. Hydrolysis of alkyl halides is a nucleophilic substitution reaction. The reaction involves an electron-pair donor, called the nucleophile, and an electron-pair acceptor, called the electrophile. Water (H2O) or hydroxides, such as sodium hydroxide (NaOH), are used as nucleophiles and add to an alkyl halide to create an alcohol. For nucleophilic substitution to occur, an sp3-hybridized electrophile must have a leaving group (X).
RX+H2OROH+HX{\rm {R{-}X}}+{\rm {H}_2{ O}}\rightarrow{\rm {R{-}OH}}+{\rm{HX}}
RX+NaOHROH+NaX{\rm {R{-}X}}+{\rm{NaOH}}\rightarrow{\rm {R{-}OH}}+{\rm{NaX}}
Adding aqueous sodium hydroxide to benzyl chloride (C7H7Cl) results in benzyl alcohol (C7H7OH) because of a substitution of the primary benzylic alkyl halide via an SN2 reaction.

Conversion of Benzyl Chloride to Benzyl Alcohol

The addition of sodium hydroxide (NaOH) to benzyl chloride (C7H7Cl) is an SN2 reaction, where chlorine is replaced by a hydroxyl group that is deprotonated to an alkoxide, which is then protonated back to benzyl alcohol (C7H7OH).
Alcohols can also be prepared via the hydration of alkenes. Hydration involves the addition of a water molecule as H{-}{\rm {H}} and OH{-}{\rm{OH}} to two adjacent carbon atoms. Hydration can be accomplished using oxymercuration-demercuration, hydroboration-oxidation, or acidic addition of water, which each produce different regiochemistry and stereochemistry. Oxymercuration-demercuration is a chemical reaction that creates a Markovnikov product through the addition of mercuric acetate (Hg(OAc)2) and water followed by a reducing agent. Markovnikov's rule states that the acidic hydrogen bonds to the carbon with the most hydrogen substituents and the OH{-}{\rm{OH}} bonds to the carbon with the most alkyl substituents.

Oxymercuration Demercuration of 1-methylcyclohexene

Oxymercuration demercuration of 1-methylcyclohexene (C7H12) with water and mercury(II) acetate (Hg(OAc)2) followed by sodium borohydride (NaBH4) gives the Markovnikov and anti-addition of an alcohol without the possibility of rearrangements.
Hydroboration-oxidation is a chemical reaction that creates products with an anti-Markovnikov orientation with the hydroxyl group attached to the carbon with the least-substituted carbon. The resulting stereochemistry is syn, which is when the two groups are on the same side of the molecule. Hydroboration-oxidation creates an alcohol through a two-step mechanism. First, BH3-Et2O is added to an alkene to create an alkylborane. Then, peroxide and a base create the final alcohol product.

Hydroboration Oxidation of 1-methylcyclohexene

Hydroboration oxidation of an alkene with borane (BH3) creates an intermediate where hydrogen adds to the more-substituted side and boron adds to the less-substituted side of the alkene. This intermediate is reduced by sodium hydroxide and peroxide to give the anti-Markovnikov syn-addition of an alcohol to the starting alkene.
Acidic addition of water to an alkene creates a Markovnikov product. The first step is an acid-base reaction where the protonation of the alkene via acidic water leads to a stable carbocation. The π\pi electrons of water (H2O) act as a Lewis base. The nucleophilic water attacks the carbocation, followed by deprotonation of the intermediate, and a racemic alcohol (mixture of syn and anti addition) forms as a result of this reaction.
CH2=CH2+H3O+HCH2CH2OH+H+{\rm{CH}}_2{=}{\rm{CH}}_2+{\rm {H}_3 {O}}^+\rightarrow{\rm{HCH}_2{-}{CH}_2OH}+{\rm H}^+