Preparation of Alcohols

CHEAlcohols: Preparation & Reactions

Alcohols are made from alkenes (hydration, hydroboration–oxidation), from carbonyls (reduction, Grignard addition), and from haloalkanes. The exam favours questions linking the method to the regiochemistry rule and to whether the product is $1^\circ$ , $2^\circ$ or $3^\circ$ .

Markovnikov hydration

CH_3CH{=}CH_2 + H_2O \xrightarrow{\text{dil. } H_2SO_4} CH_3CH(OH)CH_3

Hydroboration–oxidation (anti-Markovnikov)

CH_3CH{=}CH_2 \xrightarrow{B_2H_6} (CH_3CH_2CH_2)_3B \xrightarrow{H_2O_2,\ OH^-} CH_3CH_2CH_2OH

Grignard route

RMgX + R'CHO \rightarrow R'CH(OMgX)R \xrightarrow{H_3O^+} R'CH(OH)R

HCHO\Rightarrow 1^\circ

, other RCHO

\Rightarrow 2^\circ

, ketone

\Rightarrow 3^\circ

Carbonyl reduction

RCHO \xrightarrow{NaBH_4} RCH_2OH \qquad RCOR' \xrightarrow{NaBH_4} RCH(OH)R'

Hydrolysis of an alkyl halide

R\text{-}X + KOH\,(aq) \xrightarrow{\Delta} R\text{-}OH + KX

Acid-catalysed hydration of an alkene follows Markovnikov's rule, giving the more substituted ( $2^\circ$ / $3^\circ$ ) alcohol — propene $\rightarrow$ propan-2-ol.
Uses: methanol is a solvent, fuel and antifreeze (and toxic — metabolised to formic acid/formaldehyde, which damage the optic nerve); ethanol is used in beverages, as a solvent, antiseptic and fuel additive (gasohol); glycerol (trihydric) is used in cosmetics, medicines and to make nitroglycerin (explosives); ethylene glycol (dihydric) is the standard automobile antifreeze/coolant.
Hydroboration–oxidation ( $B_2H_6$ , then $H_2O_2$ / $OH^-$ ) is anti-Markovnikov, giving the $1^\circ$ alcohol — propene $\rightarrow$ propan-1-ol, with no carbocation rearrangement.
Grignard $RMgX$ with $HCHO$ gives a $1^\circ$ alcohol (one carbon more than the halide); with any other aldehyde gives $2^\circ$ ; with a ketone gives a $3^\circ$ alcohol after acid workup.
$NaBH_4$ reduces an aldehyde to a $1^\circ$ alcohol and a ketone to a $2^\circ$ alcohol; it does not reduce esters or carboxylic acids.
$LiAlH_4$ is a stronger reducing agent that also reduces carboxylic acids and esters to $1^\circ$ alcohols.
Haloalkanes give alcohols by aqueous alkali ( $R\text{-}X + aq.\ KOH \rightarrow R\text{-}OH$ , an $S_N$ reaction).
Ethanol conversions: $\rightarrow$ ethene (conc. $H_2SO_4$ , $443\,\text{K}$ ); $\rightarrow$ diethyl ether (conc. $H_2SO_4$ , $413\,\text{K}$ ); $\rightarrow$ ethyl acetate ( $CH_3COOH$ , conc. $H_2SO_4$ ).
Acid hydration proceeds via a carbocation, so it can rearrange and is unsuitable when a clean $1^\circ$ alcohol is wanted; hydroboration is concerted (syn addition) and rearrangement-free.
The Grignard reagent is made from $R\text{-}X + Mg$ in dry ether; it must be kept anhydrous because water (or any $\text{-}OH$ , $\text{-}NH$ ) destroys it, giving the alkane $R\text{-}H$ .
Esters on hydrolysis (acidic or alkaline) give an alcohol plus the acid/its salt — a standard route to the parent alcohol of the ester.
Industrial: ethanol is made by fermentation of sugars (enzymes invertase then zymase) and methanol by catalytic combination of $CO + 2H_2$ over a $ZnO/Cr_2O_3$ catalyst.
Diborane gives syn addition of $\text{-}H$ and $\text{-}BR_2$ ; alkaline $H_2O_2$ then replaces boron by $\text{-}OH$ with retention — so the overall hydroboration–oxidation is stereospecific and anti-Markovnikov.

Where the marks go

Predicting propan-1-ol from acid hydration of propene — acid hydration is Markovnikov and gives propan-2-ol; only hydroboration gives the $1^\circ$ product.
Letting $NaBH_4$ reduce an ester or carboxylic acid — it cannot; only $LiAlH_4$ reduces those to $1^\circ$ alcohols.
Doing the Grignard reaction in wet conditions — any trace of water destroys $RMgX$ to give $R\text{-}H$ ; the solvent must be dry ether.
Forgetting the acidic workup step in the Grignard route — the alkoxide salt $R'CH(OMgX)R$ must be hydrolysed with $H_3O^+$ to liberate the alcohol.
Assuming hydroboration needs a catalyst or gives rearranged products — it is a clean, concerted syn addition with no carbocation, hence no rearrangement.

How the board asks it

Conversionthe alkene and carbonyl preparation routes
How will you convert: (i) propene into propan-1-ol, and (ii) ethanal into propan-2-ol? Give the reagents and conditions for each step.
Predict the productmarkovnikov vs anti-markovnikov regiochemistry
Write the structure and IUPAC name of the major organic product when but-1-ene is treated with (i) dilute $H_2SO_4$ and (ii) $B_2H_6$ followed by $H_2O_2/OH^-$ , and account for the difference.
Give reasonscarbocation in acid hydration vs concerted hydroboration
Account for the fact that acid-catalysed hydration of $3,3$ -dimethylbut-1-ene gives a rearranged alcohol, whereas hydroboration-oxidation does not.
Predict the productthe grignard route and degree of the alcohol
An alcohol $A$ ( $C_4H_{10}O$ ) is obtained by treating propanone with $CH_3MgBr$ in dry ether followed by acid hydrolysis. Identify $A$ , give its IUPAC name, and state whether it is $1^\circ$ , $2^\circ$ or $3^\circ$ .
Distinguish $NaBH_4$ vs $LiAlH_4$ reducing scope
Distinguish between the action of $NaBH_4$ and $LiAlH_4$ on ethyl acetate, giving the product formed in each case.
Give reasonsanhydrous conditions for grignard reagents
Give reasons why the Grignard reagent must be prepared and used under perfectly anhydrous conditions, and state what happens if water is present.

Practise this topic

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Written for Sublevo. Question text quoted anywhere in these notes is the Council’s and carries its year and paper; the board’s own diagrams are not reproduced.