Reduction Reactions (Clemmensen & Wolff–Kishner)

CHEReactions of Aldehydes & Ketones

Both Clemmensen and Wolff-Kishner reduce a carbonyl $\text{C=O}$ all the way to a $\text{CH}_2$ group (deoxygenation to the alkane/alkyl level). The exam point is choosing between them based on whether the substrate tolerates acid or base.

Clemmensen reduction (acidic)

{>}C{=}O \xrightarrow{Zn\text{-}Hg,\ \text{conc. }HCl} {>}CH_2

strongly acidic medium; use for base-sensitive substrates

Wolff-Kishner reduction (basic)

{>}C{=}O \xrightarrow{NH_2NH_2} {>}C{=}N{-}NH_2 \xrightarrow{KOH,\ \text{glycol},\ \Delta} {>}CH_2 + N_2

via the hydrazone; strongly basic medium; use for acid-sensitive substrates

Clemmensen reduction: $\text{C=O} \xrightarrow{Zn\text{-}Hg,\,\text{conc. }HCl}$ $\text{CH}_2$ ; cyclohexanone $\rightarrow$ cyclohexane. Works in strongly acidic medium.
Wolff-Kishner reduction: $\text{C=O} \xrightarrow{NH_2NH_2}$ hydrazone $\xrightarrow{KOH/\text{ethylene glycol},\,\Delta}$ $\text{CH}_2$ ; cyclohexanone $\rightarrow$ cyclohexane. Works in strongly basic medium.
Choose Wolff-Kishner for acid-sensitive substrates (e.g. those with acid-labile groups) and Clemmensen for base-sensitive substrates - they are complementary.
Both give the same overall result: net replacement of carbonyl O by two H atoms; net product is the corresponding hydrocarbon.
Butane from butan-2-one: reduce $CH_3COCH_2CH_3$ by either Clemmensen ( $Zn\text{-}Hg/HCl$ ) or Wolff-Kishner ( $NH_2NH_2$ , $KOH$ , $\Delta$ ) to give butane - two standard alternative routes.
Contrast with $NaBH_4/LiAlH_4$ , which only reduce $\text{C=O}$ to an $\text{-OH}$ (alcohol); Clemmensen and Wolff-Kishner remove the oxygen entirely.
Wolff-Kishner proceeds through the hydrazone $\text{C=N-NH}_2$ , which on heating with strong base loses $N_2$ gas as the driving force to give the $\text{CH}_2$ - a frequently asked mechanistic detail.
Both reductions work on aldehydes too (not just ketones): $\text{RCHO} \rightarrow \text{RCH}_3$ , converting a terminal $\text{-}CHO$ into a methyl group.
Both leave $\text{C=C}$ double bonds and aromatic rings untouched - they are selective for the carbonyl, which is why they are used to deoxygenate aryl ketones from Friedel-Crafts acylation.
Synthetic use after Friedel-Crafts: acylate benzene (gives an aryl ketone) then Clemmensen/Wolff-Kishner reduce, achieving a clean straight-chain alkylbenzene that direct Friedel-Crafts alkylation cannot (alkylation rearranges).
Clemmensen would fail on a molecule with an acid-labile group (e.g. an acetal or a tertiary alcohol that dehydrates) - choose Wolff-Kishner there; Wolff-Kishner fails on base-labile groups - choose Clemmensen there.
The amalgamated zinc ( $Zn\text{-}Hg$ ) in Clemmensen supplies electrons at the metal surface; the mercury merely keeps the zinc surface active - it is not itself the reductant.

Where the marks go

Saying Clemmensen/Wolff-Kishner give an alcohol - they remove the oxygen completely to a $\text{CH}_2$ ; only $NaBH_4$ / $LiAlH_4$ stop at the alcohol.
Applying Clemmensen to an acid-sensitive substrate or Wolff-Kishner to a base-sensitive one - choose the method by which medium the molecule tolerates.
Forgetting the hydrazone intermediate and the loss of $N_2$ in Wolff-Kishner - examiners often ask for the mechanism's key step.
Thinking these reductions touch $\text{C=C}$ or the ring - they are selective for the carbonyl and leave alkenes and aromatic rings intact.
Writing concentrated HCl for Wolff-Kishner or $KOH$ for Clemmensen - the conditions are opposite (Clemmensen = acidic $Zn\text{-}Hg/HCl$ ; Wolff-Kishner = basic $NH_2NH_2/KOH$ ).

How the board asks it

Conversionthe two complementary deoxygenation routes
How will you convert butan-2-one ( $CH_3COCH_2CH_3$ ) into butane? Give the reagents and conditions for two different methods.
Distinguishacidic versus basic reaction medium
State two points of difference between the Clemmensen reduction and the Wolff-Kishner reduction with reference to the reagents used and the reaction medium.
Give reasonschoosing the method by the medium tolerated
Account for the fact that a substrate bearing an acid-labile group (such as an acetal) is best deoxygenated by the Wolff-Kishner reduction rather than by the Clemmensen reduction.
Mechanismthe hydrazone intermediate and loss of $N_2$
Name the intermediate formed when a ketone is treated with $NH_2NH_2$ in the Wolff-Kishner reduction, and state the gas evolved when this intermediate is heated with $KOH$ in ethylene glycol, which drives the reaction to completion.
Predict the productselectivity for $C=O$ over the aromatic ring
Predict the organic product formed when acetophenone ( $C_6H_5COCH_3$ ) is treated with amalgamated zinc ( $Zn\text{-}Hg$ ) and conc. $HCl$ , and state why the aromatic ring is left unchanged.
Give reasonsdeoxygenation after Friedel-Crafts acylation
Give reasons why a straight-chain alkylbenzene such as $n$ -propylbenzene is best prepared by Friedel-Crafts acylation followed by Clemmensen reduction, rather than by direct Friedel-Crafts alkylation.

Practise this topic

PreviousOxidation & Distinguishing Tests NextCarboxylic Acid Preparation & Properties

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.