Clemmensen reduction

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Clemmensen reduction
Named after Erik Christian Clemmensen
Reaction type Organic redox reaction
Reaction
Ketone or Aldehyde
+
Zn(Hg)
+
HCl
↓
Reduction product
Conditions
Catalyst
+Δ
Identifiers
Organic Chemistry Portal clemmensen-reduction
RSC ontology ID RXNO:0000038

Clemmensen reduction is a chemical reaction described as a reduction of ketones or aldehydes to alkanes using zinc amalgam and concentrated hydrochloric acid (HCl).[1][2] This reaction is named after Erik Christian Clemmensen, a Danish-American chemist.[3]

The Clemmensen reduction
Scheme 1: Reaction scheme of Clemmensen Reduction.

Clemmensen reduction conditions are particularly effective at reducing

arenes
.  

Mechanism

Scheme 2: A mechanism of Clemmensen reduction was proposed in 1975.[7][8] The carbonyl is first converted to radical anion (shown as blue), then to zinc carbenoid (shown as red), and then reduced to alkane.

Despite the reaction being first discovered in 1914, the mechanism of the Clemmensen reduction remains obscure. Due to the

heterogeneous nature of the reaction, mechanistic studies are difficult, and only a handful of studies have been disclosed.[9][10] Mechanistic proposals generally invoke organozinc intermediates, sometimes including zinc carbenoids, either as discrete species or as organic fragments bound to the zinc metal surface. Brewster proposed the possibility of the reduction occurring at the metal surface. Depending on the constitution of the carbonyl compound or the acidity of the reaction, a carbon-metal or oxygen-metal bond can form after the compound attaches to the metal surface.[9] Furthermore, Vedeja proposed a mechanism involving the formation of radical anion and zinc carbenoid, followed by reduction to alkane[7][8] (as shown above). However, alcohol and carbanion are not believed to be intermediates, since exposing alcohol to Clemmensen conditions rarely affords the alkane product.[9][11]

Application

Highly symmetrical hydrocarbon compounds have attracted much interest due to their beautiful structure and potential applications, but the challenges in the synthesis persist. Suzuki et al. synthesized dibarrelane, a type of hydrocarbon compound, using Clemmensen reduction.[12] They hypothesized that the secondary alcohol underwent an SN1 reaction, forming a chloride. Then, an excess amount of zinc reduced the chloride. Importantly, the reaction effectively reduced the two ketones, alcohol, and the methoxycarbonyl group while avoiding any by-products, giving the product in high yield (61%).

carboalkoxy. Yamamura et al. effectively reduced cholestane-3-one to cholestane using the modified Clemmensen condition and gave the product in high yield (~76%).[13]

Scheme 4: Reducing cholestane-3-one to cholestane using Clemmensen reduction[13].

Problems and alternative approaches

To perform the Clemmensen reduction, the

Wolff-Kishner reduction can reduce acid-sensitive substrates that are stable to strong bases. For substrates stable to hydrogenolysis in the presence of Raney nickel, a milder two-step Mozingo reduction
method is available.

Further reading

See also

References

  1. OCLC 69020965
    .
  2. ISBN 978-0387683546
    .
  3. ISSN 0365-9496
    .
  4. ISBN 978-0387683546
    .
  5. ISSN 0078-6209
    .
  6. ISSN 0078-6209
    .
  7. ^
    S2CID 243452810
    , retrieved 2023-04-01
  8. ^
    ISBN 978-0-471-26418-7
    , retrieved 2023-04-01
  9. ^
    ISSN 0002-7863
    .
  10. ISSN 0002-7863
    .
  11. ISBN 978-0-471-26418-7
    , retrieved 2023-03-31
  12. ^
    PMID 24564301
    .
  13. ^
    doi:10.15227/orgsyn.053.0086
    .
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