Amide reduction explained

Amide reduction is a reaction in organic synthesis where an amide is reduced to either an amine or an aldehyde functional group.[1]

Catalytic hydrogenation

Catalytic hydrogenation can be used to reduce amides to amines; however, the process often requires high hydrogenation pressures and reaction temperatures to be effective (i.e. often requiring pressures above 197 atm and temperatures exceeding 200 °C). Selective catalysts for the reaction include copper chromite, rhenium trioxide and rhenium(VII) oxide or bimetallic catalyst.[2] [3] [4]

Amines from other hydride sources

Reducing agents able to effect this reaction include metal hydrides such as lithium aluminium hydride,[5] [6] [7] [8] [9] or lithium borohydride in mixed solvents of tetrahydrofuran and methanol.[10]

Iron catalysis by triiron dodecacarbonyl in combination with polymethylhydrosiloxane has been reported.[11]

Lawesson's reagent converts amides to thioamides, which then catalytically desulfurize.[12]

Noncatalytic routes to aldehydes

Some amides can be reduced to aldehydes in the Sonn-Müller method, but most routes to aldehydes involve a well-chosen organometallic reductant.

Lithium aluminum hydride reduces an excess of N,N-disubstituted amides to an aldehyde:

R(CO)NRR' + LiAlH4 → RCHO + HNRR'With further reduction the alcohol is obtained.

Schwartz's reagent reduces amides to aldehydes,[13] and so does hydrosilylation with a suitable catalyst.

External links

Notes and References

  1. Book: Nishimura. Shigeo. Handbook of Heterogeneous Catalytic Hydrogenation for Organic Synthesis. 2001. Wiley-Interscience. New York. 9780471396987. 406–411. 1st.
  2. Mitsudome . Takato . Miyagawa . Kazuya . Maeno . Zen . Mizugaki . Tomoo . Jitsukawa . Koichiro . Yamasaki . Jun . Kitagawa . Yasutaka . Kaneda . Kiyotomi . 2017-08-01 . Mild Hydrogenation of Amides to Amines over a Platinum-Vanadium Bimetallic Catalyst . Angewandte Chemie International Edition . en . 56 . 32 . 9381–9385 . 10.1002/anie.201704199. 28649715 .
  3. Zhang . Yue . Zhang . Fan . Li . Lin . Liu . Fei . Wang . Aiqin . 2022-10-07 . Highly Chemoselective Reduction of Amides to Amines over a Ruthenium‐Molybdenum Bimetallic Catalyst . ChemistrySelect . en . 7 . 37 . 10.1002/slct.202203030 . 252725710 . 2365-6549.
  4. Pennetier . Alex . Hernandez . Willinton Y. . Kusema . Bright T. . Streiff . Stéphane . 2021-08-25 . Efficient hydrogenation of aliphatic amides to amines over vanadium-modified rhodium supported catalyst . Applied Catalysis A: General . en . 624 . 118301 . 10.1016/j.apcata.2021.118301 . 238850541 . 0926-860X.
  5. Cope. Arthur C.. Ciganek. Engelbert. N,N-Dimethylcyclohexylmethylamine. Organic Syntheses. 1959. 39. 19. 10.15227/orgsyn.039.0019.
  6. Wilson. C. V.. Stenberg. J. F.. Laurylmethylamine. Organic Syntheses. 1956. 36. 48. 10.15227/orgsyn.036.0048.
  7. Moffett. Robert Bruce. 2,2-Dimethylpyrrolidine. Organic Syntheses. 1953. 33. 32. 10.15227/orgsyn.033.0032.
  8. Park. Chung Ho. Simmons. Howard E.. Macrocyclic Diimines: 1,10-Diazacylooctadecane. Organic Syntheses. 1974. 54. 88. 10.15227/orgsyn.054.0088.
  9. Seebach. Dieter. Kalinowski. Hans-Otto. Langer. Werner. Crass. Gerhard. Wilka. Eva-Maria. Chiral Media for Asymmetric Solvent Inductions. Organic Syntheses. 1983. 61. 24. 10.15227/orgsyn.061.0024.
  10. Ookawa. Atsuhiro. Soai. Kenso. Mixed solvents containing methanol as useful reaction media for unique chemoselective reductions within lithium borohydride. The Journal of Organic Chemistry. 1986. 51. 21. 4000–4005. 10.1021/jo00371a017.
  11. Junge. S. . K.. Das. Addis. Beller . D.. Zhou . S. . M.. A Convenient and General Iron-Catalyzed Reduction of Amides to Amines. Angewandte Chemie International Edition in English. 48. 50. 9507–9510. 2009. 19784999 . 10.1002/anie.200904677.
  12. Douglass F. Taber. Org. Chem. Highlights. 5 June 2006. The Boger Route to (-)-Vindoline. Discussion of (12)→(13)..
  13. M. W. . Leighty. J. T.. Spletstoser . Gunda I. . Georg . Mild Conversion of Tertiary Amides to Aldehydes Using Cp2ZrHCl (Schwartz's Reagent). Org. Synth.. 88. 2011. 427–437. 10.1002/0471264229.os088.39. 978-0471264224.

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