Amide reduction

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Amide reduction is a reaction in organic synthesis where an amide is reduced to either an amine or an aldehyde functional group. [1] [2]

Contents

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). [1] Selective catalysts for the reaction include copper chromite, rhenium trioxide and rhenium(VII) oxide or bimetallic catalyst. [3] [4] [5]

Amines from other hydride sources

Reducing agents able to effect this reaction include metal hydrides such as lithium aluminium hydride, [6] [7] [8] [9] [10] or lithium borohydride in mixed solvents of tetrahydrofuran and methanol. [11]

Reduction of amide.svg

Iron catalysis by triiron dodecacarbonyl in combination with polymethylhydrosiloxane has been reported. [12]

Lawesson's reagent converts amides to thioamides, which then catalytically desulfurize. [13]

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:[ citation needed ]

R(CO)NRR' + LiAlH4 → RCHO + HNRR'

With further reduction the alcohol is obtained.

Schwartz's reagent reduces amides to aldehydes, [14] and so does hydrosilylation with a suitable catalyst.

References

  1. 1 2 Nishimura, Shigeo (2001). Handbook of Heterogeneous Catalytic Hydrogenation for Organic Synthesis (1st ed.). New York: Wiley-Interscience. pp. 406–411. ISBN   9780471396987.
  2. ↑ March, Jerry (1985). Advanced Organic Chemistry: Reactions, Mechanisms, and Structure (3rd ed.). New York: Wiley. ISBN   9780471854722. OCLC   642506595.
  3. ↑ 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. 56 (32): 9381–9385. doi:10.1002/anie.201704199. PMID   28649715.
  4. ↑ 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. 7 (37). doi:10.1002/slct.202203030. ISSN   2365-6549. S2CID   252725710.
  5. ↑ 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. 624: 118301. doi:10.1016/j.apcata.2021.118301. ISSN   0926-860X. S2CID   238850541.
  6. ↑ Cope, Arthur C.; Ciganek, Engelbert (1959). "N,N-Dimethylcyclohexylmethylamine". Organic Syntheses. 39: 19. doi:10.15227/orgsyn.039.0019.
  7. ↑ Wilson, C. V.; Stenberg, J. F. (1956). "Laurylmethylamine". Organic Syntheses. 36: 48. doi:10.15227/orgsyn.036.0048.
  8. ↑ Moffett, Robert Bruce (1953). "2,2-Dimethylpyrrolidine". Organic Syntheses. 33: 32. doi:10.15227/orgsyn.033.0032.
  9. ↑ Park, Chung Ho; Simmons, Howard E. (1974). "Macrocyclic Diimines: 1,10-Diazacylooctadecane". Organic Syntheses. 54: 88. doi:10.15227/orgsyn.054.0088.
  10. ↑ Seebach, Dieter; Kalinowski, Hans-Otto; Langer, Werner; Crass, Gerhard; Wilka, Eva-Maria (1983). "Chiral Media for Asymmetric Solvent Inductions". Organic Syntheses. 61: 24. doi:10.15227/orgsyn.061.0024.
  11. ↑ Ookawa, Atsuhiro; Soai, Kenso (1986). "Mixed solvents containing methanol as useful reaction media for unique chemoselective reductions within lithium borohydride". The Journal of Organic Chemistry. 51 (21): 4000–4005. doi:10.1021/jo00371a017.
  12. ↑ Zhou, S.; Junge, K.; Addis, D.; Das, S.; Beller, M. (2009). "A Convenient and General Iron-Catalyzed Reduction of Amides to Amines". Angewandte Chemie International Edition in English. 48 (50): 9507–9510. doi:10.1002/anie.200904677. PMID   19784999.
  13. ↑ Taber, Douglass F (5 June 2006). "The Boger Route to (-)-Vindoline". Org. Chem. Highlights. Discussion of (12)→(13).
  14. ↑ Leighty, M. W.; Spletstoser, J. T.; Georg, Gunda I. (2011). "Mild Conversion of Tertiary Amides to Aldehydes Using Cp2ZrHCl (Schwartz's Reagent)". Org. Synth. 88: 427–437. doi:10.1002/0471264229.os088.39. ISBN   978-0471264224.
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