amide reduction

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.{{Cite journal |last1=Mitsudome |first1=Takato |last2=Miyagawa |first2=Kazuya |last3=Maeno |first3=Zen |last4=Mizugaki |first4=Tomoo |last5=Jitsukawa |first5=Koichiro |last6=Yamasaki |first6=Jun |last7=Kitagawa |first7=Yasutaka |last8=Kaneda |first8=Kiyotomi |date=2017-08-01 |title=Mild Hydrogenation of Amides to Amines over a Platinum-Vanadium Bimetallic Catalyst |url=https://onlinelibrary.wiley.com/doi/10.1002/anie.201704199 |journal=Angewandte Chemie International Edition |language=en |volume=56 |issue=32 |pages=9381–9385 |doi=10.1002/anie.201704199|pmid=28649715 }}{{Cite journal |last1=Zhang |first1=Yue |last2=Zhang |first2=Fan |last3=Li |first3=Lin |last4=Liu |first4=Fei |last5=Wang |first5=Aiqin |date=2022-10-07 |title=Highly Chemoselective Reduction of Amides to Amines over a Ruthenium‐Molybdenum Bimetallic Catalyst |url=https://onlinelibrary.wiley.com/doi/10.1002/slct.202203030 |journal=ChemistrySelect |language=en |volume=7 |issue=37 |doi=10.1002/slct.202203030 |s2cid=252725710 |issn=2365-6549}}{{Cite journal |last1=Pennetier |first1=Alex |last2=Hernandez |first2=Willinton Y. |last3=Kusema |first3=Bright T. |last4=Streiff |first4=Stéphane |date=2021-08-25 |title=Efficient hydrogenation of aliphatic amides to amines over vanadium-modified rhodium supported catalyst |url=https://www.sciencedirect.com/science/article/pii/S0926860X2100315X |journal=Applied Catalysis A: General |language=en |volume=624 |pages=118301 |doi=10.1016/j.apcata.2021.118301 |s2cid=238850541 |issn=0926-860X}}

Reducing agents able to effect this reaction include metal hydrides such as lithium aluminium hydride,{{cite journal|last1=Cope|first1=Arthur C.|last2=Ciganek|first2=Engelbert|title=N,N-Dimethylcyclohexylmethylamine|journal=Organic Syntheses|date=1959|volume=39|page=19|doi=10.15227/orgsyn.039.0019}}{{cite journal|last1=Wilson|first1=C. V.|last2=Stenberg|first2=J. F.|title=Laurylmethylamine|journal=Organic Syntheses|date=1956|volume=36|page=48|doi=10.15227/orgsyn.036.0048}}{{cite journal|last1=Moffett|first1=Robert Bruce|title=2,2-Dimethylpyrrolidine|journal=Organic Syntheses|date=1953|volume=33|page=32|doi=10.15227/orgsyn.033.0032}}{{cite journal|last1=Park|first1=Chung Ho|last2=Simmons|first2=Howard E.|title=Macrocyclic Diimines: 1,10-Diazacylooctadecane|journal=Organic Syntheses|date=1974|volume=54|page=88|doi=10.15227/orgsyn.054.0088}}{{cite journal|last1=Seebach|first1=Dieter|last2=Kalinowski|first2=Hans-Otto|last3=Langer|first3=Werner|last4=Crass|first4=Gerhard|last5=Wilka|first5=Eva-Maria|title=Chiral Media for Asymmetric Solvent Inductions|journal=Organic Syntheses|date=1983|volume=61|page=24|doi=10.15227/orgsyn.061.0024}} or lithium borohydride in mixed solvents of tetrahydrofuran and methanol.{{cite journal|last1=Ookawa|first1=Atsuhiro|last2=Soai|first2=Kenso|title=Mixed solvents containing methanol as useful reaction media for unique chemoselective reductions within lithium borohydride|journal=The Journal of Organic Chemistry|date=1986|volume=51|issue=21|pages=4000–4005|doi=10.1021/jo00371a017}}

:File:Reduction of amide.svg

Iron catalysis by triiron dodecacarbonyl in combination with polymethylhydrosiloxane has been reported.{{Cite journal| last2 = Junge| first1 = S. | first2 = K.| last4 = Das| last3 = Addis| last5 = Beller | first3 = D.| last1 = Zhou | first4 = S. | first5 = M.| title = A Convenient and General Iron-Catalyzed Reduction of Amides to Amines| journal = Angewandte Chemie International Edition in English| volume = 48| issue = 50| pages = 9507–9510| year = 2009| pmid = 19784999 | doi = 10.1002/anie.200904677}}

Lawesson's reagent converts amides to thioamides, which then catalytically desulfurize.{{cite journal|first=Douglass F|last=Taber|journal=Org. Chem. Highlights|date=5 June 2006|url=https://www.organic-chemistry.org/Highlights/2006/05June.shtm|title=The Boger Route to (-)-Vindoline|at=Discussion of (12)→(13).}}

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|date=January 2016}}

:R(CO)NRR' + LiAlH₄ → RCHO + HNRR'

With further reduction the alcohol is obtained.

Schwartz's reagent reduces amides to aldehydes,{{cite journal | first1= M. W. |last1=Leighty|first2= J. T.|last2= Spletstoser |first3=Gunda I. |last3=Georg | title=Mild Conversion of Tertiary Amides to Aldehydes Using Cp₂ZrHCl (Schwartz's Reagent)| journal=Org. Synth.| volume= 88| year=2011| pages=427–437|doi=10.1002/0471264229.os088.39|isbn=978-0471264224|url=https://orgsyn.org/demo.aspx?prep=v88p0427}} and so does hydrosilylation with a suitable catalyst.

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• [https://www.organic-chemistry.org/synthesis/C1H/reductionamides.shtm Amide reduction @ organic-chemistry.org]

Category:Organic redox reactions