Reduction of nitro compounds

:Image:Generic reduction of nitrobenzene to aniline.svg

The reduction of nitroaromatics is conducted on an industrial scale.{{Ullmann|author=Gerald Booth|title=Nitro Compounds, Aromatic|year=2007|doi=10.1002/14356007.a17_411|isbn=978-3527306732}} Many methods exist, such as:

• Catalytic hydrogenation using: Raney nickel{{OrgSynth | author = Allen, C. F. H.; VanAllan, J. | title = 2-Amino-p-cymene | collvol = 3 | collvolpages = 63 | year = 1955 | prep = cv3p0063}} or palladium-on-carbon,{{OrgSynth | author = Bavin, P. M. G. | title = 2-Aminofluorene | collvol = 5 | collvolpages = 30 | year = 1973 | prep = cv5p0030}}{{cite book | first1 = Michael B. | last1 = Smith | first2 = Jerry | last2 = March | title = March's Advanced Organic Chemistry | publisher = John Wiley & Sons | year = 2007 | edition=6th | isbn = 978-0-471-72091-1 | page = 1816 }}{{ cite journal | journal = Tetrahedron Letters | volume = 25 | issue = 32 | year = 1984 | pages = 3415–3418 | title = A general procedure for mild and rapid reduction of aliphatic and aromatic nitro compounds using ammonium formate as a catalytic hydrogen transfer agent | first1 = Siya | last1 = Ram | first2 = Richard E. | last2 = Ehrenkaufer | doi = 10.1016/S0040-4039(01)91034-2 | hdl = 2027.42/25034 | hdl-access = free}} platinum(IV) oxide, or Urushibara nickel.
• Iron in acidic media.{{OrgSynth | author = Fox, B. A.; Threlfall, T. L. | title = 2,3-Diaminopyridine | volume = 44 | pages = 34 | year = 1964| doi=10.15227/orgsyn.044.0034}}{{cite journal |first1=S. A.|last1=Mahood|first2=P. V. L. |last2=Schaffner\doi=10.15227/orgsyn.011.0032|title=2,4-Diaminotoluene|journal=Organic Syntheses|year=1931|volume=11|page=32|doi=10.15227/orgsyn.011.0032}}{{cite journal |doi=10.15227/orgsyn.089.0274|title=O-Aminobenzaldehyde, Redox-Neutral Aminal Formation and Synthesis of Deoxyvasicinone|journal=Organic Syntheses|year=2012|volume=89|page=274|doi-access=free}}
• Sodium hydrosulfite{{OrgSynth | author = Redemann, C. T.; Redemann, C. E. | title = 5-Amino-2,3-dihydro-1,4-phthalazinedione | collvol = 3 | collvolpages = 69 | year = 1955 | prep = cv3p0069}}
• Sodium sulfide (or hydrogen sulfide and base). Illustrated by the selective reduction of dinitrophenol to the nitroaminophenol.{{OrgSynth | first1= W. W.|last1=Hartman|last2=Silloway|first2=H. L. | title = 2-Amino-4-nitrophenol | volume= 25 | pages = 5| year = 1945 | doi= 10.15227/orgsyn.025.0005}}
• Tin(II) chloride{{cite encyclopedia | last1 = Faul | first1 = Margaret M. | last2 = Thiel | first2 = Oliver R. | encyclopedia = Encyclopedia of Reagents for Organic Synthesis | year = 2005 | doi = 10.1002/047084289X.rt112.pub2 | chapter = Tin(II) Chloride | isbn = 9780470842898 }}
• Titanium(III) chloride
• Samarium{{cite journal | doi = 10.1016/S0040-4039(00)00917-5 | journal = Tetrahedron Lett. | author = Basu, M. K. | title = Ultrasound-promoted highly efficient reduction of aromatic nitro compounds to the aromatic amines by samarium/ammonium chloride | year = 2000 | pages = 5603–5606 | issue = 30 | volume = 41}}
• Hydroiodic acid{{Cite journal|last1=Kumar|first1=J. S. Dileep|last2=Ho|first2=ManKit M.|last3=Toyokuni|first3=Tatsushi|date=2001|title=Simple and chemoselective reduction of aromatic nitro compounds to aromatic amines: reduction with hydriodic acid revisited|journal=Tetrahedron Letters|volume=42|issue=33|pages=5601–5603|doi=10.1016/s0040-4039(01)01083-8}}

Metal hydrides are typically not used to reduce aryl nitro compounds to anilines because they tend to produce azo compounds. (See below)

Several methods have been described for the production of aryl hydroxylamines from aryl nitro compounds:

• Raney nickel and hydrazine at 0-10 °C{{Cite journal |author1=Ayyangar, N. R. |author2=Brahme, K. C. |author3=Kalkote, U. R. |author4=Srinivasan, K. V. | title = Facile Transfer-Reduction of Nitroarenes to N Arylhydroxylamines with Hydrazine in the Presence of Raney Nickel | journal = Synthesis | year = 1984 | volume = 1984 | issue = 11 | pages = 938 | doi = 10.1055/s-1984-31027}}
• Electrolytic reduction{{OrgSynth | author = Harman, R. E. | title = Chloro-p-benzoquinone | collvol = 4 | collvolpages = 148 | year = 1963 | prep = cv4p0148}}
• Zinc metal in aqueous ammonium chloride{{OrgSynth | author = Kamm, O. | collvol = 1 | collvolpages = 445 | year = 1941 | title = β-Phenylhydroxylamine | prep = cv1p0445}}
• Catalytic Rhodium on carbon with excess hydrazine monohydrate at room temperature {{Cite journal |author1= Ichikawa, S. |author2= Zhu, S. | author3=Buchwald, S.| title = A Modified System for the Synthesis of Enantioenriched N-Arylamines through Copper-Catalyzed Hydroamination | journal = Angewandte Chemie International Edition | year = 2018 | volume = 57 | issue = 28 | pages = 8714–8718 | doi = 10.1002/anie.201803026|pmid= 29847002 |pmc= 6033674 | hdl = 1721.1/125726 | hdl-access = free}}

{{see also|Hydrazine}}

Treatment of nitroarenes with excess zinc metal results in the formation of N,N'-diarylhydrazine.{{OrgSynth | author = Bigelow, H. E.; Robinson, D. B. | title = Azobenzene | collvol = 3 | collvolpages = 103 | year = 1955 | prep = cv3p0103}}

Image:Reduction NitroareneToAzoCompound.png

Treatment of aromatic nitro compounds with metal hydrides gives good yields of azo compounds. For example, one could use:

• Lithium aluminium hydride{{cite journal |author1=R. F. Nystrom |author2=W. G. Brown |name-list-style=amp | title = Reduction of Organic Compounds by Lithium Aluminum Hydride. III. Halides, Quinones, Miscellaneous Nitrogen Compounds | year = 1948 | journal = J. Am. Chem. Soc. | volume = 70 | issue = 11 | pages = 3738–3740 | doi = 10.1021/ja01191a057 | pmid=18102934}}
• Zinc metal with sodium hydroxide. (Excess zinc will reduce the azo group to a hydrazino compound.)

Image:Reduction NitroalkaneToAlkane.png

Hydrodenitration (replacement of a nitro group with hydrogen) is difficult to achieve but can be affected by catalytic hydrogenation over platinum on silica gel at high temperatures.{{cite journal |author1=M. J. Guttieri |author2=W. F. Maier |name-list-style=amp | title = Selective cleavage of carbon-nitrogen bonds with platinum | year = 1984 | journal = J. Org. Chem. | volume = 49 | issue = 16 | pages = 2875–2880 | doi = 10.1021/jo00190a006}}

The reaction can also be effected through radical reaction with tributyltin hydride and a radical initiator, AIBN as an example.T. V. (Babu) RajanBabu, Philip C. Bulman Page, Benjamin R. Buckley, "Tri-n-butylstannane" Encyclopedia of Reagents for Organic Synthesis 2004, John Wiley & Sons. doi:10.1002/047084289X.rt181.pub2

Image:Reduction NitroalkaneToAmine.png

Aliphatic nitro compounds can be reduced to aliphatic amines by several reagents:

• Catalytic hydrogenation using platinum(IV) oxide (PtO₂){{cite journal | author = A. T. Nielsen | title = The Isomeric Dinitrocyclohexanes. II. Stereochemistry | year = 1962 | journal = J. Org. Chem. | volume = 27 | issue = 6 | pages = 1998–2001 | doi = 10.1021/jo01053a019}} or Raney nickel{{OrgSynth | author = Dauben, Jr., H. J.; Ringold, H. J.; Wade, R. H.; Pearson, D. L.; Anderson, Jr., A. G. | title = Cycloheptanone | collvol = 4 | collvolpages = 221 | year = 1963 | prep = cv4p0221}}
• Iron metal in refluxing acetic acid{{cite journal | author = Senkus, M. | title = Iron Reduction of Some Aliphatic Nitro Compounds| journal = Ind. Eng. Chem. | year = 1948 | volume = 40 | pages = 506|doi=10.1021/ie50459a035}}
• Samarium diiodide{{cite journal |author1=A. S. Kende |author2=J. S. Mendoza |name-list-style=amp | title = Controlled reduction of nitroalkanes to alkyl hydroxylamines or amines by samarium diiodide | year = 1991 | journal = Tetrahedron Letters | volume = 32 | issue = 14 | pages = 1699–1702 | doi = 10.1016/S0040-4039(00)74307-3| doi-access = free }}
• Raney nickel, platinum on carbon, or zinc dust and formic acid or ammonium formate{{Cite journal|last=Adams|first=J. P.|date=2002|title=Nitro and related groups|journal=Journal of the Chemical Society, Perkin Transactions 1|language=en|issue=23|pages=2586–2597|doi=10.1039/b009711j}}

α,β-Unsaturated nitro compounds can be reduced to saturated amines by:

• Catalytic hydrogenation over palladium-on-carbon
• Iron metal
• Lithium aluminium hydride{{cite journal | author = A. Burger, M. L. Stein and J. B. Clements | title = Some Pyridylnitroalkenes, Nitroalkanols, and Alkylamines | year = 1957 | journal = J. Org. Chem. | volume = 22 | issue = 2 | pages = 143–144 | doi = 10.1021/jo01353a010}} (Note: Hydroxylamines and oximes are typical impurities.)
• Lithium borohydride or sodium borohydride and trimethylsilyl chloride{{Cite journal|last1=Giannis|first1=A.|last2=Sandhoff|first2=K.|date=1989|title=LiBH4(NaBH4)/Me3SiCl, an Unusually Strong and Versatile Reducing Agent|journal=Angewandte Chemie International Edition in English|language=en|volume=28|issue=2|pages=218–220|doi=10.1002/anie.198902181}}
• Red-Al{{Cite journal|last1=Butterick|first1=John R.|last2=Unrau|first2=A. M.|date=1974|title=Reduction of β-nitrostyrene with sodium bis-(2-methoxyethoxy)-aluminium dihydride. A convenient route to substituted phenylisopropylamines|journal=J. Chem. Soc., Chem. Commun.|language=en|issue=8|pages=307–308|doi=10.1039/c39740000307}}

Aliphatic nitro compounds can be reduced to aliphatic hydroxylamines using diborane.{{cite journal | author = H. Feuer, R. S. Bartlett, B. F. Vincent and R. S. Anderson | title = Diborane Reduction of Nitro Salts. A New Synthesis of N-Monosubstituted Hydroxylamines | year = 1965 | journal = J. Org. Chem. | volume = 30 | issue = 9 | pages = 2880–2882 | doi = 10.1021/jo01020a002}}

:Image:Reduction NitroalkaneToHydroxylAmine.png

The reaction can also be carried out with zinc dust and ammonium chloride:{{Citation|last1=Smith|first1=P.W.G.|title=Aliphatic Nitro Compounds and Amines|date=1965|url=https://linkinghub.elsevier.com/retrieve/pii/B9780080107462500168|work=Fundamental Aliphatic Chemistry|pages=245–266|publisher=Elsevier|language=en|doi=10.1016/b978-0-08-010746-2.50016-8|isbn=978-0-08-010746-2|access-date=2021-01-27|last2=Tatchell|first2=A.R.}}{{Cite journal|last1=Kelly|first1=Sean M.|last2=Lipshutz|first2=Bruce H.|date=2014-01-03|title=Chemoselective Reductions of Nitroaromatics in Water at Room Temperature|url= |journal=Organic Letters|language=en|volume=16|issue=1|pages=98–101|doi=10.1021/ol403079x|issn=1523-7060|pmc=4013784|pmid=24341483}}{{Cite journal|last1=Ung|first1=Stéphane|last2=Falguières|first2=Annie|last3=Guy|first3=Alain|last4=Ferroud|first4=Clotilde|date=August 2005|title=Ultrasonically activated reduction of substituted nitrobenzenes to corresponding N-arylhydroxylamines|url=https://linkinghub.elsevier.com/retrieve/pii/S0040403905014103|journal=Tetrahedron Letters|language=en|volume=46|issue=35|pages=5913–5917|doi=10.1016/j.tetlet.2005.06.126}}

: R-NO₂ + 4 NH₄Cl + 2 Zn → R-NH-OH + 2 ZnCl₂ + 4 NH₃ + H₂O

Image:Reduction NitroalkaneToOxime.png

Nitro compounds are typically reduced to oximes using metal salts, such as tin(II) chloride{{cite journal |author1=Braun, V. J. |author2=Sobecki, W. | title = Über primäre Dinitro-, Nitronitrit- und Dialdoxim-Verbindungen der Fettreihe | journal = Chemische Berichte | year = 1911 | volume = 44 | issue = 3 | pages = 2526–2534 | doi = 10.1002/cber.19110440377|url=https://zenodo.org/record/1426463}} or chromium(II) chloride.{{cite journal |author1=J. R. Hanson |author2=E. Premuzic |name-list-style=amp | title = Applications of chromous chloride--II : The reduction of some steroidal nitro-compounds | year = 1967 | journal = Tetrahedron | volume = 23 | issue = 10 | pages = 4105–4110 | doi = 10.1016/S0040-4020(01)97921-9}} Additionally, catalytic hydrogenation using a controlled amount of hydrogen can generate oximes.{{cite journal | author = C. Grundmann | title = Über die partielle Reduktion von Nitro-cyclohexan | year = 1950 | journal = Angewandte Chemie | volume = 62 | issue = 23–24 | pages = 558–560 | doi = 10.1002/ange.19500622304| bibcode = 1950AngCh..62..558G }}

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Category:Organic redox reactions