Reduction of nitro compounds explained

The reduction of nitro compounds are chemical reactions of wide interest in organic chemistry. The conversion can be effected by many reagents. The nitro group was one of the first functional groups to be reduced. Alkyl and aryl nitro compounds behave differently. Most useful is the reduction of aryl nitro compounds.

Aromatic nitro compounds

Reduction to anilines

The reduction of nitroaromatics is conducted on an industrial scale. Many methods exist, such as:

• Catalytic hydrogenation using: Raney nickel or palladium-on-carbon,^{[1] [2]} platinum(IV) oxide, or Urushibara nickel.
• Iron in acidic media.^{[3] [4]}
• Sodium hydrosulfite
• Sodium sulfide (or hydrogen sulfide and base). Illustrated by the selective reduction of dinitrophenol to the nitroaminophenol.
• Tin(II) chloride^[5]
• Titanium(III) chloride
• Samarium^[6]
• Hydroiodic acid^[7]

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

Reduction to hydroxylamines

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

• Raney nickel and hydrazine at 0-10 °C^[8]
• Electrolytic reduction
• Zinc metal in aqueous ammonium chloride
• Catalytic Rhodium on carbon with excess hydrazine monohydrate at room temperature ^[9]

Reduction to hydrazine compounds

See also: Hydrazine. Treatment of nitroarenes with excess zinc metal results in the formation of N,N-diarylhydrazine.

Reduction to azo compounds

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

• Lithium aluminium hydride^[10]
• Zinc metal with sodium hydroxide. (Excess zinc will reduce the azo group to a hydrazino compound.)

Aliphatic nitro compounds

Reduction to hydrocarbons

Hydrodenitration (replacement of a nitro group with hydrogen) is difficult to achieve but can be effected by catalytic hydrogenation over platinum on silica gel at high temperatures.^[11] The reaction can also be effected through radical reaction with tributyltin hydride and a radical initiator, AIBN as an example.^[12]

Reduction to amines

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

• Catalytic hydrogenation using platinum(IV) oxide (PtO₂)^[13] or Raney nickel
• Iron metal in refluxing acetic acid^[14]
• Samarium diiodide^[15]
• Raney nickel, platinum on carbon, or zinc dust and formic acid or ammonium formate^[16]

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

• Catalytic hydrogenation over palladium-on-carbon
• Iron metal
• Lithium aluminium hydride^[17] (Note: Hydroxylamines and oximes are typical impurities.)
• Lithium borohydride or sodium borohydride and trimethylsilyl chloride^[18]
• Red-Al^[19]

Reduction to hydroxylamines

Aliphatic nitro compounds can be reduced to aliphatic hydroxylamines using diborane.^[20]

The reaction can also be carried out with zinc dust and ammonium chloride:^{[21] [22]}

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

Reduction to oximes

Nitro compounds are typically reduced to oximes using metal salts, such as tin(II) chloride^[23] or chromium(II) chloride.^[24] Additionally, catalytic hydrogenation using a controlled amount of hydrogen can generate oximes.^[25]

Notes and References

1. Book: Michael B. . Smith . Jerry . March . March's Advanced Organic Chemistry . John Wiley & Sons . 2007 . 6th . 978-0-471-72091-1 . 1816 .
2. . 25 . 32 . 1984 . 3415–3418 . A general procedure for mild and rapid reduction of aliphatic and aromatic nitro compounds using ammonium formate as a catalytic hydrogen transfer agent . Siya . Ram . Richard E. . Ehrenkaufer . 10.1016/S0040-4039(01)91034-2 . 2027.42/25034 . free.
3. S. A.. Mahood. P. V. L. . Schaffner\doi=10.15227/orgsyn.011.0032. 2,4-Diaminotoluene. Organic Syntheses. 1931. 11. 32. 10.15227/orgsyn.011.0032.
4. 10.15227/orgsyn.089.0274. O-Aminobenzaldehyde, Redox-Neutral Aminal Formation and Synthesis of Deoxyvasicinone. Organic Syntheses. 2012. 89. 274. free.
5. Encyclopedia: Faul . Margaret M. . Thiel . Oliver R. . . 2005 . 10.1002/047084289X.rt112.pub2 . Tin(II) Chloride . 9780470842898 .
6. 10.1016/S0040-4039(00)00917-5 . . Basu, M. K. . Ultrasound-promoted highly efficient reduction of aromatic nitro compounds to the aromatic amines by samarium/ammonium chloride . 2000 . 5603–5606 . 30 . 41.
7. Kumar. J. S. Dileep. Ho. ManKit M.. Toyokuni. Tatsushi. 2001. Simple and chemoselective reduction of aromatic nitro compounds to aromatic amines: reduction with hydriodic acid revisited. Tetrahedron Letters. 42. 33. 5601–5603. 10.1016/s0040-4039(01)01083-8.
8. Ayyangar, N. R. . Brahme, K. C. . Kalkote, U. R. . Srinivasan, K. V. . Facile Transfer-Reduction of Nitroarenes to N Arylhydroxylamines with Hydrazine in the Presence of Raney Nickel . . 1984 . 1984 . 11 . 938 . 10.1055/s-1984-31027.
9. Ichikawa, S. . Zhu, S. . Buchwald, S.. A Modified System for the Synthesis of Enantioenriched N-Arylamines through Copper-Catalyzed Hydroamination . . 2018 . 57 . 28 . 8714–8718 . 10.1002/anie.201803026. 29847002 . 6033674 . 1721.1/125726 . free.
10. R. F. Nystrom . W. G. Brown . amp . Reduction of Organic Compounds by Lithium Aluminum Hydride. III. Halides, Quinones, Miscellaneous Nitrogen Compounds . 1948 . . 70 . 11 . 3738–3740 . 10.1021/ja01191a057 . 18102934.
11. M. J. Guttieri . W. F. Maier . amp . Selective cleavage of carbon-nitrogen bonds with platinum . 1984 . . 49 . 16 . 2875–2880 . 10.1021/jo00190a006.
12. 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
13. A. T. Nielsen . The Isomeric Dinitrocyclohexanes. II. Stereochemistry . 1962 . . 27 . 6 . 1998–2001 . 10.1021/jo01053a019.
14. Senkus, M. . Iron Reduction of Some Aliphatic Nitro Compounds. Ind. Eng. Chem. . 1948 . 40 . 506. 10.1021/ie50459a035.
15. A. S. Kende . J. S. Mendoza . amp . Controlled reduction of nitroalkanes to alkyl hydroxylamines or amines by samarium diiodide . 1991 . Tetrahedron Letters . 32 . 14 . 1699–1702 . 10.1016/S0040-4039(00)74307-3. free .
16. Adams. J. P.. 2002. Nitro and related groups. Journal of the Chemical Society, Perkin Transactions 1. en. 23. 2586–2597. 10.1039/b009711j.
17. A. Burger, M. L. Stein and J. B. Clements . Some Pyridylnitroalkenes, Nitroalkanols, and Alkylamines . 1957 . . 22 . 2 . 143–144 . 10.1021/jo01353a010.
18. Giannis. A.. Sandhoff. K.. 1989. LiBH4(NaBH4)/Me3SiCl, an Unusually Strong and Versatile Reducing Agent. Angewandte Chemie International Edition in English. en. 28. 2. 218–220. 10.1002/anie.198902181.
19. Butterick. John R.. Unrau. A. M.. 1974. Reduction of β-nitrostyrene with sodium bis-(2-methoxyethoxy)-aluminium dihydride. A convenient route to substituted phenylisopropylamines. J. Chem. Soc., Chem. Commun.. en. 8. 307–308. 10.1039/c39740000307.
20. H. Feuer, R. S. Bartlett, B. F. Vincent and R. S. Anderson . Diborane Reduction of Nitro Salts. A New Synthesis of N-Monosubstituted Hydroxylamines . 1965 . J. Org. Chem. . 30 . 9 . 2880–2882 . 10.1021/jo01020a002.
21. Kelly. Sean M.. Lipshutz. Bruce H.. 2014-01-03. Chemoselective Reductions of Nitroaromatics in Water at Room Temperature. Organic Letters. en. 16. 1. 98–101. 10.1021/ol403079x. 1523-7060. 4013784. 24341483.
22. Ung. Stéphane. Falguières. Annie. Guy. Alain. Ferroud. Clotilde. August 2005. Ultrasonically activated reduction of substituted nitrobenzenes to corresponding N-arylhydroxylamines. Tetrahedron Letters. en. 46. 35. 5913–5917. 10.1016/j.tetlet.2005.06.126.
23. Braun, V. J. . Sobecki, W. . Über primäre Dinitro-, Nitronitrit- und Dialdoxim-Verbindungen der Fettreihe . . 1911 . 44 . 3 . 2526–2534 . 10.1002/cber.19110440377.
24. J. R. Hanson . E. Premuzic . amp . Applications of chromous chloride--II : The reduction of some steroidal nitro-compounds . 1967 . . 23 . 10 . 4105–4110 . 10.1016/S0040-4020(01)97921-9.
25. C. Grundmann . Über die partielle Reduktion von Nitro-cyclohexan . 1950 . . 62 . 23–24 . 558–560 . 10.1002/ange.19500622304. 1950AngCh..62..558G .