Categories: N-H Bond Formation >
Reduction of nitro compounds
The combination HSiCl3 and a tertiary amine enables a mild, metal-free reduction of both aromatic and aliphatic nitro groups to amines. The reaction is of wide general applicability and tolerates many functional groups.
M. Orlandi, F. Tosi, M. Bonsignore, M. Benaglia, Org. Lett., 2015, 17, 3941-3943.
A complex of a cyclic (alkyl)(amino)carbene (CAAC) ligand with chromium catalyzes a mild, chemoselective, and efficient deoxygenative hydroboration of nitro compounds to provide a broad range of anilines, as well as heteroaryl and aliphatic amine derivatives. The CAAC ligand plays an important role in promoting polarity reversal of hydride of HBpin and serves as an H-shuttle.
L. Zhao, C. Hu, X. Cong, G. Deng, L. L. Liu, M. Luo, X. Zeng, J. Am. Chem. Soc., 2021, 143, 1618-1629.
A well-defined iron-based catalyst system enables the reduction of nitroarenes to anilines using formic acid as reducing agent. A broad range of substrates including other reducible functional groups were converted to the corresponding anilines in good to excellent yields at mild conditions. Notably, the process constitutes a rare example of base-free transfer hydrogenations.
G. Wienhöfer, I. Sorribes, A. Boddien, F. Westerhaus, K. Junge, H. Junge, R. Llusar, M. Beller, J. Am. Chem. Soc., 2011, 133, 12875-12879.
A metal-free reduction of nitro aromatics is mediated by tetrahydroxydiboron under mild conditions in water as solvent to provide various aromatic amines with good functional group tolerance and in good yields.
D. Chen, Y. Zhou, H. Zhou, S. Liu, Q. Liu, K. Zhang, Y. Uozumi, Synthesis, 2018, 50, 1765-1768.
The use of tetrahydroxydiboron as reductant and 4,4′-bipyridine as organocatalyst enables a metal-free and highly chemoselective reduction of aromatic nitro compounds within 5 min at room temperature. Under optimal conditions, sensitive functional groups, such as vinyl, ethynyl, carbonyl, and halogen were tolerated.
M. Jang, T. Lim, B. Y. Park, M. S. Han, J. Org. Chem., 2022, 87, 910-919.
4,4′-Bipyridine worked as an organocatalyst for the reduction of nitroarenes by bis(neopentylglycolato)diboron (B2nep2), followed by hydrolysis to give the corresponding anilines with broad functional group tolerance.
H. Hosoya, L. C. M. Castro, I. Sultan, Y. Nakajima, T. Ohmura, K. Sato, H. Tsurugi, M. Suginome, K. Mashima, Org. Lett., 2019, 21, 9812-9817.
A mild transition-metal- and photosensitizer-free photoredox system based on the combination of NaI and PPh3 enables a highly selective reduction of nitroarenes. This protocol tolerates a broad range of reducible functional groups such as halogen (even I), aldehyde, ketone, carboxyl, and cyano.
Z. Qu, X. Chen, S. Zhong, G.-J. Deng, H. Huang, Org. Lett., 2021, 23, 5349-5353.
Pd/C can be used as a catalyst for nitro group reductions at very low Pd loading either in the presence of triethylsilane as a transfer hydrogenating agent or simply using a hydrogen balloon. With this technology, a series of nitro compounds was reduced to the desired amines in high yields. Both the catalyst and surfactant were recycled several times without loss of activity.
X. Li, R. R. Thakore, B. S. Takale, F. Gallou, B. H. Lipshutz, Org. Lett., 2021, 23, 8114-8118.
The use of H2-fine bubbles as a new reaction medium enables an autoclave-free gas-liquid-solid multiphase hydrogenation of nitro groups on a multigram scale.
N. Mase, Y. Nishina, S. Isomura, K. Sato, T. Narumi, N. Watanabe, Synlett, 2017, 28, 2184-2188.
Palladium-catalyzed reduction of aromatic nitro groups to amines can be accomplished in high yield, with wide functional group tolerance and short reaction times at r.t. using aqueous potassium fluoride and polymethylhydrosiloxane (PMHS) for aromatic nitro groups. Aliphatic nitro compounds are reduced to the corresponding hydroxylamines using triethylsilane instead of PMHS/KF.
R. J. Rahaim, R. E. Maleczka (Jr.), Org. Lett., 2005, 7, 5087-5090.
The use of methylhydrazine as a reducing agent in combination with an easily synthesized and robust Co catalyst and a polar protic solvent enables a chemoselectively reduction of nitroarenes to arylamines in excellent yields.
D. I. Ioannou, D. K. Gioftsidou, V. E. Tsina, M. G. Kallitsakis, A. G. Hatzidimitriou, M. A. Terzidis, P. A. Angaridis, I. N. Lykakis, J. Org. Chem., 2021, 86, 2895-2906.
A selective photoinduced reduction of nitroarenes to N-arylhydroxylamines proceeds with a broad scope, excellent functional-group tolerance, and high yields in the absence of catalyst or additives and uses only light and methylhydrazine.
M. G. Kallitsaki, D. I. Ioannou, M. A. Terzidis, G. E. Kostakis, J. N. Lykakis, Org. Lett., 2020, 22, 4339-4343.
Vasicine, an abundantly available quinazoline alkaloid from the leaves of Adhatoda vasica, enables an efficient metal- and base-free reduction of nitroarenes to the corresponding anilines in water. The chemoselective method tolerates a wide range of reducible functional groups, such as ketones, nitriles, esters, halogens, and heterocyclic rings. Dinitroarenes are reduced selectively to the corresponding nitroanilines.
S. Sharma, M. Kumar, V. Kumar, N. Kumar, J. Org. Chem., 2014, 79, 9433-9439.
The combination of B2pin2 and KOtBu enables a chemoselective, metal-free reduction of aromatic nitro compounds to the corresponding amines in very good yields in isopropanol. The reaction tolerates various reducible functional groups.
H. Lu, Z. Geng, J. Li, D. Zou, Y. Wu, Y. Wu, Org. Lett., 2016, 18, 2774-2776.
The very inexpensive carbonyl iron powder (CIP), a highly active commercial grade of iron powder, enables an especially mild, safe, efficient, and environmentally responsible reduction of aromatic and heteroaromatic nitro groups in water. These reductions are conducted in a recyclable aqueous reaction medium in the presence of nanomicelles composed of TPGS-750-M.
N. R. Lee, A. A. Bikovtseva, M. Cortes-Clerget, F. Gallou, B. H. Lipshutz, Org. Lett., 2017, 19, 6518-6521.
A robust and green protocol for the reduction of functionalized nitroarenes to the corresponding primary amines relies on inexpensive zinc dust in water containing nanomicelles derived from the commercially available designer surfactant TPGS-750-M. This mild process takes place at room temperature and tolerates a wide range of functionalities including common protecting groups.
S. M. Kelly, B. H. Lipshutz, Org. Lett., 2014, 16, 98-101.
An efficient Fe/CaCl2 system enables the reduction of nitroarenes and reductive cleavage of azo compounds by catalytic transfer hydrogenation in the presence of sensitive functional groups including halides, carbonyl, aldehyde, acetyl, nitrile, and ester substituents with excellent yields. The simple experimental procedure and easy purification make the protocol advantageous.
S. Chandrappa, T. Vinaya, T. Ramakrishnappa, K. S. Rangappa, Synlett, 2010, 3019-3022.
A mild and efficient electron-transfer method for the chemoselective reduction of aromatic nitro groups using samarium(0) metal in the presence of a catalytic amount of 1,1'-dioctyl-4,4'-bipyridinium dibromide gives aromatic amines in good yield with selectivity over a number of other functional and protecting groups.
C. Yu, B. Liu, L. Hu, J. Org. Chem., 2001, 66, 919-924.
(Ph3P)3RuCl2 is an inexpensive catalyst, that enables a chemoselective reduction of alkyne, ketones, or nitro groups in the presence of Zn/water as a stoichiometric reductant. Depending on the nature of the additive and the temperature, chemoselective reduction of a nitro group in the presence of a ketone or an alkyne was possible.
T. Schabel, C. Belger, B. Plietker, Org. Lett., 2013, 15, 2858-2861.
A generally applicable method for the introduction of gaseous hydrogen into a sealed reaction system under microwave irradiation allows the hydrogenation of various substrates in short reaction times with moderate temperatures between 80 °C and 100 °C with 50 psi of hydrogen.
G. S. Vanier, Synlett, 2007, 131-135.
Poly(ethylene glycol) (PEG) (400) has been found to be a superior solvent over ionic liquids by severalfold in promoting the hydrogenation of various functional groups using Adams' catalyst. Both the catalyst and PEG were recycled efficiently over 10 runs without loss of activity, and without substrate cross contamination.
S. Chandrasekhar, S. Y. Prakash, C. L. Rao, J. Org. Chem., 2006, 71, 2196-2199.
Several bromo, chloro, iodo and multihalogenated nitroarenes have been selectively reduced with hydrazine hydrate in the presence of Pd/C to give the corresponding halogenated anilines in good yield. Using microwave irradiation at elevated temperature and pressure, dehalogenated products can be isolated.
F. Li, B. Frett, H.-y Li, Synlett, 2014, 25, 1403-1408.
A microwave-assisted, palladium-catalyzed catalytic transfer hydrogenation of different homo- or heteronuclear organic compounds using formate salts as a hydrogen source was performed in ([bmim][PF6]. Essentially pure products could be isolated in moderate to excellent yields by simple liquid-liquid extraction.
H. Berthold, T. Schotten, H. Hönig, Synthesis, 2002, 1607-1610.
A transition-metal-free synthesis of aryl- and heteroarylamines employs a small-ring organophosphorus-based catalyst and a terminal hydrosilane reductant to drive reductive intermolecular coupling of nitroarenes with boronic acids. Applications to the construction of both Csp2-N (from arylboronic acids) and Csp3-N bonds (from alkylboronic acids) are demonstrated; the reaction is stereospecific with respect to Csp3-N bond formation.
T. V. Nykaza, J. C. Cooper, G. Li, N. Mahieu, A. Ramirez, M. R. Luzung, A. T. Radosevich, J. Am. Chem. Soc., 2018, 140, 15200-15205.
Triphenylphosphine mediates a metal-free, intermolecular, reductive amination between nitroarenes and boronic acids at ambient temperature under visible-light irradiation without any photocatalyst. A wide range of nitroarenes underwent C-N coupling with aryl-/alkylboronic acids providing high yields.
K. Manna, T. Ganguly, S. Baitalik, R. Jana, Org. Lett., 2021, 23, 8634-8639.
N-Alkylaminobenzenes were prepared in a simple and efficient one-pot synthesis by reduction of nitrobenzenes followed by reductive amination with decaborane (B10H14) in the presence of 10% Pd/C.
J. W. Bae, Y. J. Cho, S. H. Lee, C.-O. M. Yoon, C. M. Yoon, Chem. Commun., 2000, 1857-1858.
A synthesis of N-arylsulfonamides from readily available nitroarenes and sodium arylsulfinates was realized in the presence of FeCl2 as catalyst and NaHSO3 as reductant under mild conditions. A broad range of functional groups were tolerated. Mechanistic studies indicated that the N-S bond might be generated through direct coupling of nitroarene with sodium arylsulfinate prior to the reduction.
W. Zhang, J. Xie, B. Rao, M. Luo, J. Org. Chem., 2015, 80, 3504-3511.
In the presence of iodide ions, an efficient and selective rhodium-catalyzed transfer hydrogenation of nitroarenes with formic acid as the hydrogen source takes place to give amines or formanilides.
Y. Wei, J. Wu, D. Xue, C. Wang, Z. Liu, Z. Zhang, G. Chen, J. Xiao, Synlett, 2014, 25, 1295-1298.
A Cu-catalyzed reductive aminocarbonylation of primary, secondary, and tertiary alkyl iodides using nitroarenes as the nitrogen source provides a diverse range of secondary N-aryl alkylamides. The single copper catalyst synergistically mediates both carbonylation of alkyl iodides and reduction of nitroarenes, to provide acyl iodides and anilines as possible reactive intermediates.
S. Zhao, N. P. Mankad, Org. Lett., 2019, 21, 10106-10110.
The combination of zinc powder as reductant and sodium chlorate as oxidant was used to provide an environmentally friendly, effective, and convenient method for the synthesis of aromatic amides in good yields from nitroarenes and aldehydes in a green solvent under atmospheric conditions. Reductants and oxidants with opposing properties can be used together without any adverse effects. In addition, a cooperation seems to improve the yield.
G. Sheng, X. Wu, X. Cai, W. Zhang, Synthesis, 2015, 47, 949-954.
An efficient one-pot procedure for the zinc-mediated reduction of nitroarenes in the presence of chloroformates leads to the corresponding N,O-bisprotected hydroxylamines in good yield under ambient conditions in THF-water mixtures. Solvolysis of the bisprotected hydroxylamines with sodium methoxide at room temperature provides access to synthetically versatile N-aryl-N-hydroxy carbamates in excellent yields.
A. Porzelle, M. D. Woodrow, N. C. O. Tomkinson, Synlett, 2009, 798-802.
An intermolecular reductive Schiff base formation from nitroarenes and benzaldehydes to yield diarylimines is carried out in the presence of iron powder and dilute acid. This process tolerates various functional groups and often proceeds quantitatively with no need for purification.
A. L. Korich, T. S. Hughes, Synlett, 2007, 2602-2604.