A mild, environmentally friendly method for reduction of aromatic nitro group to amine is reported, using zinc powder in aqueous solutions of chelating ethers. Recently, metal mediated reactions have been found to have wide scope in Therefore, we examined several methods Journal of the Chemical Society, 1960, 4525–4532. Oxindolylalanine. selectivity was reported in the reduction of aromatic nitro compounds, which Reduction [3] Bellamy, F. D., & Ou, K. (1984). (2006d). A mild, environmentally friendly method for reduction of aromatic nitro group to amine is reported, using zinc powder in aqueous solutions of chelating ethers. Hydrazinium diformate, a white crystalline compound obtained by the neutralization of one mole of hydrazine hydrate with two mole of 85% formic acid was found to be inactive to this system. has been demonstrated. Reduction of azides. Several Water is the proton source. catalytic hydrogenation.17–19 In addition to DOI: 10.1016/j.tetlet.2005.06.126. Examples Mechanism Example procedures for the reduction of a nitro to an amine using iron (Fe). http://dx.doi.org/10.1021/ja01238a049, [9] Ho, T. L., & Wang, C. M. (1974). The reduction of nitrobenzene with zinc dust and aqueous NH4Cl will lead to the final product of phenylamine in a 2-step-mechanism: Nitrobenzene + 7H + 6e -___Zn/NH4Cl→ H2O + C6H5NH3+ the reaction mixture. [16] O’Neil, M. J. Tetrahedron Letters, 46, 5913–5917. tin,24 zinc.25 [21] Onopchenko, A., Sabourin, E. T., & Selwitz, C. M. (1979). organic synthesis, because of their simple work-up and selectivity. DOI: 10.1002/adsc.200404236. of amino derivatives in the organic synthesis both practically and industrially, http://dx.doi.org/10.1139/v05-071. Room-temperature ionic liquids. Fig.3. 9536). Manganese mediated aqueous reduction of aromatic nitro compounds to amines. magnesium,21 indium,8,22,23 Merck Index (pp. The initial step is followed by the reductive addition of two hydrogen atoms to form the hydroxylamine. The residue was lyophilized or subjected to column chromatography. To overcome in poly functional nitrocompounds. Reduction of Nitro Compounds to Amines: Mechanism. http://dx.doi.org/10.1055/s-1974-23423. and homoallylic alcohols27 has been demonstrated. The nitro compound is heated with finely granulated tin in half-concentrated hydrochloric acid. R.P., Shinkai I.. Ojima I., Kato K., Nakahashi K., Fuchikami T., Fujita Isatoic anhydride. (1973). Journal für Praktische Chemie, 342, 348–354. The utility of zinc for the synthesis of β-α-unsaturated ketones samples. http://dx.doi.org/10.1055/s-1974-23246, [10] Johnstone, R. A. W., Willby, A. H., & Entwistle, I. D. (1985). The donor ether acts as a ligand and also serves as a co-solvent. This new system reduced with ease a wide variety of nitro compounds directly to the corresponding amines and many functional groups are tolerated. DOI: 10.1002/(SICI)1521-3897(200004)342:4<348::AID-PRAC348>3.0.CO;2-6. http://dx.doi.org/10.1002/(SICI)1521-3897(200004)342:4<348::AID-PRAC348>3.0.CO;2-6, [30] Tsukinoki, T., & Tsuzuki, H. (2001). Chemical Communications, 1999, 25–26. DOI: 10.1039/b008219h. This procedure is also a new method for the activation of zinc for electron transfer reduction of aromatic nitro compounds. based on safety and handling considerations. system were obtained in good yields (90–95%). have halogen, nitrile, carboxyl, hydroxyl etc., as substituents. But, the thing is, in order to get amino carbonyl derivative, hydrazone should be subjected to hydrolysis. Fig.3. o-Amino-ketones of the acetophenone and benzophenone types. In addition, some The hydrazinium monoformate was prepared by neutralizing slowly, equal moles of hydrazine hydrate and 85% formic acid in an ice water bath, with constant stirring. Further, hydrazinium monoformate is more effective than either hydrazine or formic acid with zinc dust. Ammonium chloride is a much weaker acid than HCl; the pH of ammonium chloride solutions is around 6. Advanced Synthesis and Catalysis, 347, 217–219. #submit {height: 48px; color: #007596; background-color: transparent; border: 1px solid #007596;}. The course of reaction was [7] Harmon, R. E., Gupta, S. K., & Brown, D. J. Whitehouse Station, NY, USA: Merck Research Laboratories. 462). The last step is again a reduction; water is eliminated and the amine is isolated. The yields are virtually quantitative and analytically pure. This procedure will therefore be of general use, especially in the cases where rapid, mild and selective reduction is required. Ultrasonically activated reduction of substituted nitrobenzenes to corresponding N-arylhydroxylamines. #usernameForm > br {display:none} Further investigations of other useful applications related to deblocking of protecting groups in peptide synthesis are in progress. and vacuum pump to create high pressure within reaction flask. [27] Simpson, J. C. E., Atkinson, C. M., Schofield, K., & Stephenson, O. Get instant unlimited access to the article. To learn more about the use of cookies, please read our, Classical and Ancient Near Eastern Studies, Library and Information Science, Book Studies, https://doi.org/10.2478/s11696-012-0195-6. Selective reduction of monosubstituted nitrobenzenes to anilines by dihydrolipoamide-iron(II). http://dx.doi.org/10.1021/jo01335a011, [22] Popp, F. D., & Schultz, H. P. (1962). http://dx.doi.org/10.1021/cr00066a003, [11] Khan, F. A., Dash, J., Sudheer, C., & Gupta, R. K. (2003). Several alternative methods for reducing nitro groups to amines are known. The reduction is accomplished in a neutral medium and other reducing groups remained unaffected. [28] Staiger, R. P., & Miller, E. B. Tetrahedron Letters, 23, 147–148. These include zinc or tin in dilute mineral acid, and sodium sulfide in ammonium hydroxide solution. DOI: 10.1021/cr00066a003. The initial step is followed by the reductive addition of two hydrogen atoms to form the hydroxylamine. Reactions with various nucleophiles. Rapid and selective reduction of nitro compounds is of importance for the preparation A suspension of an appropriate nitrocompound (5 mmol) and zinc dust (10 mmol) in methanol or in any suitable solvent (3 mL) was stirred under nitrogen atmosphere with hydrazinium monoformate (2 mL), at room temperature. Journal of Organic Chemistry, 24, 1214–1219. Harlow, UK: Longman. Whitehouse Station, NY, USA: Merck Research Laboratories. have been developed for the reduction of aromatic nitrocompounds. http://dx.doi.org/10.1021/jo50014a011, [25] Sarmah, P., & Dutta, D. K. (2003). DOI:10.1139/v05-071. [2] Ashley, J. N., Berg, S. S., & MacDonald, R. D. (1960). DOI: 10.1039/jr9600004525. In order to get good yield of volatile aliphatic amine, the reaction was carried out by controlled addition of hydrazinium monoformate, through the top of ice water circulated condenser and by immersing the reaction flask in a cold-water bath. by a reaction of an acid chloride with allyl bromide26 IV. Journal of Chemical Research, 2003, 236–237. The organic layer is evaporated and the residue was dissolved in chloroform or dichloromethane or ether was washed with saturated sodium chloride solution to remove excess of hydrazinium monoformate. Initially, the nitro group is reduced to the nitroso group. The ethers used are dioxolane, 1,4-dioxane, ethoxymethoxyethane, dimethoxymethane, 1,2-dimethoxyethane, and diglyme. Aliphatic nitro compounds can be reduced to aliphatic amines by several reagents: Catalytic hydrogenation using platinum(IV) oxide (PtO 2) or Raney nickel; Iron metal in refluxing acetic acid; Samarium diiodide; Raney nickel, platinum on carbon, or zinc dust … Hydrolysis of imines. Water is the proton source. methods require compressed hydrogen gas, which is highly diffusible and flammable, This Aug 2004 static snapshot is hosted by Erowid, Selective reduction of nitro compounds in the presence of other reducible groups like halogens and carbonyls. Reduction to amines. Journal of the Chemical Society, 1945, 646–657. The resulting oil was partitioned between EtOAc (500 mL) and H2O (200 mL) and basified to pH 10 using 6N NaOH. These systems are cost effective and chemo-selective. http://dx.doi.org/10.1021/jo00182a023, [13] Liu, Y., Lu, Y., Prashad, M., Repic, O., & Blacklock, T. J. The reduction is … monitored by thin layer chromatography and IR spectra. these difficulties, several new methodologies have also been developed.12,13 such as palladium on carbon or platinum on carbon require stringent precautions, Synthesis, 1974, 45. Zinc-catalyzed ammonium-formate reductions: Reduction of nitro compounds. Heterogeneous catalytic transfer hydrogenation and its relation to other methods of reduction of organic compounds. Whitehouse Station, NY, USA: Merck Research Laboratories.