The reduction of nitro aromatics is the most widely utilized and facile method to prepare functionalized anilines.[55] There are numerous methods and reaction conditions to achieve reduction of aromatic nitro groups reported in the literature, such as FeCl3·6H20
[64], Pt (nanoparticles)/C[65] and NiCl2-NaBH4.[66]
The first method of reducing nitro compounds to anilines was the Zinin reduction developed in 1842. This reaction is carried out in basic media employing divalent sulfur, such as sulfides, hydrosulfides and polysulfides, as reducing agents.[67]The Zinin reduction was soon replaced by the oldest commercial process for preparing anilines, which was the Béchamp process. The Béchamp process reduces nitro compounds in good yields with iron and diluted HCl acid.[67]
Today most large scale anilines are prepared through continuous high pressure catalytic hydrogenation of nitro aromatics with various heterogeneous catalysts.[67]
1.8 Reduction of Nitro Aromatics
The hydrogenation of nitro compounds can be performed in gas or liquid phase, by employing supported metal catalysts and organic solvents such as alcohols, acetone, benzene, ethyl acetate or aqueous acidic solutions.[68]
In the reduction of complex nitro aromatic compounds, containing other reducible substituents or acid labile functional groups, the reaction conditions during hydro-genation employing heterogenous catalysts are to harsh. When reducing complex nitro aromatic compounds, the most important factor for forming functionalized anilines is the specificity of the reduction. The need to find reduction conditions which are chemoselective towards the nitro group and leaves the substituents intact, is important.
The use of hydrogen gas in the presence of either metal or metal oxide, is one method for reduction of nitro groups to anilines.[69] The general reaction is illus-trated in Scheme 1.8.1
Scheme 1.8.1: Reduction of nitro aromatic compounds employing molecular hydrogen.[69]
The use of metal-bound catalysts brings issues with metal leaching, low catalyst loading, higher turnover cycle, recovery of catalyst and chemioselectivity. Platinum (Pt) oxide with methanol as solvent has previously been used for the chemoselec-tiv reduction of nitro aromatic compounds, with an ether functionality, without effecting the ether moiety.[70]
Another method of reduction, employing H2-gass, is the use of polysiloxane gels with Pt species [Pt]@SiC6 as recyclable heterogeneous catalyst. This system has been used to reduce various nitro aromatics, such as benzyl, alcohol, ketone, ester and ether, in excellent yields.[71]
The catalytic system Pt/SiO2 has been used to selectively reduce ester and alkene substituted nitro compounds in a hydrogen atmosphere at room temperature.[72]
The main problem with Pt catalysts is their reduction selectivity when there are other functional groups present.[65] Pt catalysts tend to reduce other functional groups, in addition to the nitro group, when used on complex nitro aromatics.
The use of colloidal nickel(0) on carboxymethylcellulose in methanol is an effective method to selectively reduce nitro aromatic compounds. The catalyst system has been used to selectively reduce nitro arenes with ester, alcohol and amine sub-stituents, in high yields.[73]
A disadvantage of molecular hydrogen in the presence of metal or metal oxide is the need for high pressure conditions. By generating hydrogen in situ under the
reduction, the need for sophisticated equipment for handling hydrogen gas can be avoided.[69] Sodium borohydrid has been used as an in situ source for generation of hydrogen in fuel cells, in which various metal bound catalysts can be employed, for the reduction of nitro aromatic compounds. The reduction can be performed with catalyst systems, such as PdCu/graphene and ethanol, Co3S4 and CuBr2 in ethanol.[74] [75] [76]The general sodium borohydrid mediate reaction is illustrated in Scheme 1.8.2
Scheme 1.8.2: Reduction of nitro aromatic compounds mediated by sodium borohydrid.[69]
Reductions mediated by sodium borohydride are safer than the use of H2-gass, however, the reactions have issues during workup with extraction of the product.
In addition functional groups which are reduced by sodium borohydride are not tolerated during this reaction.[69]
Hydrazine hydrate decomposes into nitrogen and hydrogen gas when exposed to transition metals. Hydrazine hydrate is therefore used as anin situhydrogen donor, which facilitates reduction reactions.[69] The general hydrazine hydrate facilitated reaction is illustrated in Scheme 1.8.3
Scheme 1.8.3: Reduction of nitro aromatic compounds with Hydrazine hydrate as reducing agent.[69]
Hydrazine hydrate has been used as reducing agent in combination with Pd/C in methanol or ethanol. This reducing system has shown selective reduction of halogenated nitro compounds, when refluxed in an open system. If performed in a sealed environment, dehalogenation occurs.[77] In situ generation of iron oxide nanocrystals (Fe3O4) in ethanol is a reduction system which is used in combination with Hydrazin hydrate to selectivly reduce nitro compounds with; halogen, ester, amide, nitrile or ether substituents in high yields.[78]A drawback with the use of Hydrazine as reducing agent is toxicity in addition to risk of combustion.
A method for selective reduction of nitroarenes to anilines is the use of a metal catalyst. Active metal can react with water and generate hydrogen, which can reduce nitro groups in the presence of metal. Metal can directly reduce nitroarenes
1.8 Reduction of Nitro Aromatics
through electron-transfer reaction, where water functions as a proton donor.[69]Iron nanoparticles in water, in an inert atmosphere, at room temperature have been used to selectivly reduce nitroarenes, with a widespread of substituents.[79] Iron nanoparticles have chemoselectivly reduced nitro compounds with ether, halide, aldehyde and carboxyl acid functional groups, in excellent yields.
Iron powder has also been employed in combination with ammonium chloride in aqueous ethanol, to obtain chemoselctive reduction to anilines when refluxed. In this case, the iron powder function as reducing agent and the ammonium chloride serves as proton donor.[46] [80] [81]
A powerful acidic reduction system is the use of stannous chloride (SnCl2) in com-bination with hydrochloric acid (HCl).[82] This method has been developed from only reducing water soluble nitro aromatics to a chemioselective reduction system by introducing ionic-liquids, different solvents and sonication.[83] [84] [85]
An illustration of a proposed reaction pathway for the formation of anilines from reduction of functionalized aromatic nitro compounds, is presented in Scheme 1.8.4.[72]
Scheme 1.8.4: Proposed reaction pathway for the reduction of nitroaromatics.[72]