Phenylhydroxylamines, reduction

N-phenylhydroxylamine, PhNHOH and further reduction can give azoxybenzene, azobenzene, hydrazobenzene and aniline. The most important outlet commercially for the nitro-compounds is the complete reduction to the amines for conversion to dyestufTs. This is usually done in one stage with iron and a small amount of hydrochloric acid. 

In the reduction of nitro compounds to amines, several of the iatermediate species are stable and under the right conditions, it is possible to stop the reduction at these iatermediate stages and isolate the products (see Figure 1, where R = CgH ). Nitrosoben2ene [586-96-9] C H NO, can be obtained by electrochemical reduction of nitrobenzene [98-95-3]. Phenylhydroxylamine, C H NHOH, is obtained when nitrobenzene reacts with ziac dust and calcium chloride ia an alcohoHc solution. When a similar reaction is carried out with iron or ziac ia an acidic solution, aniline is the reduction product. Hydrazobenzene [122-66-7] formed when nitrobenzene reacts with ziac dust ia an alkaline solution. Azoxybenzene [495-48-7], C22H2QN2O, is... 

The chemical production of aminophenols via the reduction of nitrobenzene occurs in two stages. Nitrobenzene [98-95-3] is first selectively reduced with hydrogen in the presence of Raney copper to phenylhydroxylamine in an organic solvent such as 2-propanol (37). With the addition of dilute sulfuric acid, nucleophilic attack by water on the aromatic ring of /V-phenylhydroxylamine [100-65-2] takes place to form 2- and 4-aminophenol. The by-product, 4,4 -diaminodiphenyl ether [13174-32-8] presumably arises in a similar manner from attack on the ring by a molecule of 4-aminophenol (38,39). Aniline [62-53-3] is produced via further reduction (40,41). 

Phenylhydroxylamine rearranges in sulfuric acid to give mainly p-aminophenol. Industrial routes to this compound have been developed in which phenylhydroxylamine, formed by hydrogenation of nitrobenzene in sulfuric acid over platinum-on-carbon, is rearranged as it is formed. Conditions are adjusted so that the rate of rearran ment is high relative to the rate of hydrogenation of hydroxylamine to aniline (15,17,86). An easy way to obtain a favorable rate ratio is to carry out the reduction with about 1% DMSO present in the sulfuric acid (79,81). 

GL 18] ]R 1] ]P 19a] For a sputtered palladium catalyst, low conversion and substantial deactivation of the catalyst were foimd initially (0.04 mol 1 60 °C 4 bar 0.2 ml min ) [60, 62]. Selectivity was also low, side products being formed after several hours of operation (Figure 5.25). After an oxidation/reduction cycle, a slightly better performance was obtained. After steep initial deactivation, the catalyst activity stabilized at 2-4% conversion and about 60% selectivity. After reactivation, the selectivity approached initially 100%. As side products, all intermediates except phenylhydroxylamine were identified. 

GL 18] [R 1] [P 19] For a sputtered palladium catalyst, all intermediates except phenylhydroxylamine were identified [60]. Their relative amoimts allowed one to judge the route by which the hydrogenation proceeds. As a result, it was concluded that species containing nitroso, azo and azoxy groups have a strong interaction with the catalyst and so are preferably involved in the reaction course. In contrast, reduction of the hydrazo species was hindered. These assumptions are in line with literature reports. 

This reduction step can be readily observed at a mercury electrode in an aprotic solvent or even in aqueous medium at an electrode covered with a suitable surfactant. However, in the absence of a surface-active substance, nitrobenzene is reduced in aqueous media in a four-electron wave, as the first step (Eq. 5.9.3) is followed by fast electrochemical and chemical reactions yielding phenylhydroxylamine. At even more negative potentials phenylhydroxylamine is further reduced to aniline. The same process occurs at lead and zinc electrodes, where phenylhydroxylamine can even be oxidized to yield nitrobenzene again. At electrodes such as platinum, nickel or iron, where chemisorption bonds can be formed with the products of the... 

I. Condensation of N-Monosubstituted Hydroxylamines with Carbonyl Compounds Condensation of N -monosubstituted hydroxylamines with carbonyl compounds is used as a direct synthesis of many acyclic nitrones. The synthesis of hydroxylamines is being carried out in situ via reduction of nitro compounds with zinc powder in the presence of weak acids (NH4CI or AcOH) (14, 18, 132). The reaction kinetics of benzaldehyde with phenylhydroxylamine and the subsequent reaction sequence are shown in Scheme 2.21 (133). 

Propanol with magnesium in reduction of chlorobenzene, 47, 104 Propionic acid, 2-(2,4,5,7-tetranitro-flcoken-9-ylideneamtnooxv)-, (+)- AND (-)-, 48, 120 Propionyl fluoride, 45, 6 Propiophenone, condensation with paraformaldehyde, 48, 91 -Propylaminc, 45, 85 -Propylhydrazine, 45, 85 C-( -Propyl)-N-phenylnitrone, generation from phenylhydroxylamine and -butyraIdehyde, 46, 97 Purification of tetrahydrofuran (Warning), 46,105 477- Pyran-4-0ne, 2-6-dimethyl-3,5-DIPHENYL-, 47, 54... 

The syntheses of N-hydroxy-N-nitrosamines are usually carried out by the nitrosation of the corresponding N-hydroxyamines (Scheme 3.8) [123, 124]. N-Hydroxyamines are readily obtained by the reduction of the corresponding nitro-compounds. The most efficient methods are neutral or basic reactions. Recent applications of this method have resulted in the preparation of a variety of cupferron derivatives (Scheme 3.8) via nitrosation of phenylhydroxylamine with amyl nitrite/ammonia [125] or methyl nitrite/ammonia [126]. Behrend and Konig have shown that the organic... 

A process for the direct reduction of nitrobenzene to -p-ammophenol, an important intermediate for the production of dyes, depends on the above interesting transformation. Nitrobenzene in alcoholic solution is mixed with concentrated sulphuric acid and electrolysed with a lead cathode. This process proves that phenylhydroxylamine is also an intermediate in the reduction of nitrobenzene in acid solution, as was mentioned above. Here, as a result of the rapidity of the rearrangement which takes place, it is not converted into aniline. 

Under the conditions prevailing during the production of aniline neither nitrosobenzene nor phenylhydroxylamine is encountered. The reason for this is that the rate of reduction of these intermediate products is much greater than that of the nitrobenzene itself (F. Haber). 

In neutral or alkaline solution the conditions are altered so as to favour the immediate precursor of the final product of hydrogenation, namely, phenylhydroxylamine. This compound is obtained from nitrobenzene, suspended in ammonium chloride solution, by reduction with zinc dust. Zinc dust can decompose water with the formation of Zn(0H)2 if a substance is present which takes up the liberated hydrogen. Molecular, i e. ordinary, oxygen is capable of doing this and is thereby converted into hydrogen peroxide (M. Traube) ... 

In the case under discussion the nitrobenzene takes the place of the oxygen. (Write the equation.) If the experiment is properly carried out, the reduction is limited in this way to the phenylhydroxylamine stage. 

One possibility, the ECEC path, i.e. alternating electron transfer and protonation steps, for the mechanism of reduction of nitrosobenzene to phenylhydroxylamine was discussed in Section II.A.l. It is pointed out there that this conversion might take place by a number of different paths. Laviron explored this question69. He found that the mechanism is CECE in acidic media and ECEC in basic media and ECCE at intermediate pH. 

The mechanism of electrochemical reduction of nitrosobenzene to phenylhydroxylamine in aqueous medium has been examined in the pH range from 0.4 to 13, by polaro-graphic and cyclic voltametry. The two-electron process has been explained in terms of a nine-membered square scheme involving protonations and electron transfer steps565. This process is part of the overall reduction of nitrobenzene to phenylhydroxylamine, shown in reaction 37 (Section VI.B.2). Nitrosobenzene undergoes spontaneous reaction at pH > 13, yielding azoxybenzene471. 

For many processes, how ever, it is necessary to employ a divided cell in which the anode and cathode compartments are separated by a barrier, allowing the diffusion of ions but hindering transfer of reactants and products between compartments. This prevents undesirable side reactions. Good examples of the need for a divided cell are seen in the reduction of nitjobenzenes to phenylhydroxylamines (p. 379) or to anilines (p. 376). In these ca.scs the reduction products are susceptible to oxidation and must be prevented from approaching the anode. The cell compartments can be divided with a porous separator constructed from sintered glass, porous porcelain or a sintered inert polymer such as polypropene or polytetra-... 

Reduction of substituted nitrobenzenes under alkaline conditions, usually with aqueous sodium acetate as electrolyte and a nickel cathode, is the classical method due to Elbs [45] for the formation of azo- and azoxy-compounds. Protons are used in the electrochemical reaction so that the catholyte becomes alkaline and under these conditions, phenylhydroxylamine reacts rapidly with nitrosobenzene to form azoxybenzene. Finely divided copper has long been known to catalyse the reduction of nitrobenzene to aniline in alkaline solution at the expense of azoxybenzene production [46]. Modem work confirms that whereas reduction of nitrobenzene at polycrystalline copper in alkaline solution gives mainly azoxybenzene, if the electrode is pre-oxidised in alkaline solution and then reduced just prior to the addition of nitrobenzene, high yields of aniline are obtained with good current efficiency... 

Ffgure 11.2. Flow celt for conversion of nilrobenzencs to the nitrosobenzene. Both of the porous electrodes are constructed from carbon fibre. They arc fed with constant current as indicated with ib, = 2 i,.. The feedstock containing nitrobenzene is introduced at a rate coiresponding to the current ib for reduction to phenylhydroxylamine. The outflow contains nitrosobenzene, sec ref (62j. 

Nitrosobenzene and phenylhydroxylamine condense rapidly in alkaline solution to give azoxybenzene. During the reduction of nitrobenzenes at high pH, the phenylhydroxylamine scavenges nitroso compound so that the azoxybenzene becomes... 

Fermenting yeast is able to reduce added nitrobenzene to the corresponding amine, aniline, to quite a considerable extent. Part of the added nitrobenzene remains unattacked, but 70% of it could be converted to aniline. Since a direct reduction of the nitro group to the amino group is improbable, Neuberg and Welde tried phytochemical treatment of the possible intermediaries, namely, nitrosobenzene and phenylhydroxylamine on the one hand and azoxybenzene and azobenzene on the other hand. 

It seems remarkable that phenylhydroxylamine in the concentration employed does not noticeably inhibit fermentation and nitrosobenzene causes only a transitory reduction in the rate. 

Since it was observed that absorption ceased after 3.3 atoms of hydrogen were taken up per mole of nitrobenzene, Equation 14 is shown as producing 4 moles of cyanocobaltate(II) per mole of substrate via reaction of the latter with CoH. Since further absorption of hydrogen occurred only upon introduction of alkali, it is implied that an intermediate complex, X, is formed which is not subject to further reaction with CoH but may be decomposed by alkali. The stoichiometry of this equation requires formulation of complex X as [Co(CN)5(C6H5NH)]—3. However, since absorption ceased after two atoms of hydrogen had been absorbed per atom of cobalt present, it is implied that a binuclear complex is formed, perhaps involving phenylhydroxylamine, azobenzene, or some other reduction intermediate. 

The reduction of nitro groups may also be catalyzed by microsomal reductases and gut bacterial enzymes. The reduction passes through several stages to yield the fully reduced primary amine, as illustrated for nitrobenzene (Fig. 4.39). The intermediates are nitrosobenzene and phenylhydroxylamine, which are also reduced in the microsomal system. These intermediates, which may also be produced by the oxidation of aromatic amines (Fig. 4.21), are involved in the toxicity of nitrobenzene to red blood cells after oral administration to rats. The importance of the gut bacterial reductases in this process is illustrated by the drastic reduction in nitrobenzene toxicity in animals devoid of gut bacteria, or when nitrobenzene is given by the intraperitoneal route. 

Nitrosobenzene can be prepared by the oxidation of aniline with permonosulfuric acid 1 or peracetic acid 2 and by the oxidation of /3-phenylhydroxylamine,3 which is prepared by the reduction of nitrobenzene. 

Aniline may be made (I) hy Ihe reduction, with iron or tin in HOI, of nitrobenzene, and (2) by the amination of chlorobenzene by healing with ammonia to a high temperature corresponding to a pressure of over 200 atmospheres in the presence of a catalyst (a mixture of cuprous chloride and oxide). Aniline is the end-point of reduction of most mono-nitrogen substituted benzene nuclei, as nitrosobenzene, beta-phenylhydroxylamine. azoxybenzene, azobenzene, hydrazobenzene. Aniline is detected by the violet coloration produced by a small amount of sodium hypochlorite. 

Compounds related to aniline, either directly or by oxidation, and to nitrobenzene by reduction, are numerous and important. When nitrobenzene is reduced in the presence of hydrochloric acid by tin or iron, the product is aniline (colorless liquid in die presence of water by zinc, the product is phenylhydroxylamine (white solid) in the presence of methyl alcohol by sodium alcoholate 01 by magnesium plus ammonium chloride solution, the product is azoxybenzene (pale yellow solid) by sodium stannitc, or by water plus sodium amalgam, the product is azobcnzcnc (red solid) in the presence of sodium hydroxide solution by zinc, the product is hydrazobenzene (pale yellow solid). The behavior of other nitrocompounds is similar to that of nitrobenzene. 

Azoxybenzene has been prepared by reduction of nitrobenzene with alcoholic potassium hydroxide,1 with sodium amalgam,2 with hydrogen in the presence of lead oxide,3 with methyl alcohol and sodium hydroxide,4 with sodium methylate and methyl alcohol,5 and by electrolytic reduction 6 by oxidation of azobenzene with chromic anhydride 7 by treatment of /9-phenylhydroxylamine with alkaline potassium permanganate,8 with nitrobenzene,9 with mineral adds,10 and with mercury acetamide,11 and by oxidation of aniline with hydrogen peroxide,12 and with acid permanganate solution in the presence of formaldehyde.13 The procedure described above is a slight modification of one described in the literature.14... 

Cupferron has usually been prepared from a mixture of alkyl nitrite and /3-phenylhydroxylamine in the presence of ammonia in ether or benzene solution,6 but it has also been made by the zinc dust reduction of nitrobenzene in the presence of amyl nitrite and ammonium hydroxide solution.7... 

Although phenylhydroxylamine may be prepared by catalytic reduction,1 by the oxidation of aniline,2 and by electrolytic reduction of nitrobenzene,3 the most feasible method is still based upon the original zinc reduction method of Bamberger 4 and of Wohl.5 Various solvents and catalysts have been used in this reduction, and copper-coated and amalgamated zinc, as well as aluminium amalgam,6 have been substituted for zinc dust. The method herein recommended is essentially one previously described 7 but it has been found 8 that cooling is not an essential, as claimed in the patents. The preparation of the oxalate is also a more recent contribution.9... 

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