Nitrobenzene, aniline from synthesis

Despite the availability of methods for extracting aniline from coal tar, this source hardly provided an abundant supply of the aromatic amine. Some chemists worked on the development of the two-step synthesis from coal-tar benzene. They included Hofmann s assistant Charles Blachford Mansfield, who pioneered the separation by distillation of coal-tar hydrocarbons, undertook nitration of benzene, and reduction of the nitrobenzene, probably by the method of Zinin. Mansfield s experiments came to an abrupt end early in 1855 when, while preparing samples for the Paris International Exhibition, a still in his laboratory caught fire. He was badly burned and died in hospital a few days later. 

Desulfurization of petroleum feedstock (FBR), catalytic cracking (MBR or FI BR), hydrodewaxing (FBR), steam reforming of methane or naphtha (FBR), water-gas shift (CO conversion) reaction (FBR-A), ammonia synthesis (FBR-A), methanol from synthesis gas (FBR), oxidation of sulfur dioxide (FBR-A), isomerization of xylenes (FBR-A), catalytic reforming of naphtha (FBR-A), reduction of nitrobenzene to aniline (FBR), butadiene from n-butanes (FBR-A), ethylbenzene by alkylation of benzene (FBR), dehydrogenation of ethylbenzene to styrene (FBR), methyl ethyl ketone from sec-butyl alcohol (by dehydrogenation) (FBR), formaldehyde from methanol (FBR), disproportionation of toluene (FBR-A), dehydration of ethanol (FBR-A), dimethylaniline from aniline and methanol (FBR), vinyl chloride from acetone (FBR), vinyl acetate from acetylene and acetic acid (FBR), phosgene from carbon monoxide (FBR), dichloroethane by oxichlorination of ethylene (FBR), oxidation of ethylene to ethylene oxide (FBR), oxidation of benzene to maleic anhydride (FBR), oxidation of toluene to benzaldehyde (FBR), phthalic anhydride from o-xylene (FBR), furane from butadiene (FBR), acrylonitrile by ammoxidation of propylene (FI BR)... 

Fig. 7.3 Aniline chemical synthesis, (a) nitrobenzene, prepared from benzene with nitric acid by electrophUic substitution reaction and further treatment with niquel at 600 °C or (b) from chlorobenzene by heating with ammonia in the presence of a copper catalyst...

Kim KD, Lee SM, Cho NS, Oh JS, Lee CW, Lee JS (1992) Palladium-catalyzed N,AT-diphenylurea synthesis from nitrobenzene, aniline, and carbon monoxide. Part 3. Evidence of carbamoyl intermediate. J Mol Catal 75(1) L1-L6... 

Many substituted quinolines are intermediates for antimalarials. The 2,4-di-substituted quinolines are produced from aniline and 1,3-diketones by the Combes quinoline synthesis (28). The reaction of aniline with nitrobenzene in the presence of dry sodium hydroxide at 140°C leads to formation of phenazine [92-82-0] and by-products (Wohl-Aue synthesis) (29). 

W 0 H L - A U E Phenazine synthesis Synthesis of phenazine N-oxide from anilines and nitrobenzene... 

Figure 5.12 In this one-pot multistep synthesis, benzyl alcohol is first oxidized to benzaldehyde in a hydrogen-purged autoclave at 1 bar H2. On raising the H2 pressure to 13 bar, nitrobenzene is reduced to aniline which rapidly reacts with the aldehyde to form the Schiff base 5 in 91% yield. (Reproduced from ref. 24, with permission.)...

An alternate and more controlled approach to the synthesis of phenothiazines involves sequential aromatic nucleophilic displacement reactions. This alternate scheme avoids the formation of the isomeric products that are sometimes observed to form from the sulfuration reaction when using substituted aryl rings. The first step in this sequence consists of the displacement of the activated chlorine in nitrobenzene (30-1) by the salt from orf/io-bromothiophenol (30-2) to give the thioether (30-3). The nitro group is then reduced to form aniline (30-4). Heating that compound in a solvent such as DMF leads to the internal displacement of bromine by amino nitrogen and the formation of the chlorophenothiazine (30-4). Alkylation of the anion from that intermediate with 3-chloro-l-dimethylaminopropane affords chlorpromazine (30-5) [31]. 

The use of a fixed-bed cell with Cu particles as the cathode 576 has been suggested for the synthesis. p-Aminophenol, produced by electrochemical reduction of nitrobenzene, was used for the synthesis of hydroquinone 577). According to recent work, the addition of emulsifiers, for example, trialkylamine oxides 578), is supposed to suppress the formation of aniline as a byproduct. The electrosynthesis of p-amino-phenol from nitrobenzene is carried out industrially in India 276). 

Dipheny[amine (7) is prepared industrially either by heating aniline with aniline hydrochloride at 140 °C under pressure, or by heating aniline with phenol at 260 °C in the presence of zinc chloride. The most convenient laboratory synthesis uses the Ullmann reaction (Scheme 8.9) (see Chapter 10), in which acetanilide is refluxed with bromobenzene in the presence of potassium carbonate and copper powder in nitrobenzene solvent. Triphenylamine is similarly prepared from diphenylamine and iodobenzene. 

Suggest a synthesis of the following compounds from the indicated starting material (a) l,.T5-lrichlorobenzene from aniline (b) 4-ch orobenzoic acid from aniline (c) l-chloro-4-nitrobenzene from aniline (d) 1-bromo-3-fluorobenzene from benzene (e) 3-chloroac-etanilide from benzene. 

Perhaps the most generally useful method for preparing substituted quinolines is the Skraup synthesis. In the simplest example, quinoline itself is obtained from the reaction of aniline with glycerol, concentrated sulfuric acid, nitrobenzene, and ferrous sulfate. 

This dyestuff is prepared by heating -nitroalizarin with glycerine and sulphuric acid. It is peculiar in so far that it possesses the lake-forming properties characteristic of the alizarin dyes, and is at the same time a weak base. Alizarin blue was discovered by Prud homme [28], and the determination of its constitution by Graebe [29] led to the synthesis of quinoline by Skraup from glycerine, nitrobenzene, and aniline. 

The synthesis of aminobenzenes from reduction of nitrobenzenes was beyond any doubt a pivotal discovery, and the original preparation of aniline by Nikolai Zinin is still kept in the Museum of Kazan School of Chemistry (Russia) http //www.kazan.ru/tat ru/universitet/ museums/chmku/eng/s2.php... 

The electrochemical reduction of nitrobenzene is believed to be operating commercially in India where aniline is the required product, and in Japan where 4-aminophenol is the desired product.The latter process relies on the in situ rearrangement of phenylhydroxylamine, the conditions of electrolysis being selected to maximize the production of this intermediate in the process. Also at BASF it is believed that a pilot plant synthesis of 4-anisidine from nitrobenzene is being operated. This process relies not only on in situ rearrangement of phenylhydroxylamine but also on in situ methylation of... 

This reaction was initially reported by Doebner and von Miller in 1881 as a modification of the original Skraup Reaction, and it was subsequently modified by Beyer in 1886 It is an acidic condensation between primary aromatic amines (e.g., anilines) and Q ,j8-unsaturated carbonyl compounds (mostly o ,y3-unsaturated aldehydes) to give 2,3-disubstituted quinolines. Therefore, this reaction is generally known as the Doebner-Miller reaction, or Doebner-Miller synthesis." In addition, this reaction is also referred to as the Doebner-von Miller quinoline synthesis, Skraup-Doebner-von Miller reaction, Skraup-Doebner-von Miller quinoline synthesis, Doebner-Miller condensation, and Doebner-Miller Quinaldine Synthesis. For comparison, the modification from Beyer, known as the Beyer method for quinoline, is an acidic condensation between anilines and Q ,j8-unsaturated carbonyl compounds generated in situ from aldehyde or aldehyde and methyl ketone to afford 2,4-disubstituted quinolines." The optimal condition of this reaction is to heat the mixture of aniline/aldehyde (1 2) at 100°C for 6 h with hydrochloric acid and zinc chloride in addition, an oxidizing reagent is also needed in this reaction, such as nitrobenzene. However, it has been reported that A -alkylanilines are also formed in this reaction. The nature and... 

This two-step process is analogous to, but much more efficient than, the classic Wohl-Aue synthesis of phenazines [233]. The versatility of this approach has been demonstrated by the synthesis of 1-methoxyphenazine that can be obtained from two different pairs nitroarene-aniline , namely, nitrobenzene-wta-anisidine or weta-nitroanisole-aniline (Scheme 98) [84]. 

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