Nitration, Reduction, and Diazotization

Nitration of polystyrene was originally carried out a long time ago. A nitrating mixture of nitric and sulfuric acids dissolves the polymer and a nitro derivative forms at 50 °C within three hours  

The reaction is accompanied by a loss of molecular weight. Nitration of isotactic polystyrene yields a more crystalline product (about 1.6 N02/ring) than the parent compound. Here too, however, a loss in molecular weight accompanies the reaction. Polystyrene can be nitrated under mild conditions using acetyl nitrate. The product contains approximately 0.6 nitro groups per each benzene ring.  

The nitro groups of polynitrostyrene are reduced by phenyl hydrazine that acts as a hydrogen 

Polyaminostyrene can undergo typical reactions of aromatic amines, such as diazotization. The diazonium salt decomposes with ferrous ions to yield polymeric free-radicals  

Functional polystyrene derivatives are starting materials for further reactions in many multistep 

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Subs tituted-1,2,3-oxadiazolo[4,5-/]quinoline 47 originated after nitration, reduction, and diazotization of alkaloid quinine during the study of its stmcture and reactions (53RZC495, 54RZC61). 

Some time ago Tedder (1957) recommended a process which he called direct introduction of the diazonium group , because it replaces the steps of nitration, reduction, and diazotization of an aromatic compound by a one-pot operation with three equivalents of a nitrosating reagent in acidic solution. The first step (Scheme 2-35) is a C-nitrosation and the following steps (Scheme 2-36) are the reduction of the nitroso-arene. 

The phenol we desire may itself be synthesized from a diazonium salt which was made in the typical sequence of nitration, reduction and diazotization. The diazotizing agent, nitrous acid, was generated from sodium nitrite and a protic acid. 

Recently, layer-by-layer assemblies of polystyrene-based diazonium salt (DPS) and sulfonated reduced graphene oxide (SRGrO) were deposited on quartz, silicon, and ITO substrates [300]. The DPS was prepared from polystyrene (PS) through nitration, reduction, and diazotization reaction, whereas SRGrO was prereduced with NaBH4, modified with diazonium salt of sulfanilic acid, and reduced by hydrazine. Besides a spontaneous reaction between DPS and SRGrO, the... 

The plant required for the manufacture of dyes usually depends on unit processes. The unit processes such as nitration, sulfonation, reduction, and diazotization are treated extensively in the textbooks of organic chemistry and will not be included here. The general operation sequences in dye and intermediate manufacture are shown in Fig. 8.1. 

The key to the synthesis is the introduction of a group that is a much stronger ortho,para director than —CH3, and that can be easily removed after it has done its job of directing bromine to the correct position. Such a group is the —NHCOCH3 group it is introduced into the para position of toluene via nitration, reduction, and acetylation it is readily removed by hydrolysis, diazotization, and reduction. 

Table 2 summarizes some of the transformations of substituents which have been carried out on azetidines without effect on the ring <79CRV33l). Other transformations of interest are the base catalyzed epimerization, H exchange and alkylation of the activated H-3 in azetidines (26) (69JHC153) and the nitration, reduction, diazotization and hence further modification of the aromatic ring in 3-phenyl-fV-acetylazetidine (27) (61LA 647)83). 

Many different nucleophiles—halide, hydride, cyanide, and hydroxide among others—react with arenediazonium salts, yielding many different kinds of substituted benzenes. The overall sequence of (1) nitration, (2) reduction, (3) diazotization, and (4) nucleophilic substitution is perhaps the single most versatile method of aromatic substitution. 

Fig. 21 Reaction scheme for the detection of aromatics, by means of the reaction sequence, nitration, reduction, diazotization and coupling to an azo dye, and of aliphatic nitro compounds by detection of the primary amino group produced on reduction.

Figure 19.22 Phenolic compounds may be derivatized to contain reactive diazonium groups by nitration with tetranitromethane followed by reduction with sodium dithionite and diazotization with sodium nitrite in dilute HCI.

A colorimetric procedure for phenytoin developed by Dill et al24f provided the first reliable means for determining blood and tissue levels of this drug. The procedure involves quantitative nitration, reduction of the nitro group to a primary amine, diazotization and coupling with the Bratton-Marshall reagent. 

Alternative methods for the formation of the catechol (5) were examined, and these serve to show other methods for introduction of the hydroxy group. Nitration of triene (6) followed by reduction to the amine and diazotization in the presence of methanol gave the phenol (8), but only in poor yield. The best method developed appears to be acetylation of the triene (6) with titanium tetrachloride/acetyl chloride to give the ketone (9), followed by Baeyer-Villiger oxidation to die acetate (10), which on hydrolysis afforded the catechol (8) in 70% overall yield. 

The synthesis of quinones from arenes is an area which demands further research, despite the number of reagents presently available for this transformation. This is highlighted by the synthesis of the naphthoquinone (3). Direct oxidation of the dibromoarene (1) was unsatisfactory, and therefore Bruce and coworkers had to resort to a multistep sequence involving nitration, reduction, diazotization, displacement by hydroxide and finally oxidation of the phenol (2) with Fremy s salt (Scheme 1). Although there are examples of the oxidation of polynuclear aromatic hydrocarbons to quinones, the direct oxidation of an arene to a quinone is a process not encountered in the synthesis of more complex mt ecules. 

Miyake and co-workers (40) have published a synthesis of ellipticine that features a novel reductive phenylation of nitroarenes (41) (Scheme 4). Nitration of 5,8-dimethyl-l, 2,3,4-tetrahydroisoquinoline (22) gave an inseparable mixture of nitro compounds 23. Treatment of this mixture with iron pentacarbonyl and triflic acid in the presence of benzene gave a 2 1 mixture of amines 24 and 25. Separation of these isomers and diazotization of each with nitrous acid, conversion to the azide, and thermolysis yielded ellipticine (1) and isoellipticine (27) (5,11-dimethyl-10f/-pyrido[3,4- )]carbazole), respectively, following Pd/C dehydrogenation of the initially formed nitrene insertion product (e.g., 26). The overall yield of ellipticine is 9%. 

The manufacture of a dye from primary raw materials involves a number of prior synthetic stages and transformations, commonly referred to as unit processes. Such processes include nitration, sulfona-tion, diazotization, oxidation, reduction, chlorination, and others. The products, precursors of the dyes themselves, are collectively known as intermediates. Intermediates are produced by a variety of reactions. Many dye intermediates are manufactured by repeated, and often difficult, chemical reactions to obtain the desired product. Such conversion may be exemplified by the manufacture of a relatively simple intermediate, for example, N,-N-diabenzylaniline disulfonic acid. This conversion requires a number of unit processes, namely the nitration of benzene, the reduction of nitrobenzene, to give aniline, the alkylation of aniline leading to N,N-dibenzylaniline the sulfonation of which gives, finally, the disulfonic acid [11]. 

Schnider and Grtissner in the same way prepared 3- and 2- (or 4) hydroxy-N-methylmorphinane, obtained the same compounds from N-methylmorphinane by way of the nitro and amino compounds, and also synthesized the 3-hydroxy-derivative from [liv] by nitration, reduction, diazotization, c., followed by cyclization [25]. They have more recently resolved [lxxih] and prepared 3-hydroxy-N-allyl-morphinane [26], Schnider and Hellerbach [27] prepared an isomer of [lxxiii] and also synthesized dZ-tetrahydrodesoxycodeine [lxxv] by the cyclization of [lxxvi], in which reaction a small amount of 2 3-dihy-droxy-N-methylmorphinane [lxxvii], isomeric with dZ-tetrahydrodes-oxymorphine, was also obtained. Both [lxxhi] and [lxxvii] exhibit marked analgesic properties to about the same extent, whilst the 2- (or 4) hydroxy-compound is much less active [25, 27]. 

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