Nitration substituted benzene derivatives

When a mono-substituted benzene derivative, C6H5Y, undergoes further electrophilic substitution, e.g. nitration, the incoming substituent may be incorporated at the o-, m- or p-position, and the overall rate at which substitution takes place may be faster or slower than with benzene itself. What is found in practice is that substitution... 

Aromatic nitro compounds are obtained by nitrating appropriately substituted benzene derivatives with nitric acid. This reagent can be employed in a more or less concentrated form and is often used in combination with concentrated sulfu-... 

Benzo[6 jthiophenes with nitro groups at the 4-, 5-, 6- or 7-positions may be synthesized by ring closure reactions of appropriately substituted benzene derivatives. Nitration of 5-acetaminobenzo[6]thiophene gives the 4-nitro derivative, which can be hydrolyzed and deaminated to yield 4-nitrobenzo[6]thiophene (equation 44). 5-Nitrobenzo[6]thiophene is conveniently available by decarboxylation of 5-nitrobenzo[6]thiophene-2-carboxylic acid, which in turn is available by a Perkin reaction of 4-nitro-2-formylphenylthioglycoIic ester (equation 45 Section 3.15.2.3). The 7-nitro isomer may be obtained similarly. 

However, in contrast to benzene, ferrocene is sensitive to oxidation, and the ferrocenium cation, FeCpj, a paramagnetic 17-electron species, is readily formed in the presence of various oxidants. The ferrocenium cation is reluctant to undergo electrophilic substitution, and therefore reactions such as halogenation and nitration, which are important routes to substituted benzene derivatives, cannot be used for the synthesis of substituted ferrocenes. Only electrophilic substitution under nonoxidizing conditions (e.g., Friedel-Crafts acylation, Mannich reaction, borylation, lithiation or mercuration), and radical substitution are available as an entry into the chemistry of substituted ferrocenes. 

Aromatic alcohols (phenols) can be prepared by treatment of a diazonium salt (ArN2 ) with water, acid, and heat. In this substitution reaction, water acts as a nucleophile and replaces the excellent nitrogen leaving group (N2) on the diazonium salt. The diazonium salt is prepared in three steps from benzene (or a substituted benzene derivative, but such compounds will be addressed in a later part of this book). First, nitration of benzene with HNO3 and H2SO4... 

A brief account of aromatic substitution may be usefully given here as it will assist the student in predicting the orientation of disubstituted benzene derivatives produced in the different substitution reactions. For the nitration of nitrobenzene the substance must be heated with a mixture of fuming nitric acid and concentrated sulphuric acid the product is largely ni-dinitrobenzene (about 90 per cent.), accompanied by a little o-dinitrobenzene (about 5 per cent.) which is eliminated in the recrystallisation process. On the other hand phenol can be easily nitrated with dilute nitric acid to yield a mixture of ortho and para nitrophenols. It may be said, therefore, that orientation is meta with the... 

If, on the other hand, the encounter pair were an oriented structure, positional selectivity could be retained for a different reason and in a different quantitative sense. Thus, a monosubstituted benzene derivative in which the substituent was sufficiently powerfully activating would react with the electrophile to give three different encounter pairs two of these would more readily proceed to the substitution products than to the starting materials, whilst the third might more readily break up than go to products. In the limit the first two would be giving substitution at the encounter rate and, in the absence of steric effects, products in the statistical ratio whilst the third would not. If we consider particular cases, there is nothing in the rather inadequate data available to discourage the view that, for example, in the cases of toluene or phenol, which in sulphuric acid are nitrated at or near the encounter rate, the... 

Aniline is an important derivative of benzene that can be made in two steps by nitration to nitrobenzene and either catalytic hydrogenation or acidic metal reduction to aniline. Both steps occur in excellent yield. Almost all nitrobenzene manufactured (97%) is directly converted into aniline. The nitration of benzene with mixed acids is an example of an electrophilic aromatic substitution involving the nitronium ion as the attacking species. The hydrogenation of nitrobenzene has replaced the iron-... 

Like other electrophilic substitutions, nitration of a substituted benzene, where the substituent is electron withdrawing (N02, C02H, CN, and so on Table 22-6), generally produces the 1,3-isomer. To prepare the 1,4-isomer, less direct routes are necessary— the usual strategem being to use benzene derivatives with substituent groups that produce the desired orientation on... 

The production of anthraquinone dyes generally proceeds from a few key products generated by electrophilic substitution of unsubstituted anthraquinone or by synthesis of the nucleus. The major methods employed to prepare anthraquinone derivatives substituted in the a-position are sulfonation and nitration. Preparation of b-substituted anthraquinones and of quinizarin (1,4-dihydroxyan-thraquinone) generally is accomplished by synthesis of the nucleus starting from phthalic anhydride and a benzene derivative. 

During their work on the arylation of aromatic compounds by substitution, Fujiwara, et al. observed biaryl formation when aromatic compounds were placed in the presence of olefin-palladium complexes and silver nitrate.80 Developing this reaction as a method for biphenyl synthesis, these authors showed that the more stable the olefin-palladium complex was, the lower the yield. Ethylene dichloropalladium proved to be the best choice, when used with silver nitrate. However, the reaction required stoichiometric amounts of both catalysts (Scheme 10.47). Benzene derivatives substituted by electron-donating or -withdrawing groups reacted as well, but a mixture of regioisomers was produced, except for nitrobenzene, which only gave m,m -dinitrobiphenyl. 

A number of authors have studied substitution with the nitro group in benzene derivatives containing ortho-para directing substituents, when nitric acid with acetic anhydride was used. The experiments led to the conclusion that replacement of water in the nitrating mixtures by acetic anhydride produces an increase of the ratio of ortho- to para- isomers. 

It is characteristic that the new entrant methyl group assumes the ortho position to the nitro group and thus a substitution occurs which is similar to nucleophilic attack. Recently it has been found by Jackson and Waters [72] that higher nitrated benzene derivatives such as m- dinitrobenzene, or 1,3,5-trinitrobenzene, become homolytic hydrogen acceptors at temperatures of 80-100°C especially in the presence of the 2-cyano-2-propyl radical, which is formed by thermal decomposition of a,a -azo-bis-isobutyronitrile... 

One or two nitro groups can be introduced by the direct nitration of benzene. The introduction of a third can be accomplished only with great difficulty and the yield obtained is relatively poor. For this reason trinitro derivatives of benzene are prepared by indirect methods. Higher nitrated derivatives of benzene-tetra- and hexanitrobenzene-are also known they can be obtained by special methods. Dinitrobenzene is the most important of them as an explosive. It was the most used substitute for trinitrotoluene. 

Notice that the regioselectivity is the same as it was with pyrrole—the 2-position is more reactive than the 3-position in both cases. The product ketones are less reactive towards electrophiles than the starting heterocycles and deactivated furans can even be nitrated with the usual reagents used for benzene derivatives. Notice that reaction has occurred at the 5-position in spite of the presence of the ketone. The preference for 2- and 5-substitution is quite marked. 

These relative rate constants are compared with the figures for nitration (HNO3/AC2O) and phenylation (phenyl radicals) 32). Table 9 gives partial rate factors for substitution with various benzene derivatives. 

Toward electrophilic substitution pyridine resembles a highly deactivated benzene derivative. It undergoes nitration, sulfonation, and halogenation only under very vigorous conditions, and does not undergo the Friedcl-Crafts reaction at all. 

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