Aromatic Compounds with Nitro Substituents

PART 5 AROMATIC COMPOUNDS WITH NITRO SUBSTITUENTS 

These are readily produced by nitration of aromatic compounds and are important explosives. The amines formed by reduction are able to undergo a nnmber of reactions, and have a wide range of application in the production of agrochemicals, dyestnffs, and pharmaceuticals. 

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A wide range of mechanisms are involved in the degradation and transformation of aromatic compounds with nitro substituents. These include reduction of the nitro group, and dioxygenation, monooxygenation, and reduction of the aromatic ring. A review devoted to 2,4,6-trinitrotolune is available (Esteve-Nunez et al. 2001). 

Musk ambrette (4), a synthetic musk, essential in perfumes to enhance and retain the odour, is an aromatic compound with five substituents on the benzene ring. The nitro groups are by far the most electron-withdrawing so we can disconnect them first. 

A wide variety of aromatic, heterocyclic, and aliphatic compounds with nitro substituents has achieved medicinal utility [458]. Certain 5-nitropyri-midines and their nitroso counterparts deserve mention as compounds of chemotherapeutic interest. Some of these have already been discussed in preceding sections, including 5-nitrouracil, 5-nitrocytosines and isocytosines and 5-nitrohydropyrimidines. 

Manufacture of many important amino intermediates used for dyes and other purposes is usually by conversion or replacement of a substituent. For example, as already mentioned, in substituted nitro compounds, the nitro groups may be reduced with iron/hydrochloric acid, hydrogen and catalyst, or zinc in aqueous alkali. Partial reductions can be brought about with sodium sulfide. Amino groups may be introduced by replacing halogens in the aromatic ring. Another approach to amination is by attack on a substituted aromatic compound with ammonia or amines. Thus, for example, direct amination of p-chloronitrobenzene (15a) in the presence of a copper catalyst affords p-nitroaniline (15b) in almost quantitative yield l,4-dichloro-2-nitrobenzene (16) is converted in a similar way to 4-chloro-2-nitroaniline (17). Reactions of ammonia with carboxylic acids or anhydrides are carried out on an industrial scale. 

By carefully combining electrophilic and nucleophilic substitution it is possible to make aromatic compounds with substituents arranged in a precise and predictable fashion. So, if we nitrate o-dichlorobenzene, all positions are favourable but the nitro group goes in para to one Cl atom because of steric hindrance at the ortho positions. Although chlorine is small, two chlorines next to each other have a butressing effect as each pushes the other away. It is difficult to get three adjacent substituents on a benzene ring. If we now do a nucleophilic... 

Various substituted styrenes also anionically polymerize readily. These include methyl, methoxy, dimethylamino, t- butyl and other groups which are electron donating to the benzene ring and do not themselves react with carbanion centers. Substituents such as chloro or nitro can be anionically polymerized only at imder very carefolly controlled conditions. 2,3, or 4 vinylpyridine can also be anionically polymerized. Any aromatic or condensed aromatic compounds with a vinyl substituent is potentially anionically polymerizable, or co polymerizable with any other anionically polymerizable monomer. 

Recently, based on this opportunity, dodecaborate-containing donor-acceptor compounds with nitro-, perfluorophenyl-, and o-carborane as acceptors (Figure 13.17) could be achieved by palladium-catalyzed coupling reactions (Voge, dissatation 2009). Papagni et al. (2002) prepared pentafluoro stilbenes with dimethyl- and diphenylamino substituents as electron donors. They demonstrated that in these push-pnU compounds the incorporated perflnorinated aromatic system serves as an inductive electron-withdrawing acceptor and hence this perflnoro stilbene seemed to be a possibility of a connection with the dodecaborate (Figure 13.17). 

Under these first-order conditions the rates of nitration of a number of compounds with acetyl nitrate in acetic anhydride have been determined. The data show that the rates of nitration of compounds bearing activating substituents reach a limit by analogy with the similar phenomenon shown in nitration in aqueous sulphuric and perchloric acids ( 2.5) and in solutions of nitric acid in sulpholan and nitro-methane ( 3.3), this limit has been taken to be the rate of encounter of the nitrating entity with the aromatic molecule. 

The most common types of aryl halides m nucleophilic aromatic substitutions are those that bear o ox p nitro substituents Among other classes of reactive aryl halides a few merit special consideration One class includes highly fluormated aromatic compounds such as hexafluorobenzene which undergoes substitution of one of its fluorines on reac tion with nucleophiles such as sodium methoxide... 

A mechanism of this type permits substitution of certain aromatic and ahphatic nitro compounds by a variety of nucleophiles. These reactions were discovered as the result of efforts to explain the mechanistic basis for high-yield carbon alkylation of the 2-nitropropane anion by p-nitrobenzyl chloride. p-Nitrobenzyl bromide and iodide and benzyl halides that do not contain a nitro substituent give mainly the unstable oxygen alkylation product with this ambident anion ... 

A wide variety of aromatic compounds can be brominated. Highly reactive ones, such as anilines and phenols, may undergo bromination at all activated positions. More selective reagents such as pyridinium bromide perbromide or tetraalkylammonium tribromides can be used in such cases.18 Moderately reactive compounds such as anilides, haloaromatics, and hydrocarbons can be readily brominated and the usual directing effects control the regiochemistry. Use of Lewis acid catalysts permits bromination of rings with deactivating substituents, such as nitro and cyano. 

With the nitro group successfully introduced, the aromatic fluoride substituent in 11 was ready to undergo the nucleophilic aromatic substitution with the hydrox-ypyridine 9. The reaction proceeded smoothly in DMF at 55 °C using an equimolar amount of cesium carbonate as the base and provided a 90% isolated yield of 23 after crystallization. With compound 23 in hand, only the reduction of the nitro... 

The traditional technique of reducing nitro compounds with iron powder in dilute acid (Bechamps-Brimmeyr reduction) continues to be used for nitro compounds that are adversely affected by the catalytic reduction method with hydrogen. The list of examples includes aromatic nitro compounds carrying halogen substituents, especially if these are attached in ortho or para position to the nitro group. The solution containing only a small amount of acid (such as acetic acid) is almost neutral and allows iron to precipitate as Fe304. 

Substituted aromatic nitro compounds having a substituent with a positive Hammett sigma constant can be reduced with potassium borohydride to the azoxy stage. 

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