Nitrobenzene 3 Substitution products

Aromatic rings can be nitrated by reaction with a mixture of concentrated nitric and sulfuric acids. The electrophile is the nitronium ion, N02+, which is generated from HNO3 by protonation and loss of water. The nitronium ion reacts with benzene to yield a carbocation intermediate, and loss of H+ from this intermediate gives the neutral substitution product, nitrobenzene (Figure 16.4). 

In DMSO as solvent and in the presence of nitrobenzene, aryl-de-diazoniation of the unsubstituted benzenediazonium ion leads mainly via meta substitution to 3-nitrobiphenyl, whereas in the case of the 4-nitrobenzenediazonium ion the formation of o- and -substituted products (2,4 -and 4,4 -dinitrobiphenyl) prevails (Gloor et al., 1972). 

Nitrobenzene reacts with the O-trimethylsilyl ketene acetal 663 in the presence of tris(dimethylamino)sulfur(trimefhylsilyl)difluoride (Me2N)3S(Me3SiF2) (TASF) to give the O-silylated adduct 1007 a, which can be oxidized in situ, e. g. by bromine, to give the 4-substituted nitrobenzene 1008 in an overall yield of 79% [87] (Scheme 7.28). With less hindered ketene-acetals, however, mixtures of ortho- and para-substituted nitrobenzenes are obtained. Yet, on reaction of 4-fluoronitroben-zene with the cyclic O-trimethylsilyl ketene acetal 1009 the ortho-substitution product 1010 is obtained in 79% yield [87]. 

In general, heterocyclic nitro compounds undergo cine substitution reactions more readily than nitrobenzenes. For example, the reaction of 5-acyl- or 5-alkoxycarbonyl-2-nitrofurans with the anion of nitroalkanes gives cine substitution products in excellent yields (Eq. 5.66).104... 

The use of ammonia for the protonation of nitroarenes leads frequently to formation of aduct ions, e.g. [M + NH4]+, but not to the protonated species (MH+)112,113. The ammonia chemical ionization spectrum of nitrobenzene shows, in addition to a series of adduct ions, a dominant signal corresponding to the anilinium ion (m/z 94)112114115. Evidence for the isomerization of the [M + NR ]"1" adduct followed by successive loss of NO and OH or NH3 to give ions corresponding to the substitution products, e.g. the anilinium ion, has been given115 see Scheme 41. 

An attempt to combine electrochemical and micellar-catalytic methods is interesting from the point of view of the mechanism of anode nitration of 1,4-dimethoxybenzene with sodinm nitrite (Laurent et al. 1984). The reaction was performed in a mixture of water in the presence of 2% surface-active compounds of cationic, anionic, or neutral nature. It was established that 1,4-dimethoxy-2-nitrobenzene (the product) was formed only in the region of potentials corresponding to simultaneous electrooxidation of the substrate to the cation-radical and the nitrite ion to the nitrogen dioxide radical (1.5 V versus saturated calomel electrode). At potentials of oxidation of the sole nitrite ion (0.8 V), no nitration was observed. Consequently, radical substitution in the neutral substrate does not take place. Two feasible mechanisms remain for addition to the cation-radical form, as follows ... 

Halogen substituents are ortho, para-directing, and the disposition in m-dichlorobenzene is such that their effects reinforce each other. The major product is 2,4-dichloro-l-nitrobenzene. Substitution at the position between the two chlorines is slow because it is a sterically hindered position. 

Isoxazole rings were annelated onto 5-nitroquinoline and isoquinoline-based o-nitrobenzyl-p-tolylsulfones by treatment with potassium phenoxide, which acted as both base and reductant (Equation (42)) <95H(40)187>. In the cases of quinolines as starting materials, product benzisoxazoles (75) both with and without phenoxy substitution were obtained, but in the case of an isoquinoline starting material no phenoxy-substituted product was generated. The reaction is thought to proceed via a nitrosobenzylsulfone carbanion intermediate, and can be applied to nitronaphthalenes but not to less active nitrobenzenes. 

The reduction scheme sketched by Haber for the reduction of nitrobenzene also holds true for the substitution products of nitrobenzene in so far as the formation of their reduction phases can be coordinated to the same reduction, condensation, or molecular rearrangement processes. But the decisive influ-... 

The driving force presumably lies in the stability of the halide leaving group. Formal replacement of hydride is possible with an appropriate nucleophile. Reaction of nitrobenzene with the anion from chloro-methylphenyl sulfone gives the substitution product in 72% yield as a 1 1 ortho to para mixture. Use of bulkier anions gives exclusively para product. When the para position is substituted, the nucleophile enters ortho. 

Pinnavaia and Fay 432) have found that the zirconium and hafnium species containing the same halogen are isomorphous, but the chloro species are not isomorphous with the bromo species. The monohalogen substitution products M(acac)3X, except for the iodide show no significant dissociation as observed by molecular weight and conductivity experiments. In the case of the iodide in tetrahydrofuran, the ionic species is assumed to be Zr(acac)a+. In the chloro and bromo compounds it appears that the species in solution is the 7-coordinate molecule. The infrared spectra show that all the carboxyl groups are coordinated. The dihalo species in solution are assumed to be 6-coordinate since conductance data in nitrobenzene indicate only 2-5% dissociation. 

Sodium Hydroxide and Methyl Alcohol. On reacting nitrobenzene with methanol and caustic soda, azoxybenzene is the main reduction product formed. Sodium formate is obtained as the oxidation product of the methanol used. Naphthoquinone and its substitution products are promoters of this reaction. ... 

It has been stated that the aromatic compounds differ markedly from the paraffins and the unsaturated hydrocarbons related to ethylene and acetylene. The reactions which take place when benzene and its derivatives are treated with nitric acid, sulphuric acid, or oxidizing agents are characteristic of this group of compounds. Only the higher paraffins react with nitric acid, and in the case of these compounds reaction results to but a slight degree and only after heating for many hours (26). The aromatic hydrocarbons and their substitution-products form well characterized compounds when treated with nitric acid. When benzene is warmed with concentrated nitric acid nitrobenzene is formed —... 

Trichloro-2-thienyllithium prepared from tetrachlorothiophene by lithium-chlorine exchange (Bu"Li) reacted with aldehydes and ketones to generate carbinols. Treatment of the (2-hydroxymethyl) trichlorothiophene (406) with catalytic TsOH in refluxing benzene gave the electrophilic substitution product (407). Replacement of benzene with nitrobenzene as solvent led to... 

Figure 4. Effect of water on nitrobenzene conversion and reaction selectivity. Selectivity is defined as the ratio of para substituted products to ortho substituted products.

Because it is aromatic, benzene does not react directly with reagents such as HBr or HCl, or even with diatomic bromine or chlorine. Benzene reacts with cationic species to ve a resonance-stabilized carbocation intermediate, which loses a hydrogen to give a substitution product. This reaction is called electrophilic aromatic substitution. The most common method for generating reactive cations in the presence of benzene is to treat certain reagents with strong Lewis acids. Lewis acids or mixtures of strong acids can be used to convert benzene to chlorobenzene, bromobenzene, nitrobenzene, or benzenesulfonic acid. 

Diphenylamines may be prepared by nitro group displacement from o- or p-dinitrobenzenes or from cyano-substituted nitrobenzenes. Thus, reaction with acidic anilines containing electron-withdrawing substituents in DMSO in the presence of potassium carbonate yields [234] products such as (88). Orf/jo-dinitrobenzene will also react with tervalent phosphorus compounds, such as trialkylphosphites, in acetonitrile to give substituted products (89) is formed from trieth-ylphosphite [235]. 

PROBLEM 14.71 When l,2-dichloro-4-nitrobenzene is treated with an excess of sodium methoxide, three different substitution products (two monosubstituted, one disubstituted) could, in principle, be formed. In fact, only a single product is obtained. 

The nitrobenzene produced is a yellow, oily substance. The reaction is carried out at a temperature between 45 °C and 55 °C. Restricting the temperature to below 55 °C helps to minimize the formation of multi-substitution products such as di- or tri-nitrobenzene. 

---