Nitration of monosubstituted benzenes

Nitration of monosubstituted benzenes by HNO3 in CH3NO2 or AC2O 0 or 25 -6.22... 

Figs. 3-4. The failure of the Hammett cj-constants for the correlation of log (kjk-g) for (3) the nitration of monosubstituted benzenes—substituents with large resonance interactions are denoted by broken circles and (4) the chlorination of monosubstituted benzenes. 

Isomer Distributions in the Chlorination and Nitration of Monosubstituted Benzenes... 

Tabic II, Relative Amounts of ortho, para, and incta Isomers Formed in the Nitration of Monosubstituted Benzenes... 

A common problem in the manufacture of fine chemicals is that a substrate may have more than one reactive site. A well known, but intractable, problem is the nitration of monosubstituted benzenes, which always leads to a mixture of isomers. Reactions which involve nucleophilic substitution are more amenable to control of regioselectivity by choice of solvent. An excellent review on the reactivity of ambident anions is available, in which this subject is treated [17]. An instructive example is the alkylation of phenol with allyl chloride [18] (equation 12.10). Table 12.13 shows how the properties of O- and C-alkylation are affected by solvent. 

We have discussed orientation in the case of monosubstituted benzenes entirely in terms of attack at the ortho, meta, and para positions, but attack at the position bearing the substituent (called the ipsoposition ) can also be important. Ipso attack has mostly been studied for nitration. When NOj attacks at the ipso position there are at least five possible fates for the resulting arenium ion (13). 

A review of experimental work prompted the suggestion of the importance of dipolar interactions (Hammond and Hawthorne, 1956). de la Mare and Kidd (1959), observing a parallelism in the parajmeta and ortho/meta ratios, predicted the ortho effect to be primarily electronic in origin. Norman and Radda (1961) explored the general significance of this idea. They studied the orthojpara ratios for the substitution of a series of monosubstituted benzenes by two reagents with the same electrophilic properties but different steric requirements. The reactions, nitration by N02+ and chlorination by CI+, fulfill the requirements. The results are summarized in Table 3. 

MO studies of aromatic nitration cast doubt on the existence of jt-complexes and electron-transfer complexes in liquid-phase nitrations.14 The enthalpy of protonation of aromatic substrates provides a very good index of substrate reactivity to nitration. Coulomb interaction between electrophile and substituent can be a special factor influencing regioselectivity. A detailed DFT study of the reaction of toluene with the nitronium ion has been reported.15 Calculated IR spectra for the Wheland intermediates suggest a classical SE2 mechanism. MO calculations of cationic localization energies for the interaction of monosubstituted benzenes with the nitronium ion correlate with observed product yields.16... 

Nitration of monosubstituted aromatics, toluene in particular, has been extensively studied using zeolites in order to direct the reaction towards the formation of the desired para-isomer. Toluene has been nitrated para-selectively with benzoyl nitrate over zeolite catalysts.[14,15] For example, when mordenite is used as a catalyst, MNTs are formed in almost quantitative yields, giving 67 % of the para-isomer in 10 min, but tetrachloromethane is required as solvent. However, the main problems associated with the use of benzoyl nitrate are handling difficulties due to its sensitivity toward decomposition, and the tendency toward detonation upon contact with rough surfaces. Nagy et a/.[19 21] reported the nitration of benzene, chlorobenzene, toluene and o-xylene with benzoyl nitrate in the presence of an amorphous aluminosilicate, as well as with zeolites HY and ZSM-11, in hexane as a... 

In electrophilic aromatic substitution of a monosubstituted benzene, three products are possible the new group may become oriented ortho, meta, or para to the existing group. Table 22.1 shows the orientation of nitration of a series of monosubstituted benzenes. 

Pankratov in 2000 computed relative a-complex energies for nitration, which he referred to as cationic localization energies, for a large number of monosubstituted benzenes by the use of the semiempirical PM3 method [91]. Good linear relationships were found for predicting the positional selectivity from the a-complex energies. However, different scaling factors were needed for the different positions, that is, the ortho, meta, and para positions. 

Nitration of aromatic compounds such as toluene is important for the synthesis of small-molecule precursors for further use in fine chemicals such as dyes, pharmaceuticals, perfumes, plastics, and explosives. Typically, it is the para nitration product of monosubstituted benzene compounds that is the most desirable. The traditional aromatic nitration method that is still widely used today is the homogeneous... 

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... 

Orientation and Rate Data for Nitration of Some Monosubstituted Benzene Derivatives3... 

Using Menke s conditions, Smith et al.[29,30] have described a method for the nitration of benzene, alkylbenzenes and halogenobenzenes using zeolites with different topologies (HBeta, HY, HZSM-5 and HMordenite) as catalysts and a stoichiometric amount of nitric acid and acetic anhydride. The reactions were carried out without solvent at temperatures between -50 °C and 20 °C. For the nitration of toluene, tridirectional zeolites HBeta and HY were the most active catalysts achieving >99 % conversion in 5 min reaction time. However, HY exhibited selectivity to the p-nitrotoluene very similar to the homogeneous phase, while with HBeta, selectivities to p-nitrotoluene higher than 70% could be achieved. HBeta zeolite exhibited excellent para-selectivity for the nitration of the different monosubstituted aromatics (Table 5.1). The catalyst can be recycled and the only by-product, acetic acid, can be separated by vacuum distillation. 

Holleman [55] gives the following data on the composition of the nitration products obtained in the nitration of different monosubstituted benzene derivatives with mixtures of nitric and sulphuric acids (Table 2). As appears from the data shown below, the substituent already present affects the orientation of the group which is being introduced. It is evident that nitration can be influenced by the steric factor. For exampl tert.-butylbenzene is mainly nitrated in para (72.7%) and to a much lesser extent in ortho (15.8%) positions (H. C. Brown and Nelson [88]). 

After our success in nitrating moderately active monosubstituted benzenes with acetic anhydride and nitric acid over zeolite p,11 we decided to try the use of trifluoroacetic anhydride and nitric acid over zeolite p for nitration of deactivated substrates. Although trifluoroacetyl nitrate is known to be more active than acetyl nitrate, it has not been widely used in nitration reactions.15 Nitrobenzene has been successfully nitrated using fuming nitric acid and trifluoroacetic anhydride in equimolar proportions at 45-55 °C.16 However, no dinitration of toluene was reported. 

These authors studied the action of several electrophilic and nucleophilic reagents on unsubstituted 1,2-benzoisoselenazole and found that while electrophiles attack the benzene ring, nucleophiles either substitute the 3-position of the heterocycle or cleave the ring. Thus nitration and bromina-tion led to the formation of monosubstituted derivatives at the 5 and 7 position. Potassium amide, however, gave the 3-amino derivative (5) [Eq. (5)]. 

The relative rates of nitration in the meta or para position of a monosubstituted benzene provide a particularly good example. 

The effect of multiple substituents is usually described in terms of the same resonance (Lewis structure) approaches that are described here for benzene and its monosubstituted derivatives. For a discussion, see Bures, M. G. Roos-Kozel, B. L. Jorgensen, W. L. /. Org. Chem. 1985,107,4490. 180 Perrin, C. /. Am. Chem. Soc. 1977, 99, 5516. Although the conclusions of this paper were questioned (reference 181), there is experimental evidence for the electron transfer pathway in the nitration of naphthalene Johnston, J. F. Ridd, J. H. Sandall, J. P. B. /. Chem. Soc. Chem. Commun. 1989, 244. 

Chlorobenzene and bromobenzene, for example, undergo nitration at a rate approximately 30 times slower than benzene. The relative percentages of monosubstituted products that are obtained when chlorobenzene is chlorinated, brominated, nitrated, or sulfonated are shown in Table 15.1. 

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