Electrophilic aromatic substitution nitro group

The functional group transformations are derived from either electrophilic aromatic substitution or nucleophilic aromatic substitution reactions. The electrophilic aromatic substitution functional group transform is shown with a simple X group, where X is chlorine, bromine, nitro, or sulfonyl. The reagents are different, but the basic principle for the formation of such compounds is the same. 

A nitro group behaves the same way m both reactions it attracts electrons Reaction is retarded when electrons flow from the aromatic ring to the attacking species (electrophilic aromatic substitution) Reaction is facilitated when electrons flow from the attacking species to the aromatic ring (nucleophilic aromatic substitution) By being aware of the connection between reactivity and substituent effects you will sharpen your appreciation of how chemical reactions occur... 

The reaction exhibits other characteristics typical of an electrophilic aromatic substitution. Examples of electrophiles that can effect substitution for silicon include protons and the halogens, as well as acyl, nitro, and sulfonyl groups. The feet that these reactions occur very rapidly has made them attractive for situations where substitution must be done under very mild conditions. ... 

Trifluoromethyl)benzene (benzotrifluoride, 15) was the first organic fluoride to incorporate a trifluoromethyl group. By a standard nitration process, it formed l-nitro-3-(trifluoromethyl)-benzene (16) which was reduced to the 1-amino derivative, 17. This we a-directive influence on electrophilic aromatic substitution contrasted with that for fluorobenzene, which gave 4-and 2-nitro products. 

Exercise 22-24 Draw the structures of the intermediate cations for nitration of nitrobenzene in the 2, 3, and 4 positions. Use the structures to explain why the nitro group is meta-orienting with deactivation. Use the same kind of arguments to explain the orientation observed with —CF3, —CHO, —CH2Ci, and —NH2 groups in electrophilic aromatic substitution (Table 22-6),... 

Two of three nitrofluorobenzene isomers react with methoxide, but the third is unreactive. Obtain energies of methoxide anion (at left), ortho, meta and para-nitrofluorobenzene, and the corresponding ortho, meta and para-methoxide anion adducts (so-called Meisenheimer complexes). Calculate the energy of methoxide addition to each of the three substrates. Which substrate is probably unreactive What is the apparent directing effect of a nitro group Does a nitro group have the same effect on nucleophilic aromatic substitution that it has on electrophilic aromatic substitution (see Chapter 13, Problem 4) Examine the structures and electrostatic potential maps of the Meisenheimer complexes. Use resonance arguments to rationalize what you observe. 

Electrophilic aromatic substitution leads to replacement of one of the hydrogens directly attached to the ring by the electrophile. All four of the ring hydrogens of p-xylene are equivalent so it does not matter which one is replaced by the nitro group. 

The isopropyl group is ortho, para-directing, and the nitro group is meta-directing. In this case their orientation effects reinforce each other. Electrophilic aromatic substitution takes place ... 

The situation is more complicated if there is more than one substituent on the benzene ring. However, it is usually possible to predict the major products that are formed in an electrophilic aromatic substitution reaction. When the substituents direct to the same position, the prediction is straightforward. For example, consider the case of 2-nitrotoluene. The methyl group directs to the positions ortho and para to itself—that is, to positions 4 and 6. The nitro group directs to positions meta to itself—that is, also to positions 4 and 6. When the reaction is run, the products are found to be almost entirely 2,4-dinitrotoluene and 2,6-dinitrotoluene, as expected ... 

We have already described how nitration leads eventually to aromatic amines by reduction of the nitro group. In the next chapter you will meet the further development of these amines into diazoni-um salts as reagents for nucleophilic aromatic substitution by the S l mechanism with loss of nitrogen. In this chapter we need to address their potential for electrophilic aromatic substitution without the loss of nitrogen as this leads to the important azo dyes. Treatment of the amine with nitrous acid (H0N=0) at around 0°C gives the diazonium salt. 

Since the nitro group is usually introduced by electrophilic aromatic substitution (Chapter 22) and halides direct ortho/para in nitration reactions, a common sequence is nitration followed by nucleophilic substitution. 

Thyroxine has two aromatic rings, and you should be prepared to draw upon what you learned about aromatic chemistry in Chapters 22 and 23. It is also an amino acid and, in order to make the synthesis as cheap as possible, the chemists at Glaxo who developed the method used the amino acid tyrosine as a starting material. Nitration of tyrosine puts two nitro groups ortho to the OH group in an electrophilic aromatic substitution (make sure that you understand why ). 

With 2-substituted benzo[7]furans, the regioselective electrophilic aromatic substitutions of formyl and nitro groups to C-3 of 2-aryl-7-methoxy-2-phenylbenzo[ ]furans were achieved (Equation 62). Further synthetic transformations of the resulting formyl group into methyl, hydroxymethyl, 1-hydroxyethyl, and cyano groups were also reported <1992JOC7248>. 

Hitherto we have concentrated on electrophilic aromatic substitution. However, certain n-deficient aromatic rings are deactivated towards electrophilic attack but are susceptible to nucleophilic addition and a subsequent elimination. A particular example is 2,4-dinitrochloroben-zene. The electron-withdrawing nitro groups facilitate a Michael-type addition of a nucleophile to give a so-called Meisenheimer intermediate (Scheme 4.8). Collapse of the Meisenheimer intermediate and reversion to the aromatic system may lead to expulsion of the halide ion, as exemplified by the preparation of 2,4-dinitrophenylhydrazine. 2,4-Dinitrofluorobenzene is known as Sanger s reagent and is used for the detection of the N-terminal amino acids in peptides. 

The aromatic nitro group is a deactivating substituent as far as electrophilic aromatic substitution is concerned. Further electrophilic substitution requires vigorous conditions and takes place at the least deactivated position. Thus the preparation of 2,4,6-trinitrotoluene (TNT) from 4-nitrotoluene requires fuming nitric acid and fuming sulfuric acids. Nitrobenzene is sufficiently unreactive towards electrophilic substitution to be used as a solvent for the Friedel-Crafts alkylation of more reactive aromatic systems. 

To determine why a nitro group (NO2) directs electrophilic aromatic substitution to the meta position, follow the same procedure. 

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