Meta-directing substituents

A related problem concerns the synthesis of p nitrobenzoic acid Here two meta directing substituents are para to each other This compound has been prepared from toluene according to the procedure shown... 

The Gattermann-Koch synthesis is suitable for the preparation of simple aromatic aldehydes from ben2ene and its substituted derivatives, as well as from polycychc aromatics. The para isomers are produced preferentially. Aromatics with meta-directing substituents cannot be formylated (108). 

Draw resonance structures of cyanobenzene (C H5CN) that show how it functions as a meta-directing substituent. 

In formulas 32-41, methyl and nitro groups have been chosen as typical ortho-para and meta-directing substituents, respectively.)... 

The orienting power of the meta directing substituents is much smaller throughout than that of the Class 1 substituents. This is the reason that, as a rule, ortho and para isomers are formed as byproducts along with the meta compound., ... 

Okamoto, Y., Inukai, T. and Brown, H.C. (1958b). Rates of Solvolysis of Phenyldimethylcarbinyl Chlorides Containing Meta Directing Substituents. JAm.Chem.Soc., 80, 4969-4972. 

The nature of the substituent in a substituted aromatic compound influences the position of hydroxylation. Thus, o-/7-directing substituents, such as amino groups, result in o- and p-hydroxylated metabolites such as the o- and /7-aminophenols from aniline (figure 4.8). Meta-directing substituents such as nitro groups lead to m- and /7-hydroxylated products, for example nitrobenzene is hydroxylated... 

Unsubstituted aromatic compounds (see p. 167) and those with ortho/para-directing (see p. 168) or, above all, meta-directing substituents (see p. 168) in the nucleus can be brominated and iodinated by this method and some analogous chlorinations have also been described.376 The reaction can be run in non-aqueous or in aqueous media it is also often carried out without a solvent. 

RO- and HO-substituted benzenes are halogenated without the Lewis acid. Benzene rings with meta-directing substituents cannot undergo Friedel-Crafts reactions. Aniline and A-substi-tuted anilines also cannot undergo Friedel-Crafts reactions. 

Later, Titov( ) proposed a different reaction scheme in vdiich NO" " reacts with the aromatic to form a nitroso compound which rearranges to a nitrophenol. This mechanism will be discussed later. Bennett and Youle(7,8,9) also found phenolic impurities amounting to about 2% of the yield in the nitration of several different aromatic compounds. They observed that the hydroxyl group enters the aromatic molecule according to the normal orientation rule for the substituent originally present and that the amount of by-products is greater for meta-directing substituents. 

An ortAo,para-directing substituent on a benzene ring directs a second electrophile to positions ortho and para to it on the ring. A meta-directing substituent directs a second electrophile to a position meta to it. 

The influence of meta-directing substituents can he explained using the same kinds of arguments used for ortho and para directors. Look at the nitration of henzaldehyde, for instance (Figure 9.19). Of the three possible carhocation intermediates, the meta intermediate has three favorable resonance forms, while the ortho and para intermediates have only two. In both ortho and para intermediates, the third resonance form is unfavorable because it places the positive charge directly on the carbon that hears the aldehyde group, where it is disfavored by a repulsive interaction with the positively polarized carbon atom of the C=0 group. Hence, the meta intermediate is more favored and is formed faster than the ortho and para intermediates. 

Friedel-Crafts reactions are the slowest of the electrophilic aromatic substitution reactions. Therefore, if a benzene ring has been moderately or strongly deactivated— that is, if it has a meta-directing substituent—it will be too unreactive to undergo either Friedel-Crafts acylation or Friedel-Crafts alkylation. In fact, nitrobenzene is so unreactive that it is often used as a solvent for Friedel-Crafts reactions. 

Benzene rings with meta-directing substituents cannot undergo Friedel-Crafts reactions. 

Another application of diazotization in synthetic strategy is illustrated in the synthesis of 1,3-dibromobenzene (m-dibromobenzene). Direct electrophilic bromination of benzene is not feasible for this purpose after the first bromine has been introduced, the second will attack ortho or para. What is required is a meta-directing substituent that can be transformed eventually into bromine. The nitro group is such a substituent. Double nitration of benzene furnishes 1,3-dinitrobenzene (m-dinitrobenzene). Reduction (Section 16-5) leads to the ben-zenediamine, which is then converted into the dihalo derivative. 

Which of the following is not a meta-directing substituent when present on a benzene ring ... 

Ortho, Para-directing Substituents and Meta-directing Substituents... 

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