Why does nitration occur in the meta position

So this oxygen has a negative 1 formal charge and this nitrogen has a plus 1 formal charge like that. So over here we have our other nitro group in the ortho position. We have pi electrons here, and we just moved some pi electrons over to this position. So let's go ahead and highlight those too.

So over here in red, these pi electrons have moved over to here, taking a bond away from this top carbon here. So that's where our plus 1 charge goes now. So we have a plus 1 formal charge on this top carbon here.

And this is a destabilizing resonance structure. And we know that because we have a positive 1 formal charge on this nitrogen and a positive 1 formal charge on this carbon on our ring. And so like charges repel, and therefore destabilize this resonance structure, So we have a destabilizing resonance structure.

But one of those resonance structures is destabilizing, which means that this sigma complex is not very likely to form. So let's go ahead and look at a meta attack. And you'll see that we will not have a destabilizing resonance structure when we do a meta attack. So let's go ahead and once again show our nitrobenzene and our nitronium ion. And this time we will do a meta attack. So if I want to show a nitro group adding onto the meta position I would once again use these pi electrons.

So nucleophilic attack pushes these electrons off. And so we're going to once again show the resulting carbocation. So we have a nitro group right here. And this time we're showing the nitro group adding on meta. And once again there's a hydrogen attached to our ring. And these pi electrons here are forming the bonds between this carbon and our nitrogen, taking a bond away from this carbon.

So that carbon gets a plus 1 formal charge. And we still have, of course, pi electrons in our ring. And so that's our first resonance structure. We can draw another one.

I could take these pi electrons and move them over to here. So let's go ahead and show the next resonance structure with our ring. Our nitro group here, our nitro group in the meta position, and hydrogen also attached to that carbon. Pi electrons here, and pi electrons have moved over to here. So let me highlight those. So these pi electrons have moved over to here, taking a bond away from this carbon. So we get a plus 1 formal charge here. We can draw another resonance structure taking these pi electrons and moving them over to here.

So let's go ahead and do that. We have our ring once again. We have a nitro group in the top carbon. We have a nitro group in the meta position. Once again, we have hydrogen, we have these pi electrons, and we now have moved the pi electrons over to here, so let me highlight those.

So in red, these pi electrons have moved over to this position, taking a bond away from this carbon. So we get a plus 1 formal charge on that carbon. And so these are the three resonance structures that show up for a meta attack. And notice, we don't have a destabilizing one. So in our three resonance structures, none of them have the two positive charges right next to each other as we saw in the previous example.

So it's not so much that the sigma complex for a meta attack is extra stable. It's just that the sigma complex for a meta attack doesn't have any destabilizing like charges repelling each other. A two-step mechanism has been proposed for these electrophilic substitution reactions. In the first, slow or rate-determining, step the electrophile forms a sigma-bond to the benzene ring, generating a positively charged benzenonium intermediate. In the second, fast step, a proton is removed from this intermediate, yielding a substituted benzene ring.

The following four-part illustration shows this mechanism for the bromination reaction. Also, an animated diagram may be viewed. These may be viewed repeatedly by continued clicking of the "Next Slide" button. This mechanism for electrophilic aromatic substitution should be considered in context with other mechanisms involving carbocation intermediates. To summarize, when carbocation intermediates are formed one can expect them to react further by one or more of the following modes:.

The cation may bond to a nucleophile to give a substitution or addition product. The cation may transfer a proton to a base, giving a double bond product. The cation may rearrange to a more stable carbocation, and then react by mode 1 or 2. S N 1 and E1 reactions are respective examples of the first two modes of reaction. The second step of alkene addition reactions proceeds by the first mode, and any of these three reactions may exhibit molecular rearrangement if an initial unstable carbocation is formed.

The carbocation intermediate in electrophilic aromatic substitution the benzenonium ion is stabilized by charge delocalization resonance so it is not subject to rearrangement. In principle it could react by either mode 1 or 2, but the energetic advantage of reforming an aromatic ring leads to exclusive reaction by mode 2 ie.

When substituted benzene compounds undergo electrophilic substitution reactions of the kind discussed above, two related features must be considered:. The first is the relative reactivity of the compound compared with benzene itself. Experiments have shown that substituents on a benzene ring can influence reactivity in a profound manner.

For example, a hydroxy or methoxy substituent increases the rate of electrophilic substitution about ten thousand fold, as illustrated by the case of anisole in the virtual demonstration above. In contrast, a nitro substituent decreases the ring's reactivity by roughly a million.

This activation or deactivation of the benzene ring toward electrophilic substitution may be correlated with the electron donating or electron withdrawing influence of the substituents, as measured by molecular dipole moments.

In the following diagram we see that electron donating substituents blue dipoles activate the benzene ring toward electrophilic attack, and electron withdrawing substituents red dipoles deactivate the ring make it less reactive to electrophilic attack. The influence a substituent exerts on the reactivity of a benzene ring may be explained by the interaction of two effects:. The first is the inductive effect of the substituent.

Most elements other than metals and carbon have a significantly greater electronegativity than hydrogen. Consequently, substituents in which nitrogen, oxygen and halogen atoms form sigma-bonds to the aromatic ring exert an inductive electron withdrawal, which deactivates the ring left-hand diagram below.

The second effect is the result of conjugation of a substituent function with the aromatic ring. This conjugative interaction facilitates electron pair donation or withdrawal, to or from the benzene ring, in a manner different from the inductive shift.

Finally, polar double and triple bonds conjugated with the benzene ring may withdraw electrons, as in the right-hand diagram. Note that in the resonance examples all the contributors are not shown.

In both cases the charge distribution in the benzene ring is greatest at sites ortho and para to the substituent. In the case of the nitrogen and oxygen activating groups displayed in the top row of the previous diagram, electron donation by resonance dominates the inductive effect and these compounds show exceptional reactivity in electrophilic substitution reactions. The three examples on the left of the bottom row in the same diagram are examples of electron withdrawal by conjugation to polar double or triple bonds, and in these cases the inductive effect further enhances the deactivation of the benzene ring.

Alkyl substituents such as methyl increase the nucleophilicity of aromatic rings in the same fashion as they act on double bonds. The second factor that becomes important in reactions of substituted benzenes concerns the site at which electrophilic substitution occurs. Since a mono-substituted benzene ring has two equivalent ortho-sites, two equivalent meta-sites and a unique para-site, three possible constitutional isomers may be formed in such a substitution.

Again we find that the nature of the substituent influences this product ratio in a dramatic fashion. Bromination of nitrobenzene requires strong heating and produces the meta-bromo isomer as the chief product. Some additional examples of product isomer distribution in other electrophilic substitutions are given in the table below. It is important to note here that the reaction conditions for these substitution reactions are not the same, and must be adjusted to fit the reactivity of the reactant C 6 H 5 -Y.

The kinetically favored C1 orientation reflects a preference for generating a cationic intermediate that maintains one intact benzene ring. By clicking on the diagram a second time , the two naphthenonium intermediates created by attack at C1 and C2 will be displayed. The structure and chemistry of more highly fused benzene ring compounds, such as anthracene and phenanthrene show many of the same characteristics described above.

The chief products are phenol and diphenyl ether see below. This apparent nucleophilic substitution reaction is surprising, since aryl halides are generally incapable of reacting by either an S N 1 or S N 2 pathway. The presence of electron-withdrawing groups such as nitro ortho and para to the chlorine substancially enhance the rate of substitution, as shown in the set of equations presented on the left below. To explain this, a third mechanism for nucleophilic substitution has been proposed.

This two-step mechanism is characterized by initial addition of the nucleophile hydroxide ion or water to the aromatic ring, followed by loss of a halide anion from the negatively charged intermediate. This is illustrated by clicking the "Show Mechanism" button next to the diagram. The sites over which the negative charge is delocalized are colored blue, and the ability of nitro, and other electron withdrawing, groups to stabilize adjacent negative charge accounts for their rate enhancing influence at the ortho and para locations.

Three additional examples of aryl halide nucleophilic substitution are presented on the right. Only the 2- and 4-chloropyridine isomers undergo rapid substitution, the 3-chloro isomer is relatively unreactive. Nitrogen nucleophiles will also react, as evidenced by the use of Sanger's reagent for the derivatization of amino acids.

The resulting N-2,4-dinitrophenyl derivatives are bright yellow crystalline compounds that facilitated analysis of peptides and proteins, a subject for which Frederick Sanger received one of his two Nobel Prizes in chemistry. Such addition-elimination processes generally occur at sp 2 or sp hybridized carbon atoms, in contrast to S N 1 and S N 2 reactions.

When applied to aromatic halides, as in the present discussion, this mechanism is called S N Ar. Some distinguishing features of the three common nucleophilic substitution mechanisms are summarized in the following table.

Elimination There is good evidence that the synthesis of phenol from chlorobenzene does not proceed by the addition-elimination mechanism S N Ar described above. However, ortho-chloroanisole gave exclusively meta-methoxyaniline under the same conditions.

These reactions are described by the following equations. The explanation for this curious repositioning of the substituent group lies in a different two-step mechanism we can refer to as an elimination-addition process.

The intermediate in this mechanism is an unstable benzyne species, as displayed in the above illustration by clicking the "Show Mechanism" button. In contrast to the parallel overlap of p-orbitals in a stable alkyne triple bond, the p-orbitals of a benzyne are tilted ca. In the absence of steric hindrance top example equal amounts of meta- and para-cresols are obtained. The steric bulk of the methoxy group and the ability of its ether oxygen to stabilize an adjacent anion result in a substantial bias in the addition of amide anion or ammonia.

For additional information about benzyne and related species , Click Here. Addition Although it does so less readily than simple alkenes or dienes, benzene adds hydrogen at high pressure in the presence of Pt, Pd or Ni catalysts. The product is cyclohexane and the heat of reaction provides evidence of benzene's thermodynamic stability. Substituted benzene rings may also be deduced in this fashion, and hydroxy-substituted compounds, such as phenol, catechol and resorcinol, give carbonyl products resulting from the fast ketonization of intermediate enols.

Nickel catalysts are often used for this purpose, as noted in the following equations. Benzene is more susceptible to radical addition reactions than to electrophilic addition. We have already noted that benzene does not react with chlorine or bromine in the absence of a catalyst and heat. In strong sunlight or with radical initiators benzene adds these halogens to give hexahalocyclohexanes. It is worth noting that these same conditions effect radical substitution of cyclohexane, the key factors in this change of behavior are the pi-bonds array in benzene, which permit addition, and the weaker C-H bonds in cyclohexane.

The addition of chlorine is shown below; two of the seven meso-stereoisomers will appear if the "Show Isomer" button is clicked. The Birch Reduction Another way of adding hydrogen to the benzene ring is by treatment with the electron rich solution of alkali metals, usually lithium or sodium, in liquid ammonia.

To see examples of this reaction, which is called the Birch Reduction , Click Here. Practice Problems The following problems review various aspects of aromatic chemistry.

The first two questions review some simple concepts. The next two questions require you to analyze the directing influence of substituents. The fifth question asks you to draw the products of some aromatic substitution reactions. The sixth question takes you through a mutistep synthesis. The last selection leads to a large number of multiple choice questions. Compounds in which a hydroxyl group is bonded to an aromatic ring are called phenols. The chemical behavior of phenols is different in some respects from that of the alcohols, so it is sensible to treat them as a similar but characteristically distinct group.

A corresponding difference in reactivity was observed in comparing aryl halides, such as bromobenzene, with alkyl halides, such as butyl bromide and tert-butyl chloride. Thus, nucleophilic substitution and elimination reactions were common for alkyl halides, but rare with aryl halides.

Acidity of Phenols On the other hand, substitution of the hydroxyl hydrogen atom is even more facile with phenols, which are roughly a million times more acidic than equivalent alcohols. This phenolic acidity is further enhanced by electron-withdrawing substituents ortho and para to the hydroxyl group, as displayed in the following diagram. The alcohol cyclohexanol is shown for reference at the top left. It is noteworthy that the influence of a nitro substituent is over ten times stronger in the para-location than it is meta, despite the fact that the latter position is closer to the hydroxyl group.

Furthermore additional nitro groups have an additive influence if they are positioned in ortho or para locations. The trinitro compound shown at the lower right is a very strong acid called picric acid. Why is phenol a much stronger acid than cyclohexanol? To answer this question we must evaluate the manner in which an oxygen substituent interacts with the benzene ring. As noted in our earlier treatment of electrophilic aromatic substitution reactions, an oxygen substituent enhances the reactivity of the ring and favors electrophile attack at ortho and para sites.

It was proposed that resonance delocalization of an oxygen non-bonded electron pair into the pi-electron system of the aromatic ring was responsible for this substituent effect. Formulas illustrating this electron delocalization will be displayed when the "Resonance Structures" button beneath the previous diagram is clicked.

A similar set of resonance structures for the phenolate anion conjugate base appears below the phenol structures. The resonance stabilization in these two cases is very different.

An important principle of resonance is that charge separation diminishes the importance of canonical contributors to the resonance hybrid and reduces the overall stabilization.

The contributing structures to the phenol hybrid all suffer charge separation, resulting in very modest stabilization of this compound. On the other hand, the phenolate anion is already charged, and the canonical contributors act to disperse the charge, resulting in a substantial stabilization of this species.

The conjugate bases of simple alcohols are not stabilized by charge delocalization, so the acidity of these compounds is similar to that of water. An energy diagram showing the effect of resonance on cyclohexanol and phenol acidities is shown on the right.

Since the resonance stabilization of the phenolate conjugate base is much greater than the stabilization of phenol itself, the acidity of phenol relative to cyclohexanol is increased.

Supporting evidence that the phenolate negative charge is delocalized on the ortho and para carbons of the benzene ring comes from the influence of electron-withdrawing substituents at those sites. The additional resonance stabilization provided by ortho and para nitro substituents will be displayed by clicking the "Resonance Structures" button a second time.

You may cycle through these illustrations by repeated clicking of the button. Substitution of the Hydroxyl Hydrogen As with the alcohols, the phenolic hydroxyl hydrogen is rather easily replaced by other substituents. For example, phenol reacts easily with acetic anhydride to give phenyl acetate. Likewise, the phenolate anion is an effective nucleophile in S N 2 reactions, as in the second example below.

Electrophilic Substitution of the Aromatic Ring The facility with which the aromatic ring of phenols and phenol ethers undergoes electrophilic substitution has been noted.

Two examples are shown in the following diagram. The second reaction is interesting in that it further demonstrates the delocalization of charge that occurs in the phenolate anion. Carbon dioxide is a weak electrophile and normally does not react with aromatic compounds; however, the negative charge concentration on the phenolate ring enables the carboxylation reaction shown in the second step. The sodium salt of salicylic acid is the major ptoduct, and the preference for ortho substitution may reflect the influence of the sodium cation.

This is called the Kolbe-Schmidt reaction , and it has served in the preparation of aspirin, as the last step illustrates. Oxidation of Phenols Phenols are rather easily oxidized despite the absence of a hydrogen atom on the hydroxyl bearing carbon. Among the colored products from the oxidation of phenol by chromic acid is the dicarbonyl compound para-benzoquinone also known as 1,4-benzoquinone or simply quinone ; an ortho isomer is also known.

These compounds are easily reduced to their dihydroxybenzene analogs, and it is from these compounds that quinones are best prepared. Note that meta-quinones having similar structures do not exist. The redox equilibria between the dihydroxybenzenes hydroquinone and catechol and their quinone oxidation states are so facile that milder oxidants than chromate Jones reagent are generally preferred.

One such oxidant is Fremy's salt , shown on the right. Reducing agents other than stannous chloride e. NaBH 4 may be used for the reverse reaction. The position of the quinone-hydroquinone redox equilibrium is proportional to the square of the hydrogen ion concentration, as shown by the following half-reactions electrons are colored blue. The electrode potential for this interconversion may therefore be used to measure the pH of solutions.

Although chromic acid oxidation of phenols having an unsubstituted para-position gives some p-quinone product, the reaction is complex and is not synthetically useful. It has been found that salcomine , a cobalt complex, binds oxygen reversibly in solution, and catalyzes the oxidation of various substituted phenols to the corresponding p-quinones. The structure of salcomine and an example of this reaction are shown in the following equation.

The solvent of choice for these oxidations is usually methanol or dimethylformamide DMF. Practice Problems The first problem concerns the relative acidity of different functional groups.