Directing effects, addition reactions and carcinogenic arenes

The first group steers the second

Nitrate benzene and you get nitrobenzene. Nitrate nitrobenzene and you get m-dinitrobenzene, but it needs hotter and stronger conditions. Nitrate toluene and you get a mixture of the ortho and para isomers, with very little meta, and the reaction is faster than for benzene.

So a group already on the ring does two things.

• It changes the rate. An activating group makes the ring react faster than benzene. A deactivating group makes it react slower.
• It decides the position. It is ortho and para directing or meta directing.

The three classes

• Activating, ortho and para directing: $\text{OH}$, $\text{OCH}_{3}$ and $\text{NH}_{2}$ (strong), $\text{NHCOCH}_{3}$ (moderate), and $\text{CH}_{3}$ and other alkyl groups (weak).
• Deactivating, ortho and para directing: the halogens, $\text{F}$, $\text{Cl}$, $\text{Br}$ and $\text{I}$.
• Deactivating, meta directing: $\text{NO}_{2}$, $\text{CN}$, $\text{SO}_{3}\text{H}$, $\text{CHO}$, $\text{COCH}_{3}$, $\text{COOH}$, $\text{COOCH}_{3}$, $\text{CF}_{3}$ and $\text{NR}_{3}^{+}$.

Why do the groups fall into these classes? Look at the arenium ion formed in the slow step. The positive charge sits on the carbon atoms next to the new group, and on the carbon opposite to it, that is, on the ortho and para positions.

• A group that gives electrons, by a lone pair or by an alkyl group, steadies that charge. In the ortho and para attack, one resonance form puts the charge on the carbon that holds the group, and the group can help. So the ortho and para ions are more stable than the meta ion. Attack goes there, and the reaction is fast.
• A group that takes electrons, such as the nitro group, makes the carbon that bears it electron-poor. A positive charge next to it is very unfavourable. In ortho or para attack, one resonance form has exactly that. In meta attack, the charge never lands on the carbon with the group. The meta ion is the least bad. The reaction is slow, and meta wins.
• The halogens are a special case. They are more electronegative than carbon, so they pull electrons through the sigma bond, and the ring is deactivated. But they have lone pairs that can flow into the ring, which steadies the ortho and para ions. The pull decides the rate. The lone pair decides the position.

If all positions were equally likely, the products would be $40\ \%$ ortho, $40\ \%$ meta and $20\ \%$ para, because there are two ortho positions, two meta positions and one para position. The data below show how far real products depart from this.

For an ortho and para director, para is usually the larger share. The new group has more room there. For a large group, such as a tert-butyl group, para is almost all.

Practise with new numbers

Planning a synthesis

The order of the steps decides which isomer you get.

• m-Bromonitrobenzene. Nitrate benzene first. The nitro group directs the bromine to the meta position. Then brominate.
• p-Bromonitrobenzene. Brominate benzene first. The bromine directs the nitro group to the ortho and para positions. Then nitrate, and separate the para isomer from the ortho isomer.
• p-Nitrobenzoic acid from toluene. Nitrate toluene, separate the para isomer, and then oxidise the methyl group to $\text{COOH}$. If you oxidised first, the acid group would direct the nitro group to the meta position.

Reactions of the side chain

A methyl group on the ring has its own chemistry.

• Halogen in light, or at high temperature. Chlorine replaces the hydrogen atoms of the side chain by a free-radical chain, as in an alkane. Toluene gives benzyl chloride, $\text{C}_{6}\text{H}_{5}\text{CH}_{2}\text{Cl}$.
• Halogen with a Lewis acid, in the dark. The ring reacts. Toluene gives ortho and para chlorotoluene.
• Oxidation. Hot alkaline or acid permanganate oxidises an alkyl side chain to a carboxyl group, whatever the length of the chain. Toluene gives benzoic acid. The carbon next to the ring must have a hydrogen atom: tert-butylbenzene is not oxidised.

Remember it as a rule. Light for the side chain. A Lewis acid for the ring.

Addition reactions of benzene

Benzene will add reagents, but only under severe conditions, because it must give up its stability.

• Hydrogen. With nickel at high temperature and pressure, three moles of hydrogen add. The product is cyclohexane, $\text{C}_{6}\text{H}_{12}$.
• Chlorine in sunlight. Three moles of chlorine add by a free-radical chain. The product is 1,2,3,4,5,6-hexachlorocyclohexane, $\text{C}_{6}\text{H}_{6}\text{Cl}_{6}$, also called benzene hexachloride. One of its isomers, lindane, was used as an insecticide. Many countries now restrict it, because it persists in the environment and is toxic.
• Combustion. $2\text{C}_{6}\text{H}_{6}\ +\ 15\text{O}_{2}\ \longrightarrow \ 12\text{CO}_{2}\ +\ 6\text{H}_{2}\text{O}$. The flame is sooty, because the carbon content is high.

Carcinogenic arenes

Benzene itself is a carcinogen, as we saw. Larger aromatic molecules made of several fused rings are called polynuclear aromatic hydrocarbons. Some of them cause cancer.

The best known is benzo[a]pyrene, with five fused rings. It forms when organic matter burns without enough air. It is found in tobacco smoke, in soot, in coal tar, in vehicle exhaust and on food that has been charred. The body tries to get rid of it by oxidising it. This makes a very reactive epoxide, which joins to the DNA of a cell. The DNA is then copied with errors, and a cell can start to grow out of control.

Compounds of this kind include 1,2-benzanthracene, 3-methylcholanthrene and benzo[a]pyrene. The way to avoid them is to avoid burning materials in poor air, to avoid tobacco smoke and to avoid charring food.

Try it in Python

The program counts the isomers of benzene derivatives with different groups. It tries every placement and counts a molecule once when turning or flipping the ring gives the same one.

Common mistakes

• Saying all deactivating groups direct to the meta position. The halogens deactivate, but they direct ortho and para.
• Mixing up the roles. Rate comes from the pull of electrons. Position comes from the resonance of the arenium ion.
• Getting the order of the steps wrong. The first group decides where the second goes.
• Using a Lewis acid for side-chain halogenation. The side chain needs light. The Lewis acid goes to the ring.
• Expecting tert-butylbenzene to be oxidised. It has no benzylic hydrogen atom.

Remember these

• Activating and ortho-para directing: $\text{OH}$, $\text{NH}_{2}$, $\text{OR}$, alkyl groups.
• Deactivating and ortho-para directing: the halogens.
• Deactivating and meta directing: $\text{NO}_{2}$, $\text{CN}$, $\text{CHO}$, $\text{COR}$, $\text{COOH}$, $\text{SO}_{3}\text{H}$.
• Side chain: halogen in light. Ring: halogen with a Lewis acid. Permanganate turns an alkyl group into $\text{COOH}$.
• Benzene adds $\text{H}_{2}$ with nickel and $\text{Cl}_{2}$ in sunlight only under severe conditions.
• Benzo[a]pyrene and other polynuclear aromatic hydrocarbons cause cancer.

Check yourself

Try each one on your own first. If you are stuck, open a hint. Then check with Show the answer.

1. Which group directs the next substituent to the meta position: $\text{CH}_{3}$, $\text{NO}_{2}$ or $\text{Cl}$?

2. What are the main products of nitrating chlorobenzene?

3. How can you make m-bromonitrobenzene from benzene?

4. Toluene is treated with chlorine in the presence of ultraviolet light, and then in the dark with iron(III) chloride. How do the products differ?

5. Why does benzene add hydrogen only under severe conditions?

References

• OpenStax Organic Chemistry (McMurry), chapter 16, the section "Substituent Effects in Electrophilic Substitutions".
• NCERT Chemistry, Class 11, Part II, the chapter "Hydrocarbons" (directive influence of a functional group, addition reactions, carcinogenicity).
• The ortho, meta and para percentages are rounded values from Morrison and Boyd, Organic Chemistry.