Halogen compounds

Making a halogenoarene: substituting a halogen into an arene ring

A halogenoarene, also called an aryl halide, is a compound in which a halogen atom is bonded directly to a carbon atom of a benzene ring. Chlorobenzene, C6H5Cl, is the simplest one. It is made by substitution, in which a halogen takes the place of one of the hydrogen atoms of benzene: C6H6 + Cl2 -> C6H5Cl + HCl. Nothing adds across the ring, and the ring itself survives intact, which is the first important difference from the reactions of alkenes.

The catalyst is the part you must never leave out. Chlorine and bromine on their own will not attack a benzene ring under ordinary laboratory conditions, because a halogen molecule is not a strong enough electrophile to disturb a delocalised pi system. Anhydrous aluminium chloride, AlCl3, is added instead, and it acts as a halogen carrier: it polarises the halogen molecule and produces a species with Cl+ character that the ring can attack. Bromine works with anhydrous aluminium bromide, AlBr3, in the same way and gives bromobenzene and hydrogen bromide.

Every one of these catalysts must be dry. Water hydrolyses aluminium chloride to aluminium hydroxide and hydrogen chloride, destroying the carrier, so the flask, the condenser and the benzene are dried, and a drying tube is fitted to keep moist air out. The reaction is also kept in the dark, away from ultraviolet light. Sunlight splits a halogen molecule into radicals, and those radicals attack a side chain rather than the ring, so a reaction left in the light gives the wrong product for the wrong reason.

• Benzene with Cl2 and anhydrous AlCl3, in the dark, gives chlorobenzene and HCl by substitution in the ring.
• Benzene with Br2 and anhydrous AlBr3, in the dark, gives bromobenzene and HBr.
• The catalyst must be anhydrous, because water hydrolyses AlCl3 and destroys the halogen carrier.
• Ultraviolet light must be excluded, or free-radical substitution takes place at a side chain instead of the ring.

The halogen carrier and the mechanism of ring chlorination

Start with the electrophile. Aluminium chloride is a Lewis acid, so it accepts a lone pair of electrons. In curly-arrow terms, a lone pair on the aluminium atom of AlCl3 attacks a chlorine atom of the Cl2 molecule; the Cl-Cl bond breaks heterolytically and both of its electrons go onto the other chlorine atom, which becomes bonded to the aluminium as the AlCl4- ion. What is left facing the ring is a strongly electrophilic species with Cl+ character: Cl2 + AlCl3 -> Cl+ + AlCl4-. This is why AlCl3 is called a halogen carrier rather than just a catalyst.

The substitution itself then follows the same two steps as every electrophilic substitution of an arene. In step one, a lone pair of the delocalised pi system of the ring attacks the electrophile and a new carbon-chlorine bond forms. Only four pi electrons are left to be delocalised, and they are now spread over five carbon atoms, so the intermediate carries a positive charge: that is the arenium ion. The charge is spread over the five carbons that do not carry the chlorine, never sitting on one carbon on its own.

In step two the ring repairs itself. The pair of electrons in the C-H bond on the carbon that has just taken the chlorine swings back into the ring and the hydrogen leaves as a proton, H+. The six pi electrons are delocalised again, the ring is aromatic once more, and the overall change is that a hydrogen atom has been replaced by a chlorine atom. The proton released combines with AlCl4- to give hydrogen chloride and regenerate AlCl3, so the aluminium chloride is a true catalyst and only a small amount is needed.

Two exam traps live in that mechanism. The electrophile does not attack the ring - the ring attacks the electrophile, because the ring is the electron-rich species. And the proton must be lost from the same carbon atom that took the chlorine, because that is the only way the C-H electrons can return to the ring and restore its delocalisation.

• Step 1: a lone pair of the ring's pi system attacks the electrophile, giving the arenium ion with the charge delocalised over five carbons.
• Step 2: the C-H bond electrons on the substituted carbon return to the ring and H+ is lost, restoring the delocalised ring.
• The proton released regenerates the catalyst: H+ + AlCl4- -> HCl + AlCl3.
• Describe curly arrows in words: pi bond to electrophile for step 1, C-H bond pair back into the ring for step 2.

Chlorinating methylbenzene: 2-chloromethylbenzene and 4-chloromethylbenzene

Run the same reaction on methylbenzene and the methyl group decides where the chlorine goes. With chlorine and anhydrous aluminium chloride, in the dark, the products are 1-chloro-2-methylbenzene, also written as 2-chloromethylbenzene, and 1-chloro-4-methylbenzene, also written as 4-chloromethylbenzene. The 4-isomer is the main product, because the methyl group and the chlorine are then as far apart as possible and steric hindrance is least.

The methyl group is electron-donating, so it raises the electron density in the ring and activates it: methylbenzene reacts more readily than benzene. It raises that density most at the 2-, 4- and 6-positions, so the electrophile is most likely to attack at the 2- or the 4-position. The full explanation is the stability of the intermediate. Attack at the 2- or the 4-position gives an arenium ion with a resonance form in which the positive charge sits on the carbon that carries the methyl group, and the electron-releasing methyl group helps to stabilise that charge. Attack at the 3-position gives no such resonance form, so that intermediate is less stable and the 3-isomer is only a minor product.

Do not confuse this ring chlorination with side-chain chlorination. Leave the aluminium chloride out, and shine ultraviolet light on methylbenzene with chlorine, and the substitution is free-radical at the carbon next to the ring, giving (chloromethyl)benzene, C6H5CH2Cl, in which the chlorine sits on the side chain and the ring is untouched. Ring chlorination needs the halogen carrier and the dark; side-chain chlorination needs the light and no carrier. Mix the two sets of conditions and you get a mixture of both products.

Chloroethane: a polar C-Cl bond that a nucleophile can attack

Chloroethane, CH3CH2Cl, behaves like any other halogenoalkane. Chlorine is more electronegative than carbon, so the C-Cl bond is polar and the carbon carries a partial positive (delta-positive) charge that attracts a nucleophile. Heat it with aqueous sodium hydroxide under reflux and hydrolysis takes place: CH3CH2Cl + NaOH -> CH3CH2OH + NaCl. The hydroxide ion uses a lone pair to attack the delta-positive carbon, the C-Cl bond breaks heterolytically with both electrons going to the chlorine, and the chloride ion leaves to be replaced by an -OH group. The product is ethanol.

The mechanism is SN2, a single concerted step, because chloroethane is a primary halogenoalkane and the carbon carrying the chlorine is not crowded: the hydroxide attacks from the side opposite the chlorine as the C-Cl bond breaks, and the rate depends on both reactants, rate = k[RX][OH-]. The carbon passes through a transition state in which it is partly bonded to five groups, and there is no carbocation intermediate. The C-Cl bond enthalpy in chloroethane is only about 340 kJ mol-1 - roughly the same as a C-C bond - so a reflux at about 70 C supplies plenty of energy to break it.

Two simple laboratory observations confirm how easily that chloride ion comes away. Warmed with aqueous silver nitrate in ethanol, chloroethane releases chloride ions that are precipitated as a white precipitate of silver chloride, Ag+ + Cl- -> AgCl(s); the ethanol is the solvent because it dissolves both the halogenoalkane and the silver nitrate and so brings them into the same phase. Chloroethane also reacts with KCN in ethanol on heating to give propanenitrile, and with ammonia in ethanol heated under pressure to give ethylamine, and with sodium hydroxide in ethanol on heating it eliminates to give ethene instead of ethanol. The point to carry forward is that this C-Cl bond is reactive: nucleophiles can and do break it under ordinary laboratory conditions.

• Chloroethane with NaOH(aq), heat under reflux: CH3CH2Cl + NaOH -> CH3CH2OH + NaCl, a hydrolysis by nucleophilic substitution.
• Mechanism: SN2 for the primary compound, one concerted step with a backside attack, rate = k[RX][OH-].
• Chloroethane with AgNO3(aq) in ethanol gives a white precipitate of silver chloride, showing the chloride ion is released readily.
• The C-Cl bond enthalpy in chloroethane is only about 340 kJ mol-1, so reflux conditions are enough to break it.

Chlorobenzene: why the chlorine is locked into the ring

Chlorobenzene has the same C-Cl bond on paper, but its chlorine atom also has a lone pair, and that lone pair sits on an atom attached to a ring with a delocalised pi system. The lone pair is drawn into the ring: a resonance structure can be drawn in which the chlorine forms a double bond to carbon 1 and the ring's pi electrons shift round so that a positive charge appears on the 2- or the 4-position. Because of this delocalisation the C-Cl bond in chlorobenzene is not a plain single bond - it has partial double bond character, and that shows up in the measurements.

The evidence is the bond itself. The C-Cl bond in chlorobenzene is about 0.170 nm long, while the C-Cl bond in chloroethane is about 0.177 nm: shorter means stronger, and the bond enthalpy in chlorobenzene is correspondingly greater, about 400 compared with about 340 kJ mol-1. A stronger bond needs a higher activation energy to break, so a nucleophile that has to displace the chloride has a much higher barrier to climb. Because chloride is a weaker base than hydroxide, and the resulting would-be intermediate would have to put a negative charge on a ring carbon from which the delocalised electrons would rather keep away, the substitution is very strongly disfavoured.

The result is dramatic. Chlorobenzene is not hydrolysed by aqueous sodium hydroxide even under prolonged reflux; it is unchanged. It gives no precipitate with aqueous silver nitrate in ethanol, because no chloride ions are released. To make it react with hydroxide at all the conditions have to be extreme: heating with aqueous sodium hydroxide at about 300 C under high pressure in a sealed reactor, which gives phenol, C6H5OH, and sodium chloride. Industrially phenol is more usually made by the cumene process, precisely because forcing that substitution is so expensive in energy and equipment.

At the same time the delocalised lone pair changes what chlorobenzene does react with. It does not behave like a halogenoalkane at all; it behaves like an arene. With the same electrophilic reagents used for benzene it undergoes substitution in the ring: nitration with concentrated nitric and sulphuric acids gives mainly 1-chloro-4-nitrobenzene, and further chlorination with Cl2 and AlCl3 gives mainly 1,4-dichlorobenzene. The -Cl group is deactivating but a 2,4-director: it withdraws electron density inductively through the sigma bond, which makes the ring less reactive than benzene, but it donates through the delocalised lone pair, which directs the next electrophile to the 2- and 4-positions.

• The lone pair on the chlorine is delocalised into the ring, giving the C-Cl bond partial double bond character.
• C-Cl in chlorobenzene is about 0.170 nm, against about 0.177 nm in chloroethane, so it is shorter and stronger.
• Chlorobenzene is not hydrolysed by NaOH(aq) under reflux and gives no precipitate with AgNO3 in ethanol.
• Forcing conditions - aqueous NaOH at about 300 C under high pressure - hydrolyse it to phenol.
• With electrophiles it substitutes in the ring: nitration gives mainly 1-chloro-4-nitrobenzene.

Chloroethane against chlorobenzene: the comparison the exam asks for

The two compounds differ in exactly one structural feature: in chlorobenzene the carbon that carries the chlorine is part of an aromatic ring. Everything else follows from that. In chloroethane the C-Cl bond is an isolated polar single bond, so the delta-positive carbon is exposed to nucleophiles and the bond breaks at around 70 C under reflux. In chlorobenzene the chlorine lone pair is drawn into the delocalised pi system, giving the bond partial double bond character, so the carbon is far less electrophilic, the bond is shorter and stronger, and the ring's pi electrons repel an approaching nucleophile.

The practical test of the difference is the silver nitrate in ethanol test. Chloroethane releases chloride ions readily and gives a white precipitate of silver chloride on warming. Chlorobenzene releases no chloride ions at all, so it gives no precipitate, however long it is warmed. The same test, run on an unknown compound, therefore does more than identify the halogen: it tells you whether the halogen is on an alkyl carbon or on an aromatic ring.

Be careful with the reason, because it is easy to get the wrong way round. It is not simply that chlorine is stabilised by the ring; it is specifically that the lone pair on the chlorine is delocalised into the ring, which gives the bond a share of double bond character. Say that, give the bond length or bond enthalpy as your evidence, and then explain the consequence - the much higher activation energy for heterolytic breaking of the bond, and hence the need for conditions of about 300 C and high pressure before any hydrolysis is seen.

Where halogenoarenes are used, and why their inertness matters

Chlorobenzene is made in large quantities and is useful for two quite different reasons. In industry it is both a solvent and a chemical intermediate, because it is unreactive towards water, acids and bases in the way its boiling point and polarity make it handy for dissolving other organic compounds. The old industrial route to phenol hydrolysed it with aqueous sodium hydroxide at about 300 C and high pressure - the Dow process - and although the cumene process has largely replaced that route, the hydrolysis reaction itself is still the standard example of how forcing conditions have to be before an aryl chloride will react with a nucleophile.

The chlorine in chlorobenzene is also useful when it is kept. Nitration of chlorobenzene with a mixture of concentrated nitric and sulphuric acids gives mainly 1-chloro-4-nitrobenzene, and reducing that nitro group with tin and concentrated hydrochloric acid gives 4-chlorophenylamine, a building block for azo dyes and for medicines. The combination of an aryl carbon-chlorine bond that resists nucleophilic attack with a ring that happily accepts electrophiles is exactly what makes these routes work: the chlorine stays where it is put while the ring is modified around it.

The same stability has a darker side. The organochlorine insecticide DDT, 2,2-bis(4-chlorophenyl)-1,1,1-trichloroethane, is an arene with several carbon-chlorine bonds, and those bonds are so resistant to hydrolysis and to biological attack that the compound persists in soils and accumulates in the fatty tissue of animals up the food chain. That persistence, rather than direct toxicity to humans, is why its use was banned or severely restricted in many countries. The inertness of the aryl carbon-chlorine bond is a chemical property with an environmental consequence.

• Chlorobenzene is used as a solvent and as an intermediate in the manufacture of phenol, dyes and medicines.
• Hydrolysis with aqueous NaOH at about 300 C under high pressure gives phenol; the cumene process has largely replaced this route.
• Nitration gives 1-chloro-4-nitrobenzene, which is reduced to 4-chlorophenylamine for azo dyes.
• The persistence of organochlorine compounds such as DDT follows from the resistance of aryl C-Cl bonds to hydrolysis and to metabolism.