Carboxylic acids and derivatives (A Level)

Why a carboxylic acid is acidic: argue at the anion

A carboxylic acid contains the carboxyl group, -COOH: a carbonyl group, C=O, joined to an O-H group on the same carbon atom. The O-H bond is polarised, so the acid can donate a proton to water, and the species left behind is the carboxylate ion, RCOO-. In that ion the negative charge does not sit on one oxygen atom: it is delocalised over both oxygen atoms, because the two C-O bonds are identical and each oxygen carries half of the charge. Spreading a charge over two electronegative atoms lowers the energy of the ion, so the carboxylate ion is unusually stable and the acid ionises readily.

Compare that with an alcohol. Ethanol also has an O-H bond, but when it loses a proton the ethoxide ion, CH3CH2O-, carries the whole negative charge on a single oxygen atom with no C=O group beside it to help. A localised charge on one atom is far less stable than a delocalised one, so ethanol releases a proton only very reluctantly. Phenol sits between the two: the phenoxide ion, C6H5O-, delocalises the negative charge into the pi system of the benzene ring, which is good, but the charge still ends up on carbon atoms as well as oxygen, which is not as good as sharing between two oxygens. That gives the order you must know: carboxylic acid > phenol > water > alcohol.

The numbers behind the order are worth remembering in rough form. The pKa of ethanoic acid is about 4.8, of phenol about 10 and of ethanol about 16. A lower pKa means a stronger acid, because it means the equilibrium of the ionisation lies further to the right; ethanoic acid is therefore about five powers of ten stronger an acid than phenol, and phenol is far stronger than ethanol.

You can see the order in the test tube, and examiners like evidence. Ethanoic acid reacts with sodium carbonate with brisk effervescence of carbon dioxide, because a carboxylic acid is strong enough to protonate the carbonate ion. Phenol does not give carbon dioxide with sodium carbonate, because it is too weak an acid to force the equilibrium that far; it needs sodium hydroxide instead, forming sodium phenoxide. Ethanol reacts with neither reagent. Whenever you are asked why one acid beats another, finish the argument at the conjugate base: the stronger acid is the one whose anion spreads out its negative charge best.

Chlorine-substituted carboxylic acids and the inductive effect

Replace one hydrogen of the methyl group of ethanoic acid with chlorine and the acid becomes much stronger: the pKa of chloroethanoic acid, ClCH2COOH, is about 2.9 against about 4.8 for ethanoic acid. Chlorine is more electronegative than carbon, so it pulls electron density towards itself through the sigma bonds of the chain. This is the inductive effect, written -I for an electron-withdrawing group, and it is transmitted along the chain rather than through space. The carboxyl group feels the pull: electron density is drawn away from the O-H bond and away from the carboxylate ion.

Withdrawing electron density from the carboxylate ion disperses the negative charge even further, on top of the delocalisation over the two oxygen atoms, so the conjugate base is stabilised and the O-H bond is weakened and breaks more easily. The equilibrium RCOOH + H2O <-> RCOO- + H3O+ moves to the right, so the acid is stronger and the pKa is lower.

The effect is cumulative and it fades with distance. Two chlorine atoms withdraw more than one and three withdraw more still, so the pKa falls in the order chloroethanoic acid (about 2.9) > dichloroethanoic acid (about 1.3) > trichloroethanoic acid (about 0.7). Move the chlorine one carbon further away and it has less influence, because there are more intervening sigma bonds for the pull to travel through, so 2-chloropropanoic acid, CH3CHClCOOH, is a stronger acid than 3-chloropropanoic acid, ClCH2CH2COOH.

Alkyl groups do the opposite, because they are weakly electron-pushing. That is why ethanoic acid is very slightly weaker than methanoic acid, HCOOH. Do not confuse this explanation with the one you use for phenol: phenol is a stronger acid than an alcohol because its charge is delocalised into the ring, while the chlorine-substituted acids are stronger because of the electron-withdrawing inductive effect. Choosing the wrong one of those two is a common way to lose marks.

• A chlorine atom withdraws electron density inductively along the sigma-bond framework (-I effect).
• Withdrawal stabilises the carboxylate ion, weakens the O-H bond and lowers the pKa, so the acid is stronger.
• More chlorine atoms, stronger acid: ClCH2COOH (about 2.9) > Cl2CHCOOH (about 1.3) > Cl3CCOOH (about 0.7).
• The effect fades with distance: 2-chloropropanoic acid is stronger than 3-chloropropanoic acid.
• Alkyl groups push electron density in, so ethanoic acid is marginally weaker than methanoic acid.

Making benzoic acid: oxidising an alkyl side chain

Benzoic acid, C6H5COOH, is made in the laboratory from methylbenzene (toluene) by oxidising the methyl side chain. Methylbenzene is boiled under reflux with hot alkaline potassium manganate(VII), that is KMnO4 solution made alkaline with sodium hydroxide. The purple manganate(VII) is decolourised as it is reduced and a brown precipitate of manganese(IV) oxide settles out, and the methyl group is oxidised all the way to a carboxylate group. The organic change is C6H5CH3 + 3[O] -> C6H5COOH + H2O, where [O] stands for oxygen from the oxidising agent.

The product of the oxidation is not the free acid but its salt, potassium benzoate, because the mixture is alkaline. To obtain the acid you cool the mixture and add dilute hydrochloric acid (or dilute sulfuric acid), which protonates the benzoate ion: C6H5COO- + H+ -> C6H5COOH. Benzoic acid is only sparingly soluble in cold water, so it crystallises out and is filtered off and recrystallised. Both steps are needed for the mark: the alkaline oxidation, then the acidification.

The oxidation attacks the benzylic carbon, the carbon of the side chain that is directly attached to the ring. Any alkylbenzene with at least one hydrogen on that carbon is oxidised, and the whole side chain is cut back to a single -COOH group, so ethylbenzene gives benzoic acid just as methylbenzene does. A ring carrying two methyl groups, such as 1,2-dimethylbenzene, gives a dicarboxylic acid, benzene-1,2-dicarboxylic acid. If the benzylic carbon carries no hydrogen at all, as in 2-methyl-2-phenylpropane, the side chain resists oxidation.

Industrially benzoic acid is made on a large scale by the air oxidation of toluene over cobalt and manganese carboxylate catalysts, which is cheaper than using manganate(VII). The laboratory route above is the one the syllabus asks about, and it is also the standard way of showing that a benzene ring is attached to an alkyl chain rather than to a carboxyl group already.

Turning a carboxylic acid into an acyl chloride

An acyl chloride is a compound in which the -OH of a carboxylic acid has been replaced by -Cl, giving the group -COCl. Ethanoyl chloride, CH3COCl, and benzoyl chloride, C6H5COCl, are the two you will meet most often. Three reagents will do the job, and you must know the conditions that go with each: PCl3 with heat, PCl5 at room temperature, and SOCl2 (thionyl chloride) at room temperature.

The equations are straightforward, and each produces a different set of by-products. Phosphorus(V) chloride: RCOOH + PCl5 -> RCOCl + POCl3 + HCl. Phosphorus(III) chloride: 3RCOOH + PCl3 -> 3RCOCl + H3PO3. Thionyl chloride: RCOOH + SOCl2 -> RCOCl + SO2 + HCl.

Thionyl chloride is the reagent of choice in practice for one practical reason: both of its by-products, sulphur dioxide and hydrogen chloride, are gases. They bubble out of the mixture, so the acyl chloride is left behind and can be purified by distillation without having to separate a liquid phosphorus compound such as POCl3. If you use PCl5 or PCl3 you have to distil the acyl chloride away from a liquid by-product, which is slower and gives a lower yield.

Acyl chlorides are extremely reactive towards water, so they fume in moist air as they are hydrolysed back to the carboxylic acid and HCl. Keep the apparatus dry, work in a fume cupboard, and store the product in a stoppered vessel. That reactivity is exactly why they are useful: it lets you make esters and amides under very mild conditions, at room temperature and without a catalyst.

The carboxylic acids that can still be oxidised

Most carboxylic acids are at the end of the oxidation road, but two examples are not. Methanoic acid, HCOOH, has a hydrogen atom on the carboxyl carbon instead of an alkyl group, so it has a C-H bond next to the C=O in the same arrangement as an aldehyde. That makes it reducing as well as acidic, and it is oxidised further to carbon dioxide and water: HCOOH + [O] -> CO2 + H2O. Ethanoic acid has a methyl group in that position and no hydrogen on the carboxyl carbon, so none of these mild oxidising agents touches it. The difference between methanoic and ethanoic acid is the single hydrogen atom on the carboxyl carbon.

Methanoic acid is oxidised by Tollens' reagent, giving a silver mirror on the inside of the tube, and by Fehling's solution, giving a red-brown precipitate of copper(I) oxide. It is also oxidised by acidified KMnO4, which is decolourised from purple to colourless, and by acidified K2Cr2O7, which turns from orange to green. Learn the four reagents with the four observations; they are pure recall marks.

Ethanedioic acid, HOOCCOOH, usually called oxalic acid, is a dicarboxylic acid in which the two carboxyl groups are joined directly to each other. Each carboxyl carbon is in the +3 oxidation state, and oxidation to carbon dioxide takes it to +4, so ethanedioic acid can be oxidised by warm acidified potassium manganate(VII) to carbon dioxide and water: 2MnO4- + 5HOOCCOOH + 6H+ -> 2Mn2+ + 10CO2 + 8H2O. Notice that this is the one case where there is no hydrogen on the carboxyl carbon at all: the two carboxyl carbons are joined by a carbon-carbon bond, and it is that bond which breaks as each carbon leaves as a molecule of CO2.

The titration of ethanedioic acid with manganate(VII) has a feature worth knowing. The purple colour disappears very slowly at first, and then the reaction speeds up as Mn2+ ions accumulate. The manganese(II) ions produced catalyse the reaction, so ethanedioic acid is an example of an autocatalytic reaction. In practice the solution is warmed to about 60 degrees C and acidified with dilute sulfuric acid, no indicator is needed because the manganate(VII) is self-indicating, and the endpoint is the first permanent pink colour. Because pure ethanedioic acid can be weighed out accurately and keeps well, it is used as a primary standard to standardise potassium manganate(VII) solutions; it is also the active ingredient of some rust-removing cleaners.

Acyl chlorides with water, alcohols and phenol

Every reaction of an acyl chloride has the same shape: a nucleophile attacks the electron-deficient carbon of the C=O, and the chloride is driven out as HCl. Hydrolysis happens when you add water at room temperature. Ethanoyl chloride reacts violently, fuming in moist air and giving the carboxylic acid and hydrogen chloride: CH3COCl + H2O -> CH3COOH + HCl. The solution left behind is strongly acidic because of the HCl, and this is also why an acyl chloride must be kept dry.

An alcohol at room temperature gives an ester and HCl. Ethanol and ethanoyl chloride give ethyl ethanoate, CH3COOC2H5, and HCl, and methanol gives methyl ethanoate in the same way. There are two things to notice. First, this is a fast reaction at room temperature with no catalyst needed, unlike the slow, concentrated-sulfuric-acid-catalysed esterification of ethanoic acid with ethanol. Second, the mixture fumes with HCl, and the gas turns damp blue litmus paper red, which is a neat way of showing that HCl is a product.

Phenol also reacts with an acyl chloride at room temperature, giving an ester and HCl, but here it is the -OH group of the phenol that attacks, not a carboxylic acid. Phenol and benzoyl chloride give phenyl benzoate, C6H5COOC6H5, a white crystalline solid, and this acylation needs no catalyst and no heat. Phenol is a weaker nucleophile than an alcohol, because the lone pair on its oxygen is partly delocalised into the ring, so the reaction with phenol is slower than the corresponding reaction with ethanol; even so, it happens at room temperature, whereas making phenyl ethanoate from phenol and ethanoic acid would need a catalyst and prolonged heating.

A practical point for the examination: acyl chlorides are lachrymatory and hydrolyse in moist air, so these reactions are done in a fume cupboard with dry glassware. Any water present simply converts the expensive acyl chloride back into the carboxylic acid before it can react with the alcohol or phenol.

• Water at room temperature: carboxylic acid + HCl. Ethanoyl chloride + H2O -> ethanoic acid + HCl.
• Ethanol at room temperature: ester + HCl, with no catalyst. Ethanoyl chloride + ethanol -> ethyl ethanoate + HCl.
• Phenol at room temperature: ester + HCl, with no catalyst. Benzoyl chloride + phenol -> phenyl benzoate + HCl.
• All three are fast at room temperature because the acyl chloride carbon is strongly delta-positive and chloride is a good leaving group.

Ammonia, amines and the addition-elimination mechanism

Ammonia at room temperature gives an amide and HCl: CH3COCl + NH3 -> CH3CONH2 + HCl, so ethanoyl chloride gives ethanamide. A primary amine such as methylamine gives an N-substituted amide, N-methylethanamide, and a secondary amine such as dimethylamine gives N,N-dimethylethanamide, in each case with HCl. Ammonia and amines bring a lone pair on nitrogen, so they are nucleophiles and behave in exactly the same way as water, an alcohol or a phenol; the extra hydrochloric acid is neutralised by a second molecule of the amine, which is why amines are usually used in excess.

The mechanism is nucleophilic addition-elimination, and you should describe it in three clear stages. Attack: the carbon of the C=O is delta-positive because oxygen is more electronegative than carbon, so it is the electron-deficient centre; a lone pair on the nitrogen of the ammonia attacks that carbon. Addition: the pi bond of the C=O breaks and both of its electrons move onto the oxygen, leaving a tetrahedral intermediate whose carbon carries a CH3 group, the nitrogen, the chlorine and a negatively charged oxygen, with a positive charge on the nitrogen. Elimination: a lone pair on the negatively charged oxygen forms a new pi bond to the carbon, re-forming the C=O, and at the same time the C-Cl bond breaks heterolytically with both electrons going to the chlorine, which leaves as a chloride ion. The nitrogen then loses a proton, and the products are ethanamide and HCl.

The elimination step is the reason the whole reaction is so favourable. Re-forming the C=O releases a great deal of energy, because a carbon-oxygen double bond is strong, and the group that leaves is a chloride ion, which is a stable anion, a weak base and therefore an excellent leaving group. A reaction only has to be easy if its products are stable, and here the driving force is the same feature that makes the acid chloride reactive in the first place: the electron-poor carbon flanked by a C=O and a chlorine.

That reasoning explains the order of ease of hydrolysis, acyl chloride > alkyl chloride > halogenoarene. In an acyl chloride the carbon carries a C=O and an electronegative chlorine, so it is strongly delta-positive, and the addition-elimination route with chloride as the leaving group is easy: hydrolysis is complete in cold water in seconds. In chloroethane there is no C=O group, so the carbon is only slightly delta-positive and there is no low-energy addition-elimination route; nucleophilic attack by water is slow and hydrolysis needs hot aqueous sodium hydroxide. In chlorobenzene the lone pair on the chlorine is delocalised into the pi system of the ring, so the C-Cl bond has partial double-bond character and is shorter and stronger than a normal single bond; the carbon is not electron-deficient, and chlorobenzene is not hydrolysed by water or dilute alkali at all. Breaking that bond needs very harsh conditions, such as heating with concentrated sodium hydroxide solution at high temperature and pressure.