Carbonyls, carboxylic acids and chirality

The C=O group is the busiest functional group in organic chemistry. This topic covers aldehydes, ketones, carboxylic acids and the compounds made from them, the mirror-image molecules that some of their reactions produce, and the instrumental methods (NMR, mass spectrometry and chromatography) that chemists use to work out what they have made.

Naming the compounds in this topic

• Aldehydes and carboxylic acids always have their functional carbon at the end of the chain, so it is carbon 1 and needs no number. In a nitrile, the carbon of the C≡N counts as part of the chain: CH₃CH₂CN has three carbons.
• Esters are named from two parts: the alkyl group from the alcohol comes first, then the part from the acid (including the C=O carbon) ending in -oate. CH₃CH₂COOCH₃ is methyl propanoate.
• Hydroxynitriles are named as nitriles, with the C≡N carbon as carbon 1: CH₃CH(OH)CN is 2-hydroxypropanenitrile.

Chirality and optical isomerism

A carbon atom joined to four different groups is a chiral centre (an asymmetric carbon). The four groups are arranged tetrahedrally, and there are two ways of doing that which are mirror images of each other. No amount of turning makes one fit exactly on top of the other: they are non-superimposable mirror images, like your left and right hands. The two forms are enantiomers, or optical isomers.

• Same chemistry: enantiomers have identical physical properties and react in the same way with most reagents.
• Different effect on light: each enantiomer rotates the plane of plane-polarised light, by the same angle but in opposite directions. One turns it clockwise, the other anticlockwise.
• Racemic mixture (racemate): a 50 : 50 mixture of the two enantiomers. The rotations cancel, so it has no effect on plane-polarised light: it is optically inactive.
• Draw enantiomers in 3D: two bonds in the plane of the paper, one wedge (towards you) and one dashed (away from you), with the second molecule drawn as the mirror image of the first.

How reaction mechanisms decide optical activity

Whether a reaction gives one enantiomer or a racemic mixture depends on the shape of the particle that the attacking species meets.

• Attack on a planar group gives a racemate. A trigonal planar C=O group or carbocation can be attacked equally from above and below. If the new carbon is chiral, the two directions of attack give the two enantiomers in equal amounts. This happens in nucleophilic addition of HCN to aldehydes and most ketones, in the S_N1 substitution of a tertiary halogenoalkane, and in electrophilic addition of HBr to an unsymmetrical alkene such as but-1-ene, where the carbocation is planar.
• S_N2 inverts the chiral centre. In S_N2 the nucleophile attacks from the side opposite the leaving group in one step, through a transition state with five groups partly bonded to carbon. The other three groups flip over like an umbrella in the wind, so a single enantiomer of the reactant gives a single enantiomer of the product with the opposite arrangement. The product is optically active.
• S_N1 goes through a planar carbocation: the leaving group goes first, then the nucleophile can attack either face, so an optically active reactant gives an optically inactive racemic product. Measuring the optical activity of the product is therefore evidence for which mechanism happened.

Aldehydes and ketones

In the C=O group oxygen is much more electronegative than carbon, so the bond is polar, C^δ+=O^δ−. The electron-poor carbon is attacked by nucleophiles, unlike the C=C in alkenes, which attracts electrophiles. The C=O bond is also stronger than a C=C bond, so carbonyls do not take part in the electrophilic addition reactions of alkenes.

• Boiling points: carbonyl molecules cannot hydrogen bond to each other (no H on O), but they have permanent dipole–dipole forces as well as London forces. Their boiling points are higher than alkanes of similar size but lower than alcohols.
• Solubility: small carbonyls such as propanone mix with water, because water molecules hydrogen bond to the lone pairs on the carbonyl oxygen. Solubility falls as the hydrocarbon chain gets longer.

Oxidation: telling aldehydes from ketones

An aldehyde has a hydrogen on its carbonyl carbon and is easily oxidised to a carboxylic acid. A ketone has no such hydrogen, and mild oxidising agents leave it alone. Primary alcohols oxidise to aldehydes and then acids, secondary alcohols to ketones, and tertiary alcohols not at all.

Full equations, with ethanal being oxidised to ethanoic acid in each case:

• Dichromate: 3CH₃CHO + Cr₂O₇²⁻ + 8H⁺ → 3CH₃COOH + 2Cr³⁺ + 4H₂O (or simply RCHO + [O] → RCOOH).
• Fehling's: CH₃CHO + 2Cu²⁺ + 2H₂O → CH₃COOH + Cu₂O + 4H⁺
• Tollens': CH₃CHO + 2Ag⁺ + H₂O → CH₃COOH + 2Ag + 2H⁺

Reduction with lithium tetrahydridoaluminate

LiAlH₄ in dry ether, at room temperature, reduces aldehydes to primary alcohols and ketones to secondary alcohols. Write the reducing agent as [H]:

• CH₃CH₂CHO + 2[H] → CH₃CH₂CH₂OH (propanal → propan-1-ol)
• CH₃COCH₃ + 2[H] → CH₃CH(OH)CH₃ (propanone → propan-2-ol)
• The ether must be dry because LiAlH₄ reacts violently with water.

Nucleophilic addition of hydrogen cyanide

HCN adds across the C=O bond to give a hydroxynitrile, adding one carbon to the chain. The reagent is HCN with some potassium cyanide, at room temperature; HCN itself barely dissociates, so the KCN supplies enough cyanide ions, the actual nucleophile, to start the reaction.

• CH₃CHO + HCN → CH₃CH(OH)CN (2-hydroxypropanenitrile)
• CH₃COCH₃ + HCN → (CH₃)₂C(OH)CN (2-hydroxy-2-methylpropanenitrile)

Two more tests

• 2,4-dinitrophenylhydrazine (2,4-DNPH, Brady's reagent) gives an orange precipitate with any aldehyde or ketone, but not with other C=O compounds such as acids or esters. Purify the precipitate by recrystallisation and measure its melting point: comparing with tables of known values identifies the exact carbonyl compound.
• The iodoform test: warm with iodine and sodium hydroxide. A pale yellow precipitate of triiodomethane (iodoform, CHI₃), with an antiseptic smell, shows a CH₃CO– group: methyl ketones and ethanal (the only aldehyde that gives it). Alcohols with a CH₃CH(OH)– group also give a positive result, because the alkaline iodine first oxidises them to CH₃CO– compounds.
  CH₃COCH₃ + 3I₂ + 4NaOH → CHI₃ + CH₃COONa + 3NaI + 3H₂O

Carboxylic acids

• Hydrogen bonding: the –COOH group hydrogen bonds strongly, so carboxylic acids have high boiling points. In the pure liquid, and in non-polar solvents, pairs of molecules hydrogen bond into dimers, which is why ethanoic acid can appear to have M_r 120 rather than 60.
• Solubility: acids with up to four carbons mix completely with water because they hydrogen bond to water molecules; longer chains make them less soluble.
• Weak acids: CH₃COOH ⇌ CH₃COO⁻ + H⁺, only slightly dissociated, but still strong enough to release CO₂ from carbonates.
• Why they are acidic at all: in the carboxylate ion the negative charge is delocalised over both oxygen atoms (the two C–O bonds become the same length). Spreading the charge stabilises the ion, which encourages the O–H bond to break.
• Effect of substituents: alkyl groups push electrons towards the COO⁻ group, concentrating its charge and making the ion less stable, so propanoic acid is slightly weaker than ethanoic acid. Electronegative chlorine atoms pull electron density away, spreading the charge, so chloroethanoic acid is stronger.

Making carboxylic acids

• Oxidising a primary alcohol or an aldehyde with excess acidified potassium dichromate(VI), heating under reflux so the aldehyde formed on the way cannot escape: CH₃CH₂CH₂OH + 2[O] → CH₃CH₂COOH + H₂O.
• Hydrolysing a nitrile by heating under reflux with dilute hydrochloric or sulfuric acid: CH₃CH₂CN + 2H₂O + H⁺ → CH₃CH₂COOH + NH₄⁺. Together with HCN addition, this lets you lengthen a carbon chain and finish with an acid.

Reactions of carboxylic acids

• Tests for –COOH: fizzing with sodium carbonate or sodium hydrogencarbonate solution (CO₂ turns limewater milky), and misty fumes of HCl with PCl₅ (PCl₅ also reacts with alcohols, so it shows an –OH group of either kind).
• Methanoic acid is the exception that can be oxidised: HCOOH has a structure like an aldehyde (an H on the C=O carbon). It is oxidised to carbonic acid, which breaks down to CO₂ and water, so it gives a positive result with Tollens' and Fehling's.
• Esterification is slow and reversible, giving only a modest equilibrium yield; acyl chlorides (below) make esters much better.

Acyl chlorides

Acyl chlorides are far more reactive than carboxylic acids. The carbonyl carbon carries two electronegative atoms, O and Cl, making it strongly δ+, and Cl⁻ is a good leaving group. They react with nucleophiles at room temperature, quickly and completely, and every reaction gives off steamy fumes of HCl (or makes a chloride salt if a base is present).

With ammonia and amines, the HCl formed is neutralised by a second molecule of the base, so two are needed; with ammonia you see white smoke of ammonium chloride. The reaction with an alcohol is a better way of making esters than using the carboxylic acid, because it is fast and goes to completion.

Esters and polyesters

• Uses: many esters smell sweet and fruity, so they are used in perfumes and flavourings (a perfume ester must also be volatile, non-toxic, and unreactive with water). Ethyl ethanoate is a common solvent for glues and inks.
• Physical properties: esters are polar but cannot hydrogen bond to each other, so they boil at much lower temperatures than the acids they come from, and they are almost insoluble in water.
• Acid hydrolysis: heat under reflux with dilute acid. This is esterification in reverse, so it is reversible and incomplete: CH₃CH₂COOCH₃ + H₂O ⇌ CH₃CH₂COOH + CH₃OH.
• Alkaline hydrolysis: heat under reflux with aqueous sodium hydroxide. It goes to completion, giving the salt of the acid and the alcohol: CH₃CH₂COOCH₃ + NaOH → CH₃CH₂COONa + CH₃OH. The carboxylate ion is not attacked by the alcohol, so the reaction cannot reverse.

Condensation polymers: polyesters

In condensation polymerisation monomers join and a small molecule, usually water or HCl, is lost at each link. To build a chain, each monomer needs a reactive group at both ends. A polyester forms from:

• a dicarboxylic acid and a diol, losing water at each ester link (slow, needs a catalyst);
• a diacyl dichloride and a diol, losing HCl at each link (fast, complete, but the HCl fumes are hazardous);
• a single hydroxy acid, whose –OH and –COOH react with neighbouring molecules: 2-hydroxypropanoic acid (lactic acid) gives poly(lactic acid), a biodegradable plastic.

Terylene (PET), used for clothing fibres and drinks bottles, is made from benzene-1,4-dicarboxylic acid and ethane-1,2-diol. Its repeat unit is –OC–C₆H₄–COO–CH₂CH₂–O–. To find the repeat unit of any polyester, take one of each monomer, remove the atoms lost as water or HCl, and join them through the ester link, with bonds left open at both ends.

Spectroscopy: what radiation does to molecules

NMR spectroscopy

Nuclei with an odd number of protons or neutrons, such as ¹H and ¹³C, behave like tiny magnets. In a strong magnetic field they can line up with or against the field, and radio waves of exactly the right frequency flip them between the two. The frequency needed depends on the chemical environment of each nucleus: electronegative atoms nearby pull electron density away and shift the signal. This shift is measured on the δ scale in parts per million (ppm), relative to a reference.

• TMS, tetramethylsilane, Si(CH₃)₄, is the reference, set at δ = 0. All twelve of its hydrogens are equivalent, so it gives one strong signal, well away from almost every other signal; it is inert, non-toxic, and has a low boiling point so it is easily removed afterwards.
• Solvents must not contain ¹H, or they would swamp the spectrum: CDCl₃ (D is deuterium, ²H) or CCl₄.

¹³C NMR

Each different carbon environment gives one peak, so the number of peaks is the number of carbon environments. Carbons near electronegative atoms or in C=O groups appear at higher δ. Symmetry matters: propanone has three carbons but only two environments, so two peaks.

High resolution ¹H NMR

A proton NMR spectrum gives four pieces of information:

1. Number of peaks = the number of different hydrogen environments. Hydrogens in the same environment are equivalent; ethanol, CH₃CH₂OH, has three.
2. Chemical shift, δ, tells you what is near each hydrogen (table below).
3. Relative peak area (the integration trace) is proportional to the number of hydrogens in each environment: 3 : 2 : 1 for ethanol.
4. Splitting: each peak is split by the hydrogens on the neighbouring carbon atoms. A peak with n neighbouring hydrogens splits into n + 1 lines (the n + 1 rule). Equivalent hydrogens do not split each other, and O–H protons normally appear as a singlet that does not split its neighbours.

Mass spectrometry

In the mass spectrometer an electron is knocked off each molecule, forming the molecular ion, M⁺, which is both a positive ion and a radical:

M → [M]^+• + e⁻

The molecular ion peak is the one with the highest m/z (ignoring the small M+1 peak from ¹³C), and it gives the relative molecular mass. Many molecular ions break up, or fragment: a covalent bond breaks to give a positive ion, which is detected, and a radical, which is not: [M]^+• → X⁺ + Y^•. The more stable the ion, the taller its peak; acylium ions, R–C≡O⁺, and secondary or tertiary carbocations are especially common.

Chromatography

Chromatography separates the components of a mixture between a mobile phase, which moves, and a stationary phase, which does not. Each component is shared between the two phases to a different extent: one that dissolves better in the mobile phase, or is held less strongly by the stationary phase, travels faster. A solid stationary phase separates by adsorption; a liquid stationary phase separates by relative solubility.

• Thin-layer chromatography (TLC): the stationary phase is a thin layer of silica or alumina on a plate; the mobile phase is a solvent. Draw the start line in pencil (ink would dissolve and run), spot tiny amounts of each sample, and stand the plate in a covered tank with the solvent below the start line. Remove it before the solvent reaches the top, mark the solvent front, and show colourless spots with UV light (or ninhydrin spray for amino acids). Wear gloves, so skin oils do not contaminate the plate, and work in a fume cupboard.
• \( R_f = \dfrac{\text{distance moved by the spot}}{\text{distance moved by the solvent front}} \). Compare with known substances run on the same plate. Similar compounds may have similar R_f values and not separate.
• Column chromatography uses the same principles in a vertical column, so larger amounts can be separated and collected.
• Gas chromatography (GC): the mobile phase is an unreactive carrier gas such as helium or nitrogen; the stationary phase is a high-boiling liquid coated on a solid support inside a long coiled column in an oven. Each component has a characteristic retention time, and the area under its peak shows how much is present. It suits volatile liquids.
• HPLC (high-performance liquid chromatography): the mobile phase is a liquid forced under high pressure through a column packed with very small solid particles, giving fast, efficient separations.
• GC–MS: each component leaving a gas chromatograph is fed straight into a mass spectrometer, and its spectrum is matched against a database. It is used in forensic science, airport security, drug testing and environmental monitoring.

Putting the techniques together

Quick checks

Interactive diagrams