An introduction to A Level organic chemistry

All four subtopics here are printed under "A Level subject content" in the 9701 syllabus, and every objective carries the tier "A Level". None of it is AS, and it is the A Level counterpart to the AS topic 13, "An introduction to AS Level organic chemistry". It is examined on Paper 4. Paper 1 is the AS multiple-choice paper and the whole 9701 bank on this site comes from it, so no practice here is tagged to this topic.

This topic is the toolkit for topics 30 to 37. Nothing in it is difficult on its own, and everything in it is used constantly afterwards, so it repays being learned properly rather than skimmed.

Syllabus points

29.1 Formulas, functional groups and the naming of organic compounds

• Understand that the compounds in the table on page 47 of the syllabus contain a functional group which dictates their physical and chemical properties.
• Interpret and use the general, structural, displayed and skeletal formulas of the classes of compound stated in that table.
• Understand and use systematic nomenclature of simple aliphatic organic molecules (including cyclic compounds containing a single ring of up to six carbon atoms) with those functional groups, up to six carbon atoms (six plus six for esters and amides, straight chains only for esters and nitriles).
• Understand and use systematic nomenclature of simple aromatic molecules with one benzene ring and one or more simple substituents, for example 3-nitrobenzoic acid or 2,4,6-tribromophenol.

29.2 Characteristic organic reactions

• Understand and use the following terminology associated with types of organic mechanism: electrophilic substitution; addition-elimination.

29.3 Shapes of aromatic organic molecules; sigma and pi bonds

• Describe and explain the shape of benzene and other aromatic molecules, including sp² hybridisation, in terms of sigma bonds and a delocalised pi system.

29.4 Isomerism: optical

• Understand that enantiomers have identical physical and chemical properties apart from their ability to rotate plane polarised light and their potential biological activity.
• Understand and use the terms optically active and racemic mixture.
• Describe the effect on plane polarised light of the two optical isomers of a single substance.
• Explain the relevance of chirality to the synthetic preparation of drug molecules, including the potential different biological activity of the two enantiomers, the need to separate a racemic mixture into two pure enantiomers, and the use of chiral catalysts to produce a single pure optical isomer.

Formulas and functional groups

A functional group is the atom or group of atoms responsible for the characteristic chemical properties of a compound. It is why every alcohol behaves like an alcohol regardless of the length of its carbon chain, and it is why organic chemistry can be learned as a set of functional groups rather than as thousands of separate compounds.

Four ways of writing a formula are examined:

• General formula: the formula for a whole homologous series in terms of n, for example C_nH_2n+1OH for an alcohol.
• Structural formula: the minimum detail needed to show the arrangement unambiguously, for example CH₃CH(OH)CH₃.
• Displayed formula: every atom and every bond shown, so a C-H bond must be drawn.
• Skeletal formula: carbon and hydrogen atoms omitted, with the carbon chain shown as a zig-zag of lines and only the functional groups and heteroatoms written in. Each vertex and each free end is a carbon.

Skeletal formulas are the working language for the rest of the course, because a benzene ring or a long chain is unreadable when drawn fully. Practise converting between all four, since a question that asks for a displayed formula and receives a skeletal one gets nothing.

The new functional groups introduced at A Level include the arene ring, the phenol group (an OH attached directly to a benzene ring), amines, amides, nitriles and acyl chlorides.

Naming

The systematic name has three parts: a prefix for the substituents, a stem for the longest carbon chain, and a suffix for the principal functional group.

The routine, in order:

1. Find the longest continuous carbon chain that contains the principal functional group, and name it: meth, eth, prop, but, pent, hex.
2. Add the suffix for the principal functional group: -ol, -al, -one, -oic acid, -amine, -amide, -nitrile, -oate.
3. Number the chain so that the principal functional group gets the lowest possible number, and add substituent prefixes in alphabetical order.
4. Use di, tri and tetra for repeats, separate numbers with commas and numbers from letters with hyphens.

Cyclic compounds with a single ring of up to six carbons take the prefix cyclo: cyclohexane, cyclohexanol, cyclohexene.

Aromatic compounds with one benzene ring are named either as substituted benzenes or, where the ring is the substituent, using phenyl. Number the ring so the substituents get the lowest set of numbers, giving names like 3-nitrobenzoic acid and 2,4,6-tribromophenol. Where the principal group is on the ring, that carbon is number 1 by definition, which is why the nitro group in 3-nitrobenzoic acid is at position 3 and not position 1.

Two new mechanism types

Two mechanism names are introduced here and used repeatedly later.

Electrophilic substitution. An electrophile, an electron-pair acceptor, attacks a region of high electron density and replaces an atom or group. This is the characteristic reaction of the benzene ring, and the reason it substitutes rather than adds is the whole point of the next section: adding across the ring would destroy the delocalised system and the stability that goes with it, whereas substitution preserves it.

Addition-elimination. A nucleophile adds to a carbonyl or acyl carbon, and then a small molecule is eliminated, typically HCl or water. It is the characteristic reaction of acyl chlorides, and it also describes the reaction of a carbonyl compound with 2,4-dinitrophenylhydrazine. Sometimes called condensation, and the key feature is that the overall result is a substitution accomplished in two stages.

The shape of benzene

Benzene is C₆H₆, a planar regular hexagon with all bond angles 120°, and all six carbon-to-carbon bonds of the same length, intermediate between a single and a double bond.

The explanation runs through hybridisation:

1. Each carbon atom is sp² hybridised: one 2s and two 2p orbitals mix to give three sp² hybrid orbitals in a plane at 120° to one another, leaving one unhybridised 2p orbital perpendicular to that plane.
2. The three sp² orbitals form three sigma bonds, by head-on overlap: two to the neighbouring carbon atoms and one to a hydrogen. That gives the planar hexagonal skeleton with its 120° angles.
3. The six unhybridised 2p orbitals, one on each carbon, are parallel and perpendicular to the ring, and they overlap sideways with one another.
4. That sideways overlap forms a delocalised pi system, with the electron density in two rings, one above and one below the plane. The six pi electrons are not localised between any pair of carbons but spread over all six.

Three consequences are examinable:

• All six C-C bonds are identical in length, about 0.139 nm, between the 0.154 nm of a single bond and the 0.134 nm of a double bond. X-ray diffraction shows this directly, and it is the evidence against the Kekulé structure of alternating single and double bonds.
• Benzene is more stable than the Kekulé structure predicts, by an amount worked out below.
• Benzene undergoes substitution rather than addition, because addition would break up the delocalised system and lose that stabilisation, whereas substitution keeps it.

Worked example, the delocalisation energy. The enthalpy change of hydrogenation of cyclohexene, which has one double bond, is -120 kJ mol⁻¹. Three isolated double bonds would therefore give

3 × -120 = -360

that is -360 kJ mol⁻¹, yet the measured value for benzene is -208 kJ mol⁻¹. Benzene releases less energy than expected, so it started lower and is more stable. The difference

360 - 208 = 152

is 152 kJ mol⁻¹ of delocalisation energy, and it is the standard numerical argument for delocalisation.

A sigma bond is formed by head-on overlap of orbitals, with the electron density concentrated along the line between the nuclei, and it allows free rotation. A pi bond is formed by sideways overlap of p orbitals, with the electron density above and below that line, and it prevents rotation.

Optical isomerism

A carbon atom bonded to four different groups is a chiral centre, and a molecule containing one has no plane of symmetry. It therefore exists as two non-superimposable mirror images, called enantiomers or optical isomers.

The test to apply is exactly that: look for a carbon with four different groups attached. In 2-hydroxypropanoic acid, CH₃CH(OH)COOH, the middle carbon carries CH₃, OH, COOH and H, all different, so it is chiral.

Properties

Enantiomers have identical physical and chemical properties, the same melting point, boiling point, density and solubility, and they react identically with achiral reagents. There are exactly two differences:

• They rotate the plane of plane polarised light in opposite directions by equal amounts. One rotates it clockwise and is called dextrorotatory, or (+); the other rotates it anticlockwise and is called laevorotatory, or (-).
• They may have different biological activity, because the receptors and enzymes they interact with are themselves chiral, so only one enantiomer fits.

A substance that rotates plane polarised light is optically active.

A racemic mixture is an equal mixture of the two enantiomers. It is optically inactive, because the rotations produced by the two are equal and opposite and therefore cancel exactly.

Racemic mixtures arise naturally from certain mechanisms. In nucleophilic substitution by the S_N1 route, the intermediate carbocation is planar, so the nucleophile is equally likely to attack from either face, and the product is a 50:50 racemic mixture. The same is true of nucleophilic addition to a planar carbonyl group. Recognising that a planar intermediate produces a racemic mixture is a favourite question.

Chirality and drug molecules

This is where the syllabus asks for judgement rather than recall.

The two enantiomers may behave completely differently in the body. One may be the active drug while the other is inactive, produces unwanted side effects, or is toxic. The receptor site is chiral, so it binds one enantiomer and not the other, in the same way that a right hand fits only a right-handed glove.

A racemic mixture is therefore usually unsatisfactory. At best half of what is administered is useless, which means a doubled dose and a doubled load on the body to excrete the inactive half. At worst the other enantiomer is harmful.

Separating a racemic mixture is difficult and expensive, precisely because the two enantiomers have identical physical properties, so distillation, crystallisation and chromatography on ordinary stationary phases cannot tell them apart.

The better solution is not to make the mixture in the first place. A chiral catalyst provides a reaction environment that is itself asymmetric, so one enantiomer forms far faster than the other and the product is essentially a single pure optical isomer. The advantages are a higher yield of the wanted product, no separation step, less waste and lower cost.

Note that a compound may contain more than one chiral centre, in which case more than two stereoisomers exist. The syllabus states explicitly that knowledge of meso compounds and of terms such as diastereoisomers is not required.

Common mistakes

• Drawing a skeletal formula when a displayed formula is asked for, so the C-H bonds are missing.
• Numbering a chain from the wrong end, so the functional group gets a higher number than necessary.
• Choosing a carbon chain that is not the longest one containing the functional group.
• Drawing benzene with alternating single and double bonds when asked to show the delocalised structure, or drawing the circle inside a ring that also shows double bonds.
• Saying benzene is stable because it has double bonds. It is stable because the pi electrons are delocalised over all six carbons.
• Describing a pi bond as formed by head-on overlap, or a sigma bond as sideways.
• Forgetting that sp² hybridisation leaves one unhybridised p orbital per carbon, and it is those six that delocalise.
• Saying enantiomers have different melting points or different chemical reactions with ordinary reagents. Only plane polarised light and chiral environments distinguish them.
• Saying a racemic mixture rotates plane polarised light. It does not; the two rotations cancel.
• Identifying a chiral centre on a carbon that carries two identical groups.
• Saying a chiral catalyst separates the enantiomers. It prevents the unwanted one from forming.