Organic chemistry

Unit 7 introductionWhat organic chemistry is

Organic chemistry is the study of the preparation, properties, identification and modification of organic compounds. Every organic compound contains carbon. Almost all of them also contain hydrogen, and many contain oxygen, nitrogen, halogens, sulphur or phosphorus. A short definition used in the key points of the book is: organic chemistry is the chemistry of hydrocarbons and their derivatives.

Organic compounds are everywhere in daily life: carbohydrates, proteins and fats in food, medicines, cloth fibres, plastics (polymers), insecticides, cosmetics and dyes. Many industries exist only to make them.

A few simple carbon compounds are still treated as inorganic: carbon monoxide, carbon dioxide, carbonates such as $\mathrm{CaCO}{}_3$, hydrogencarbonates, cyanides and carbides. So a compound containing carbon is not automatically organic; organic compounds are built on a framework of carbon atoms bonded to hydrogen and to each other.

Nearly 19 to 20 million organic compounds are known. One big reason for this huge number is isomerism: the same set of atoms can be joined in different ways, or arranged differently in space, to give different compounds. Isomers exist because covalent bonds are directional (they point in fixed directions), so the shape of a molecule is fixed.

Recap (grade 11)Why carbon forms so many compoundsOften examined

This is a recap from grade 11, and a favourite short question. Carbon forms more compounds than all other elements put together because of a few special properties of the carbon atom.

1. Catenation

Catenation is the ability of atoms of an element to bond to each other to form long chains, branched chains and rings. Carbon shows it more than any other element because the $\mathrm{C}-\mathrm{C}$ bond is strong (about $348\mathrm{kJ}\mathrm{mo}{\mathrm{l}}^{-1}$). Silicon, the element below carbon, also catenates, but the $\mathrm{Si}-\mathrm{Si}$ bond is weaker (about $226\mathrm{kJ}\mathrm{mo}{\mathrm{l}}^{-1}$), so long silicon chains are not stable.

2. Tetravalency

A carbon atom has four valence electrons ($1{\mathrm{s}}^{2}2{\mathrm{s}}^{2}2{\mathrm{p}}^2$), so it forms four covalent bonds. In an $\mathrm{s}{\mathrm{p}}^3$ carbon the four bonds point to the corners of a tetrahedron ($109.5^{\circ }$ apart). With four bonds per atom, chains can branch in many ways, and each carbon can carry different atoms or groups.

3. Multiple bonds

Carbon forms stable double and triple bonds, both with itself ($\mathrm{C}=\mathrm{C}$, $\mathrm{C}\equiv \mathrm{C}$) and with oxygen and nitrogen ($\mathrm{C}=\mathrm{O}$, $\mathrm{C}\equiv \mathrm{N}$). This multiplies the number of possible structures. Carbon's small size lets the p orbitals of two carbon atoms come close enough for good sideways overlap, which is why its $\pi$ bonds are strong.

4. Bonding with other elements

Carbon bonds strongly with H, O, N, S, P and the halogens. These atoms form functional groups (such as $-\mathrm{OH}$, $-\mathrm{COOH}$, $-\mathrm{NH}{}_2$), and each functional group gives a new family of compounds.

5. Isomerism

The same molecular formula can have many structures. The number of possible isomers grows very fast as the number of carbon atoms increases:

Recap (grade 11)Classification of organic compounds

Organic compounds are classified by the way their carbon atoms are joined: in open chains, or in closed rings.

Open-chain (acyclic or aliphatic) compounds

The carbon atoms form straight or branched chains, not rings. Saturated ones have only single bonds (alkanes). Unsaturated ones have at least one $\mathrm{C}=\mathrm{C}$ or $\mathrm{C}\equiv \mathrm{C}$ (alkenes, alkynes).

Closed-chain (cyclic) compounds

The atoms form one or more rings.

Homocyclic (carbocyclic) compounds

The ring contains only carbon atoms. Alicyclic compounds (such as cyclohexane) behave like open-chain compounds. Aromatic compounds contain a benzene-type ring with delocalised $\pi$ electrons (such as benzene and naphthalene).

Heterocyclic compounds

The ring contains at least one atom other than carbon (a heteroatom), usually N, O or S. Examples: pyridine, furan, thiophene.

Recap (grade 11)Functional groupsOften examined

A functional group is an atom or group of atoms in a molecule that decides its characteristic chemical reactions. The rest of the molecule, the hydrocarbon part, is written $\mathrm{R}$ (an alkyl group such as $\mathrm{CH}{}_3{}^{-}$ or $\mathrm{C}{}_2\mathrm{H}{}_5{}^{-}$). All compounds with the same functional group react in a similar way, so learning one member teaches you the whole family.

Recap (grade 11)Homologous seriesOften examined

A homologous series is a family of organic compounds that have the same functional group and the same general formula, in which each member differs from the next by one $-\mathrm{CH}{}_2-$ unit. Each member is a homologue of the others.

• All members have the same general formula, for example $\mathrm{C}{}_n\mathrm{H}{}_{2n+2}$ for alkanes.
• Successive members differ by $-\mathrm{CH}{}_2-$, which is $14$ units of relative molecular mass.
• All members have the same functional group, so they have similar chemical properties.
• Physical properties (boiling point, melting point, density) change gradually as the chain gets longer.
• Members can be made by similar general methods.

Recap (grade 11)IUPAC names: a quick recap

You need names to talk about isomers, so here is a short reminder of the IUPAC system. A name has three parts: prefix (substituents such as methyl or chloro, with their positions), word root (number of carbons in the main chain) and suffix (the family: -ane, -ene, -ol and so on).

1. Find the longest chain that contains the functional group or the multiple bond.
2. Number it from the end that gives the functional group (or the \ce{C=C}) the lowest number; then give the side chains the lowest numbers.
3. Name side chains as prefixes in alphabetical order, each with its position number; use di-, tri-, tetra- for repeats (2,3-dimethyl).
4. Use commas between numbers and hyphens between numbers and words (2,3,4-trimethylhept-3-ene).
5. For stereoisomers put cis/trans or (E)/(Z) in front of the name: trans-but-2-ene, (E)-but-2-ene.

7.1IsomerismOften examined

Isomerism is the existence of two or more compounds with the same molecular formula but different structures. The compounds are called isomers. Isomers are different substances: they have different physical properties, and often different chemical properties too.

Isomerism is divided into two broad classes:

Structural (constitutional) isomerism

The atoms are joined in a different order (different connectivity), so the isomers have different structural formulae. Example: butane and 2-methylpropane, both \ce{C4H10}.

Stereoisomerism (configurational isomerism in the book)

The atoms are joined in the same order (same structural formula) but are arranged differently in space. Example: cis- and trans-but-2-ene.

Recap (grade 11)Structural isomerismOften examined

The book revises structural isomerism only briefly, but it is examined (for example 'draw three structural isomers of \ce{C4H10O}'). There are five types.

1. Chain isomerism

The isomers have different carbon skeletons (straight or branched chains). Example: the three isomers of \ce{C5H12}.

2. Position isomerism

Same carbon skeleton and same functional group, but the functional group (or multiple bond) is at a different position.

3. Functional group isomerism

Same molecular formula, but different functional groups, so the isomers belong to different families.

4. Metamerism

Different alkyl groups on the two sides of the same functional group, such as \ce{-O-}, \ce{-CO-} or \ce{-NH-}.

5. Tautomerism

Two structural isomers that change into each other rapidly by the movement of a hydrogen atom and a double bond, and exist together in equilibrium. The common case is keto-enol tautomerism:

propanone (keto form, over 99.9%) \rightleftharpoons prop-1-en-2-ol (enol form)

7.1.1StereoisomerismOften examined

Stereoisomers are molecules that have the same molecular formula and the same structural formula (the same atoms joined in the same order) but a different arrangement of atoms or groups in space. The phenomenon is called stereoisomerism.

Why does this matter? Most reactions in our body are controlled by enzymes. An enzyme's active site has a fixed 3D shape, so it accepts only the stereoisomer that fits it. A medicine made as the wrong stereoisomer may not work, or may cause side effects, because it does not fit the target site.

Conformational isomers (conformers)

Different arrangements of the same molecule produced by rotation about a single bond. No bond is broken, the energy needed is small, and conformers change into each other millions of times a second at room temperature, so they cannot be separated.

Configurational isomers

Stereoisomers that can be changed into each other only by breaking and re-forming bonds. They are stable, separable compounds. They are of two kinds: geometrical (cis-trans) and optical isomers.

Enantiomers

Configurational isomers that are non-superimposable mirror images of each other.

Diastereomers

Stereoisomers that are not mirror images of each other, for example meso-tartaric acid and (+)-tartaric acid.

7.1.1 (1)Geometric isomerism and restricted rotationOften examined

Geometric isomers have the same molecular formula and the same structural formula (same connectivity) but a different arrangement of atoms or groups around a double bond. This type of stereoisomerism is called geometric isomerism (or cis-trans isomerism).

Bonding in an alkene

Each carbon atom of the \ce{C=C} bond is \mathrm{sp^2} hybridised. Its three \mathrm{sp^2} orbitals lie in one plane at 120^\circ to each other, and one unhybridised \mathrm{2p_z} orbital stands at right angles to that plane.

• The **sigma (\sigma) bond forms by head-on overlap** of one \mathrm{sp^2} orbital from each carbon, along the line joining the two nuclei.
• The **pi (\pi) bond forms by sideways (parallel) overlap** of the two \mathrm{2p_z} orbitals. Its electron cloud lies above and below the plane of the molecule.

Why rotation is restricted

To rotate one carbon of a double bond relative to the other, the two p orbitals must stop being parallel, so the \pi bond must break. Breaking the \pi bond of ethene needs about 264\,\mathrm{kJ\,mol^{-1}}. Molecules at room temperature do not have this much energy, so there is no free rotation about a \ce{C=C} bond. The groups attached to it are locked in place.

In an alkane, rotating about the \ce{C-C} single bond does not break anything, because the \sigma bond is symmetrical around the bond axis. It needs only about 12\,\mathrm{kJ\,mol^{-1}} (the staggered to eclipsed barrier), which collisions easily supply. So a major difference between alkanes and alkenes is the freedom of rotation: free about \ce{C-C}, restricted about \ce{C=C}.

Conditions for geometric isomerism

1. Restricted rotation: a \ce{C=C} bond (or a ring).
2. Two different groups on each doubly bonded carbon: the alkene must be \ce{abC=Cab} or \ce{abC=Cde} with a\ne b and d\ne e.

If one carbon of the double bond carries two identical atoms or groups, swapping the positions of the groups on the other carbon gives the same molecule, so no geometric isomers exist. The book shows this with but-1-ene: C1 carries two hydrogen atoms, and 'rotating' the double bond only turns the molecule over.

7.1.1 (i)The cis-trans system of namingOften examined

IUPAC recommends two ways of naming geometric isomers: the cis-trans system and the E/Z system. The cis-trans system was first used for disubstituted alkenes of the type \ce{RCH=CHR'}.

cis isomer

The two similar groups (or the two main-chain carbons) are on the same side of the double bond. 'Cis' is Latin for 'on the same side'.

trans isomer

The two similar groups (or the two main-chain carbons) are on opposite sides of the double bond. 'Trans' is Latin for 'across'.

In but-2-ene the two methyl groups (C1 and C4 of the main chain) decide the name. They are on the same side in cis-but-2-ene and on opposite sides in trans-but-2-ene.

Pent-2-ene has three different kinds of substituent (methyl, ethyl and hydrogen), which looks harder. Treat every alkyl group as a 'main-chain' group: the cis isomer has the two alkyl groups on the same side and the two hydrogen atoms on the same side. Equivalently (book's key information), you can decide cis or trans by looking only at the two hydrogen atoms on the double-bond carbons.

7.1.1Properties of cis and trans isomersOften examined

Cis and trans isomers are different compounds, so their physical properties (melting point, boiling point, density, solubility, dipole moment) are different. Their chemical properties are similar, because they have the same functional groups, but not identical.

Polarity and boiling point

In cis-1,2-dichloroethene both polar \ce{C-Cl} bonds point towards the same side, so their bond dipoles add up to a resultant dipole moment of about 1.9\,\mathrm{D}. The molecule is polar. In the trans isomer the two equal bond dipoles point in opposite directions and cancel, so the resultant dipole moment is zero and the molecule is non-polar.

Polar cis molecules attract each other by dipole-dipole forces as well as London forces, so the cis isomer usually has the higher boiling point. The more symmetrical trans molecules pack more neatly in a crystal, so the trans isomer usually has the higher melting point.

Stability and reactivity

In the cis isomer the two bulky groups sit close together on the same side of the double bond. Their electron clouds repel each other (steric hindrance or steric strain), which raises the energy of the molecule. So the cis isomer is less stable than the trans isomer. Because it has more energy stored, the cis isomer is also more reactive. The book adds that the electron cloud of the cis isomer is pushed towards one side, which leaves the \pi bond more exposed to attack by electrophiles.

Both isomers give the same product (butane), so the difference in heat released is the difference in their energies.

A chemical difference: maleic and fumaric acid

Maleic acid (cis) has both \ce{-COOH} groups on the same side, close enough to lose a molecule of water on heating to about 140^\circ\mathrm{C} and form a cyclic anhydride. Fumaric acid (trans) cannot do this, because its \ce{-COOH} groups are too far apart.

Different behaviour in living things

7.1.1 (key points)The E/Z system

The book's key points and exercise use the E/Z system, but the text does not explain it, so here it is. The cis-trans names work well only when each double-bond carbon carries one hydrogen atom. For tri- and tetra-substituted alkenes they become unclear. For example, in 1-bromo-1-chloroprop-1-ene the carbon C1 carries Br and Cl and no hydrogen, so 'cis' has no clear meaning. IUPAC therefore recommends the E/Z system, which works for every alkene.

Cahn-Ingold-Prelog (CIP) priority rules

Look at each carbon of the double bond separately and decide which of its two groups has the higher priority:

1. Rule 1. Compare the atoms directly attached to the double-bond carbon. The atom with the higher atomic number has higher priority: \ce{I}>\ce{Br}>\ce{Cl}>\ce{S}>\ce{F}>\ce{O}>\ce{N}>\ce{C}>\ce{H}.
2. Rule 2. If these atoms are the same, move one atom further out and compare the sets of atoms attached, at the first point of difference. For example \ce{-CH2CH3} (C, H, H) beats \ce{-CH3} (H, H, H), and \ce{-CH2OH} (O, H, H) beats \ce{-C(CH3)3} (C, C, C) because O beats C at the first point of difference.
3. Rule 3. A double or triple bond counts its atoms twice or three times: \ce{-CH=CH2} is treated as (C, C, H).
4. Rule 4. For isotopes, the higher mass number wins: D beats H.

Z isomer

The two higher-priority groups are on the same side of the double bond (German zusammen, together).

E isomer

The two higher-priority groups are on opposite sides (German entgegen, opposite).

SLO (see also unit 8)Shape of benzene and other aromatic molecules

The SLO box asks for the shape of benzene, which is treated in detail in unit 8. Benzene, \ce{C6H6}, is a flat regular hexagon of six carbon atoms, each carrying one hydrogen atom.

• Each carbon atom is **\mathrm{sp^2} hybridised**. Its three \mathrm{sp^2} orbitals form three \sigma bonds: two \ce{C-C} bonds (by \mathrm{sp^2}-\mathrm{sp^2} overlap) and one \ce{C-H} bond (by \mathrm{sp^2}-\mathrm{1s} overlap).
• All 12 atoms lie in one plane and every bond angle is 120^\circ. This planar set of \sigma bonds is the **\sigma framework**.
• Each carbon keeps one unhybridised \mathrm{2p} orbital (holding one electron) at right angles to the ring. Each p orbital overlaps sideways with the p orbitals on both neighbours, not just one.
• The result is a continuous ring of \pi electron density above and below the plane of the ring: a **delocalised \pi system** holding 6 electrons that belong to all six carbons.

Evidence for delocalisation: all six \ce{C-C} bonds have the **same length, 139\,\mathrm{pm}**, between a single bond (154\,\mathrm{pm}) and a double bond (134\,\mathrm{pm}). Benzene is also much more stable than a ring of three separate double bonds would be: its enthalpy of hydrogenation is about -208\,\mathrm{kJ\,mol^{-1}}, not the 3\times(-120)=-360\,\mathrm{kJ\,mol^{-1}} expected, so it is about 150\,\mathrm{kJ\,mol^{-1}} more stable.

Other aromatic molecules have the same features: a flat ring of \mathrm{sp^2} atoms with a delocalised \pi cloud. Naphthalene (two fused rings) and pyridine (one N in the ring) are examples.

Benzene and isomerism

Disubstituted benzenes show position isomerism: the two groups can be at positions 1,2 (ortho), 1,3 (meta) or 1,4 (para). Benzene does not show cis-trans isomerism, because all the substituents lie in the flat plane of the ring, so there are no two 'sides' to put them on.

7.1.2Optical isomerism and chiralityOften examined

The easiest way to understand optical isomerism is to look at your hands. Your right hand is the mirror image of your left hand, yet the two cannot be placed one on top of the other so that every part matches, however you turn them. They are non-superimposable mirror images. A right-handed glove does not fit your left hand for the same reason.

Chiral

An object or molecule that is non-superimposable on its mirror image (Greek 'cheir', meaning hand). Examples of chiral objects: hands, gloves, shoes, scissors, screws.

Achiral

An object or molecule that is superimposable on its mirror image. It usually has a plane of symmetry. Examples: a ball, a cup, a pencil.

Chirality

The property of 'handedness': having a left-handed and a right-handed form.

Chiral (asymmetric) carbon

A carbon atom bonded to four different atoms or groups. It is also called a chiral centre or stereocentre and is marked with an asterisk (\ce{C}^*).

Many organic molecules exist as a pair of non-superimposable mirror images. Such molecules usually contain a chiral carbon. For example, bromochlorofluoromethane, \ce{CHBrClF}, has a carbon bonded to H, F, Cl and Br: four different atoms. Its mirror image cannot be superimposed on it. But in \ce{CHBrF2} the carbon carries two identical F atoms; the molecule has a plane of symmetry, and its mirror image is the same molecule.

Enantiomers

A pair of stereoisomers that are non-superimposable mirror images of each other, like a right and a left hand (Greek 'enantion', opposite). The phenomenon is enantiomerism.

The book's example is 3-methylhexane. Its C3 carries four different groups, H, \ce{CH3}, \ce{C2H5} and \ce{C3H7}, so it exists as two enantiomers. Even a simple alkane can be chiral.

In each pair above the two drawings are identical except that the wedge and the hashed bond are swapped. Swapping any two groups on a chiral carbon turns one enantiomer into the other.

7.1.2Plane-polarized light and optical activityOften examined

Ordinary light is a wave whose vibrations occur in all planes at right angles to its direction of travel. When it passes through a polarizing filter, such as a calcite (Nicol) prism or a Polaroid sheet, only the vibrations in one plane get through. Light vibrating in only one plane is called plane-polarized light.

Optically active substance

A substance that rotates the plane of plane-polarized light. Chiral compounds (optical isomers) are optically active.

Optical isomerism

Isomerism shown by compounds that rotate the plane of polarized light, either clockwise or anticlockwise. The isomers are optical isomers.

Dextrorotatory, (+)

Rotates the plane clockwise (to the right, as seen by the observer). Latin 'dexter' means right.

Levorotatory, (-)

Rotates the plane anticlockwise (to the left). Latin 'laevus' means left.

Polarimeter

The instrument that measures the rotation and so detects optical activity.

The two enantiomers of a compound rotate the plane by the same angle but in opposite directions. For example, a standard solution of one enantiomer of butan-2-ol rotates the plane by +13.5^\circ and the other by -13.5^\circ. The older symbols 'd' (dextro) and 'l' (levo) are now obsolete; IUPAC recommends (+) and (-).

7.1.2Racemic mixtures and meso compoundsOften examined

Racemic mixture

A racemic mixture (racemate) contains equal amounts (50:50) of the two enantiomers: 50% dextrorotatory and 50% levorotatory. It is optically inactive. Each enantiomer rotates the plane by the same angle in opposite directions, so the two effects cancel. This cancelling between molecules of two different kinds is called external compensation. A racemic mixture is written with the prefix (\pm).

A reaction that makes a chiral centre from achiral starting materials gives a racemic mixture, because the reagent attacks the two faces of the flat reactant equally often. For example, lactic acid made in the laboratory is (\pm), while the lactic acid formed in our muscles is a single enantiomer.

Meso compounds

A meso compound has two (or more) chiral carbon atoms but also an internal plane of symmetry. One half of the molecule is the mirror image of the other half, so the rotation caused by one half is cancelled by the other half inside the same molecule. This is internal compensation. A meso compound is superimposable on its mirror image, so it is optically inactive (the book: 'optically inactive although it has chiral carbon atoms').

Tartaric acid, \ce{HOOC-CH(OH)-CH(OH)-COOH}, has two chiral carbons. It exists as three stereoisomers: a pair of enantiomers, (+)- and (-)-tartaric acid, and meso-tartaric acid. Meso-tartaric acid is a diastereomer of each of the other two.

Molecules with more than one chiral centre

A molecule with n chiral carbons can have at most 2^n stereoisomers. If the molecule can be divided into two identical halves, meso forms appear and the number is smaller. Tartaric acid has n=2, so up to 2^2=4 are possible, but only 3 exist because the 'fourth' isomer is the meso form again.

The book's second example is 1,2-dimethylcyclobutane. Its trans isomer is chiral and exists as a pair of enantiomers. Its cis isomer has a plane of symmetry through the ring, so it is a meso compound.

Natural products are often chiral. Nicotine, made by the tobacco plant, has one chiral carbon (the ring carbon joined to the pyridine ring), and the plant makes only one enantiomer, (-)-nicotine.

7.1.3Properties of optical isomersOften examined

Enantiomers have identical physical and chemical properties in an ordinary (achiral) environment: the same melting point, boiling point, density and solubility, and the same reactions with achiral reagents. For example, both enantiomers of a compound have the same density and the same melting point.

They differ in only two ways: (1) they rotate plane-polarized light by the same angle in opposite directions, and (2) they behave differently towards other chiral things, such as enzymes, receptors in the nose and tongue, and drug targets in the body.

Pharmacokinetics

The study of how the body absorbs, distributes, metabolises and excretes a drug.

Pharmacodynamics

The study of what the drug does to the body and how it binds to its target site.

7.2Chirality and preparation of drugsOften examined

Designing, making and selling medicines is a huge industry, and every new drug is expensive to develop. Because the targets of drugs in the body (enzymes and receptors) are chiral, the two enantiomers of a chiral drug can act very differently, so chemists must know which enantiomer does what.

Propoxyphene: one enantiomer is an analgesic (pain reliever) and its mirror image relieves coughing. The two were even sold under mirror-image trade names, Darvon and Novrad.

The thalidomide tragedy

Thalidomide was sold from 1957 as a racemic mixture and prescribed as a sedative and for morning sickness (nausea) in pregnant women. It was then found to cause serious birth defects (for example, missing or shortened limbs) in thousands of babies whose mothers took it, and it was withdrawn in 1961. Research showed that the (+)-enantiomer is the useful sedative, while the (-)-enantiomer is teratogenic (causes birth defects).

Unfortunately, the two enantiomers of thalidomide interconvert in the body. The hydrogen on the chiral carbon sits next to a \ce{C=O} group, so it can be removed and put back from either side under body conditions. A dose of pure (+)-thalidomide therefore turns partly into the harmful (-) form within hours, and giving one enantiomer does not prevent the harm.

7.2.1Separation of racemic thalidomideOften examined

Most chiral drugs are first made as racemic mixtures (50% (+) and 50% (-)), because ordinary reactions cannot tell the two faces of a flat reactant apart. Health professionals do not advise racemic drugs, because one enantiomer may be active while the other is inactive, less effective or even harmful, as thalidomide showed. There are two ways to obtain a single enantiomer.

Method 1: optical resolution

Optical resolution is the separation of a racemic mixture into its two enantiomers, after which the unwanted (-)-thalidomide is removed. Enantiomers have identical physical properties, so ordinary distillation or crystallisation cannot separate them; a chiral 'helper' is needed:

• High-performance liquid chromatography (HPLC) on a column packed with a chiral stationary phase: one enantiomer is held more strongly and comes out later.
• Crystallisation: the racemate is reacted with a pure chiral acid or base (a resolving agent). This gives two diastereomeric salts, which have different solubilities and can be separated by fractional crystallisation; each pure enantiomer is then set free again.
• Enzymes: an enzyme is chiral, so it reacts with (or is made to act on) only one enantiomer, leaving the other untouched.

Method 2: chiral (asymmetric) synthesis

Asymmetric synthesis makes mainly the desired enantiomer, such as (+)-thalidomide, and suppresses the formation of the other. It uses a chiral catalyst, which creates a chiral environment around the reacting molecule so that the reaction on one face is much faster than on the other. The book mentions BINOL (1,1'-bi-2-naphthol) catalysts combined with palladium or rhodium.

In the route described by the book, a \ce{C=C} double bond in the starting molecule (at the position that will become the chiral carbon) is selectively hydrogenated in the presence of the chiral catalyst. The catalyst lets \ce{H2} add from one face only, so one enantiomer forms in preference to the other.

Advantages of chiral catalysts: a small amount of catalyst makes a large amount of product; no half of the product is thrown away as the unwanted isomer; fewer separation steps are needed, so the process is cheaper and produces less waste. The 2001 Nobel Prize in Chemistry (Knowles, Noyori and Sharpless) was awarded for chiral catalysts of this kind.

Formula sheet

Key terms

Organic chemistry

The chemistry of hydrocarbons and their derivatives: their preparation, properties, identification and modification.

Catenation

The ability of atoms of an element to bond to each other to form chains and rings; carbon shows it most because the \ce{C-C} bond is strong.

Tetravalency

The ability of a carbon atom to form four covalent bonds, because it has four valence electrons.

Functional group

An atom or group of atoms in a molecule that decides its characteristic chemical properties, for example \ce{-OH}, \ce{-CHO}, \ce{-COOH}.

Homologous series

A family of compounds with the same functional group and the same general formula, in which each member differs from the next by a \ce{CH2} unit; members show similar chemical properties and gradually changing physical properties.

Isomers

Compounds with the same molecular formula but different structures or different arrangements of atoms in space.

Structural isomerism

Isomerism in which the atoms are joined in a different order; types are chain, position, functional group, metamerism and tautomerism.

Chain isomerism

Structural isomers that differ in the carbon skeleton (straight or branched chain).

Position isomerism

Structural isomers that have the same carbon skeleton and functional group but the group is at a different position.

Functional group isomerism

Structural isomers that have different functional groups, for example an alcohol and an ether of the same formula.

Metamerism

Isomerism in which different alkyl groups are attached on either side of the same polyvalent functional group, for example in ethers.

Tautomerism

A special structural isomerism in which two isomers change into each other by the movement of a hydrogen atom, for example keto-enol tautomerism in propanone.

Stereoisomerism

Isomerism in which compounds have the same structural formula but a different arrangement of atoms or groups in space; its types are geometric and optical isomerism.

Geometric (cis-trans) isomerism

Stereoisomerism caused by restricted rotation about a double bond (or in a ring), when each doubly bonded carbon carries two different groups.

Cis isomer

The geometric isomer in which similar groups are on the same side of the double bond.

Trans isomer

The geometric isomer in which similar groups are on opposite sides of the double bond.

E/Z system

A naming system for geometric isomers based on priority (atomic number) rules: Z (zusammen) when the higher-priority groups are on the same side, E (entgegen) when they are on opposite sides.

Chiral molecule

A molecule that is non-superimposable on its mirror image (it has handedness).

Chiral carbon (chiral centre)

A carbon atom bonded to four different atoms or groups; it is also called an asymmetric carbon.

Enantiomers

A pair of stereoisomers that are non-superimposable mirror images of each other.

Optical isomerism

Stereoisomerism in which isomers differ in their effect on plane-polarized light.

Plane-polarized light

Light whose vibrations occur in one plane only; it is produced by passing ordinary light through a Nicol prism or polaroid.

Optically active

Able to rotate the plane of plane-polarized light.

Dextrorotatory (+)

An optical isomer that rotates the plane of polarized light clockwise (to the right).

Laevorotatory (−)

An optical isomer that rotates the plane of polarized light anticlockwise (to the left).

Polarimeter

The instrument that measures the angle and direction through which an optically active substance rotates plane-polarized light.

Racemic mixture

An equimolar (50:50) mixture of the dextro and laevo forms of a compound; it is optically inactive by external compensation.

Meso compound

A compound that has chiral carbons but is optically inactive because it has an internal plane of symmetry (internal compensation).

Resolution

The separation of a racemic mixture into its two pure enantiomers.

Chiral catalyst

A catalyst that is itself chiral and makes one enantiomer much faster than the other, so a single pure optical isomer is produced.

Thalidomide

A drug sold in the 1950s as a sedative; one enantiomer relieves morning sickness while the other causes birth defects (teratogenic).

Delocalised pi system

In benzene, the six unhybridised p orbitals overlap sideways all round the ring, so six \pi electrons are spread over all six carbon atoms.

FBISE 2026 questions

Questions from the FBISE HSSC-II 2026 (1st Annual) papers that belong to this unit, answered the way an examiner expects.

Exam focus

1. Why does carbon form more compounds than any other element? (short)
   Asked in the 2026 old-syllabus paper (1.5 + 1.5 marks); catenation and tetravalency are the two expected reasons.
   Go to answer
2. Draw cis and trans isomers of but-2-ene and say which is more stable. (short)
   Asked in 2026 Set D Q.2 (vi); also a book long question. Steric strain and hydrogenation enthalpies give the reason.
   Go to answer
3. Why can propene not show cis-trans isomerism? (long)
   The condition 'two different groups on each doubly bonded carbon' is tested every year.
   Go to answer
4. Identify chiral carbons and decide whether a molecule is optically active. (short)
   Three 2026 questions (Set B Q.2 (vi), Set D Q.2 (vii), old-syllabus MCQ 10) test only this skill.
   Go to answer
5. Draw a pair of enantiomers of butan-2-ol and mark the chiral centre. (short)
   Asked in 2026 Set D Q.2 (viii); wedge-dash drawing on both sides of a mirror earns the marks.
   Go to answer
6. Racemic mixture and meso compound: why are both optically inactive? (short)
   External versus internal compensation is a standard short question and MCQ.
   Go to answer
7. Designate alkenes as E or Z using priority rules. (short)
   Book short question (i); needs the atomic-number priority rule applied to each carbon.
   Go to answer
8. Importance of chirality in drugs and the thalidomide example; separation of a racemic mixture. (long)
   Book long questions (iii) and (iv) and short questions (iii), (ix), (x) all come from this SLO.
   Go to answer
9. Why is the trans isomer more stable while the cis isomer has the higher boiling point? (long)
   Book long questions (v) and (vi): stability from steric strain, boiling point from polarity.
   Go to answer
10. Structural isomers of \ce{C4H10O} and types of structural isomerism. (short)
    Asked in the 2026 old-syllabus paper (Q.2 (ix) OR); also common in MCQs.
    Go to answer