Appearance
10.7 — Organic Chemistry Essentials
Ten million carbon compounds are known and more are made every day. Memorising them is impossible and unnecessary, because they organise into about a dozen families, and within each family every member behaves the same way.
A functional group is a specific arrangement of atoms that reacts in a characteristic way regardless of what it is attached to. Learn twelve groups and you can predict the chemistry of most of the ten million.
Why carbon does this
Chapter 9.6 gave the four reasons, and they bear repeating in one line: carbon makes four bonds, bonds strongly to itself, forms stable double and triple bonds, and has an electronegativity right in the middle.
No other element has all four, and the nearest competitor, silicon, fails on three of them.
The consequence is combinatorial. Chapter 10.2 noted that C₃₀H₆₂ has over four billion structural isomers. The number of possible carbon compounds is effectively unbounded.
The skeleton
Alkanes — only single bonds, C_nH_{2n+2}. Saturated, meaning no more hydrogen can be added.
| Name | Formula | Boiling point | Use |
|---|---|---|---|
| Methane | CH₄ | -161 °C | Natural gas |
| Ethane | C₂H₆ | -89 °C | |
| Propane | C₃H₈ | -42 °C | Bottled gas |
| Butane | C₄H₁₀ | -0.5 °C | Lighters |
| Octane | C₈H₁₈ | 126 °C | Petrol |
| Hexadecane | C₁₆H₃₄ | 287 °C | Diesel |
| C₂₀+ | Wax, bitumen |
The boiling points rise smoothly with chain length, because dispersion forces grow with molecular surface area (Chapter 10.3). Fractional distillation of crude oil is entirely this one trend, separating a mixture by boiling point into fuel gas, petrol, kerosene, diesel, lubricating oil and bitumen.
Alkanes are unreactive — that is what "saturated" means chemically. C–C and C–H bonds are strong and barely polar, so there is no site for a reagent to attack. They burn, and that is about all they do easily, which is exactly why they are fuels.
Alkenes contain C=C, C_nH_{2n}. Reactive, because the pi bond's electrons are exposed above and below the plane and are easily attacked.
Alkynes contain C≡C, C_nH_{2n-2}. More reactive still.
Arenes contain benzene rings, and Chapter 10.2 explained why the delocalisation makes them stable and why they substitute rather than add.
The functional groups
Each group has a characteristic reactivity, and the reason is almost always the same: a polar bond or a lone pair.
| Group | Structure | Name ending | Example |
|---|---|---|---|
| Alkene | C=C | -ene | Ethene |
| Halide | C–X | halo- | Chloroethane |
| Alcohol | C–OH | -ol | Ethanol |
| Ether | C–O–C | -yl ether | Diethyl ether |
| Amine | C–NH₂ | -amine | Methylamine |
| Aldehyde | CHO | -al | Ethanal |
| Ketone | C=O (internal) | -one | Propanone |
| Carboxylic acid | COOH | -oic acid | Ethanoic acid |
| Ester | COO–C | -oate | Ethyl ethanoate |
| Amide | CONH₂ | -amide | Ethanamide |
| Nitrile | C≡N | -nitrile | Ethanenitrile |
| Thiol | C–SH | -thiol | Ethanethiol |
The carbonyl group, C=O, is the most important of all, because it appears in aldehydes, ketones, acids, esters and amides — and because oxygen's electronegativity of 3.44 against carbon's 2.55 makes it strongly polarised.
\text{C}^{\delta+}\!\!=\!\!\text{O}^{\delta-}
The carbon is electron-poor and attracts anything with a lone pair. That single fact drives most of organic chemistry and most of biochemistry.
Alcohols
C–OH. The oxygen carries two lone pairs and the O–H bond is polar, so alcohols hydrogen bond (Chapter 10.3).
Consequences. Ethanol boils at 78 °C while propane, of similar mass, boils at -42 °C — 120 degrees, from one hydrogen bond. And short alcohols mix with water in all proportions.
Solubility falls with chain length. Methanol, ethanol and propanol are fully miscible; butanol is partly soluble; anything above about six carbons is not. The non-polar tail eventually outweighs the polar head, which is exactly the balance that makes soap work.
Classification by how many carbons attach to the carbon bearing the OH: primary, secondary, tertiary. This determines what oxidation does:
\text{Primary} \to \text{aldehyde} \to \text{carboxylic acid}
\text{Secondary} \to \text{ketone (and stops)}
\text{Tertiary} \to \text{no reaction}
Tertiary alcohols cannot be oxidised because there is no hydrogen on the carbon to remove. The mechanism explains the rule, which is the pattern throughout this chapter.
Methanol is toxic and ethanol is not, and the reason is exactly this oxidation. The same enzyme, alcohol dehydrogenase, oxidises both — ethanol to acetaldehyde and then harmless acetate, methanol to formaldehyde and then formic acid, which attacks the optic nerve and causes acidosis.
The treatment is to give the patient ethanol, which competes for the enzyme and lets the methanol be excreted unchanged. A competitive inhibition problem, treated with whisky.
Carboxylic acids
COOH. Acidic, with p$K_a$ around 4–5 (Chapter 10.5).
Why acidic when alcohols are not? Because the conjugate base is stabilised by resonance. After losing the proton, the negative charge is delocalised over both oxygens, and the two C–O bonds become identical in length. An alkoxide from an alcohol has the charge stuck on one oxygen.
Delocalisation lowers the energy of the anion, which shifts the equilibrium towards dissociation. Acetic acid's p$K_a$ is 4.76; ethanol's is 16 — eleven orders of magnitude, from one resonance structure.
And substituents shift it further. Adding electronegative atoms pulls electron density away and stabilises the anion more:
| Acid | p$K_a$ |
|---|---|
| Acetic, CH₃COOH | 4.76 |
| Chloroacetic, ClCH₂COOH | 2.86 |
| Dichloroacetic | 1.29 |
| Trichloroacetic | 0.65 |
Three chlorines make it a thousand times stronger, and the effect falls off rapidly with distance — an inductive effect transmitted through sigma bonds.
Esters and amides
Esters form from an acid and an alcohol, with water lost:
\text{RCOOH}+\text{R}'\text{OH} \rightleftharpoons \text{RCOOR}'+\text{H}_2\text{O}
Reversible, so Le Chatelier applies (Chapter 10.4) — remove water to drive it forward, add water to reverse it.
Esters smell. Ethyl butanoate is pineapple, isoamyl acetate is banana, methyl salicylate is wintergreen. Most artificial flavourings are esters, and so are most natural fruit aromas.
Fats and oils are triesters of glycerol with three long-chain fatty acids. Saponification — boiling a fat with sodium hydroxide — hydrolyses them to glycerol and sodium salts of the fatty acids. Those salts are soap, with a polar head and a long non-polar tail, which is why soap has worked since about 2800 BC.
Amides form from an acid and an amine, and they are far more stable than esters because the nitrogen's lone pair delocalises into the carbonyl, giving the C–N bond partial double-bond character.
That partial double bond is rigid, and it is what makes protein structure possible. The peptide bond is an amide, and its rigidity restricts the backbone to a limited set of conformations — which is why proteins fold into definite shapes rather than random tangles (Chapter 10.8).
And nylon is a polyamide, made from a diacid and a diamine, with exactly the same bond as a protein.
Mechanisms
A mechanism shows where the electrons go, using curly arrows: each arrow starts at an electron pair and points where it moves.
Two species types:
Nucleophile — electron-rich, seeking positive charge. Anything with a lone pair or a pi bond.
Electrophile — electron-poor, seeking electrons. Anything with a partial positive charge or an empty orbital.
Nucleophiles attack electrophiles. That is the entire logic.
Substitution: SN1 and SN2
Replacing one group with another, and there are two distinct routes with completely different behaviour.
SN2 — one step. The nucleophile attacks the back side while the leaving group departs.
\text{rate} = k[\text{substrate}][\text{nucleophile}]
Second order, since both are in the rate-determining step.
And it inverts the stereochemistry. The nucleophile comes in opposite to the leaving group, so a chiral centre flips — like an umbrella turning inside out. This is the Walden inversion, and it is direct evidence for the mechanism.
It requires access to the back side, so it is fast for primary carbons and impossible for tertiary ones, which are shielded by three bulky groups.
SN1 — two steps. The leaving group departs first, forming a carbocation, which the nucleophile then attacks.
\text{rate} = k[\text{substrate}]
First order, because only the substrate is in the slow step. The nucleophile's concentration does not appear in the rate law at all, which is a striking prediction and it is observed.
And it gives a mixture of both stereochemistries, because the carbocation is flat and can be attacked from either face.
It requires a stable carbocation, and stability runs tertiary > secondary > primary, because alkyl groups donate electron density to the positive centre.
\boxed{\text{Primary} \to \text{SN2}. \quad \text{Tertiary} \to \text{SN1}. \quad \text{Secondary} \to \text{either.}}
The two mechanisms have opposite substrate preferences and opposite stereochemical outcomes, which is why organic chemistry teaches them together.
Addition to alkenes
The pi bond's electrons attack an electrophile.
\text{CH}_2=\text{CH}_2+\text{HBr} \to \text{CH}_3\text{CH}_2\text{Br}
Markovnikov's rule: with an unsymmetrical alkene, the hydrogen adds to the carbon that already has more hydrogens.
The rule is a summary; the mechanism is the reason. Protonation can give two possible carbocations, and the more substituted one is more stable, so it forms preferentially, and the nucleophile then attacks it.
\text{CH}_3\text{CH}=\text{CH}_2+\text{HBr} \to \text{CH}_3\text{CHBrCH}_3\ \text{(not CH}_3\text{CH}_2\text{CH}_2\text{Br)}
Learn the carbocation stability order and Markovnikov's rule is a consequence rather than a fact.
Aromatic substitution
Benzene substitutes rather than adds (Chapter 10.2), because addition would destroy 150 kJ/mol of delocalisation energy.
\text{C}_6\text{H}_6+\text{HNO}_3 \xrightarrow{\text{H}_2\text{SO}_4} \text{C}_6\text{H}_5\text{NO}_2+\text{H}_2\text{O}
And existing substituents direct where the next one goes.
Electron-donating groups (–OH, –NH₂, –CH₃) activate the ring and direct to the ortho and para positions.
Electron-withdrawing groups (–NO₂, –COOH, –CN) deactivate and direct to meta.
The reason is which intermediate is stabilised. Attack at each position gives a different set of resonance structures, and the directing effect is simply which set the substituent can stabilise. This is how substituted aromatics are made in a controlled way, and it underlies most dye and pharmaceutical synthesis.
Polymers
Long chains of repeating units.
Addition polymers — alkenes joining with nothing lost:
n\,\text{CH}_2\!\!=\!\!\text{CH}_2 \to -(\text{CH}_2\text{CH}_2)_n-
| Monomer | Polymer | Use |
|---|---|---|
| Ethene | Polyethene | Bags, bottles |
| Propene | Polypropene | Containers, fibres |
| Chloroethene | PVC | Pipes, flooring |
| Tetrafluoroethene | PTFE | Non-stick |
| Phenylethene | Polystyrene | Packaging |
PTFE is non-stick because the fluorines completely shield the carbon backbone and have such low polarisability that dispersion forces to anything else are minimal (Chapter 10.3).
Condensation polymers — a small molecule is lost at each join:
Polyester (PET) from a diacid and a diol, losing water. Bottles and clothing.
Nylon from a diacid and a diamine, losing water. The amide link makes it strong, because interchain hydrogen bonds hold the fibres together.
And biological polymers use the same chemistry. Proteins are polyamides, and DNA and RNA are polyesters of phosphoric acid.
Structure controls properties. High-density polyethene has linear chains that pack closely, giving a rigid material; low-density has branched chains that cannot pack, giving a flexible film. Same monomer, same chemistry, different physical properties from chain architecture alone.
Chirality, again
Chapter 10.2 introduced it. Its consequences in drug chemistry deserve restating, because it is where the abstract idea has the most concrete effect.
A chiral drug's two enantiomers can differ completely:
| Drug | One enantiomer | The other |
|---|---|---|
| Ibuprofen | Anti-inflammatory | Inactive |
| Naproxen | Anti-inflammatory | Liver toxin |
| Ethambutol | Treats tuberculosis | Causes blindness |
| Thalidomide | Sedative | Teratogen |
| Propranolol | Beta blocker | Contraceptive effect |
The receptor is chiral, being made of L-amino acids, so it distinguishes the two forms exactly as a left hand distinguishes a left glove from a right one.
Regulators now require enantiomers to be evaluated separately, which is a direct consequence of the thalidomide disaster.
Making a single enantiomer is hard, because ordinary synthesis from achiral starting materials gives a 50:50 mixture. Three approaches exist: separate them afterwards (wasteful, throwing away half), start from a natural chiral molecule, or use a chiral catalyst. Asymmetric catalysis won the 2001 Nobel Prize (Knowles, Noyori, Sharpless) and the 2021 prize for organocatalysis (List, MacMillan).
Spectroscopy
How structures are actually determined.
Infrared (Chapter 7.4). Each bond vibrates at a characteristic frequency, so the spectrum lists which functional groups are present.
| Bond | Wavenumber (cm⁻¹) |
|---|---|
| O–H | 3200–3600, broad |
| N–H | 3300–3500 |
| C–H | 2850–3000 |
| C≡N | 2200–2260 |
| C=O | 1670–1780, strong |
| C=C | 1620–1680 |
The carbonyl peak is the most useful single signal in organic chemistry — strong, sharp, and in a region where little else absorbs.
Nuclear magnetic resonance. Nuclei with spin ½ (¹H, ¹³C) align in a magnetic field and absorb radio waves at a frequency that depends on their electronic environment.
Three pieces of information:
Chemical shift — what the nucleus is attached to. Integration — how many nuclei of that type. Splitting — how many neighbours, following the n+1 rule.
NMR determines complete structures, and it is the single most powerful tool in organic chemistry. It is also the physics behind MRI, with the same hardware imaging the water in tissue instead of a molecule in a tube.
Mass spectrometry (Chapter 4.5). Ionise, accelerate, bend in a magnetic field, and measure m/q. Gives the molecular mass and, from the fragmentation pattern, structural information.
And the isotope patterns are diagnostic. Chapter 9.P noted chlorine's 3:1 doublet; bromine gives a 1:1 doublet two units apart. You can identify halogens by eye from the peak pattern.
Where this shows up in your life
Everything plastic — about 400 million tonnes a year.
Every medicine. Aspirin is an ester, paracetamol an amide, penicillin has a strained four-membered amide ring that is the source of both its activity and its instability.
Fuel. Petrol is C₅–C₁₂ alkanes, and the octane rating measures resistance to premature ignition (Chapter 3.4).
Food. Fats are triesters, sugars are polyalcohols, proteins are polyamides, and flavour compounds are mostly esters, aldehydes and ketones.
Soap and detergent — the polar head and non-polar tail.
Fabrics. Cotton is cellulose (a polysaccharide), wool and silk are proteins, polyester and nylon are synthetic condensation polymers.
And the smell of almost everything is a small volatile organic molecule fitting a receptor in your nose, with the fit depending on shape and, often, on handedness.
What the next chapter fixes
Organic chemistry describes molecules that are made in flasks and found in oil. The same chemistry, in a cell, is alive, and the transition is not marked by any new physics or any new kind of bond. Chapter 10.8 covers the four molecular families that make up living things, shows how energy is actually moved around inside a cell, and closes Volume IV's chemistry by explaining where the boundary between chemistry and biology is — and why there may not be one.