Organic Chemistry: Reaction Mechanisms and Analysis

Naming a molecule correctly answers the question of what it is. It says nothing about what it will do. Two molecules can react instantly on contact, or sit together indefinitely without the slightest change, and understanding that difference means going past structure entirely, into mechanism: a step-by-step account of exactly which bond breaks, which new bond forms, how electrons actually move between the two, and how fast the whole sequence unfolds. A reaction, in this more precise picture, always starts with a substrate, the molecule supplying carbon to a new bond, meeting a reagent, an attacking species that seeks it out for a specific reason, an imbalance of electrons one has and the other needs. Understanding that imbalance, and the handful of ways a covalent bond can actually break to satisfy it, turns organic chemistry from a subject about memorising what happens into a subject about predicting what should happen, and this chapter builds exactly that predictive machinery, alongside the practical laboratory skills, purifying a compound, then proving what it actually contains, that put the theory to real use.

A covalent bond can break in exactly two ways, and the difference between them decides almost everything that follows. In heterolytic cleavage, the shared electron pair does not split evenly: it leaves entirely with one fragment, abandoning the other. Break a C-Br bond this way and the carbon fragment, now short two electrons it used to share, becomes positively charged, a carbocation, while the bromine fragment leaves with a full negative charge as bromide. Carbocations are electron-deficient, unstable, and highly reactive, exactly the kind of species a nucleophile, an electron-rich attacker, goes looking for. Run the same kind of split the other way, and the fragment that keeps the electron pair becomes negatively charged instead, a carbanion. In homolytic cleavage, by contrast, the electron pair splits perfectly evenly, one electron to each fragment, and neither fragment ends up charged at all; instead, each carries a single unpaired electron, making it a free radical, shown in diagrams by a single dot rather than the plus or minus sign carbocations and carbanions carry. Homolytic cleavage typically needs a real energy trigger, heat or light, and produces species just as reactive and short-lived as their charged cousins, just without any charge at all.

A carbocation's positive carbon is short an entire pair of electrons, leaving it with only six electrons around its nucleus instead of a full octet, sp2 hybridised, flat and trigonal planar, with a genuinely empty p orbital sitting perpendicular to that plane. That empty orbital is exactly what makes carbocations so reactive: it is a ready-made space for any nearby electron pair to fill. Not all carbocations are equally unstable, though, and the pattern is worth remembering precisely because it explains so much of organic chemistry downstream: stability increases methyl < primary < secondary < tertiary, tert-butyl cation more stable than isopropyl, isopropyl more stable than ethyl, ethyl more stable than methyl. More alkyl groups directly attached to that positively charged carbon means more stability, for two compounding reasons explored properly later in this chapter, inductive donation of electron density from the alkyl groups, and hyperconjugation. A carbanion is the mirror opposite: carbon keeps the electron pair instead of losing it, ending up negatively charged, sp3 hybridised, and shaped like a distorted tetrahedron with a lone pair standing in for the fourth substituent. A free radical splits the difference: uncharged, but carrying one unpaired electron, and just as reactive as either charged species, with the exact same stability order, tertiary most stable, methyl least, showing up here too.

Once a reactive site exists, whether a full carbocation or just a partial positive charge, something has to come looking for it, and organic chemists have precise names for both sides of that meeting. A nucleophile is an electron-rich species, carrying a lone pair or a negative charge, that actively seeks out an electron-poor site and donates a pair of electrons to form a new bond; hydroxide, cyanide, and even neutral molecules like water or ammonia, wherever they carry an available lone pair, all qualify. An electrophile is the opposite: an electron-poor species that accepts an electron pair instead of offering one, carbocations themselves being the most obvious example, alongside neutral molecules carrying a polarised bond, like the carbon of a carbonyl group or the carbon of an alkyl halide, both left slightly electron-short by a more electronegative neighbour. During an actual reaction, this exchange is shown with curved-arrow notation, an arrow drawn from the source of an electron pair to its destination, tracking exactly where those electrons end up. And underlying almost every organic reaction is one single, quietly universal fact: it is the substrate that has to supply an electron-poor or electron-rich site in the first place, and the reagent that arrives specifically because that site exists.

When two atoms of different electronegativity share a bond, the shared electrons do not sit exactly halfway between them; they shift toward whichever atom pulls harder, leaving that atom with a small negative charge and its partner with a small positive one, denoted delta-plus and delta-minus. Chloroethane's C-Cl bond is a clean example: chlorine, more electronegative, pulls electron density toward itself, leaving carbon-1 delta-positive and chlorine delta-negative. That polarity does not stop at the bond where it started, either. Carbon-1's new partial positive charge tugs, in turn, on the electrons of the very next bond, inducing a smaller positive charge on carbon-2 as well, a chain reaction of induced polarity called the inductive effect, permanent, and passed through the molecule bond by bond, though it fades fast: by the third bond away from the original source, the effect is close to negligible. Substituent groups earn a reputation from this behaviour: halogens, nitro, cyano and carboxyl groups all pull electron density toward themselves and are called electron-withdrawing; alkyl groups like methyl and ethyl push electron density away instead and are called electron-donating. Knowing which is which, for any group attached to a carbon skeleton, predicts a surprising amount about how reactive, and specifically how acidic or basic, the resulting compound will be.

Draw benzene the traditional way, alternating single and double bonds around a hexagonal ring, and the structure makes a testable prediction: two different carbon-carbon bond lengths, shorter where the double bonds sit, longer where the single bonds sit. Measure benzene's actual bonds, though, and every single one of its six carbon-carbon bonds turns out to be exactly the same length, a value sitting neatly between a true single bond and a true double bond. No single Lewis structure, drawn with fixed single and double bonds anywhere on the ring, can represent that. The real structure is a resonance hybrid: benzene is not flickering back and forth between two different structures, and it is not really a 50-50 blend of two separate molecules either; it is one single, stable structure that simply cannot be drawn with the fixed-bond notation available, best approximated by combining two or more contributing (or canonical) structures that individually misrepresent it. Some contributing structures matter more than others, and a small set of rules predicts which: more covalent bonds and complete octets make a structure more stable and more important, while separated positive and negative charges, especially placed on the wrong atoms, a positive charge on an electronegative atom or a negative charge on an electropositive one, make a structure less important. The gap in energy between the real molecule and its single most stable contributing structure is called the resonance energy, and the larger that gap, the more stabilised, and often the less reactive, the real molecule turns out to be.

Resonance is not just a drawing convention; it has a real electronic consequence called the resonance (or mesomeric) effect, the polarity a molecule develops when a pi bond sits next to either another pi bond or a lone pair, a combination called a conjugated system. In aniline, the nitrogen's lone pair delocalises directly into the benzene ring, pushing electron density away from the substituent and building it up at specific positions around the ring instead, a positive resonance effect. In nitrobenzene, the flow runs the opposite way: electron density is pulled from the ring toward the electron-hungry nitro group, a negative resonance effect. Crucially, this is a permanent feature of the molecule's actual structure, present with or without any reagent nearby. The electromeric effect looks superficially similar but is not permanent at all: it appears only in the instant an attacking reagent actually approaches a double or triple bond, and vanishes the moment that reagent is gone. A positive electromeric effect shifts a pi electron pair toward the very atom the reagent is bonding to; a negative electromeric effect shifts it toward the other atom instead. Both resonance and electromeric effects only exist in molecules containing a pi bond or a conjugated system to begin with, and where the two effects, along with the permanent inductive effect from the previous section, happen to point in different directions on the very same bond, it is worth knowing which one usually wins: the electromeric effect, being the larger and more immediate shift, generally dominates in the moment a reaction actually occurs.

One more electron-donating effect completes the toolkit, and it belongs specifically to alkyl groups sitting directly next to an unsaturated system or a positively charged carbon. Hyperconjugation is the delocalisation of electrons from a carbon-hydrogen sigma bond into an adjacent empty p orbital or pi system, a sideways donation that, unlike a true pi bond, does not require the two orbitals to be perfectly aligned by hybridisation, only reasonably close in orientation. In the ethyl cation, one of the methyl group's three C-H bonds can align with the empty p orbital on the adjacent positively charged carbon, spilling some of its electron density into that empty space and spreading out, and thereby stabilising, what would otherwise be a sharply localised positive charge. This is precisely the mechanism behind the tertiary-more-stable-than-primary carbocation trend introduced earlier: a tertiary carbocation simply has more C-H bonds correctly positioned to donate this way than a primary one does, nine possible hyperconjugating hydrogens on a tert-butyl cation against only three on an ethyl cation, and the methyl cation, with no adjacent C-H bonds available to donate into its empty orbital at all, gets no hyperconjugative help whatsoever, and sits at the very bottom of the stability order as a direct result. With fission, nucleophiles and electrophiles, and all four electron-displacement effects now in place, organic reactions themselves sort into four broad families: substitution, one atom or group replacing another; addition, two reactants combining into one without anything left over; elimination, one reactant splitting into two, typically losing a small molecule like water or a hydrogen halide; and rearrangement, where a reactant's own atoms reorganise into a new skeleton entirely. Later units work through each family in real, worked detail.

A freshly extracted or freshly synthesised organic compound is essentially never pure on its own; it needs purification before anything about it can be reliably tested, and the right technique always depends on exactly what property separates the compound from its impurities. Sublimation exploits compounds that pass directly from solid to vapour without ever melting, leaving behind any impurity that does not share that same unusual property. Crystallisation exploits solubility instead: the impure solid is dissolved in a solvent where it is only sparingly soluble cold but generously soluble hot, concentrated to near saturation, then cooled, so that the pure compound crystallises back out cleanly while impurities stay dissolved in the remaining mother liquor, occasionally with a passage over activated charcoal first to strip out any colour-causing impurities. Distillation separates liquids by boiling point: a straightforward setup works when boiling points differ substantially, but liquids with close boiling points need fractional distillation instead, repeatedly condensing and re-vaporising as vapour climbs a fractionating column, each cycle enriching the rising vapour in the more volatile component, a principle scaled up industrially to split crude oil into its separate fractions. Two further variants handle awkward cases: distillation under reduced pressure lowers the external pressure on a liquid's surface, letting it boil at a lower temperature, essential for anything that would decompose before reaching its normal boiling point; steam distillation lets a water-insoluble compound boil below 373 K by combining its own vapour pressure with steam's, exactly how aniline is separated cleanly from a water mixture.

Some mixtures are not solid-liquid problems at all but liquid-liquid ones, an organic compound dissolved in water, say, more soluble in an organic solvent that simply will not mix with water. Differential extraction exploits exactly that immiscibility: shake the aqueous mixture with the organic solvent in a separating funnel, let the two layers settle back apart, and the compound partitions itself, mostly, into whichever layer it actually prefers, ready to be drawn off separately, with continuous extraction as a variant for compounds so poorly soluble that a single shake could never pull out more than a trace. Chromatography solves an even harder problem, separating and identifying several different compounds within one mixture at once, by exploiting how differently each one interacts with two phases, a stationary phase that stays still and a mobile phase that moves across or through it. Adsorption chromatography uses a solid stationary phase, silica gel or alumina, that holds onto different compounds with different strength; run as column chromatography, the least strongly adsorbed compound washes down and off the column first, while run as thin layer chromatography, a solvent instead climbs a thin adsorbent-coated plate, carrying each compound a different measurable distance, expressed as its retardation factor, or Rf value, the ratio of how far the compound travelled to how far the solvent itself travelled. Partition chromatography works on a related but different principle, continuous partitioning between two phases rather than simple adsorption strength, and paper chromatography, using the water trapped inside chromatography paper as its stationary phase, is the most familiar everyday version of it.

Purity solves one problem; identity solves another, and qualitative analysis exists specifically to answer it: exactly which elements does this compound actually contain? Carbon and hydrogen are detected together by heating the compound with copper(II) oxide, which oxidises carbon to carbon dioxide, confirmed by turning limewater turbid, and hydrogen to water, confirmed by turning anhydrous copper sulphate blue. Nitrogen, sulphur, halogens and phosphorus need a different approach entirely: Lassaigne's test fuses the compound with sodium metal, converting whatever covalently bound nitrogen, sulphur or halogen it contains into ionic sodium salts, sodium cyanide, sodium sulphide, sodium halide, that dissolve out cleanly into water as the sodium fusion extract and can then be tested by ordinary ionic chemistry. Nitrogen's presence is confirmed by a strikingly specific colour change, Prussian blue, produced when the extract's cyanide first forms an iron(II) complex, then an iron(III) one. Sulphur turns lead acetate solution black, forming lead sulphide, or turns sodium nitroprusside solution violet. Halogens form a silver halide precipitate with silver nitrate, and the precise colour and solubility in ammonia, white and freely soluble for chloride, pale yellow and only partly soluble for bromide, distinctly yellow and insoluble for iodide, distinguishes exactly which halogen is present. Phosphorus, oxidised first to phosphate, forms a yellow precipitate with ammonium molybdate. Each test targets one specific element through one specific, unmistakable colour or precipitate, precisely so that a chemist never has to guess.

Identifying which elements are present is only half of quantitative chemistry's job; the other half is measuring exactly how much of each, since the mass percentage of every element is precisely what a molecular formula is built from. Carbon and hydrogen are estimated together by completely burning a known mass of compound with copper(II) oxide and weighing the carbon dioxide and water produced, each mass converted back to a percentage using the known molar masses involved. Nitrogen has two established methods: the Dumas method heats the compound with copper oxide in a carbon dioxide atmosphere, freeing nitrogen gas that is collected and measured over concentrated potassium hydroxide, which conveniently absorbs the carbon dioxide out of the mixture, leaving pure nitrogen behind to measure; Kjeldahl's method instead converts the compound's nitrogen into ammonium sulphate using concentrated sulphuric acid, liberates ammonia from it with excess sodium hydroxide, and measures that ammonia by titration against a standard acid, though it has one real, specific limitation worth remembering: it fails completely on nitro and azo compounds, and on nitrogen locked inside an aromatic ring like pyridine, none of which convert to ammonium sulphate the way an ordinary amine does. Halogens are estimated by the Carius method, heating the compound with fuming nitric acid and silver nitrate in a sealed tube until the halogen precipitates completely as silver halide, weighed directly. Sulphur and phosphorus follow a related logic, oxidised fully and precipitated as barium sulphate or ammonium phosphomolybdate respectively, each weighed and converted back to a percentage using nothing more than the compound's atomic and molecular masses. Oxygen, alone among the common elements, is rarely measured directly at all; it is simply calculated by difference, one hundred percent minus the combined percentage of everything else already found.