Organic Reaction Mechanisms, Step by Step with Curly Arrows

Substitution

In a substitution, a nucleophile replaces a leaving group on a saturated carbon. Whether it happens in one step (SN2) or through a carbocation (SN1) depends on the substrate, the nucleophile and the solvent.

Amine from a halogenoalkane and ammoniaAmmonia substitutes for bromide, then a second ammonia molecule removes a proton. Excess ammonia keeps the amine from…Nitrile from a halogenoalkane (SN2)Cyanide attacks the δ+ carbon from behind as bromide leaves, in one step. The chain gains a carbon, and the nitrile…Alcohol to chloroalkane (SN1)A tertiary alcohol is protonated, loses water to form a carbocation, and chloride attacks. This is why tertiary…SN2 substitutionA nucleophile replaces a leaving group in one concerted step. Best for methyl and primary substrates; the carbon inverts…SN1 substitutionThe leaving group departs first to give a carbocation, which the nucleophile then traps. Best for tertiary substrates; g…Epoxide ring opening (base)Under basic conditions a nucleophile opens the strained three-membered ring by SN2 at the less hindered carbon.Williamson ether synthesisAn alkoxide displaces a halide by SN2 to make an ether. Use a primary halide, otherwise elimination competes.Epoxide ring opening (acid)Under acid the epoxide oxygen is protonated first; the nucleophile then attacks the more substituted carbon, which carri…

Elimination

In an elimination, a proton and a leaving group are removed from neighbouring carbons and a C=C forms. Strong bases and heat favour elimination over substitution.

Dehydration of an alcohol (E1)Acid turns OH into water, a good leaving group. Water leaves to give a carbocation, which loses a proton from the next…E2 eliminationA strong base removes a proton next to the leaving group as the C=C forms and the leaving group departs, in one step. Th…Acid-catalysed dehydration (E1)An alcohol is protonated so water can leave, the carbocation loses a neighbouring proton and an alkene forms. Follows Za…

Addition to alkenes

The π electrons of a C=C are exposed and electron-rich, so alkenes react with electrophiles. The two new groups add across the double bond.

Addition of HBr to an alkeneThe π bond grabs H⁺ to make the more stable carbocation (Markovnikov), then bromide adds.Bromination of an alkeneBr₂ adds across the C=C through a cyclic bromonium ion, so the two bromines end up anti (on opposite faces).Acid-catalysed hydration of an alkeneThe alkene is protonated to give the more stable carbocation, water adds, and the oxonium ion loses H⁺. Markovnikov alco…Epoxidation with a peroxyacidThe alkene attacks the weak O–O bond of a peroxyacid in one concerted step, so both C–O bonds form on the same face (ste…

Carbonyl addition

The carbon of a C=O is δ+, so nucleophiles attack it and the π electrons move onto oxygen. Weak nucleophiles often need acid to activate the carbonyl first.

Cannizzaro reactionWith concentrated alkali, an aldehyde that has no α-hydrogen is both oxidised and reduced: hydroxide adds to one…Cyanohydrin formationCyanide attacks the carbonyl carbon (at about 107°, the Bürgi–Dunitz angle); the alkoxide is then protonated by HCN, reg…Reduction with NaBH₄Borohydride delivers hydride (H⁻) to the carbonyl carbon; protonation of the alkoxide gives the alcohol. Ketones give se…Grignard additionThe C–Mg bond is polarised so carbon is nucleophilic; it adds to the carbonyl carbon making a new C–C bond. Acidic worku…Hemiacetal formation (acid)Protonating the carbonyl makes it more electrophilic so a weak nucleophile, an alcohol, can add. Loss of H⁺ gives the he…Wittig reactionA phosphorus ylide adds to an aldehyde or ketone; a four-membered oxaphosphetane forms and falls apart into an alkene an…Imine formationA primary amine adds to an aldehyde or ketone, then water is lost to give C=N. Fastest at about pH 5: enough acid to pro…Acetal formationA hemiacetal loses water (helped by the neighbouring oxygen) to give an oxonium ion, which a second alcohol traps. Aceta…

Enolates

A C–H next to a carbonyl is acidic, because the anion formed (an enolate) is stabilised by resonance. Enolates are carbon nucleophiles that make new C–C bonds.

Aldol reactionBase removes an α-hydrogen to give an enolate, which attacks a second carbonyl molecule. Protonation gives a β-hydroxy c…Keto–enol tautomerism (acid)Protonation of the carbonyl oxygen, then loss of an α-proton, converts the keto form into the enol. The keto form is usu…Claisen condensationAn ester enolate attacks a second ester; the tetrahedral intermediate expels alkoxide to give a β-keto ester. Deprotonat…Conjugate (Michael) additionSoft nucleophiles add to the end carbon (β-carbon) of a C=C–C=O system. The enolate formed is then protonated on carbon.Aldol condensation (E1cB)On heating, the aldol product loses water: base forms the enolate, which then pushes out hydroxide (E1cB). The product i…

Acyl substitution

Carboxylic acid derivatives react by nucleophilic addition followed by elimination: the nucleophile adds to C=O, then the leaving group is expelled and the C=O reforms.

Ester hydrolysis (saponification)Hydroxide adds to the ester C=O to form a tetrahedral intermediate, which collapses and expels the alkoxide. The final p…Amide from an acyl chlorideAmmonia adds to the very electrophilic acyl chloride; the tetrahedral intermediate expels chloride, the best leaving gro…Fischer esterificationAcid makes the carboxylic acid carbonyl more electrophilic; the alcohol adds, a proton moves, water leaves and a proton …Reduction of an ester with LiAlH₄Hydride adds to the ester, the tetrahedral intermediate expels alkoxide to give an aldehyde, and a second hydride reduce…Hydrolysis of an acyl chlorideEven water is nucleophilic enough to attack an acyl chloride. Addition, then elimination of chloride, gives the carboxyl…

Pericyclic

Pericyclic reactions happen in one step through a cyclic transition state, with electrons moving around a ring. No intermediates form.

Diels–Alder reactionA diene and a dienophile join in one concerted step through a cyclic six-electron transition state, making a cyclohexene…

Aromatic substitution

Benzene keeps its stable aromatic ring by substituting rather than adding. An electrophile attacks, then a proton is lost to restore aromaticity.

Azo couplingThe diazonium ion is a weak electrophile, so it needs the very electron-rich phenoxide ion. Attack at the 4-position,…Bromination of phenolThe oxygen lone pair pushes electron density into the ring, so phenol attacks bromine without a halogen carrier. Shown…Nitration of benzeneElectrophilic aromatic substitution: the ring attacks NO₂⁺ to give a cation (Wheland intermediate), then loses H⁺ to res…Friedel–Crafts acylationAlCl₃ turns an acyl chloride into an acylium ion, which the benzene ring attacks. Loss of H⁺ restores the ring. The prod…Bromination of benzeneFeBr₃ polarises Br₂ so the ring can attack it. The cationic intermediate then loses H⁺ and aromaticity returns. Benzene …Friedel–Crafts alkylationA carbocation (made from an alkyl halide and AlCl₃) is attacked by the ring, then H⁺ is lost. Problems: rearrangements a…

Acids and bases

An acid–base reaction moves a proton from an acid to a base. Curly arrows start from the base's lone pair, and the old bond's electrons stay on the conjugate base.

Acid–base proton transferThe base uses a lone pair to take the proton; the O–H electrons stay on oxygen. The equilibrium favours the side with th…