Follow the electrons,predict the product.

Why mechanisms matter

A reaction equation tells you what goes in and what comes out. A mechanism tells you how: which bonds break, which form, in what order, and through which intermediates. That is what lets you predict products you have never seen, explain stereochemistry and choose conditions.

Almost every polar organic reaction is the same event repeated: an electron-rich atom shares a pair of electrons with an electron-poor atom. Learn to spot the two partners and you can read most mechanisms.

Nucleophiles, electrophiles and curly arrows

A nucleophile is electron-rich and donates a pair of electrons: a lone pair on oxygen or nitrogen, a negative charge, or a π bond. Hydroxide, cyanide, amines, enolates and alkenes are typical. An electrophile is electron-poor and accepts the pair: a carbonyl carbon, a carbocation, the carbon of an alkyl halide, or a proton.

Curly arrows show the movement of an electron pair. Each arrow starts at the electrons, a lone pair or a bond, and ends where they go, an atom or the space between two atoms where a new bond forms. Arrows never start at a nucleus or at a positive charge. Count charges after every step: the total charge must be the same on both sides.

Substitution: SN2 and SN1

In an SN2 reaction the nucleophile attacks the carbon from the side opposite the leaving group, and the old bond breaks as the new one forms, in a single step. The rate depends on both partners, rate = k[substrate][nucleophile], and the configuration at the carbon inverts. Steric hindrance slows it sharply: methyl and primary substrates react fastest, tertiary ones essentially not at all. Polar aprotic solvents such as DMSO or acetone help, because they do not cage the nucleophile.

In an SN1 reaction the leaving group departs first, giving a planar carbocation, which the nucleophile then attacks from either face. The rate depends only on the substrate, rate = k[substrate], and a stereocentre usually ends up largely racemised. Tertiary, allylic and benzylic substrates, which give stabilised carbocations, react this way, especially in polar protic solvents such as water or alcohols. Carbocations can also rearrange by hydride or alkyl shifts to a more stable cation before the nucleophile arrives.

In both cases the leaving group matters: good leaving groups are weak bases. Iodide, bromide, tosylate and water (from a protonated alcohol) leave well; hydroxide and alkoxide do not, which is why alcohols are activated before substitution.

Elimination: E2 and E1

Bases can remove a proton next to the carbon bearing the leaving group instead of attacking carbon, forming a C=C double bond. In E2 this happens in one step, and the proton and leaving group must be anti-periplanar. Strong bases favour it, and bulky bases such as potassium tert-butoxide favour elimination over substitution and often give the less substituted alkene.

E1 goes through the same carbocation as SN1 and competes with it; heat favours elimination. As a rule of thumb, E1 and most E2 reactions give the more substituted, more stable alkene (Zaitsev's rule).

Carbonyl chemistry

The carbonyl carbon is the most important electrophile in organic chemistry. Nucleophiles add to it to give a tetrahedral intermediate. With aldehydes and ketones, which have no leaving group, the intermediate is usually protonated to an alcohol; Grignard reagents and hydride reductions work this way.

Carboxylic acid derivatives carry a leaving group, so the tetrahedral intermediate collapses and expels it: nucleophilic acyl substitution. Reactivity follows leaving-group ability: acid chlorides > anhydrides > esters > amides. That order tells you which conversions go downhill easily, such as an acid chloride to an ester, and which need forcing conditions, such as hydrolysing an amide.

A carbon next to a carbonyl is weakly acidic, and its conjugate base, an enolate, is a carbon nucleophile. When an enolate attacks another carbonyl you get the aldol reaction, one of the main ways to build C–C bonds.

Aromatic substitution

Benzene rings are nucleophiles too, but reluctant ones, because reacting costs their aromatic stability. In electrophilic aromatic substitution a strong electrophile such as the nitronium ion is attacked by the ring, giving a cationic intermediate that quickly loses a proton to restore aromaticity. Substituents already on the ring decide where the next one goes: electron-donating groups such as –OH or –CH3 direct ortho and para and speed the reaction up; most electron-withdrawing groups such as –NO2 direct meta and slow it down.

How to work through a new mechanism

Draw all lone pairs and charges. Find the best nucleophile and the best electrophile under the conditions given. Draw one step at a time with curly arrows, and check charges and atom counts after each. Ask whether an intermediate would be stable; if a step creates a primary carbocation, look for another path. Finally, compare the product with the conditions: acid, base, heat and solvent all leave fingerprints on the mechanism.