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Organic Chemistry Unit 3: Substitution and elimination reactions

Alkyl halides undergo substitution or elimination by SN1, SN2, E1 or E2 mechanisms, chosen by substrate, nucleophile, solvent and temperature.

Covers: Nucleophiles and electrophiles, SN2, SN1 and carbocations, E2 and Zaitsev's rule, E1, predicting substitution vs. elimination, leaving groups

Study guide

A nucleophile is an electron-rich species that donates an electron pair, and an electrophile is electron-poor and accepts one. In alkyl halides, the carbon bonded to the halogen is electrophilic. Good leaving groups are weak bases, like I⁻, Br⁻, Cl⁻ and tosylate; OH⁻ is a poor leaving group unless it's protonated to water. Substitution replaces the leaving group with a nucleophile; elimination removes it and a neighboring hydrogen to form an alkene.

SN2 is a one-step, bimolecular reaction: rate = k[substrate][nucleophile]. The nucleophile attacks from the back side, causing inversion of configuration. SN2 works best with methyl and primary substrates (less steric hindrance), strong nucleophiles and polar aprotic solvents like DMSO, DMF and acetone. SN1 is a two-step, unimolecular reaction: the leaving group leaves to form a carbocation (the slow step), then the nucleophile attacks. Rate = k[substrate]. It favors tertiary substrates, weak nucleophiles and polar protic solvents like water and alcohols, and gives racemization at a stereocenter. Carbocation stability is tertiary > secondary > primary > methyl, because of hyperconjugation and induction, and carbocations can rearrange by hydride or methyl shifts.

E2 is one step: a strong base removes a β-hydrogen as the leaving group leaves, requiring an anti-periplanar arrangement. E1 proceeds through a carbocation, like SN1, and is favored by heat. Zaitsev's rule says the more substituted (more stable) alkene is usually the major product, but bulky bases like tert-butoxide give the less substituted Hofmann product. To predict the mechanism: methyl and primary substrates favor SN2 (or E2 with bulky bases); secondary substrates give SN2 with good nucleophiles that are weak bases and E2 with strong bases; tertiary substrates give E2 with strong bases and SN1/E1 with weak nucleophiles; heat favors elimination.

Nucleophilicity rises with negative charge (an anion is a better nucleophile than its conjugate acid) and falls with steric bulk. In polar protic solvents it increases down a group (I⁻ > Br⁻ > Cl⁻ > F⁻), because small ions are held tightly by solvent molecules. In polar aprotic solvents it roughly follows basicity. In a cyclohexane, E2 happens only when the leaving group and the β-hydrogen are both axial on adjacent carbons, trans to each other (trans-diaxial). A leaving group locked in the equatorial position reacts slowly or not at all.

Allylic and benzylic carbocations are stabilized by resonance, so allylic and benzylic halides and alcohols react quickly by SN1. They are also especially reactive in SN2. With an allylic cation, the nucleophile can attack at either end, giving a mixture of products.

Key ideas

• Good leaving groups are weak bases.
• SN2 is one step with backside attack and inversion; it favors primary substrates.
• SN1 goes through a carbocation and favors tertiary substrates.
• E2 needs a strong base and an anti-periplanar hydrogen.
• Zaitsev products are more substituted; bulky bases give Hofmann products.

Formulas and rules

Common mistakes

• Using SN2 for a tertiary substrate; steric hindrance blocks backside attack.
• Forgetting carbocation rearrangements in SN1 and E1 reactions.

Words to know

Nucleophile

An electron-pair donor that attacks an electrophile.

Electrophile

An electron-pair acceptor.

Leaving group

The group that departs with an electron pair.

Substitution

Replacing one group with another.

Elimination

Removing atoms to form a double bond.

SN2

One-step bimolecular substitution with backside attack.

Inversion of configuration

Flipping of stereochemistry at a carbon in SN2.

SN1

Two-step unimolecular substitution through a carbocation.

Carbocation

A positively charged carbon with three bonds.

Hyperconjugation

Stabilization from neighboring C–H or C–C bonds.

Hydride shift

Movement of H⁻ to form a more stable carbocation.

Racemization

Forming both enantiomers from one stereocenter.

E2

One-step bimolecular elimination.

E1

Two-step unimolecular elimination through a carbocation.

Anti-periplanar

H and leaving group on opposite sides in the same plane.

Zaitsev's rule

The more substituted alkene is usually the major product.

Hofmann product

The less substituted alkene, favored by bulky bases.

Polar aprotic solvent

A polar solvent without O–H or N–H bonds, like DMSO.

Polar protic solvent

A polar solvent with O–H or N–H bonds, like water.

Sample practice questions

5 more questions like these, from level 1 to 5, are in the practice set.