06 Substitution and Elimination Reactions

A framework for the four pathways

Substitution replaces a leaving group attached to carbon with a nucleophile. Elimination removes a leaving group and a neighboring hydrogen to form a carbon–carbon double bond. The four principal pathways are SN1, SN2, E1, and E2.

A useful first distinction is whether the reaction is concerted or proceeds through an intermediate:

• SN2 and E2 are concerted: the relevant bonds form and break in a single step.

• SN1 and E1 proceed through a carbocation intermediate.

The numbers in the pathway names correspond to the number of reactants involved in the rate-determining step. For the idealized mechanisms, the rate laws are:

• SN2 and E2: $\mathrm{rate}=k[\text{substrate}][\text{nucleophile or base}]$

• SN1 and E1: $\mathrm{rate}=k[\text{substrate}]$

These patterns are useful guides, but reaction conditions and substrate structure work together; no single factor always determines the outcome.

Nucleophilic substitution

In SN2, the nucleophile attacks the carbon from the side opposite the leaving group. As the new bond forms, the bond to the leaving group breaks. This backside attack inverts the geometry at a stereogenic reaction center. The geometry inverts, although the formal $R$ or $S$ label does not necessarily change because substituent priorities may differ between reactant and product.

SN2 is most accessible at methyl and primary carbons, can be slower at secondary carbons, and is generally blocked by crowding at tertiary carbons. A strong, unhindered nucleophile and a good leaving group favor this pathway. Polar aprotic solvents such as acetone, DMSO, and acetonitrile commonly keep anionic nucleophiles relatively reactive.

For example, cyanide can replace bromide on a primary carbon:

In SN1, the leaving group departs first, forming a planar, approximately $\mathrm{sp^2}$-hybridized carbocation. A nucleophile then attacks; if the nucleophile is neutral, a proton-transfer step may follow. Because carbocation formation is usually the slow step, the rate depends on substrate concentration rather than nucleophile concentration.

SN1 is favored when the substrate can form a stable carbocation, as is common for tertiary, benzylic, and allylic substrates. Polar protic solvents help stabilize ions, and weak or neutral nucleophiles can participate. Attack on either face of a chiral carbocation often gives partial to substantial racemization, but not necessarily a perfectly even mixture. Hydride or alkyl shifts may occur if they create a more stable carbocation.

For instance, tert-butyl bromide can react with water to form tert-butanol: bromide leaves, water attacks the carbocation, and deprotonation produces the alcohol. Takeaway: substrate accessibility and nucleophile strength help distinguish the concerted SN2 route from the carbocation-based SN1 route.

Elimination and alkene formation

In E2, a base removes a β-hydrogen—a hydrogen attached to a carbon neighboring the carbon bearing the leaving group. The electrons from the carbon–hydrogen bond form the double bond as the leaving group departs. A strong base favors E2, especially with secondary and tertiary substrates; a bulky base can favor elimination over substitution.

The carbon–hydrogen bond and carbon–leaving-group bond generally need to be anti-periplanar. This geometrical requirement makes E2 stereospecific: the arrangement of the substrate constrains the alkene product. In cyclohexane rings, the relevant hydrogen and leaving group usually must both be axial and trans to one another.

When more than one alkene can form, a small base often favors the more substituted Zaitsev product. A bulky base may instead favor the less substituted Hofmann alkene because it can more readily remove a less hindered β-hydrogen. These are trends, not guarantees; available hydrogens and geometric constraints matter. For example, 2-bromobutane with ethoxide gives mainly 2-butene, with some 1-butene, while a bulky base can increase the proportion of 1-butene.

In E1, the leaving group departs first to form a carbocation. A base then removes a β-hydrogen, and the electrons from the carbon–hydrogen bond form the double bond. E1 shares its first step with SN1, so the pathways often compete under conditions that support carbocations. Heating often increases elimination relative to substitution. Rearrangements can occur before the alkene forms, and the more substituted, more stable alkene is generally favored when possible. Takeaway: E2 depends on base strength and suitable geometry, whereas E1 proceeds through a carbocation and often competes with SN1.

Predicting the pathway and product

Use the following evidence together to predict the likely pathway and product:

1. Check the substrate. Methyl and primary substrates commonly favor SN2 with a good nucleophile. Tertiary substrates are too crowded for ordinary SN2; they commonly undergo E2 with a strong base or SN1/E1 when a stable carbocation can form. Secondary substrates depend strongly on the conditions.

2. Classify the reagent. A strong nucleophile that is not a strong base favors SN2 on an accessible substrate. A strong base favors E2, particularly with secondary or tertiary substrates. Weak, neutral nucleophiles such as water or alcohols can support SN1/E1 when carbocation formation is favorable.

3. Consider solvent and temperature. Polar aprotic solvents commonly support SN2. Polar protic solvents stabilize ions and commonly support SN1/E1. Heating often increases the relative importance of elimination.

4. Draw the mechanism and check the product. For substitution, replace the leaving group and account for SN2 inversion or SN1 carbocation stereochemistry. For elimination, remove a β-hydrogen, form the double bond, and check regiochemistry and E2 geometry. Include competing products when more than one pathway is plausible.

Leaving-group ability matters in all four pathways. Iodide, bromide, and sulfonate groups such as tosylate are common good leaving groups. Hydroxide is generally a poor leaving group unless it is converted into water or another better leaving group.

As a compact comparison: choose between concerted and carbocation pathways first, then use substrate, reagent, solvent, temperature, leaving-group ability, and stereochemical constraints to refine the prediction. These guidelines describe common introductory cases; unusual substrates and competing pathways can change the outcome.