11.12 A Summary of Reactivity: SN1, SN2, E1, E1cB, and E2

Reaction Mechanisms and Conditions

Five reaction pathways compete whenever an alkyl halide meets a nucleophile or base: SN1, SN2, E1, E1cB, and E2. Predicting which one wins depends on the substrate, the nucleophile/base, and the solvent. This section lays out each mechanism, then shows how those three factors steer the outcome.

Types of Substitution and Elimination Reactions

SN2 (Substitution Nucleophilic Bimolecular)

The nucleophile attacks the electrophilic carbon in a single concerted step, displacing the leaving group via backside attack. Because everything happens at once, the rate depends on both the substrate and the nucleophile (second-order kinetics: rate = k[substrate][nucleophile]).

• Favored with methyl and primary alkyl halides (least steric crowding)
• Works with secondary substrates, but more slowly
• Requires a strong nucleophile and a polar aprotic solvent (e.g., DMSO, DMF, acetone)
• Produces inversion of configuration at the carbon center

SN1 (Substitution Nucleophilic Unimolecular)

The leaving group departs first to form a carbocation intermediate, then the nucleophile attacks in a separate step. Only the first step (carbocation formation) is rate-determining, so the rate depends only on substrate concentration (first-order kinetics: rate = k[substrate]).

• Favored with tertiary, allylic, and benzylic substrates (these form stable carbocations)
• Requires a weak nucleophile and a polar protic solvent (e.g., water, ethanol, methanol) to stabilize the carbocation
• Produces a racemic mixture (nucleophile can attack from either face of the planar carbocation)

E2 (Elimination Bimolecular)

A strong base removes a $\beta$-hydrogen at the same time the leaving group departs, forming a double bond in one concerted step. Like SN2, the rate depends on both reactants (second-order).

• Favored with secondary and tertiary substrates, especially with a strong, bulky base (e.g., $t$-BuOK)
• Also occurs with primary substrates when a strong base is present
• Requires anti-periplanar geometry: the $\beta$-hydrogen and the leaving group must be 180° apart
• Polar aprotic solvents enhance the base's reactivity

E1 (Elimination Unimolecular)

Like SN1, the leaving group departs first to form a carbocation. Then a base (often the solvent) removes a $\beta$-hydrogen to form the alkene. First-order kinetics.

• Favored with tertiary, allylic, and benzylic substrates
• Requires a weak base, polar protic solvent, and often heat
• Typically competes alongside SN1; heating the reaction shifts the balance toward E1
• Follows Zaitsev's rule (more substituted alkene is the major product)

E1cB (Elimination Unimolecular, Conjugate Base)

A strong base first removes the $\beta$-hydrogen to form a carbanion intermediate (the conjugate base). The leaving group then departs in a second step. This pathway is less common and requires special structural features.

• Occurs when the $\beta$-hydrogens are unusually acidic (e.g., adjacent to a carbonyl, nitrile, or other electron-withdrawing group)
• Requires a strong base
• The carbanion must be stabilized by the electron-withdrawing group for this pathway to compete

How Substrate Class Steers the Mechanism

Primary alkyl halides

• SN2 dominates with a strong nucleophile in a polar aprotic solvent
• E2 takes over when a strong, bulky base is used instead
• SN1/E1 are essentially not observed (primary carbocations are too unstable)

Secondary alkyl halides

• The trickiest case because all pathways can compete
• SN2 with a strong, non-bulky nucleophile in a polar aprotic solvent
• E2 with a strong, bulky base in a polar aprotic solvent
• SN1/E1 with a weak nucleophile/base in a polar protic solvent (but slower than with tertiary substrates)

Tertiary alkyl halides

• SN2 does not occur (too much steric hindrance for backside attack)
• SN1 and E1 dominate in polar protic solvents with weak nucleophiles/bases
• E2 occurs with a strong base (even in protic solvents, a strong base can force E2)
• Heat favors elimination (E1) over substitution (SN1)

Factors Influencing Reaction Outcomes

Nucleophile/Base Strength

The strength and size of the nucleophile or base is often the single most important variable you can control.

• Strong nucleophiles (e.g., $\text{NaOH}$, $\text{NaCN}$, $\text{NaOCH}_3$) push toward SN2 or E2
• Weak nucleophiles (e.g., $\text{H}_2\text{O}$, $\text{ROH}$) push toward SN1 or E1
• Bulky strong bases (e.g., $t\text{-BuOK}$, LDA) strongly favor E2 over SN2 because they can't easily access the electrophilic carbon

A useful shortcut: if the reagent is both a good nucleophile and a strong base, you need to look at the substrate to decide between substitution and elimination. If it's bulky, lean toward E2.

Solvent Polarity

• Polar protic solvents (water, methanol, ethanol)
  • Stabilize carbocation intermediates through solvation, favoring SN1 and E1
  • Solvate (surround) nucleophiles and bases with hydrogen bonds, reducing their effective strength
• Polar aprotic solvents (DMSO, DMF, acetone, acetonitrile)
  • Do not stabilize carbocations well, so SN1/E1 are disfavored
  • Leave nucleophiles and bases "naked" (unsolvated), making them more reactive and favoring SN2 and E2

Substrate Structure

• Degree of substitution is the biggest structural factor:
  • More substitution → more stable carbocation → favors SN1/E1
  • Less substitution → less steric hindrance → favors SN2/E2
• Resonance-stabilizing groups (allylic, benzylic) stabilize carbocations, making SN1/E1 viable even for some primary/secondary substrates (e.g., benzyl chloride undergoes SN1 more readily than a simple primary halide)
• Electron-withdrawing groups adjacent to the $\beta$-carbon (carbonyls, nitriles, nitro groups) increase the acidity of $\beta$-hydrogens, opening the door to the E1cB pathway

Reaction Kinetics and Energy Diagrams

Kinetics summary:

• SN1 and E1: first-order (rate = k[substrate]). Only the substrate appears in the rate law because the rate-determining step is unimolecular ionization.
• SN2, E2, and E1cB: second-order (rate = k[substrate][nucleophile/base]). Both species are involved in or before the rate-determining step.

Energy diagrams are a visual way to compare these pathways:

• SN2 and E2 have a single transition state (one energy maximum) with no intermediate
• SN1 and E1 have two transition states separated by a carbocation intermediate (an energy minimum between two maxima). The first transition state (ionization) is typically the highest point and therefore rate-determining.
• E1cB also has two transition states, but the intermediate is a carbanion rather than a carbocation

When you're reading an energy diagram, the height of the tallest peak relative to the reactants is the activation energy ($E_a$). A lower $E_a$ means a faster reaction under the same conditions.