Difficulty: Intermediate | Prerequisites: Organic Chemistry I (functional groups, bonding, acid-base chemistry, basic stereochemistry)

These reactions form the backbone of Organic Chemistry II. You met simple substitution and elimination in Orgo I, but here you need to predict which pathway wins for a given substrate, nucleophile, base and solvent, and to control regiochemistry and stereochemistry in additions to pi systems. If you can reliably distinguish SN1 from SN2 from E1 from E2, and predict Markovnikov versus anti-Markovnikov outcomes, you have the decision-making framework for roughly a third of a typical Orgo II exam.

TL;DR

Nucleophilic substitutions (SN1, SN2) and eliminations (E1, E2) compete for the same substrates, and the outcome depends on substrate class, nucleophile strength, base strength and solvent. Electrophilic additions to alkenes and alkynes follow either Markovnikov or anti-Markovnikov regiochemistry depending on the reagent, and the stereochemical outcome (syn or anti addition) is set by the mechanism. Master the decision tree for substitution versus elimination, and learn to predict regiochemistry and stereochemistry for each addition reagent, and you can handle most of the reactions in the first half of Orgo II.

Key Terms

SN2 (bimolecular nucleophilic substitution)

A one-step mechanism in which the nucleophile attacks the electrophilic carbon at the same time as the leaving group departs, with inversion of stereochemistry (Walden inversion). In simple terms, the nucleophile kicks the leaving group out the back door.

SN1 (unimolecular nucleophilic substitution)

A two-step mechanism: the leaving group departs first to form a carbocation, then the nucleophile attacks. Produces racemisation because the carbocation is planar and can be attacked from either face.

E2 (bimolecular elimination)

A one-step mechanism in which a strong base removes a proton anti-periplanar to the leaving group, forming a double bond as the leaving group departs simultaneously. Think of it as: the base and the leaving group must be on opposite sides.

E1 (unimolecular elimination)

A two-step mechanism: leaving group departs to form a carbocation, then a base removes a neighbouring proton to form the most substituted alkene (Zaitsev product). In simple terms, same first step as SN1, but the carbocation loses a proton instead of gaining a nucleophile.

Markovnikov's rule

In electrophilic additions to alkenes, the electrophile (typically H) adds to the less substituted carbon, placing the nucleophile (OH, Br, etc.) on the more substituted carbon. Think of it as: "the rich get richer" in terms of substitution.

Anti-Markovnikov addition

The opposite regiochemistry: the nucleophilic group ends up on the less substituted carbon. Occurs with hydroboration-oxidation and radical (peroxide-mediated) HBr addition.

Bromonium ion

A three-membered ring intermediate formed when Br2 adds to an alkene. The ring blocks one face, forcing the second nucleophile to attack from the opposite side (anti addition).

Carbocation

A positively charged carbon intermediate. Stability order: 3° > 2° > 1° > methyl. Rearrangements (hydride and methyl shifts) can occur to reach a more stable carbocation.

Anti-periplanar

The geometric requirement for E2 elimination: the H being removed and the leaving group must be on opposite sides of the C-C bond, at a dihedral angle of 180°. In simple terms, they need to be as far apart as possible.

Zaitsev's rule

Elimination reactions preferentially form the more substituted (more stable) alkene. The base removes the proton that leads to the most substituted double bond.

Syn addition

Both groups add to the same face of the double bond. Occurs in hydroboration, catalytic hydrogenation and OsO4 dihydroxylation.

Anti addition

The two groups add to opposite faces of the double bond. Occurs in halogenation (Br2), halohydrin formation and epoxide opening.

Hydroboration-oxidation

A two-step sequence (BH3, then H2O2/NaOH) that adds water across an alkene with anti-Markovnikov regiochemistry and syn stereochemistry. No carbocation intermediate, so no rearrangement.

Oxymercuration-demercuration

A two-step sequence (Hg(OAc)2/H2O, then NaBH4) that adds water across an alkene with Markovnikov regiochemistry. No carbocation rearrangement.

Core Content: Nucleophilic Substitutions and Eliminations

Deciding between SN1, SN2, E1 and E2

• Substrate class is the first filter:

  • Methyl and primary substrates: favour SN2 (strong nucleophile) or E2 (strong, bulky base such as tert-butoxide).

  • Secondary substrates: SN2 with a strong, unhindered nucleophile in an aprotic solvent; E2 with a strong base; SN1/E1 in polar protic with a weak nucleophile, though this is less common.

  • Tertiary substrates: cannot do SN2 (too hindered). Strong base gives E2. Weak nucleophile in polar protic gives SN1 and E1 (elimination usually dominates at higher temperatures).

• Nucleophile vs. base character:

  • Good nucleophile, weak base (e.g. I-, RS-, CN-): favours substitution.

  • Strong base, poor nucleophile (e.g. tert-butoxide, LDA): favours elimination.

  • Strong nucleophile and strong base (e.g. OH-, RO-): competition depends on substrate and conditions.

• Solvent:

  • Polar aprotic (DMSO, DMF, acetone): favours SN2 by not solvating the nucleophile.

  • Polar protic (water, alcohols): favours SN1/E1 by stabilising the carbocation and solvating the nucleophile.

Key reactions

• Tosylate (secondary, S configuration) + NaCN produces a nitrile with inversion to R configuration (SN2). CN- is a good nucleophile, and tosylate is an excellent leaving group.

• Cyclic ether + excess HBr with heat gives a dibromide or bromo-alcohol. The ring opens via SN1 or SN2 at the less hindered carbon.

• Primary alkyl halide + strong base (e.g. NaOEt) gives the alkene via E2. The geometry must be anti-periplanar.

• Tertiary alkyl halide + weak nucleophile in a polar protic solvent undergoes SN1 (racemisation) or E1 (Zaitsev product). Heat pushes the equilibrium toward elimination.

Core Content: Electrophilic Additions to Alkenes and Alkynes

Additions to alkenes

• Alkene + HBr (no peroxide): Markovnikov addition via carbocation. H adds to the less substituted carbon, Br to the more substituted. Rearrangements possible.

• Alkene + HBr + peroxide: anti-Markovnikov addition via radical mechanism. Br adds to the less substituted carbon.

• Alkene + Br2: anti addition through a bromonium ion intermediate. Produces a vicinal dibromide with trans stereochemistry.

• Alkene + Br2/H2O: bromohydrin formation. Anti addition, Markovnikov regiochemistry (OH ends up on the more substituted carbon, Br on the less substituted).

• Alkene + BH3, then H2O2/NaOH (hydroboration-oxidation): anti-Markovnikov, syn addition. No rearrangement. Produces the alcohol on the less substituted carbon.

• Alkene + Hg(OAc)2/H2O, then NaBH4 (oxymercuration-demercuration): Markovnikov, no rearrangement. Produces the alcohol on the more substituted carbon.

• Alkene + H2/Pd or Pt: catalytic hydrogenation. Syn addition of H2 to give the alkane.

Additions to alkynes

• Internal alkyne + H2O, H2SO4, HgSO4: Markovnikov hydration to give a ketone (via enol tautomerisation). With a terminal alkyne this produces a methyl ketone.

• Alkyne + Lindlar's catalyst/H2: partial reduction to the cis-alkene. The poisoned catalyst stops at the alkene stage.

• Internal alkyne + Na/NH3 (liquid): dissolving metal reduction to the trans-alkene. The mechanism goes through a radical anion.

Regiochemistry and stereochemistry summary

• Markovnikov (nucleophilic group to more substituted carbon): HBr (no peroxide), Br2/H2O (OH placement), oxymercuration, acid-catalysed hydration of alkynes.

• Anti-Markovnikov (nucleophilic group to less substituted carbon): HBr + peroxide, hydroboration-oxidation.

• Syn addition (same face): hydroboration, catalytic hydrogenation, OsO4 dihydroxylation.

• Anti addition (opposite faces): Br2, Br2/H2O, epoxide opening, halogenation.

Key Reagent Summary

Common Misconceptions

• Students often assume SN1 and SN2 differ only in speed. They do not. SN2 is a single concerted step with inversion; SN1 is two steps with racemisation. The mechanism, not the rate law alone, determines the stereochemical outcome.

• Markovnikov's rule is frequently misremembered as "hydrogen goes to the carbon with more hydrogens." That is the correct outcome but the wrong reason. The rule exists because the more substituted carbocation is more stable. When the mechanism changes (radical addition with peroxides), the regiochemistry flips.

• Students often forget that hydroboration-oxidation and oxymercuration-demercuration both give alcohols from alkenes but with opposite regiochemistry. Hydroboration is anti-Markovnikov; oxymercuration is Markovnikov. Mixing them up on an exam is one of the most common errors.

• Anti-periplanar geometry for E2 is not optional. If the H and the leaving group cannot achieve a 180° dihedral angle, E2 will not occur, even if a strong base is present. This matters especially in cyclohexane rings, where the H and leaving group must both be axial.

Why It Matters / Exam Flags

• ⚠️ "Given this substrate and these conditions, predict the major product" is the single most common question format. You need to identify the mechanism (SN1/SN2/E1/E2) before you can predict the product.

• ⚠️ Stereochemistry of the product is almost always tested alongside the reaction. SN2 = inversion. SN1 = racemisation. E2 = anti-periplanar geometry determines which alkene forms.

• ⚠️ Hydroboration vs. oxymercuration: expect a question that gives you an alkene and asks for the alcohol product. You must know which reagent set gives Markovnikov and which gives anti-Markovnikov.

• ⚠️ Radical HBr addition (with peroxides) vs. ionic HBr addition (without peroxides) is a classic "one-word difference" exam trap. Peroxide = anti-Markovnikov. No peroxide = Markovnikov.

Quick Self-Test

1. True or False: SN2 reactions proceed with retention of configuration. (False: SN2 gives inversion.)

1. Fill in the blank: A tertiary substrate with a strong base undergoes ______ elimination. (E2)

1. True or False: Hydroboration-oxidation gives the Markovnikov alcohol. (False: it gives the anti-Markovnikov alcohol.)

1. Fill in the blank: The intermediate in bromination of an alkene is a ______ ion. (Bromonium)

1. True or False: Adding peroxide to an HBr reaction switches the regiochemistry from Markovnikov to anti-Markovnikov. (True)

Practice Q&A

Q: A secondary tosylate (S configuration) is treated with NaCN in DMSO. What is the product, and what is its configuration?

A: The product is a nitrile with R configuration. NaCN is a strong nucleophile, DMSO is a polar aprotic solvent, and the substrate is secondary, so the mechanism is SN2 with inversion.

Q: An alkene is treated with BH3 followed by H2O2/NaOH. A different sample of the same alkene is treated with Hg(OAc)2/H2O followed by NaBH4. How do the two alcohol products differ?

A: Hydroboration-oxidation gives the anti-Markovnikov alcohol (OH on the less substituted carbon, syn addition). Oxymercuration-demercuration gives the Markovnikov alcohol (OH on the more substituted carbon). The regiochemistry is opposite.

Q: Predict the major product when 2-bromobutane is treated with potassium tert-butoxide in tert-butanol.

A: 2-Butene (the more substituted, Zaitsev alkene) via E2. Potassium tert-butoxide is a strong, bulky base. The substrate is secondary. E2 dominates.

Q: An alkene is treated with Br2 in water. What is the regiochemistry and stereochemistry of the product?

A: Bromohydrin. Markovnikov regiochemistry (OH on the more substituted carbon). Anti stereochemistry (Br and OH on opposite faces) due to the bromonium ion intermediate.

Q: Why does a tertiary alkyl halide not undergo SN2, even with a strong nucleophile?

A: Steric hindrance. Three bulky substituents on the electrophilic carbon block the backside attack that SN2 requires.

Connections to Other Topics

This material connects directly to carbonyl chemistry: nucleophilic addition and acyl substitution use the same nucleophile logic, and enolate alkylation is an SN2 reaction at its core. Stereochemistry from these addition and substitution reactions carries into multi-step synthesis planning, where you must track configuration through each step. Electrophilic addition to alkenes also sets the stage for electrophilic aromatic substitution, which follows a related mechanism but on an aromatic ring.

Related Terms / Search Tags

SN1, SN2, E1, E2, nucleophilic substitution, elimination reaction, Markovnikov, anti-Markovnikov, bromonium ion, carbocation, carbocation rearrangement, anti-periplanar, Zaitsev rule, Saytzeff, syn addition, anti addition, hydroboration, oxymercuration, demercuration, Walden inversion, racemisation, electrophilic addition, alkene reactions, alkyne hydration, vicinal dibromide, halohydrin, radical addition, peroxide effect, HBr addition, catalytic hydrogenation, Lindlar catalyst, dissolving metal reduction, polar aprotic solvent, polar protic solvent, leaving group, nucleophile, base, Orgo 2, organic chemistry II, CHEM 210