Nucleophilic Substitution (SN1 & SN2)

⚗️ Nucleophilic Substitution

Part 1 of 7 — Introduction to Substitution

1. Nucleophilic substitution

nucleophile replaces leaving group

2. Nu

⁻ + R-LG → R-Nu + LG:⁻

3. Two mechanisms

SN1 and SN2

4. Mechanism depends on substrate, nucleophile, solvent, leaving group

Mechanism depends on substrate, nucleophile, solvent, leaving group

Concept Check 🎯

Key Concepts Summary

• Nucleophilic substitution: nucleophile replaces leaving group
• Nu: ⁻ + R-LG → R-Nu + LG:⁻
• Two mechanisms: SN1 and SN2
• Mechanism depends on substrate, nucleophile, solvent, leaving group

Concept Check 🎯

Fill in the Blanks 🔍

SN2 Mechanism

Part 2 of 7 — SN2 Mechanism

1. SN2

one-step, concerted mechanism

2. Rate = k[substrate][nucleophile] (bimolecular)

Rate = k[substrate][nucleophile] (bimolecular)

3. Backside attack → inversion of configuration (Walden inversion)

Backside attack → inversion of configuration (Walden inversion)

4. Best with

methyl/primary substrates, strong nucleophiles, polar aprotic solvents

Concept Check 🎯

Key Concepts Summary

• SN2: one-step, concerted mechanism
• Rate = k[substrate][nucleophile] (bimolecular)
• Backside attack → inversion of configuration (Walden inversion)
• Best with: methyl/primary substrates, strong nucleophiles, polar aprotic solvents

Concept Check 🎯

Fill in the Blanks 🔍

SN1 Mechanism

Part 3 of 7 — SN1 Mechanism

1. SN1

two-step mechanism via carbocation intermediate

2. Step 1

leaving group departs (rate-determining)

3. Step 2

nucleophile attacks carbocation

4. Rate = k[substrate] (unimolecular); racemization at stereocenter

Rate = k[substrate] (unimolecular); racemization at stereocenter

Concept Check 🎯

Key Concepts Summary

• SN1: two-step mechanism via carbocation intermediate
• Step 1: leaving group departs (rate-determining)
• Step 2: nucleophile attacks carbocation
• Rate = k[substrate] (unimolecular); racemization at stereocenter

Concept Check 🎯

Fill in the Blanks 🔍

Substrate & Nucleophile Effects

Part 4 of 7 — Substrate & Nucleophile Effects

1. SN2 favored

methyl > primary > secondary >> tertiary (steric hindrance)

2. SN1 favored

tertiary > secondary >> primary (carbocation stability)

3. Strong nucleophiles favor SN2; weak nucleophiles favor SN1

Strong nucleophiles favor SN2; weak nucleophiles favor SN1

4. Nucleophilicity

I⁻ > Br⁻ > Cl⁻ > F⁻ (in polar aprotic)

Concept Check 🎯

Key Concepts Summary

• SN2 favored: methyl > primary > secondary >> tertiary (steric hindrance)
• SN1 favored: tertiary > secondary >> primary (carbocation stability)
• Strong nucleophiles favor SN2; weak nucleophiles favor SN1
• Nucleophilicity: I⁻ > Br⁻ > Cl⁻ > F⁻ (in polar aprotic)

Concept Check 🎯

Fill in the Blanks 🔍

Solvent & Leaving Group Effects

Part 5 of 7 — Solvent & Leaving Group Effects

1. Polar aprotic solvents favor SN2 (DMSO, DMF, acetone)

Polar aprotic solvents favor SN2 (DMSO, DMF, acetone)

2. Polar protic solvents favor SN1 (water, alcohols)

Polar protic solvents favor SN1 (water, alcohols)

3. Good leaving groups

weak bases (I⁻ > Br⁻ > Cl⁻)

4. Tosylates (OTs) and mesylates (OMs) are excellent leaving groups

Tosylates (OTs) and mesylates (OMs) are excellent leaving groups

Concept Check 🎯

Key Concepts Summary

• Polar aprotic solvents favor SN2 (DMSO, DMF, acetone)
• Polar protic solvents favor SN1 (water, alcohols)
• Good leaving groups: weak bases (I⁻ > Br⁻ > Cl⁻)
• Tosylates (OTs) and mesylates (OMs) are excellent leaving groups

Concept Check 🎯

Fill in the Blanks 🔍

Problem-Solving Workshop

Part 6 of 7 — Problem-Solving Workshop

1. Predicting SN1 vs SN2 from reaction conditions

Predicting SN1 vs SN2 from reaction conditions

2. Drawing mechanisms with curved arrows

Drawing mechanisms with curved arrows

3. Predicting stereochemical outcomes

Predicting stereochemical outcomes

4. Analyzing substrate, nucleophile, solvent, and leaving group effects

Analyzing substrate, nucleophile, solvent, and leaving group effects

Concept Check 🎯

Key Concepts Summary

• Predicting SN1 vs SN2 from reaction conditions
• Drawing mechanisms with curved arrows
• Predicting stereochemical outcomes
• Analyzing substrate, nucleophile, solvent, and leaving group effects

Concept Check 🎯

Fill in the Blanks 🔍

Synthesis & Review

Part 7 of 7 — Synthesis & Review

1. Substitution reactions are foundational in synthesis

Substitution reactions are foundational in synthesis

2. SN1 and SN2 have opposite preferences

SN1 and SN2 have opposite preferences

3. Stereochemistry is a key diagnostic tool

Stereochemistry is a key diagnostic tool

4. Review

predicting substitution outcomes

Concept Check 🎯

Key Concepts Summary

• Substitution reactions are foundational in synthesis
• SN1 and SN2 have opposite preferences
• Stereochemistry is a key diagnostic tool
• Review: predicting substitution outcomes

Concept Check 🎯

Fill in the Blanks 🔍