Substitution vs Elimination

SN2 Reactions

1) 0°>1°>2°>3° (less sterically hindered

2)*Leaving Group should be weak base (I-, Br-, Cl-) OTs-, OMs-, OTf-

3) Strong nucleophiles --> strong bases

-exception1 Bulky bases strong bases (weak nuc)

-e.g. LDA, t-Butoxide (---> these are E2)

-exception2 big atom nucs (weak base, good nuc)

-e.g. I-, (-)SR, RSH, SH2

4) Faster in Polar aprotic solvents

-e.g. ketone, MeCN, DMF, DMSO

*bad leaving groups can be converted to good ones with sulfonates (mesylate,tosylate, triflate)

SN1 Reactions

1) Substrates that form stabilized carbocations are best: 3°>2°>1°>0°

2)*Leaving Group should be weak base (I-, Br-, Cl-)

3) PoorNucleophile -> weak bases

-.e.g. H2O, ROH, RCO2H, RSH, X-

4)Polar protic solvents

-e.g. MeOH, AcOH,EtOH, :NH3

*Carbocation rearrangement possible

Solvolysis- substitution with nucleophilic solvent

*bad LG can be converted using acid (such as H2SO4)

Polar Aprotic Solvents

(not h-bond donor so does not hinder h-bonding network)

- Strongest bases are best nucs

Across Row:

Nucleophility increases as basicity increases

Down Group: Decreasing nucleophility

F(-)>Cl(-)>Br(-)>I(-)

Examples of polar aprotic solvents:ketone, MeCN, DMF, DMSO

Polar Protic Solvents

(H bond donor, hinders h-bonding network)

Across Row:

Nucleophility increases as Basicity increases

Down Group: Increasing nucleophility

I(-)>Br(-)>Cl(-)>F(-)

Examples of polar protic solvents: MeOH, AcOH, EtOH, :NH3

SN2 quick and dirty

1) Electrophile: 0>1>2>3 (sterics)

2) LG: Good LG (weak bases) ex. I- , Br- , Cl-

3) Nucleophile: Str. bases, anionic (-), big atom ex. I- , RSH, (-)SR, PR3

4) Solvent: Polar Aprotic

Product outcome : Substitution

Stereochemistry : inversion

Reaction Condition : Usually strong basic

SN1 quick and dirty

1)Electrophile: 3>2>1>0 (stability of carbocation rearrangement)

2) LG: Good LG (weak bases) ex. I- , Br- , Cl-

3) Nucleophile: Weak base, neutral (H2O,ROH,RCo2H,RSH,X-)

4) Solvent: Polar Protic solvent (MeOH, AcOH etc)

Product outcome : Substitution, rearrangement possible

Stereochemistry : Racemization

Reaction Condition : Neutral or acidic

E2 Reaction

Produces Alkene

Competitive with SN2

Strong base a requirement.

Alkene is Zaitsev (more substituted alkene) when in the presence of small,strong bases (ex. OH-)

Alkene is Hofmann (Less substituted alkene) when in the presence of bulky, strong bases.

Stereochemistry: Anti-periplanar

**E2 is favored with 2° and 3° alkyl halides (and sulfonates) that have beta-hydrogens and strong bases

**E2 is favored by strong, non-nucleophilic bases

When in polar protic solvent (meant for SN1), it slows down SN2, so E2 is favored

Increased substitution at the Beta-carbon slows down SN2, so E2 is favored

E1 Reaction

Produces Alkene

Competitive with SN1

No strong bases/nucleophiles under SN1/E1

Stereochemistry: Trans-alkene preferred but if no choice doesn't matter. (no required anti-periplanar)

Usually SN1> E1

E1 favored at high temperatures

Acid-Catalyzed Alcohol Dehydration

Reagents: 2° or 3° alcohol + acid (H2SO4) + heat (Δ)

Product: alkene (E1)

Know mechanism