SN1 vs SN2 vs E1 vs E2

Sn1 Reaction stereochemistry

substitution with a mix of retention and inversion @ stereocenter

Sn1 Rate Law

sensitive to the concentration of the substrate ONLY

nucleophile ID and concentration does not matter

FIRST Order

Rate = k [R-X]

Sn1 Substrate preference

fastest for tertiary, slowest for primary

Sn1 Mechanism

STEPWISE

1. leaving group leaves (slow step), forming a carbocation intermediate

2. carbocation intermediate is attacked by nucleophile (fast step)

Sn2 Stereochemistry

substitution occurs with inversion of configuration at chiral centers

Sn2 Rate Law

rate is sensitive to concentration of substrate AND nucleophile

Rate = k [R-X][Nu^-]

second order

Sn2 Substrate

slowest with tertiary, fastest for primary/methyl (steric hindrance repels nu-)

bulky groups slow down backside attack

Sn2 Mechanism

1-step backside attack

results in inversion of stereochemistry

substitution, nucleophilic, bimolecular

what solvent works best for Sn1?

polar protic (have H⁺ on electroneg. atom, lets them bond to cations and anions)

ex:

1. alcohols (R-OH)

   1. methanol (CH3OH)

   2. ethanol (CH3CH2OH)

2. H2O

What solvent favors Sn2?

polar aprotic — Nu^- needs to be readily available to push leaving group

ex:

1. DMSO (dimethyl sulfoxide)

2. acetyl nitrile (CH3CN)

3. acetone (C3H6O or CH3COCH3)

4. dimethylformamide (HCON(CH₃)₂)

What kind of nucleophile do Sn1 prefer?

weak - generally neutral

What kind of nucleophile does Sn2 prefer?

strong (generally bearing a negative charge)

Comparing Sn1 vs Sn2: step 1

Identify leaving group

• halogens (Cl, Br, I) or tosylates/mesylates (OTs, OMs)

• if acid is present, look for alcohols (OH)

Comparing Sn1 vs Sn2: step 2

inspect the carbon that the leaving group is attached to

• if the C is tertiary —> Sn1 (not Sn2 b/c steric hindrance)

• if the C is primary —> Sn2 (not Sn1 b/c carbocation would be unstable, except for in the case of resonance stabilization)

Comparing Sn1 vs Sn2: step 3

examine nucleophile

• negative nucleophile —> generally Sn2

• neutral nucleophile (H2O or R-OH) —> generally Sn1

Comparing Sn1 vs Sn2: step 4

check solvent

polar aprotic (DMSO, acetone, acetonitrile, DMF) —> generally Sn2

polar protic (H2O, ROH) —> generally Sn1

E1 rate law

unimolecular

depends on concentration of SUBSTRATE

rate = k [substrate]

What is the “big barrier” for E1?

forming a carbocation (stability)

tertiary > secondary > primary

E1 vs E2: is there a strong base?

no strong base = E1

strong base present/req. = E2

Stereochemistry requirements for E1

none

E2 reaction rate law

bimolecular

rate = [base][substrate]

depends on BOTH substrate and base!

“big barrier” for E2

no big barrier

stereochemistry of E2 reaction

leaving group must be anti to hydrogen removed

E1 mechanism rate-determining step =?

unimolecular rate determining step = loss of leaving group to form a carbocation

proceeds faster when a more stable carbocation can be formed

Steps:

1. loss of leaving group

2. deprotonation

E2 mechanism

1-step, concerted reaction

strong base simultaneously removes a beta-hydrogen, a pi bond forms between the two carbons

leaving group departs, leading to an alkene