sn2 – substitution, nucleophilic bimolecularchemistry.bd.psu.edu/justik/chem 210/chem 210...

CHEM210ReviewofSN1,SN2,E1andE2

SN2–Substitution,NucleophilicBimolecularOnestep,concertedreactionwherebothnucleophileandsubstrateparticipateinthisratelimitingstep(bimolecular)

Mechanism:

DevelopmentalProblemSet:ShowSN2productsforthefollowingreactions:

a.

b.

c.

d.

e.

f.

g.

h.

i.

j.

k.

NaClDMSO

CH3Br

NaOHCH3CN

CH3Br

KOCH3CN

CH3Br

NaCNCH3CN

CH3Br

NaCNCH3CN

CH3CH2CH2I

CH3CH2ONaDMF

CH3CH2CH2Br

Br NaClDMSO

I NaClDMSO

OTs NaClDMSO

OMs NaClDMSO

Br NaOHCH3CN

l.

m.

n.

o.

p.

q.

r.

s.

t.

u.

v.

w.

x.

Br KOCH3CH3CN

Br LiOCH3CN

Br NaCNCH3CN

BrCH3CN

OK

O

CH3CNCl KCN

CH3CNOK

O

Cl

OTsNaClDMSO

OTsNaClDMSO

BrNaCNDMF

NaSHCH3CNH

Br

NaSHHMPA

H

Cl

KOCH3CN

OBr

KOCH3CN

Br

SN1–Substitution,NucleophilicUnimolecularTwostepreactionwhereonlythesubstrateparticipatesinthisratelimitingstep(unimolecular)

Rate=k[R-X]

Mechanism:

DevelopmentalProblemSet:ShowSN1productsonly(evenwhenE1competes)forthefollowingreactions:

a.

b.

c.

d.

e.

f.

g.

h.

i.

BrH2O

BrCH3OH

BrOH

BrOH

O

I OH

NaSH

I OH

NaS

TsO OH

NaCN

H2OCl

OH

OCl

CC X

Nu

Nu C

racemic

Step 1slow

Step 2

or

fastC

X

For nucleophiles of the type H-Nuthere is a third deprotonation stepusually to give H-X

j.

k.

l.

m.

n.

o.

p.

q.

r.

s.

t.

u.

NaSHH2O

Br

OH

NaCNOMs

OHBr

Br

OH

OHBr

H2OBr

OK

OBr

H2O

Br

H2ONaCN

H2ONaSHBr

NaCNBr

OH

OHBr ONa

O

OHBr KCN

E2–Elimination,BimolecularOnestep,concertedreactionwherebothbaseandsubstrateparticipateinthisratelimitingstep(bimolecular)

Rate=k[B:][R-X]

Mechanism:

DevelopmentalProblemSet:ShowE2productsonlyforthefollowingreactions:

a.

b.

c.

d.

e.

f.

g.

h.

i.

j.

Br

OK

DMSO, Δ

I DMSO, ΔDBN

Br DMF, Δ

tBuOK

Cl DMF, ΔLiOH

OTf CH3CN, ΔCH3OK

CH3CN, ΔCH3OK

Br

CH3CN, ΔDBNBr

Br OK

DMSO, Δ

Cl OK

DMSO, Δ

Cl OK

DMSO, Δ

C

C X XH

B C

C

B H

anit-periplanargeometry

k.

l.

m.

n.

o.

p.

q.

r.

s.

t.

u.

v.

Br

DMSO, ΔDBN

Br OK

HMPA, Δ

Br OK

DMSO, Δ

Br OKPh

DBU, Δ

OK

DMSO, Δ

I

DMSO, ΔDBN

Br

DMSO, ΔDBN

I

Br

OK

DBU, Δ

Ph

OTs

DMSO, ΔLDA

Ph

OTs

DMSO, ΔLDA

DMSO, ΔDBN

Br

DMSO, ΔDBN

Br

E1–EliminationUnimolecularTwostepreactionwhereonlythesubstrateparticipatesinthisratelimitingstep(unimolecular)

Rate=k[R-X]

Mechanism:

DevelopmentalProblemSet:ShowE1productsonlyforthefollowingreactions:

a.

b.

c.

d.

e.

f.

g.

h.

Br H2O, Δ

I CH3OH, Δ

OMs OH, Δ

OH, Δ

Br

H2O, Δ

Cl

OTs

CH3OH, Δ

OTs

CH3OH, Δ

OTs

CH3OH, Δ

CC X

C

Step 1slow

Step 2

fast

X

H CH

C

CHB

C

CB H

i.

j.

k.

l.

m.

n.

o.

p.

q.

r.

s.

t.

u.

v.

Br

OH, Δ

O

H2O, Δ

Br

Br

CH3OH, Δ

I

CH3OH, Δ

BrCH3OH, Δ

Br CH3OH, Δ

OTs

H2O, Δ

CH3OH, Δ

Br

H2O, Δ

Br

Cl

CH3OH, Δ

Br H2O, Δ

I CH3OH, Δ

OMs OH, Δ

OH, Δ

Br

KEYSN2a.

CH3Cl

b.

c.

d.

e.

f.

CH3CH2CH2OCH2CH3

g.

h.

i.

j.

k.

l.

m.

NaClDMSO

CH3Br

NaOHCH3CN

CH3Br CH3OH

KOCH3CN

CH3Br H3CO

NaCNCH3CN

CH3Br CH3CN

NaCNCH3CN

CH3CH2CH2I CH3CH2CH2CN

CH3CH2ONaDMF

CH3CH2CH2Br

Br NaClDMSO Cl

I NaClDMSO Cl

OTs NaClDMSO Cl

OMs NaClDMSO Cl

Br NaOHCH3CN

OH

Br KOCH3CH3CN

OCH3

Br LiOCH3CN

O

n.

o.

p.

q.

r.

s.

t.

u.

v.

w.

x.

Br NaCNCH3CN

CN

BrCH3CN

OK

OO

O

CH3CNCl KCN

CN

CH3CNOK

O

Cl O

O

OTsNaClDMSO

Cl

OTsNaClDMSO

Cl

BrNaCNDMF

CN

NaSHCH3CNH

Br

H

SH

NaSHHMPA

H

Cl

SH

H

KOCH3CN

OBr O

O

KOCH3CN

Br O

KEYSN1a.

b.

c.

d.

e.

f.

g.

h.

i.

j.

k.

l.

m.

BrH2O

HO

BrCH3OH

H3CO

BrOH

O

BrOH

O

O

O

I OH

NaSHHS

I OH

NaSS

TsO OH

NaCNNC

H2OCl OH

OH

OCl O

O

NaSHH2O

Br SH

OH

NaCNOMs CN

OHBr O

Br

OHO

n.

o.

p.

q.

r.

s.

t.

u.

OHBr O

H2OBr OH

OK

OBr

H2OO

O

O

O

+

Br

H2ONaCN CN CN

+

H2ONaSHBr SH SH

+

NaCNBr

OH

CN CN+

OHBr ONa

O

+O

O

H

H

O

O

OHBr KCN

+H

CN

CN

H

KEYE2a.

b.

c.

d.

e.

f.

g.

h.

i.

j.

k.

l.

m.

Br

OK

DMSO, Δ

I DMSO, ΔDBN

Br DMF, Δ

tBuOK

Cl DMF, ΔLiOH

OTf CH3CN, ΔCH3OK

CH3CN, ΔCH3OK

Br

CH3CN, ΔDBNBr

Br OK

DMSO, Δ

+ +major

Cl OK

DMSO, Δ

+ +major

Cl OK

DMSO, Δ+

major

Br

DMSO, ΔDBN +

major

Br OK

HMPA, Δ

Br OK

DMSO, Δ

n.

o.

p.

q.

r.

s.

t.

u.

v.

Br OKPh

DBU, Δ

Ph

+

major

OK

DMSO, Δ

I

DMSO, ΔDBN

Br

DMSO, ΔDBN

I+

major

Br

OK

DBU, Δ

Ph

OTs

DMSO, ΔLDA H

Ph

Ph

OTs

DMSO, ΔLDA H

Ph

DMSO, ΔDBN

Br

DMSO, ΔDBN

Br

KEYE1a.

b.

c.

d.

e.

f.

g.

h.

i.

j.

k.

l.

m.

Br H2O, Δ

I CH3OH, Δ

OMs OH, Δ

OH, Δ

Br

H2O, Δ

Cl

OTs

CH3OH, Δ

OTs

CH3OH, Δ

OTs

CH3OH, Δ+ +

major

Br

OH, Δ

O + +major

H2O, Δ

Br+

major

Br

CH3OH, Δ+ +

major

I

CH3OH, Δ+

BrCH3OH, Δ

n.

o.

p.

q.

r.

s.

t.

u.

v.

Br CH3OH, Δ+

major

OTs

H2O, Δ

CH3OH, Δ

Br

H2O, Δ

Br + +

major

Cl

CH3OH, Δ

+

major

Br H2O, Δ

I CH3OH, Δ

OMs OH, Δ

OH, Δ

Br