Williamson Ether Synthesis

Schematic representation of the Williamson Ether Synthesis.

Mechanism of the Williamson Ether Synthesis

Mechanism of the Williamson Ether Synthesis

Original publication	Philosophical Magazine. 1850, 37, 350. J. Org. Chem.. 2011, 76, 8070.
Review

Sample reactions

intermediate structure

KOH, Me2SO4

H2O, MeOH

Reflux, 90 min, 90%

intermediate structure

intermediate structure

Na2CO3

THF

Reflux, , 80% (2 steps)

intermediate structure

intermediate structure

BnBr, TMS2NK

THF

0 °C to RT, 20 min, 92%

intermediate structure

intermediate structure

MeI, NaH

DMF

0 °C to RT, 2 h, 93% (3 steps)

intermediate structure

intermediate structure

BnBr, KH, n-Bu4N+ I-

Et2O

RT, 2 h, 87%

intermediate structure

intermediate structure

BnBr, NaH, n-Bu4N+ I-

THF

0 °C to RT, 4.5 h, 98%

intermediate structure

intermediate structure

BnBr, K2CO3, n-Bu4N+ I-

DMF

RT, 6 h, 93%

intermediate structure

intermediate structure

BnBr, K2CO3, n-Bu4N+ I-

DMF

RT, 53 h, 50-57%

intermediate structure

intermediate structure

NaH, AllylBr

PhH

70 °C, 3.5 h

intermediate structure

intermediate structure

Me2CuLi, AllylCl

HMPA, THF

-78 °C to RT

intermediate structure

intermediate structure

BnBr, TMS2NNa, n-Bu4N+ I-

THF

0 °C to RT, 70 min

intermediate structure

intermediate structure

NaH, n-Bu4N+ I-, 2-Bromomethylnaphthalene

DMF

0 °C to RT, 36 h, 96%

intermediate structure

intermediate structure

KH, MeI, 18-Crown-6

THF

0 °C to RT, 2 d, 77%

intermediate structure

intermediate structure

MeI, NaH

DMF

-15 °C, 60 min, 82% (2 steps)

intermediate structure

intermediate structure

KH, MeI

THF

RT to Reflux, 2 h, 90%

intermediate structure

intermediate structure

K2CO3, Me2SO4, NaHSO3

Acetone

RT, 3 h, 82-86%

intermediate structure

intermediate structure

intermediate structure

KOt-Bu

DMSO

50 °C, 5 h

intermediate structure

intermediate structure

K2CO3, Me2SO4

Acetone

Reflux, 16 h, 96%

intermediate structure

intermediate structure

intermediate structure

NaH

DMF

intermediate structure

intermediate structure

MeI, NaH

THF

0 °C to RT, 60 min, 96%

intermediate structure

intermediate structure

BnBr, NaH

DMF

0 °C to RT, 19 h, 92%

intermediate structure

intermediate structure

intermediate structure

KH

THF

0 °C to RT, 90 min, 60%

intermediate structure

intermediate structure

K2CO3, Me2SO4

Acetone

Reflux, 2 h, 90%

intermediate structure

intermediate structure

K2CO3, Me2SO4

Acetone

80 °C, 60 min, 90% (2 steps)

intermediate structure

intermediate structure

intermediate structure

K2CO3

Acetone

Reflux, 8 h, 66%

intermediate structure

intermediate structure

BnBr, K2CO3

Acetone

RT, 6 h, 95%

intermediate structure

intermediate structure

K2CO3, MeI

DMF

RT, 60 min, 87%

intermediate structure

intermediate structure

BnBr, K2CO3

Acetone

Reflux, 2 h, 92%

intermediate structure

intermediate structure

BnBr, NaH

DMF

RT, , 99%

intermediate structure

intermediate structure

Me2SO4, NaOH

H2O

RT to 100 °C

intermediate structure

intermediate structure

K2CO3, MeI

DMF

RT, 18 h, 45% (2 steps)

intermediate structure

intermediate structure

K2CO3, MeI

DMF

RT, 24 h, 99%

intermediate structure

intermediate structure

KOH, Et2SO4

H2O

100 °C, 30 min, 68%

intermediate structure

intermediate structure

K2CO3, MeI

Acetone

RT, 6 h, 85%

intermediate structure

intermediate structure

KH, n-Bu3SnCH2I

THF

RT, 3.5 h, 95%

intermediate structure

intermediate structure

LiOH, Me2SO4

THF

50 °C, 3 h, 86%

intermediate structure

intermediate structure

BnBr, K2CO3

CHCl3, MeOH

Reflux, 4 h, 71%

intermediate structure

intermediate structure

K2CO3, MeI

Acetone

Reflux, , 84%

intermediate structure