Williamson Ether Synthesis

Schematic representation of the Williamson Ether Synthesis.
Mechanism of the Williamson Ether Synthesis
Mechanism of the Williamson Ether Synthesis
Original publication
Review
Sample reactions
intermediate structure
Me2SO4, KOH
MeOH, H2O
Reflux, 90 min, 90%
intermediate structure
intermediate structure
Na2CO3
THF
Reflux, , 80% (2 steps)
intermediate structure
intermediate structure
TMS2NK, BnBr
THF
0 °C to RT, 20 min, 92%
intermediate structure
intermediate structure
NaH, MeI
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
THF, HMPA
-78 °C to RT
intermediate structure
intermediate structure
TMS2NNa, BnBr, n-Bu4N+ I-
THF
0 °C to RT, 70 min
intermediate structure
intermediate structure
NaH, 2-Bromomethylnaphthalene, n-Bu4N+ I-
DMF
0 °C to RT, 36 h, 96%
intermediate structure
intermediate structure
KH, 18-Crown-6, MeI
THF
0 °C to RT, 2 d, 77%
intermediate structure
intermediate structure
NaH, MeI
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
Me2SO4, K2CO3, NaHSO3
Acetone
RT, 3 h, 82-86%
intermediate structure
intermediate structure intermediate structure
KOt-Bu
DMSO
50 °C, 5 h
intermediate structure
intermediate structure
Me2SO4, K2CO3
Acetone
Reflux, 16 h, 96%
intermediate structure
intermediate structure intermediate structure
NaH
DMF
intermediate structure
intermediate structure
NaH, MeI
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
Me2SO4, K2CO3
Acetone
Reflux, 2 h, 90%
intermediate structure
intermediate structure
Me2SO4, K2CO3
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
MeI, K2CO3
DMF
RT, 60 min, 87%
intermediate structure
intermediate structure
BnBr, K2CO3
Acetone
Reflux, 2 h, 92%
intermediate structure