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
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