POTASSIUM HYDROXIDE–18-CROWN-6
1
Potassium Hydroxide–18-Crown-6
O
O
O
O
O
O
KOH
+
(KOH)
[1310-58-3]
HKO
(MW 56.11)
InChI = 1/K.H2O/h;1H2/q+1;/p-1/fK.HO/h;1h/qm;-1
InChIKey = KWYUFKZDYYNOTN-GDVMLVAHCS
(18-crown-6)
[17455-13-9]
C
12
H
24
O
6
(MW 264.36)
InChI = 1/C12H24O6/c1-2-14-5-6-16-9-10-18-12-11-17-8-7-
15-4-3-13-1/h1-12H2
InChIKey = XEZNGIUYQVAUSS-UHFFFAOYAP
(dicyclohexano-18-crown-6)
[16069-36-6]
C
20
H
36
O
6
(MW 372.56)
InChI = 1/C20H36O6/c1-2-6-18-17(5-1)23-13-9-21-11-15-25-
19-7-3-4-8-20(19)26-16-12-22-10-14-24-18/h17-20H,1-16H2
InChIKey = BBGKDYHZQOSNMU-UHFFFAOYAJ
(dibenzo-18-crown-6)
[14187-32-7]
C
20
H
24
O
6
(MW 360.44)
InChI = 1/C20H24O6/c1-2-6-18-17(5-1)23-13-9-21-11-15-25-
19-7-3-4-8-20(19)26-16-12-22-10-14-24-18/h1-8H,
9-16H2
InChIKey = YSSSPARMOAYJTE-UHFFFAOYAB
(ester hydrolysis; nucleophilic substitutions; ketone alkylation)
Physical Data:
see entries for Potassium Hydroxide, 18-Crown-
6, Dicyclohexano-18-crown-6, and Dibenzo-18-crown-6.
Hydrolysis of Sterically Hindered Esters.
Methyl and t-
butyl esters of mesitoic acid were saponified by the KOH complex
of dicyclohexano-18-crown-6 in aromatic hydrocarbons such as
toluene at reflux temperature (104–111
◦
C) for 5 h to give mesitoic
acid in high yields (eq 1).
1
CO
2
R
(1)
CO
2
H
KOH, toluene
dicyclohexano-18-crown-6
R = Me, 93%; t-Bu, 94%
104–111 °C, 5 h
Aromatic Nucleophilic Substitutions.
The KOH/dicyclo-
hexano-18-crown-6 complex in toluene was prepared by solvent
exchange from MeOH.
1
It contained 11% hydroxide ion and 89%
methoxide ion.
2
Reaction of o-dichlorobenzene with this com-
plex at 90
◦
C for 1 h gave o-chloroanisole in 40–50% yield. No
phenol or other products from hydroxide ion were obtained. m-
Chloroanisole was obtained from m-dichlorobenzene in a low
yield.
2
2-Alkoxy-3-cyanopyridines were prepared by the nucleophilic
displacement of 2-chloro-3-cyanopyridine with alcohols in
toluene and KOH/18-crown-6. Primary alcohols reacted within
3 h at 25
◦
C and gave the 2-alkoxy-3-cyanopyridines in about
85% yields (eq 2). Secondary alcohols reacted slower and gave
lower yields, while t-BuOH did not react. The less reactive 2-
chloropyridine required heating.
3
Similar results were obtained
from Sodium Hydroxide–Aliquat 336 in toluene (see Methyltri-
octylammonium Chloride–Alkali).
N
CN
Cl
(2)
KOH, toluene
18-crown-6
N
CN
OR
+
ROH
Time
3 h
3 h
18 h
Yield (%)
85
85
67
R
Bn
C
8
H
17
i
-Pr
20–25 °C
Removal of Benzylidene Blocking Groups.
Benzylidene
groups blocking the α-methylene positions of several ketones
were removed under relatively mild conditions when treated with
4-aminobutyric acid and KOH in DMSO or HMPA in the presence
of dibenzo-18-crown-6 as a catalyst. The reaction temperature var-
ied from 85 to 115
◦
C and the isolated yields were 41–56%. The
yields were lower in the absence of the amine and the reaction was
slower in the absence of the crown ether. The retroaldol cleavage
of the intermediate β-hydroxy ketone is facilitated by the imine
formation (eq 3).
4
O
Ph
O
O
Ph
OH
N
Ph
O
H
R
NH
R
H
2
N(CH
2
)
3
CO
2
H
KOH, H
2
O, DMSO
(3)
R = (CH
2
)
3
CO
2
K
dibenzo-18-crown-6
115 °C, 2 h
Alkylation of Arylalkynes. Terminal arylalkynes were alky-
lated efficiently with alkyl iodides in benzene at 80
◦
C in the pres-
ence of powdered KOH and a catalytic amount of 18-crown-6
(eq 4).
5
Ar
Ar
R
RI, KOH
18-crown-6
(4)
Ar = Ph, R = Me, 74%
Ar = Ph, R = C
8
H
17
, 63%
benzene, 80 °C
Permethylation of Ketones. Several ketones were completely
methylated at their α-position(s) when treated with Iodomethane,
powdered KOH, and a catalytic amount of 18-crown-6 in toluene
at 70
◦
C,
6
e.g. 2,2,6,6-tetramethylcyclohexanone was prepared
from cyclohexanone and pivalophenone from acetophenone (eq 5)
in 93% and 89%, respectively, via this procedure.
Avoid Skin Contact with All Reagents
