POTASSIUM HYDROXIDE 18-CROWN-6 1
Potassium Hydroxide 18-Crown-6 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
ć%
3 h at 25 C and gave the 2-alkoxy-3-cyanopyridines in about
O O
85% yields (eq 2). Secondary alcohols reacted slower and gave
KOH + lower yields, while t-BuOH did not react. The less reactive 2-
O O
chloropyridine required heating.3 Similar results were obtained
O O
from Sodium Hydroxide Aliquat 336 in toluene (see Methyltri-
octylammonium Chloride Alkali).
(KOH)
KOH, toluene
CN CN
[1310-58-3] HKO (MW 56.11)
18-crown-6
+ ROH (2)
InChI = 1/K.H2O/h;1H2/q+1;/p-1/fK.HO/h;1h/qm;-1
20 25 °C
N Cl N OR
InChIKey = KWYUFKZDYYNOTN-GDVMLVAHCS
R Time Yield (%)
(18-crown-6)
[17455-13-9] C12H24O6 (MW 264.36)
Bn 3 h 85
InChI = 1/C12H24O6/c1-2-14-5-6-16-9-10-18-12-11-17-8-7-
C8H17 3 h 85
i-Pr 18 h 67
15-4-3-13-1/h1-12H2
InChIKey = XEZNGIUYQVAUSS-UHFFFAOYAP
(dicyclohexano-18-crown-6)
Removal of Benzylidene Blocking Groups. Benzylidene
[16069-36-6] C20H36O6 (MW 372.56)
groups blocking the Ä…-methylene positions of several ketones
InChI = 1/C20H36O6/c1-2-6-18-17(5-1)23-13-9-21-11-15-25-
were removed under relatively mild conditions when treated with
19-7-3-4-8-20(19)26-16-12-22-10-14-24-18/h17-20H,1-16H2
4-aminobutyric acid and KOH in DMSO or HMPA in the presence
InChIKey = BBGKDYHZQOSNMU-UHFFFAOYAJ
of dibenzo-18-crown-6 as a catalyst. The reaction temperature var-
(dibenzo-18-crown-6)
ć%
ied from 85 to 115 C and the isolated yields were 41 56%. The
[14187-32-7] C20H24O6 (MW 360.44)
yields were lower in the absence of the amine and the reaction was
InChI = 1/C20H24O6/c1-2-6-18-17(5-1)23-13-9-21-11-15-25-
slower in the absence of the crown ether. The retroaldol cleavage
19-7-3-4-8-20(19)26-16-12-22-10-14-24-18/h1-8H,
of the intermediate ²-hydroxy ketone is facilitated by the imine
9-16H2
formation (eq 3).4
InChIKey = YSSSPARMOAYJTE-UHFFFAOYAB
H2N(CH2)3CO2H
KOH, H2O, DMSO
(ester hydrolysis; nucleophilic substitutions; ketone alkylation)
Ph
dibenzo-18-crown-6
Physical Data: see entries for Potassium Hydroxide, 18-Crown-
115 °C, 2 h
O O
6, Dicyclohexano-18-crown-6, and Dibenzo-18-crown-6.
(3)
Ph Ph
Hydrolysis of Sterically Hindered Esters. Methyl and t-
O OH N O NH
R H R
butyl esters of mesitoic acid were saponified by the KOH complex
R = (CH2)3CO2K
of dicyclohexano-18-crown-6 in aromatic hydrocarbons such as
ć%
toluene at reflux temperature (104 111 C) for5htogivemesitoic
acid in high yields (eq 1).1
Alkylation of Arylalkynes. Terminal arylalkynes were alky-
ć%
lated efficiently with alkyl iodides in benzene at 80 C in the pres-
CO2R CO2H
KOH, toluene
ence of powdered KOH and a catalytic amount of 18-crown-6
dicyclohexano-18-crown-6
(eq 4).5
(1)
104 111 °C, 5 h
RI, KOH
18-crown-6
(4)
Ar Ar R
R = Me, 93%; t-Bu, 94%
benzene, 80 °C
Ar = Ph, R = Me, 74%
Ar = Ph, R = C8H17, 63%
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% Permethylation of Ketones. Several ketones were completely
methoxide ion.2 Reaction of o-dichlorobenzene with this com- methylated at their Ä…-position(s) when treated with Iodomethane,
ć%
plex at 90 Cfor 1 h gave o-chloroanisole in 40 50% yield. No powdered KOH, and a catalytic amount of 18-crown-6 in toluene
ć%
phenol or other products from hydroxide ion were obtained. m- at 70 C,6 e.g. 2,2,6,6-tetramethylcyclohexanone was prepared
Chloroanisole was obtained from m-dichlorobenzene in a low from cyclohexanone and pivalophenone from acetophenone (eq 5)
yield.2 in 93% and 89%, respectively, via this procedure.
Avoid Skin Contact with All Reagents
2 POTASSIUM HYDROXIDE 18-CROWN-6
O O
treated with KOH in the presence or absence of 18-crown-6 to
MeI, KOH
give Ä…,²-unsaturated nitriles in isolated yields ranging from 50 to
18-crown-6 t-Bu
(5)
86% (eq 7).9
toluene
R R
R = H, Me, Br, Cl
R2 R2
KOH
+ MeCN (7)
O CHCN
18-crown-6
R1 R1
Reduction of Aromatic Nitro Compounds. Aromatic amines
were prepared by reduction of the corresponding nitroarenes with
Dodecacarbonyltriiron in benzene and the catalytic effect of
1. Pedersen, C. J., J. Am. Chem. Soc. 1967, 89, 7017 (appendix, p 7035).
KOH/18-crown-6 at rt under N2 in 60 84% yield. Twice the
2. Sam, D. J.; Simmons, H. E., J. Am. Chem. Soc. 1974, 96, 2252.
amount of Fe3(CO)12 at reflux temperature was needed in the
3. Duggan, A. J. S.; Grabowski, E. J. J.; Russ, W. K., Synthesis 1980, 573.
absence of the KOH/18-crown-6 system.7
4. Thomas, M. T.; Breitholle, E. G.; Fallis, A. G., Synth. Commun. 1976, 6,
113.
Decarboxylation of Activated Esters. Malonic esters, ²-keto
5. Lissel, M., Tetrahedron Lett. 1985, 26, 1843.
esters, and Ä…-cyano esters were decarboxylated via a one-pot pro-
6. Lissel, M.; Neumann, B.; Schmidt, S., Liebigs Ann. Chem. 1987, 263
cedure upon treatment with KOH and equimolar amounts of 18-
(Chem. Abstr. 1987, 106, 137 659y).
crown-6 in benzene ethanol or dioxane ethanol (eq 6).8
7. Alper, H.; Des Roches, D.; des Abbayes, H., Angew. Chem., Int. Ed. Engl.
KOH 1977, 16, 41.
X X X
18-crown-6 100 °C
8. Hunter, D. H.; Perry, R. A., Synthesis 1977, 37.
(6)
R1 CO2Et R1 CO2K R1 H
rt
9. Gokel, G. W.; DiBiase, S. A.; Lipisko, B. A., Tetrahedron Lett. 1976,
R2 R2 R2
3495.
X = CO2Et, COR3, CN
Ahmed F. Abdel-Magid
The R. W. Johnson Pharmaceutical Research Institute, Spring
Ä… ²-Unsaturated Nitriles. MeCN was con-
Synthesis of Ä… ²
Ä…,²
House, PA, USA
densed smoothly with a variety of aldehydes and ketones when
A list of General Abbreviations appears on the front Endpapers