Potassium Hydroxide-18-Crown-6


[1310-58-3]  · HKO  · Potassium Hydroxide-18-Crown-6  · (MW 56.11) (18-crown-6)

[17455-13-9]  · C12H24O6  · Potassium Hydroxide-18-Crown-6  · (MW 264.36) (dicyclohexano-18-crown-6)

[16069-36-6]  · C20H36O6  · Potassium Hydroxide-Dicyclohexano-18-crown-6  · (MW 372.56) (dibenzo-18-crown-6)

[14187-32-7]  · C20H24O6  · Potassium Hydroxide-Dibenzo-18-crown-6  · (MW 360.44)

(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

Aromatic Nucleophilic Substitutions.

The KOH/dicyclohexano-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 complex 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 Methyltrioctylammonium Chloride).

Removal of Benzylidene Blocking Groups.

Benzylidene groups blocking the a-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 varied 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 b-hydroxy ketone is facilitated by the imine formation (eq 3).4

Alkylation of Arylalkynes.

Terminal arylalkynes were alkylated efficiently with alkyl iodides in benzene at 80 °C in the presence of powdered KOH and a catalytic amount of 18-crown-6 (eq 4).5

Permethylation of Ketones.

Several ketones were completely methylated at their a-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.

Reduction of Aromatic Nitro Compounds.

Aromatic amines were prepared by reduction of the corresponding nitroarenes with Dodecacarbonyltriiron in benzene and the catalytic effect of KOH/18-crown-6 at rt under N2 in 60-84% yield. Twice the amount of Fe3(CO)12 at reflux temperature was needed in the absence of the KOH/18-crown-6 system.7

Decarboxylation of Activated Esters.

Malonic esters, b-keto esters, and a-cyano esters were decarboxylated via a one-pot procedure upon treatment with KOH and equimolar amounts of 18-crown-6 in benzene-ethanol or dioxane-ethanol (eq 6).8

Synthesis of a,b-Unsaturated Nitriles.

MeCN was condensed smoothly with a variety of aldehydes and ketones when treated with KOH in the presence or absence of 18-crown-6 to give a,b-unsaturated nitriles in isolated yields ranging from 50 to 86% (eq 7).9

1. Pedersen, C. J. JACS 1967, 89, 7017 (appendix, p 7035).
2. Sam, D. J.; Simmons, H. E. JACS 1974, 96, 2252.
3. Duggan, A. J. S.; Grabowski, E. J. J.; Russ, W. K. S 1980, 573.
4. Thomas, M. T.; Breitholle, E. G.; Fallis, A. G. SC 1976, 6, 113.
5. Lissel, M. TL 1985, 26, 1843.
6. Lissel, M.; Neumann, B.; Schmidt, S. LA 1987, 263 (CA 1987, 106, 137 659y).
7. Alper, H.; Des Roches, D.; des Abbayes, H. AG(E) 1977, 16, 41.
8. Hunter, D. H.; Perry, R. A. S 1977, 37.
9. Gokel, G. W.; DiBiase, S. A.; Lipisko, B. A. TL 1976, 3495.

Ahmed F. Abdel-Magid

The R. W. Johnson Pharmaceutical Research Institute, Spring House, PA, USA

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