Potassium Methoxide-Dicyclohexano-18-crown-6

[52374-55-7]  · C21H39KO7  · Potassium Methoxide-Dicyclohexano-18-crown-6  · (MW 442.70)

(complex provides a strongly basic and nucleophilic methoxide ion2)

Physical Data: reagent is prepared in situ.

Form Supplied in: MeOK is commercially available as a white powder in 95% purity; a mixture of the syn-cis and anti-cis crown ethers is commercially available.1

Preparative Methods: a toluene solution referred to as containing Potassium Hydroxide and Dicyclohexano-18-crown-6 is obtained by mixing the crown ether and 85% KOH in MeOH, adding toluene, removing the MeOH at 100 °C under vacuum, and filtering the mixture.3 However, the solubility of the KOH-crown ether complex is apparently much less than the MeOK complex.2 Thus the toluene solution contains ca. 89% of the methoxide ion and only 11% of the hydroxide ion.2 The direct preparation of the hydroxide complex was unsuccessful.4

Experimentally, complexes are most often generated in situ by adding 1.0 equiv or more of the crown ether to a solution of the base in MeOH or another solvent.

Handling, Storage, and Precautions: do not breathe dust from the base or vapor from the crown ether; avoid contact of both substances and the complex with the eyes, skin, or clothing. Handle reagents and conduct reactions under an inert nitrogen or argon atmosphere.1 Use in a fume hood.

Nucleophilic Substitution Reactions.

The ability of dicyclohexano-18-crown-6 to dissociate MeOK by complexation with the potassium cation clearly manifests itself in various nucleophilic aromatic substitution reactions. The complex prepared by the solvent exchange reaction described above reacts with o-dichlorobenzene at 90 °C over 16 h to give o-chloroanisole in 40-50% yield (eq 1).2 m-Dichlorobenzene is converted into m-chloroanisole under the same conditions, but the yield is much lower. Isomeric products which may arise from a benzyne intermediate are not produced in either case. Thus the nucleophilic aromatic substitution must proceed by an addition-elimination mechanism.2

The rates of nucleophilic aromatic substitution of o- and p-fluoronitrobenzene by MeOK/MeOH are approximately the same; also, the addition of dicyclohexano-18-crown-6 has a negligible effect on the ortho:para rate ratio.5 On the other hand, if Potassium t-Butoxide-t-Butyl Alcohol Complex is employed for the reaction, the ortho:para reactivity ratio is 3.6 × 102. The higher reactivity of the ortho isomer in the solvent of lower polarity, i.e. t-BuOH, is attributable to bridging between the oxygen atoms of the nitro group and the potassium cation. When 1.0 equiv of dicyclohexano-18-crown-6 is added to the t-BuOK/t-BuOH, the ortho:para reactivity ratio approaches unity because the potassium ion is strongly complexed to the crown ether and is unable to assist in the substitution reaction of the o-fluoronitrobenzene.5

When 1.0 equiv of dicyclohexano-18-crown-6 is added to a solution of MeOK in 99% PhH-MeOH, there is a 300-fold increase in the rate of nucleophilic aromatic substitution of 1-chloro-2,4-dinitrobenzene.6 However, in MeOH containing less than 50% by weight of benzene, the addition of the crown ether has a negligible effect on the rate.4 Because of the relatively high polarity of MeOH, the reactivity of the methoxide ion is not influenced significantly by the presence of the crown ether.

Dehydrohalogenation Reactions.

In the dehydrohalogenation of 2-bromobutane, the use of MeOK in MeOH, or other primary alkoxides in the corresponding alcohols, greatly favors Saytzeff elimination and gives a relatively large trans:cis-2-butene ratio, i.e. 3.34:1 (eq 2).7 However, with tertiary alkoxides, e.g. t-BuOK, in the corresponding alcohols Hofmann elimination becomes much more important and the trans:cis-2-butene ratio approaches unity.7 This trend is explained by the postulate that in the solvent of lower polarity, the elimination is promoted by the associated metal alkoxide. As expected, the addition of 1.0 equiv of dicyclohexano-18-crown-6 to the MeOK/MeOH has little effect on the 1-butene:2-butene ratio or the trans:cis-2-butene ratio.7 However, when the crown ether is added to the t-BuOK/t-BuOH, the 1-butene:2-butene ratio decreases and the trans:cis-2-butene ratio increases.

Experiments in which metal alkoxides are used to effect b-elimination of methoxide ion from 1-methoxy-2-deuterioacenaphthenes show that an ElcB mechanism is involved (eq 3).8 The more associated bases, e.g. t-BuOLi/t-BuOH, strongly favor exchange and elimination of the hydrogen syn to the methoxy group. This is attributable to strong coordination between the metal cation of the ion pair and the ether oxygen of the substrate. With a relatively dissociated base such as MeOK/MeOH, the syn and anti protons undergo exchange at comparable rates and anti elimination of the methoxide ion is slightly favored over syn elimination. The addition of dicyclohexano-18-crown-6 does not alter the stereochemistry of the exchange with MeOK. The use of t-BuOK/t-BuOH favors syn elimination and exchange somewhat, but in the presence of 1.0 equiv of the crown ether anti exchange and elimination are both favored.8 Apparently, when the potassium cation is no longer able to complex with the oxygen of the substrate, the t-butoxide ion abstracts the anti proton preferentially for steric reasons.

Other Reactions.

MeOK/dicyclohexano-18-crown-6 has been used rather infrequently for transformations other than nucleophilic aromatic substitutions and b-eliminations. However, it is a useful base for the deprotonation of a ketone in the formation of the TMS enol ether of acetophenone using ethyl trimethylsilylacetate (eq 4).9

Related Reagents.

Potassium t-Butoxide; Potassium t-Butoxide-Benzophenone; Potassium t-Butoxide-t-Butyl Alcohol Complex; Potassium t-Butoxide-18-Crown-6; Potassium t-Butoxide-Dimethyl Sulfoxide; Potassium t-Butoxide-Hexamethylphosphoric Triamide; Potassium Hydroxide-18-Crown-6; Potassium Methoxide-Dimethyl Sulfoxide; Sodium Methoxide.

1. The Sigma-Aldrich Library of Chemical Safety Data, 2nd ed.; Lenga, R. E., Ed.; Sigma-Aldrich: Milwaukee, 1988; Vol. 2, p 1176 and p 2906.
2. Sam, D. J.; Simmons, H. E. JACS 1974, 96, 2252.
3. Pedersen, C. J. JACS 1967, 89, 7017.
4. Lutz, H. D.; Jung, M.; Beckenkamp, K. J. Mol. Struct. 1988, 175, 257.
5. Del Cima, F.; Biggi, G.; Pietra, F. JCS(P2) 1973, 55.
6. Mariani, C.; Modena, G.; Scorrano, G. JCR(S) 1978, 392.
7. Bartsch, R. A. ACR 1975, 8, 239.
8. Hunter, D. H.; Shearing, D. J. JACS 1971, 93, 2348.
9. Nakamura, E.; Hashimoto, K.; Kuwajima, I. BCJ 1981, 54, 805.

Drury Caine

The University of Alabama, Tuscaloosa, AL, USA

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