Dicyclohexano-18-crown-6

(cis-syn-cis)

[15128-65-1]  · C20H36O6  · Dicyclohexano-18-crown-6  · (MW 372.50) (cis-anti-cis)

[56468-35-0]

(complexation agent; promoter of halide reactions, carbon, oxygen, and sulfur anion reactions, eliminations, oxidations, and reductions)

Physical Data: mp 38-54 °C (mixture of isomers); cis-syn-cis isomer mp 61-62 °C; cis-anti-cis isomer (two forms) mp 69-70 °C and 83-84 °C. 1H NMR: (mixture of isomers, C6D6) 3.3-4.0 ppm (20H multiplet) and 0.9-2.2 ppm (16H multiplet).

Form Supplied in: all isomers are colorless crystals.

Preparative Methods: a mixture of diastereomers is prepared in 58-69% yield by the hydrogenation of Dibenzo-18-crown-6 in n-butanol over 5% ruthenium on alumina at 1000 psi.1 This mixture has been separated into the cis-syn-cis and cis-anti-cis isomers.2 Direct synthesis of the trans-syn-trans (mp 120-121 °C) and trans-anti-trans (mp 77-80 °C) isomers from trans-1,2-cyclohexanediol has been reported.3,4

Handling, Storage, and Precautions: toxic orally; eye and skin irritant, with possible permanent injury; absorbed by skin. Use in a fume hood.

Complexation With Metal Salts.

The cavity diameter of dicyclohexano-18-crown-6 is estimated to be 2.6-3.2 Å, which is ideal for complexing with a potassium cation, which has an ionic diameter of 2.66 Å. While the selectivity of dicyclohexano-18-crown-6 for potassium salts is well documented, this macrocyclic multidentate ligand will also effectively complex with other alkali metal cations.5

Reactions.

Halides.

The Potassium Fluoride/dicyclohexano-18-crown-6 promoted elimination reaction of cis-b-bromo-p-styrene in the solvents Acetonitrile, N,N-Dimethylformamide, and n-butyl cellosolve has been studied.6

The reaction of dimethyl 2-chloroethylene-1,1-dicarboxylate with potassium fluoride/dicyclohexano-18-crown-6 in sulfolane produces dimethyl 2-fluoroethylene-1,1-dicarboxylate.7 Modest yields of dechlorodecarboxymethylation products promoted by potassium chloride/dicyclohexano-18-crown-6 in sulfolane have also been observed (eq 1).7

Dicyclohexano-18-crown-6 enhances the reactivity of potassium bromide and Potassium Iodide in nucleophilic substitution and elimination reactions.8 Second-order kinetics are observed for the reaction of n-butyl brosylate with bromide and iodide ions in Acetone. Potassium iodide/dicyclohexano-18-crown-6 complex acts as a base in aprotic solvents.8 Reaction with 2-bromooctane in DMF at 100 °C for 6 h produced only 2-octene in 75-80% yield. In acetone the crown complex of potassium iodide gives a low yield of 2-octene; the major product is mesityl oxide from the condensation of acetone.

Dicyclohexano-18-crown-6 was used as a liquid-liquid phase transfer catalyst in the reaction of the mesylate of 1-octanol, 1-bromooctane, 1-iodooctane, and the mesylate of 2-octanol with a variety of sodium and potassium halides in the form of saturated aqueous solutions.9 The relative nucleophilicity of the halides is I- >Br- > Cl- > F-; secondary substrates react more slowly than primary; excess iodide quantitatively displaces bromide. In general, dicyclohexano-18-crown-6 shows greater anion activation than Dibenzo-18-crown-6.10

Oxygen Anions.

A wide variety of p-bromophenacyl esters have been synthesized by the reaction of potassium carboxylates with p-bromophenacyl bromide in acetonitrile or benzene in the presence of dicyclohexano-18-crown-6.11-13 Sodium salts give excellent yields of product but the reaction times are longer.

Dicyclohexano-18-crown-6 activates potassium acetate more in its reaction with benzyl chloride than does 18-Crown-6 or dibenzo-18-crown-6.14

Sterically hindered esters of 2,4,6-trimethylbenzoic acid can be saponified with the Potassium Hydroxide/dicyclohexano-18-crown-6 complex in aromatic hydrocarbons. The reaction proceeds by acyl-oxygen cleavage.15 It was subsequently reported that using this procedure only 11% of the anions in toluene were hydroxide: the major species was methoxide ion.16 Reaction of this solution with o-dichlorobenzene produced o-chloroanisole. The reaction was shown to be consistent with an addition-elimination aromatic nucleophilic substitution mechanism.

The rates of alkylation of potassium phenoxide with 1-bromobutane in dioxane in the presence of a series of linear and cyclic polyether additives have been compared.17 Dicyclohexano-18-crown-6 is more effective than 18-crown-6 and dibenzo-18-crown-6.

The rates of reaction of Potassium t-Butoxide with 2-nitrofluorobenzene and 4-nitrofluorobenzene has been studied in the absence and presence of dicyclohexano-18-crown-6.18 Upon addition of a molar equivalent of crown, the rate of reaction of 2-nitrofluorobenzene increased by a factor of 3, and that of 4-nitrofluorobenzene by a factor of 2000.18

The rates of reaction of a number of oxygen nucleophiles with p-nitrophenyl phosphinate and with p-nitrophenyl benzoate in toluene containing dicyclohexano-18-crown-6 have been reported. The anions studied include t-BuOO-K+, t-BuO-K+, n-BuOO-K+, and p-MeC6H4O-K+.19

Potassium Superoxide was successfully solubilized in Dimethyl Sulfoxide, benzene, THF, and DMF containing dicyclohexano-18-crown-6.20,21 Reaction with primary and secondary alkyl halides, tosylates, and mesylates was reported to produce reasonable yields of dialkyl peroxides.21 Alcohol side products accompanied peroxide formation. Using (-)-(R)-2-octyl bromide it was demonstrated that the superoxide radical anion, as well as the intermediate alkyl peroxy anion, reacted with the alkyl halide with inversion of configuration.

Dicyclohexano-18-crown-6 is an effective phase transfer catalyst in the reactions of 4-chloromethyl-1,3-dioxolane with substituted mono- and dihydric phenols in the presence of metal hydroxide bases.22

Carbon Anions.

Dicyclohexano-18-crown-6 is used as a liquid-liquid phase-transfer catalyst in the reaction of Potassium Cyanide with 1-chlorooctane10 and in the alkylation of phenylacetone with n-butyl bromide using 50% aqueous sodium hydroxide.10 A series of kinetic studies involving the alkylation of sodio diethyl n-butylmalonate with n-butyl bromide in the solvents benzene and cyclohexane in the presence of varying concentrations of dicyclohexano-18-crown-6 has been reported.23 In benzene solution containing only 0.036 M dicyclohexano-18-crown-6 the alkylation rate is equal to that observed in neat DMF. The addition of dicyclohexano-18-crown-6 to the alkali metal salts of Ethyl Acetoacetate in dioxane causes the destruction of ionic agglomerates and formation of monomeric ion pairs.23 In the reaction of this enolate with ethyl tosylate a marked acceleration of rate is observed in the presence of the crown.24

The phase-transfer catalytic methylation of deoxybenzoin by Dimethyl Sulfate produces an oxygen-to-carbon alkylation ratio of approximately unity in the presence of dicyclohexano-18-crown-6.25 Similar results were obtained with 18-crown-6.

Eliminations.

The effect of ionic association upon positional and geometrical orientation in base-promoted b-elimination processes from 2-butyl halides and p-toluenesulfonate systems in solvents of low polarity has been extensively explored.24 The results of the reactions of 2-bromobutane and 2-butyl p-toluenesulfonate with a number of base-solvent systems to produce 1-butene and cis- and trans-2-butene in the presence and absence of dicyclohexano-18-crown-6 has been reported.26

The competition between syn and anti elimination in the reaction of trans-2-phenylcyclopentyl tosylate with potassium t-butoxide in t-butyl alcohol has been investigated.24 The 1-phenylcyclopentene was produced by a syn elimination, while the 3-phenylcyclopentene was produced via an anti pathway. Using 0.1 M potassium t-butoxide, 89% syn elimination was realized; in the presence of an equivalent quantity of dicyclohexano-18-crown-6, however, the syn product was reduced to 30%.

Base association effects have been studied using conformationally mobile systems. The effect of dicyclohexano-18-crown-6 on the syn vs. anti elimination in the reaction of 4,4,7,7-tetramethylcyclodecyl bromide and tosylate,27 chlorocyclodecane,28 and 5-decyltosylate29 has been reported.

The stereochemical course of reaction of cis- and trans-1-methoxy-d3-2-d-acenaphthene with potassium t-butoxide is dependent on the nature of the counter cation.30 The amount of syn elimination decreases in the order Li+ > K+ > Cs+ > NMe4+ > K+-crown. It is believed that the elimination mechanism proceeds through a carbanion intermediate.

The effect of dicyclohexano-18-crown-6 on the base-promoted syn and anti elimination pathways on the diastereomeric 1-deutero-2-fluoro-2-phenylthioethyl phenyl sulfone has been reported.31 The bases used were potassium phenoxide in dioxane and sodium t-butoxide in benzene/t-butanol. With potassium phenoxide, in the absence of crown the syn elimination pathway dominates, while in the presence of crown the anti pathway becomes more important. The corresponding reaction with sodium t-butoxide shows little or no effect of crown on the stereochemical course of reaction.

Sulfur Anions.

Dicyclohexano-18-crown-6 serves as an efficient phase transfer catalyst in the reaction of thiophenoxide (see Thiophenol) with 1-bromooctane under liquid-liquid phase-transfer catalytic conditions.32

Oxidations.

Dicyclohexano-18-crown-6 solubilizes Potassium Permanganate in benzene.33 The solid complex was isolated but it was unstable and slowly decomposed to adipic acid. The solubilized permanganate provides a convenient, mild, and efficient oxidant for a wide variety of organic compounds, e.g. alkenes, alcohols, aldehydes, and alkyl aromatics.

The reaction of Potassium Chromate with primary alkyl halides in Hexamethylphosphoric Triamide containing dicyclohexano-18-crown-6 produces aldehydes in good yields.34 The chromate functions both as a nucleophile and an oxidant.

Reductions.

Dicyclohexano-18-crown-6 has been employed as a liquid-liquid phase transfer catalyst in the reduction of 2-octanone in a benzene/aqueous Sodium Borohydride two-phase system.10

The solubilization of Potassium and cesium metals in THF and diethyl ether using dicyclohexano-18-crown-6 has been reported.35 Metal concentrations of approximately 0.0001 M were obtained using 0.005 M solutions of crown. Solution of the metals in THF was carried out at rt, while solution of potassium in diethyl ether was conducted at -78 °C. At -78 °C the THF solutions were stable for days. Optical absorption spectra indicated that the major anionic species in the presence of the crown was the alkali metal anion, M-.

The solubility enhancement of sodium and potassium metals in secondary amines and in straight and branched chain ethers in the presence of dicyclohexano-18-crown-6 has been studied.36 The alkali metal anions Na- and K- were identified from optical spectra.

Related Reagents.

18-Crown-6; 12-Crown-4; 15-Crown-5; Dibenzo-18-crown-6.


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Charles L. Liotta

Georgia Institute of Technology, Atlanta, GA, USA



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