18-Crown-6 polyether

DIAZACYCLOOCTADECANE, 54, 88 MACROCYCLIC POLYETHERS DIBEN-ZO—18-CROWN-6-POLYETHER AND DICYCLOHEXYL- 18-CROWN-6-POLYETHER, 52, 66 Malonaldehyde bis(diethyl acetal), 52, 139... 

Potassium acetate complex with dicyclohexyl-18-crown-6-polyether, 52, 71 Potassium amide, 52, 75 Potassium azide, 50, 10 Potassium tert-butoxide, 52,... 

MACROCYCLIC POLYETHERS DIBENZO-18-CROWN-6 POLYETHER AND DICYCL0HEXYL-18-CR0WN-6 POLYETHER... 

This product, tan fibrous crystals melting at 161-162°, amounts to 221-260 g. (39-48%) and is sufficiently pure for use in the next part of this preparation. The product may be purified further by recrystallization from benzene. The dibenzo-18-crown-6 polyether separates as white fibrous needles melting at 162.5-163.5° (Note 6). 

Dicyclohexyl-18-crown-6 polyether possesses unusual physiological properties which require care in its handling. It is likely that other cyclic polyethers with similar (iomplcxing power are also toxic, and should be handled with ccpml care. 

This residue is a mixture of stereoisomerio dicyclohexyl-18-crown-6 polyethers which may be contaminated with some unchanged dibenzo-18-crown-6 polyether and with alcohols arising from hydrogenolysis of the polyether ring. The submitter reports that this residue is sufficiently pure for many purposes such as the preparation of complexes with potassium hydroxide which are soluble in aromatic hydrocarbons. 

The preparation of dibenzo-18-crown-6 polyether directly from catechol and bis(2-chloroethyl) ether has been reported previously. The present procedure is an improvement of this method. Although dibenzo-18-crown-6 polyether can be obtained in 80% yield from bis-[2-(o-hydroxyphenoxy)-ethyl] ether and bis(2-chloroethyl) ether, the former intermediate has to be synthesized by a method involving several steps. One of the hydroxyl groups of catechol must be protected against alkali by reaction with a molecule of dihydropyran or chloromethylm ethyl ether. Then the intermediate is treated with bis(2-chloroethyl) ether in the presence of alkali and, finally, converted into the desired intermediate by acid hydrolysis. The yield of bis[2-(o-hydroxyphenoxy)-ethyl] ether was less than 40% so that the overall yield of dibenzo-18-crown-6 polyether never approached 39-48%, the yield of the present direct method. 

Oral toxicity. The approximate lethal dose of the dicyclo-hexyl-18-crown-6 polyether for ingestion by rats was 300 mg./ kg. In a 10-day subacute oral test, the compound did not exhibit any cumulative oral toxicity when administered to male rats at a dose level of 60 mg./kg./day. It should be noted that dosage at the approximate lethal dose level caused death in 11 minutes, but that a dose of 200 mg./kg. was not lethal in 14 days. 

Skin absorption. Dicyclohexyl-18-crown-6 polyether is very readily absorbed through the skin of test animals. It caused fatality when absorbed at the level of 130 mg./kg. 

The checkers prepared a crystalline complex of potassium acetate with isomer B of dicyclohexyl-18-crown-6 polyether by the following procedure. To a stirred solution of 15.0 g. (0.0404 mole) of dicyclohexyl-18-crown-6 polyether (mixture of isomers) in 50 ml. of methanol was added a solution of 5.88 g. (0.0600 mole) of anhydrous potassium acetate (dried at 100° under reduced pressure) in 35 ml. of methanol. The resulting solution was concentrated under reduced pressure with a rotary evaporator, and the residual white solid was extracted with 35 ml. of boiling methylene chloride. The resulting mixture was filtered and the filtrate was cooled in a dry ice-acetone bath and slowly diluted with petroleum ether (b.p. 30-60°, approximately 200 ml. was required) to initiate crystallization. The... 

The physical properties of many macrocyclic polyethers and their salt complexes have been already described. - Dibenzo-18-crown-6 polyether is useful for the preparation of sharpmelting salt complexes. Dicyclohexyl-18-crown-6 polyether has the convenient property of solubilizing sodium and potassium salts in aprotic solvents, as exemplified by the formation of a toluene solution of the potassium hydroxide complex (Note 13). Crystals of potassium permanganate, potassium Lbutoxide, and potassium palladium(II) tetrachloride (PdClj + KCl) can be made to dissolve in liquid aromatic hydrocarbons merely by adding dicyclohexyl-18-crown-6 polyether. The solubilizing power of the saturated macrocyclic polyethers permits ionic reactions to occur in aprotic media. It is expected that this [)ropcrty will find practical use in catalysis, enhancement of... 

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