Organic Syntheses, Coll. Vol. 6, p.395 (1988); Vol. 52, p.66 (1972).
A. Dibenzo-18-crown-6 polyether
. A dry, 5-l., three-necked flask
is fitted with a reflux condenser
, a 500-ml., pressure-equalizing dropping funnel
, a thermometer
, and a mechanical stirrer
. An inlet tube
at the top of the reflux condenser is used to maintain a static nitrogen
atmosphere in the reaction vessel throughout the reaction. The flask is charged with 330 g. (3.00 moles) of catechol (Note 2)
and 2 l. of commercial n-butanol
before stirring is started, and 122 g. (3.05 moles) of sodium hydroxide
pellets are added. The mixture is heated rapidly to reflux (about 115°), and a solution of 222 g. (1.55 moles) of bis(2-chloroethyl) ether (Note 3)
in 150 ml. of n-butanol
is added, dropwise with continuous stirring and heating, over a 2-hour period. After the resulting mixture has been refluxed with stirring for an additional hour, it is cooled to 90° and an additional 122 g. (3.05 moles) of sodium hydroxide
pellets are added. The mixture is refluxed, with stirring, for 30 minutes, and a solution of 222 g. (1.55 moles) of bis(2-chloroethyl) ether (Note 3)
in 150 ml. of n-butanol
is added, dropwise with stirring and heating, over a period of 2 hours. The final reaction mixture is refluxed, with stirring, for 16 hours (Note 4)
, then acidified by the dropwise addition of 21 ml. of concentrated hydrochloric acid
. The reflux condenser is replaced with a distillation head and approximately 700 ml. of n-butanol
is distilled from the mixture. As the distillation is continued, water is added to the flask from the dropping funnel at a sufficient rate to maintain a constant volume in the reaction flask. This distillation is continued until the temperature of the distilling vapor exceeds 99° (Note 5)
, and the resulting slurry is cooled to 30–40°, diluted with 500 ml. of acetone
, stirred to coagulate the precipitate, and filtered with suction. The residual crude product is stirred with 2 l. of water, filtered with suction, stirred with 1 l. of acetone
, and again filtered with suction. The residual product is washed with an additional 500 ml. of acetone
and dried with suction, yielding 221–260 g.
) of tan, fibrous crystals, m.p. 161–162°
, which are sufficiently pure for use in the next step. Dibenzo-18-crown-6 polyether
may be recrystallized from benzene
, giving white, fibrous needles, m.p. 162.5–163.5° (Note 6)
possesses unusual physiological properties which require care in its handling.2
It is likely that other cyclic polyethers with similar complexing power are also toxic, and should be handled with equal care.
a. Oral toxicity. The approximate lethal dose of the dicyclohexyl-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.
b. Eye irritation.
This dicyclohexyl polyether produced some generalized corneal injury, some iritic injury, and conjunctivitis when introduced as a 10% solution in propylene glycol
. Although tests are not complete, there may be permanent injury to the eye even if the eye is washed after exposure.
c. 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.
d. Skin irritation. Primary skin irritation tests run on this polyether indicate the material should be considered a very irritating substance.
Catechol of satisfactory purity may be purchased from Eastman Organic Chemicals or from Aldrich Chemical Company, Inc
Bis(2-chloroethyl) ether may be obtained from Eastman Organic Chemicals
. The checkers redistilled this material (b.p. 175–177°
) before use.
A shorter period of refluxing may be sufficient.
The bulk of the material, a n-butanol
–water azeotrope, distils at 92°.
The product has UV maxima (CH3
OH): 223 nm (ε 17,500) and 275 nm (ε 5500) with 1
H NMR peaks (CDCl3
), δ: 3.8–4.3 (m, 16H, 8CH2
O), 6.8–7.0 (m, 8H, aryl CH
). The mass spectrum exhibits the following abundant peaks: m/e
(rel. int.), 360 (M+, 29), 137 (29), 136 (74), 121 (100), 109 (23), 80 (31), 52 (21), 45 (27), and 43 (34).
It is advisable to use redistilled solvent to avoid the presence of catalyst poisons.
The 5% ruthenium-on-alumina catalyst is available from Engelhard Industries
Since the catalyst, saturated with hydrogen
, is pyrophoric, it should be kept wet with water after the filtration has been completed.
Since the product, a polyether
, is apt to be oxidized by air, especially at elevated temperatures in the molten state, the product should be stored under a nitrogen
This residue is a mixture of stereoisomeric dicyclohexyl-18-crown-6 polyethers
which may be contaminated with unchanged dibenzo-18-crown-6 polyether
and 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 submitter reports that the two major diastereoisomers present, designated isomer A, m.p. 61–62°
and isomer B, as one of two crystalline forms, m.p. 69–70°
or m.p. 83–84°
, may be separated by chromatography on alumina.3
An x-ray crystal structure determination for the complex of barium thiocyanate
with isomer A of dicyclohexyl-18-crown-6 polyether
has shown this polyether to have the cis-syn-cis
An x-ray crystal structure determination for the complex of sodium bromide
with isomer B has shown this isomer to have the cis-anti-cis
The mixture of isomers A and B
has negligible UV absorption (95% C2
OH) and exhibits 1
H NMR (C6
) multiplets at δ 0.9–2.2 (16H, aliphatic CH
) and 3.3–4.0 (20H, OCH
). The mass spectrum of the mixture exhibits the following relatively abundant peaks: m/e
(rel. int.), 372 (M+, 2), 187 (35), 143 (100), 141 (47), 99 (92), 98 (46), 97 (41), 89 (66), 87 (41), 83 (45), 82 (55), 81 (99), 73 (77), 72 (46), 69 (58), 67 (42), 57 (50), 55 (58), 45 (77), 43 (61), and 41 (58). Although the IR (CCl4
) and 1
H NMR (C6
, 100 mHz.) spectra of the pure isomers A and B differ slightly from one another, the checkers were unable to use these spectra to determine quantitatively the composition of mixtures of the two isomers. The most notable difference in these spectra is the shape of the 1
H NMR multiplet in the region 3.3–4.0 p.p.m.; this multiplet is considerably broader in isomer A than in isomer B allowing a qualitative estimate of the purity of each isomer.
The submitter prepared a toluene
solution of the complex of potassium hydroxide
with dicyclohexyl-18-crown-6 polyether
by the following procedure. A mixture of 14.9 g. (0.0402 mole) of dicyclohexyl-18-crown-6 polyether
(mixture of isomers) and 2.64 g. (0.0400 mole) of 85% potassium hydroxide
was dissolved in 50 ml. of methanol
with gentle warming on a steam bath
. The solution was diluted with 100 ml. of toluene
and then concentrated with a rotary evaporator to a volume of 50 ml. An additional 100 ml. of toluene
was added, and the solution was again concentrated to a volume of 50 ml. This solution was diluted with toluene
to a volume of 100 ml., 1 g. of decolorizing charcoal
was added, and the mixture was allowed to stand overnight under a nitrogen
atmosphere. After gravity filtration, a clear toluene
solution of the complex was obtained. Titration with standard hydrochloric acid
indicated the solution to be approximately 0.3 M
in base. This solution, which must be protected from atmospheric moisture and carbon dioxide
, has been used for the saponification of sterically hindered esters.2
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 with a rotary evaporator, and the residual white solid was extracted with 35 ml. of boiling dichloromethane
. The resulting mixture was filtered, and the filtrate was cooled in an acetone–dry-ice bath
and slowly diluted with petroleum ether (b.p. 30–60°, approximately 200 ml. was required)
to initiate crystallization. The resulting suspension of the crystalline complex was allowed to warm to room temperature and filtered with suction. Recrystallization of this complex from a dichloromethane–petroleum ether
) mixture separated 4.21–4.35 g.
) of the complex of potassium acetate with isomer B of dicyclohexyl-18-crown-6 polyether
as white needles, m.p. 165–250°
(dec.). This complex has IR absorption (CH2
) at 1570 and 1385 cm.−1
) with 1
H NMR absorption (CDCl3
), δ 1.0–2.1 (m, 16H, aliphatic CH
), 1.95 (s, 3H, CH3
CO), 3.3–4.0 (m, 20H, OCH
). A 4.21-g. sample of this complex was partitioned between 75 ml. of water and three 25-ml. portions of ether
. The combined ether
solutions were dried over anhydrous magnesium sulfate
and concentrated under reduced pressure, yielding 1.82 g.
of isomer B of dicyclohexyl-18-crown-6 polyether
as white prisms, m.p. 68–69°
The physical properties of many macrocyclic polyethers and their salt complexes have been already described.2,6 7 Dibenzo-18-crown-6 polyether
is useful for the preparation of sharp-melting 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 tert-butoxide
, and potassium palladium(II) tetrachloride
+ KCl) are dissolved 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 property will find practical use in catalysis, enhancement of chemical reactivity, separation and recovery of salts, electrochemistry, and analytical chemistry. There are some limitations. Although salts with high lattice energy, such as fluorides, nitrates, sulfates, and carbonates, form complexes with macrocyclic polyethers in alcoholic solvents as readily as more polarizable (softer) salts, their complexes cannot be isolated in the solid state because one or the other uncomplexed component precipitates on concentrating the solutions. For the same reason, these salts cannot be rendered soluble in aprotic solvents by the polyethers.
Chemical Abstracts Nomenclature (Collective Index Number);
sodium or potassium hydroxide
lithium or tetramethylammonium hydroxide
hydrochloric acid (7647-01-0)
sodium hydroxide (1310-73-2)
potassium permanganate (7722-64-7)
sodium bromide (7647-15-6)
carbon dioxide (124-38-9)
potassium hydroxide (1310-58-3)
propylene glycol (57-55-6)
magnesium sulfate (7487-88-9)
potassium acetate (127-08-2)
chloromethylmethyl ether (111-44-4)
potassium palladium(II) tetrachloride
potassium tert-butoxide (865-47-4)
Dibenzo [b,k] [1,4,7,10,13,16] hexaoxacyclooctadecin, 6,7,9,10,17,18,20,21-octahydro- (14187-32-7)
dibenzo [b,k] [1,4,7,10,13,16] hexaoxacyclooctadecin, eicosahydro- (16069-36-6)
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