Org. Synth. 1978, 58, 64
DOI: 10.15227/orgsyn.058.0064
cis-DICHLOROALKANES FROM EPOXIDES: cis-1,2-DICHLOROCYCLOHEXANE
[Cyclohexane, 1,2-dichloro-, cis-]
Submitted by James E. Oliver
1 and Philip E. Sonnet
2.
Checked by Jerrold M. Liesch and George Büchi.
1. Procedure
Caution! Benzene has been identified as a carcinogen. OSHA has issued emergency standards on its use. All procedures involving benzene should be carried out in a well-ventilated hood, and glove protection is required. A hood should be employed for the chlorination.
A 1-l., three-necked flask is charged with 95 g. (0.36 mole) of triphenylphosphine (Note 1) and 500 ml. of anhydrous benzene, and fitted with a gas-inlet (Note 2), a mechanical stirrer, and a condenser with attached drying tube. The flask is cooled in an ice bath, stirring is begun, and chlorine is introduced through the gas-inlet. Dichlorotriphenylphosphorane separates as a white solid or as a milky oil; the flow of chlorine is discontinued when the mixture develops a strong lemon-yellow color (Note 3). The gas inlet is quickly replaced by an addition funnel, and a solution of 10 g. of triphenylphosphine in 60 ml. of benzene is added dropwise fairly rapidly (Note 4). A solution of 24.5 g. (0.250 mole) of 1,2-epoxycyclohexane (Note 5) in 50 ml. of benzene is then added dropwise over ca. 20 minutes. The ice bath is replaced by a heating mantle, and the mixture, which consists of two liquid phases, is stirred and refluxed for 4 hours. It is then cooled, and excess dichlorotriphenylphosphorane is destroyed by the slow addition of 10 ml. of methanol (Note 6). The mixture is concentrated on a rotary evaporator at ca. 100 mm., and the residue, which may be a white solid or a viscous oil, is triturated with 300 ml. of petroleum ether (30–60°). The solid triphenylphosphine oxide that separates is collected by suction filtration. The cake is thoroughly broken up with a spatula and washed with three 100-ml. portions of petroleum ether. The combined filtrates, from which a little more triphenylphosphine oxide precipitates, are refiltered, then washed with 250-ml. portions of aqueous 5% sodium bisulfite (Note 7) and with water. The organic phase is dried over magnesium sulfate, filtered, concentrated on a rotary evaporator at ca. 100 mm., and distilled through a 20-cm. Vigreux column. There is very little forerun before 27–28 g. (71–73%) of cis-1,2-dichlorocyclohexane is collected at 105–110° (33 mm.), nD25 1.4977 (Note 8).
2. Notes
1.
Triphenylphosphine was purchased from Aldrich Chemical Company, Inc. Use of a considerable excess of
triphenylphosphine ensures complete reaction and obviates the need for rigorously dried glassware and reagents.
Hydrochloric acid, generated by the reaction of
dichlorotriphenylphosphorane and water, can react with the epoxide to produce a
trans-chlorohydrin, which is, however, converted to a
cis-dichloride by
dichlorotriphenylphosphorane under the conditions of the reaction.
2.
A glass tube of 7-mm. diameter is recommended. If
chlorine is introduced through a
fritted-glass tube, the
dichlorotriphenylphosphorane collects on the frit as a sticky gum.
3.
A sharp endpoint is not observed. A simple test for complete chlorination is as follows: the flow of
chlorine and the stirrer are stopped, and the mixture is allowed to settle.
Chlorine is then admitted without stirring. If unreacted
triphenylphosphine is present, a visible clouding (formation of
dichlorotriphenylphosphorane) will occur at the gas–liquid interface.
4.
Although a slight excess of
chlorine does not appear to be deleterious, a substantial excess is avoided by adding the last portion of
triphenylphosphine at this point.
5.
Commercial
1,2-epoxycyclohexane, supplied by Columbia Organic Chemicals Company, Inc., was used.
6.
The reaction mixture may be allowed to stand overnight before addition of
methanol.
7.
The distilled
cis-dichlorocyclohexane tends to become colored if the solution is not washed with a reducing agent.
8.
The checkers, using a
10-cm. Vigreux column, found that it was necessary to take a wider boiling range fraction (105–115°, 33 mm.) to obtain similar yields. The product is virtually free of
trans-1,2-dichlorocyclohexane (the isomeric 1,2-dichlorocyclohexanes are readily separated by GC on Carbowax 20M or on diethylene glycol succinate columns).
3. Discussion
This procedure is general for the conversion of epoxides to dichlorides with inversion of configuration at each of the two carbons and, in effect, provides a method for the
cis-addition of
chlorine to a double bond.
3 cis-1,2-Dichlorocyclohexane has also been prepared from
1,2-epoxycyclohexane and
sulfuryl chloride,
4 but the stereospecificity of the reaction appears to be extremely sensitive to reaction conditions, and the yield is lower than that obtained by the method described here. Other methods give
cis-1,2-dichlorocyclohexane contaminated with considerable amounts of the
trans-isomer. This method has been used to convert
cis- and
trans-4,5-epoxyoctanes to
meso- and
d,l-4,5-dichloroöctanes, respectively, and
trans-7,8-epoxyoctadecane to
threo-7,8-dichloroöctadecane. These conversions were carried out on smaller amounts of material, and the products were purified by column chromatography on silica gel. Yields were 51–63%.
Halogenations with dihalotriphenylphosphoranes have been reviewed briefly by Fieser and Fieser.
5 Dibromotriphenylphosphorane appears to have been studied somewhat more than the dichloro compound, but both reagents effectively convert alcohols to alkyl halides, carboxylic acids and esters to acid halides, etc. The reaction of
1,2-epoxycyclohexane with
dibromotriphenylphosphorane under conditions similar to those described here gives a mixture of
cis- and
trans-1,2-dibromocyclohexanes. A reagent prepared from
triphenylphosphine and
carbon tetrachloride has been used for similar transformations.
6
Appendix
Chemical Abstracts Nomenclature (Collective Index Number);
(Registry Number)
petroleum ether
threo-7,8-dichlorooctadecane
hydrochloric acid (7647-01-0)
Benzene (71-43-2)
methanol (67-56-1)
carbon tetrachloride (56-23-5)
sodium bisulfite (7631-90-5)
sulfuryl chloride (7791-25-5)
chlorine (7782-50-5)
1,2-epoxycyclohexane (286-20-4)
magnesium sulfate (7487-88-9)
triphenylphosphine (603-35-0)
triphenylphosphine oxide (791-28-6)
Dichlorotriphenylphosphorane (2526-64-9)
Dibromotriphenylphosphorane (1034-39-5)
cis-1,2-Dichlorocyclohexane,
Cyclohexane, 1,2-dichloro-, cis- (10498-35-8)
cis-dichlorocyclohexane (2108-92-1)
trans-1,2-dichlorocyclohexane (822-86-6)
trans-7,8-epoxyoctadecane
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