Org. Synth. 1967, 47, 20
DOI: 10.15227/orgsyn.047.0020
2-CARBETHOXYCYCLOOCTANONE
[2-Oxocyclooctanecarboxylic acid, ethyl ester]
Submitted by A. Paul Krapcho, Joseph Diamanti, Charles Cayen, and Richard Bingham
1.
Checked by William G. Dauben and Charles Dale Poulter.
1. Procedure
A 2-l. two-necked, round-bottomed flask equipped with a magnetic stirrer (Note 1) is fitted with a 250-ml. pressure-equalizing constant-rate dropping funnel and a condenser, the top of which is connected to a mercury trap to prevent the entrance of air during the reaction and for the detection of gas evolution. The dropping funnel is removed, and 35 g. (0.85 mole) of sodium hydride dispersed in mineral oil is added (Note 2). The mineral oil is removed by washing the dispersion four times with 100-ml. portions of benzene (Note 3). The benzene is removed with a pipet after the sodium hydride is allowed to settle (Note 4).
After most of the mineral oil has been removed, 400 ml. of benzene is added to the sodium hydride, followed by 71 g. (0.6 mole) of diethyl carbonate (Note 5). This mixture is heated to reflux, and a solution of 38 g. (0.3 mole) of cyclooctanone (Note 6) in 100 ml. of benzene is added dropwise from the dropping funnel over a period of 3–4 hours. After the addition is complete, this mixture is allowed to reflux until the evolution of hydrogen ceases (15–20 minutes).
When the reaction mixture has cooled to room temperature, 60 ml. of glacial acetic acid is added dropwise, and a heavy, pasty solid separates. Ice-cold water (about 200 ml.) is added dropwise, and the stirring is continued until all the solid material has gone into solution (Note 7). The benzene layer is separated, and the aqueous layer is extracted three times using 100-ml. portions of benzene. The combined benzene extracts are washed three times with 100-ml. portions of cold water. The benzene is removed by distillation at atmospheric pressure, and the excess diethyl carbonate is removed under water-pump pressure with gentle heating. The residual material is transferred to a 100-ml. distillation flask, and the fraction boiling at 85–87° (0.1 mm.) is collected. The yield of 2-carbethoxycyclooctanone is 54–56 g. (91–94%), n25D 1.4795–1.4800.
2. Notes
1.
The checkers found that the agitation of the reaction mixture required later in this reaction is better achieved by use of a
sealed mechanical stirrer.
2.
The
sodium hydride was obtained as a 58.6% dispersion in mineral oil from Metal Hydrides, Inc., Beverly, Massachusetts.
3.
The
benzene (Fisher certified reagent, thiophene free) was dried over
potassium hydroxide and distilled from
sodium metal.
4.
By this procedure about 80–85% of the mineral oil was removed. Because some
sodium hydride is lost in the pipetting procedure, an excess is initially employed.
5.
The product supplied by Matheson, Coleman and Bell was used as received. Lower yields were obtained when a molar equivalent of
diethyl carbonate was utilized, possibly because of self-condensation of the ketone.
6.
The
cyclooctanone was obtained from the Aldrich Chemical Co. and was utilized as received.
7.
At this point the aqueous layer should be acidic, or more
acetic acid should be added.
3. Discussion
The reaction of
cyclooctanone with
diethyl oxalate, followed by decarbonylation of the resulting glyoxylate, has been reported to yield
32% of
2-carbethoxycyclooctanone.
2 The reaction of
cyclooctanone with
sodium amide in
ether, followed by the addition of
diethyl carbonate, provided the product in
70% yield.
3The preparation of several medium- and large-sized 2-carbomethoxycycloalkanones has been accomplished by treatment of the cycloalkanone with
sodium triphenylmethyl, followed by carbonation with dry ice, and esterification with
diazomethane.
4 The yields are good but the procedure is laborious. The synthesis of
2-carbomethoxycyclooctanone via the Dieckmann cyclization of
dimethyl azelate with
sodium hydride yields 48% of this product when the procedure is carried out over a 9-day period.
54. Merits of the Preparation
The reaction described is of general synthetic utility for the preparation of a variety of cyclic β-keto esters from the corresponding ketones. Using this procedure the 2-carbethoxycycloalkanones have been prepared from cyclononanone, cyclodecanone, and cyclododecanone in yields of 85%, 95%, and 90%, respectively. The procedure is simpler and gives much higher yields than other synthetic routes to these systems.
This procedure has been patterned after the method by which the carbethoxy group is introduced into a few alicyclic ketones
6 and several cyclic ketones.
Cyclohexanone has been reported to yield
50% of
2-carbethoxycyclohexanone when treated with
sodium hydride and
diethyl carbonate using
ether as the solvent.
7 The preparation of
2-carbethoxycycloheptanone using
potassium t-butoxide and
diethyl carbonate in
benzene has been reported in
40% yield.
8 Jacob and Dev report an
80% yield of the latter compound using
sodium hydride as the base.
9This preparation is referenced from:
Appendix
Chemical Abstracts Nomenclature (Collective Index Number);
(Registry Number)
sodium triphenylmethyl
acetic acid (64-19-7)
Benzene (71-43-2)
ether (60-29-7)
hydrogen (1333-74-0)
Cyclohexanone (108-94-1)
potassium hydroxide (1310-58-3)
sodium (13966-32-0)
Thiophene (110-02-1)
Diazomethane (334-88-3)
sodium amide (7782-92-5)
2-carbethoxycyclohexanone (1655-07-8)
diethyl carbonate (105-58-8)
sodium hydride (7646-69-7)
diethyl oxalate (95-92-1)
Cyclodecanone (1502-06-3)
cyclononanone (3350-30-9)
2-Carbethoxycyclooctanone,
2-Oxocyclooctanecarboxylic acid, ethyl ester (4017-56-5)
Cyclooctanone (502-49-8)
2-carbomethoxycyclooctanone
dimethyl azelate (1732-10-1)
cyclododecanone (830-13-7)
2-carbethoxycycloheptanone (774-05-0)
potassium t-butoxide (865-47-4)
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