Org. Synth. 1968, 48, 40
DOI: 10.15227/orgsyn.048.0040
2-n-BUTYL-2-METHYLCYCLOHEXANONE
[Cyclohexanone, 2-butyl-2-methyl-]
Submitted by S. Boatman, T. M. Harris, and C. R. Hauser
1.
Checked by William G. Dauben, Michael H. Mcgann, and Noel Vietemeyer.
1. Procedure
Caution! This preparation should be carried out in a hood to avoid exposure to ammonia.
In a 3-l. three-necked flask fitted with a calcium chloride drying tube, a nitrogen-inlet tube, and a sealed mechanical stirrer are placed 54.0 g. (1.00 mole) of commercial, anhydrous sodium methoxide (Note 1) and 2 l. of anhydrous ether. The flask is purged with dry nitrogen and cooled in an ice bath. The inlet tube is replaced by an addition funnel containing a solution of 123 g. (1.10 moles) of 2-methylcyclohexanone (Note 2) and 81.4 g. (1.10 moles) of ethyl formate (Note 3). The solution is added rapidly, dropwise, and at the end of the addition the funnel is replaced by the nitrogen-inlet tube. After 15 minutes the ice bath is removed, and the mixture is stirred for 12 hours at room temperature. The thick suspension is filtered by suction, and the filter cake is washed with anhydrous ether, care being taken to protect the product from atmospheric moisture (Note 4). The solid salt is dried in a vacuum oven at ca. 70°, powdered (Note 5), and stored in a tightly capped bottle. Sodio-2-formyl-6-methylcyclohexanone, a cream-colored powder, is obtained in 80–85% (130–138 g.) yield (Note 6).
In a 1-l. three-necked flask equipped with a dry ice-acetone condenser and a sealed mechanical stirrer is placed 700 ml. of commercial, anhydrous, liquid ammonia. To the stirred ammonia is added a small piece of potassium metal. (Caution! Care should be exercised in handling potassium metal, since it is extremely reactive and it ignites on contact with water, atmospheric moisture, or alcohol. It should be manipulated under toluene or xylene, and blotted with filter paper before addition.) After the appearance of a blue color a few crystals of ferric nitrate hydrate (ca. 0.1 g.) are added, followed by small pieces of freshly cut potassium metal until 7.0 g. (0.18 g. atom) has been added. After all the potassium has been converted to the amide (Note 7), 24.9 g. (0.154 mole) of sodio-2-formyl-6-methylcyclohexanone is added carefully through a powder funnel (Note 8). After 1 hour a solution of 28.2 g. (0.21 mole) of n-butyl bromide (Note 9) in 50 ml. of anhydrous ether is added dropwise from an addition funnel. The mixture is stirred for 3 hours, and then the dry ice-acetone condenser is replaced by a water condenser. A steam bath is placed under the flask, and the ammonia is evaporated (Caution!) as 400 ml. of anhydrous ether is added. When the ammonia has been removed and the ether has refluxed for 5 minutes, 100 g. of ice is added, followed by 300 ml. of water. When the solid has dissolved, the layers are separated, and the ethereal layer is extracted twice with cold water. The combined aqueous extracts are placed in a 1-l. round-bottomed flask, and 6.4 g. of sodium hydroxide is added. The flask is warmed briefly to remove dissolved ether from the solution. The flask is equipped with an efficient condenser, and the mixture is refluxed until an enol test is no longer obtained (6–8 hours) (Note 10) and (Note 11). The mixture is cooled and extracted with three 200-ml. portions of ether. The combined ethereal extracts are washed with dilute hydrochloric acid and dried over anhydrous magnesium sulfate. The ether is evaporated, and the residue is distilled under reduced pressure to give 14–19 g. (54–74%) of 2-n-butyl-2-methylcyclohexanone, b.p. 116–118° (20 mm.) (Note 12).
2. Notes
1.
Sodium methoxide was obtained from Matheson, Coleman and Bell. The best results were obtained with material from freshly opened bottles.
2.
Eastman Organic Chemicals "Eastman grade" 2-methylcyclohexanone was distilled; b.p.
56° (20 mm.).
3.
Eastman Organic Chemicals practical grade ethyl formate was shaken for 30 minutes with anhydrous
sodium carbonate and for 30 minutes with anhydrous
magnesium sulfate, and distilled; b.p.
54°.
4.
A
rubber dam was fastened tightly over the top of the
Buchner funnel by means of rubber bands. It was pulled down onto the surface of the filter cake by the vacuum.
5.
The solid should be powdered to allow complete formation of the dianion in the following reaction. This is most readily accomplished if the solid is ground before it is completely dry (
i.e., when it appears to be dry but is still cool). The fine powder is then replaced in the oven to complete the drying.
6.
The checkers, working at one-quarter scale, obtained a yield of
86–88%.
7.
Conversion is indicated by discharge of the deep blue color. This generally requires about 20 minutes. When conversion is completed, the stirrer should be speeded up or the contents of the flask swirled so that
potassium splattered on the upper part of the flask is converted to amide; this should be done until all traces of blue color are gone.
8.
The escaping
ammonia will blow away some of the fine powder unless this is done carefully.
9.
Eastman Organic Chemicals "Eastman grade" n-butyl bromide was distilled; b.p.
101–102°.
10.
The enol test is performed with about 0.5 ml. of solution, which is neutralized with dilute
hydrochloric acid and treated with 3–5 drops of
10% ethanolic ferric chloride. A reddish brown color denotes the presence of unhydrolyzed formyl ketone.
11.
An alternative procedure is steam distillation of the basic, aqueous solution until no further organic material distills. This may be done either instead of, or after, the refluxing of the aqueous solution. The steam distillate is extracted with
ether, and the
ether is removed by distillation.
12.
A higher-boiling fraction consisting of
2-formyl-6-n-butyl-6-methylcyclohexanone, b.p.
201–203° (20 mm.), is obtained if hydrolysis is not complete.
3. Discussion
This procedure is an adaptation of one described by Boatman, Harris, and Hauser.
24. Merits of the Preparation
The present method affords 2-n-butyl-2-methylcyclohexanone uncontaminated by the isomeric 2-n-butyl-6-methylcyclohexanone.
2,2-Dimethylcyclohexanone and
2-benzyl-2-methylcyclohexanone have been prepared similarly in yields of
60% and
55%, respectively.
2 The procedure has been extended to the synthesis of
9-methyl-, 9-n-butyl-, and 9-benzyl-1-decalone from the dianion of
2-formyl-1-decalone in yields of 55%, 48%, and 58% respectively.
2
This preparation is referenced from:
Appendix
Chemical Abstracts Nomenclature (Collective Index Number);
(Registry Number)
9-methyl-, 9-n-butyl-, and 9-benzyl-1-decalone
hydrochloric acid (7647-01-0)
ammonia (7664-41-7)
ether (60-29-7)
sodium hydroxide (1310-73-2)
sodium carbonate (497-19-8)
n-butyl bromide (109-65-9)
nitrogen (7727-37-9)
sodium methoxide (124-41-4)
toluene (108-88-3)
ferric chloride (7705-08-0)
potassium (7440-09-7)
xylene (106-42-3)
ethyl formate (109-94-4)
magnesium sulfate (7487-88-9)
2-methylcyclohexanone (583-60-8)
ferric nitrate hydrate
Sodio-2-formyl-6-methylcyclohexanone
2,2-Dimethylcyclohexanone (1193-47-1)
2-Benzyl-2-methylcyclohexanone (1206-21-9)
2-formyl-1-decalone
2-n-BUTYL-2-METHYLCYCLOHEXANONE,
Cyclohexanone, 2-butyl-2-methyl- (1197-78-0)
2-formyl-6-n-butyl-6-methylcyclohexanone
2-n-butyl-6-methylcyclohexanone
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