Organic Syntheses, CV 5, 869
Submitted by Robert L. Augustine and Joseph A. Caputo
1.
Checked by William G. Dauben and Jeffrey N. Labovitz.
1. Procedure
A.
Δ1(9)-Octalone-2 and Δ9(10)-octalone-2. In a
2-l., three-necked, round-bottomed flask equipped with a
sealed stirrer, a
condenser, and a
dropping funnel is placed a solution of
102 g. (0.61 mole) of 1-morpholino-1-cyclohexene2 (Note
1) in
600 ml. of purified dioxane (Note
2) and (Note
3). To this stirred solution is added
45 g. (0.64 mole) of freshly distilled methyl vinyl ketone at such a rate that the addition requires approximately 1 hour. The resulting solution is heated under reflux for 4 hours, after which time 750 ml. of water is added, and the heating under reflux is continued for an additional 10–12 hours. The solution is cooled to room temperature and poured into 1 l. of water. The resulting mixture is extracted four times with
500-ml. portions of ether. The combined
ether extracts are washed three times with
250-ml. portions of 3N hydrochloric acid, twice with
100-ml. portions of a saturated aqueous sodium bicarbonate solution, once with a 250-ml. portion of water, once with a
200-ml. portion of a saturated aqueous sodium chloride solution, and dried over anhydrous
magnesium sulfate. The mixture is filtered, the ethereal filtrate evaporated, and the residual octalones distilled through a
short column. The yield is
54–59 g. (
59–65%) of an octalone mixture (Note
4), b.p.
75–78° (0.2 mm.),
101–103° (2 mm.).
B.
Δ1(9)-Octalone-2. A solution of
35 g. (0.23 mole) of the above octalone mixture in
200 ml. of 60–110° petroleum ether is cooled to −80° in an
acetone-dry ice bath and kept at this temperature for 1 hour. The crystalline
Δ1(9)-octalone-2 is filtered by suction through a jacketed
sintered-glass funnel kept at −80°. The residue is washed with
100 ml. of cold petroleum ether, removed from the funnel, and recrystallized a second time in the same way. After the second recrystallization the white crystals are removed from the funnel, allowed to melt by warning to room temperature, and distilled. The yield of purified
Δ1(9)-octalone-2 (Note
5), b.p.
143–145° (15 mm.), is
20–25 g. (
34–46% based on starting enamine). The
petroleum ether mother liquors can be distilled to yield a fraction boiling at
143–145° (15 mm.) which is enriched in
Δ9(10)-octalone-2.
2. Notes
1. The enamine should be utilized as soon as possible after distillation.
3.
Absolute ethanol and dry
benzene are also useful solvents for enamine reactions. In this instance, however, the use of these solvents results in a lower yield of octalones.
4. The octalone mixture contains
10–20% of the Δ
9(10)-isomer. This mixture may be used as such for many purposes.
5. The purified octalone still contains
1–3% of the Δ
9(10)-isomer which cannot be removed even on further crystallization.
3. Discussion
4. Merits of the Preparation
The present procedure is a general method for the preparation of monoalkylated ketones from enamines of aldehydes and ketones with electrophilic olefins.
3 There are many advantages in this method of alkylation. Generally only monoalkylation occurs, even when such reactive species as
acrylonitrile are used; and, when a cyclic ketone like
2-methylcyclohexanone is used, reaction occurs only at the lesser substituted center. In a general base-catalyzed reaction, substitution occurs on the more substituted center.
Another advantage of this method is that no catalyst is needed for the addition reaction; this means that the base-catalyzed polymerization of the electrophilic olefin (i.e., α,β-unsaturated ketones, esters, etc.) is not normally a factor to contend with, as it is in the usual base-catalyzed reactions of the Michael type. It also means that the carbonyl compound is not subject to aldol condensation which often is the predominant reaction in base-catalyzed reactions. An unsaturated aldehyde can be used only in a Michael addition reaction when the enamine method is employed.
This preparation is referenced from:
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