Organic Syntheses, CV 5, 76
Submitted by Fritz Elsinger
1
Checked by William G. Dauben and W. Todd Wipke.
1. Procedure
A.
2-Benzyl-2-carbomethoxycyclopentanone. A dry
2-l. three-necked flask is fitted with a
Vibromischer stirrer (Note
1), a
reflux condenser, and a
250-ml. dropping funnel with a
pressure-equalizing side tube.
2 A
nitrogen-inlet tube is connected to the top of the dropping funnel, and an outlet tube is placed on the top of the condenser and connected to a
mercury valve. The latter consists of a U-tube the bend of which is just filled with
mercury.
To the flask are added
13.4 g. (0.58 mole) of clean sodium and
200 ml. of absolute toluene. The Vibromischer stirrer is activated, the
toluene heated to reflux, and the agitation continued at this temperature until all the
sodium is pulverized into a very fine sand. The agitation is ceased, and the solution is allowed to cool to room temperature. The
nitrogen flow rate is increased, the Vibromischer stirrer is replaced with a conventional sealed
mechanical stirrer with a
Teflon® blade, and a solution of
85 g. (0.6 mole) of 2-carbomethoxycyclopentanone (Note
2) in
450 ml. of absolute benzene is placed in the addition funnel.
The stirrer is started, and the solution in the addition funnel is added over a 2-hour period without external heating (Note
3). After the addition is complete, the mixture is heated under reflux for 2.5 hours, at the end of which time the mixture has a pasty consistency. A solution of
106 g. (0.84 mole) of benzyl chloride in
100 ml. of dry benzene is added in one portion, the mixture heated under reflux for 14 hours, and the solution (Note
4) poured into 600 ml. of water. The
benzene layer is separated, the aqueous layer extracted twice with
ether, and the combined
benzene-
ether extract washed with 100 ml. of water and dried over anhydrous
sodium sulfate. The solvent is removed under reduced pressure using a
rotary evaporator, and the residual liquid distilled to yield
108–116 g. (
81–86%) of colorless
2-benzyl-2-carbomethoxycyclopentanone, b.p.
126–128° (0.5 mm.) (Note
5).
B.
2-Benzylcyclopentanone. A mixture of
30 g. (0.177 mole) of lithium iodide dihydrate (Note
6) and (Note
7) and
140 ml. of dry 2,4,6-collidine (Note
8) in a
300-ml. three-necked flask fitted with a dropping funnel, a reflux condenser, and a nitrogen-inlet system (as in step A) is heated to reflux. As soon as all the
lithium iodide has dissolved (Note
9),
30 g. (0.129 mole) of 2-benzyl-2-carbomethoxycyclopentanone dissolved in
30 ml. of 2,4,6-collidine (Note
10) is added to the boiling, faintly yellow solution; and during this process the solution turns darker in color and a precipitate forms (Note
11). Evolution of
carbon dioxide begins immediately, and its formation can be followed by passing the
nitrogen flush through a saturated
barium hydroxide solution. The mixture is heated under reflux and a
nitrogen atmosphere for 19 hours, at the end of which time the evolution of
carbon dioxide is very slow (Note
12).
The mixture is cooled and poured onto a mixture of
200 ml. of 6N hydrochloric acid,
200 ml. of ether, and 100 g. of ice. The residue in the flask is dissolved in a mixture of 6
N hydrochloric acid and
methylene chloride, and this mixture is added to the main reaction. The aqueous layer is separated and extracted with two
100-ml. portions of ether. The combined ethereal solution is washed once with
70 ml. of 6N hydrochloric acid, once with 2
N sodium carbonate solution, twice with saturated
sodium chloride solution, and dried over anhydrous
sodium sulfate. The solvent is removed under reduced pressure, and the residue is distilled to yield
16–17 g. (
72–76%) of colorless
2-benzylcyclopentanone, b.p.
83–85° (0.3 mm.),
108–110° (0.75 mm.) (Note
13).
2. Notes
1. This stirring apparatus is available from Ag. für Chemie Apparatebau, Mannedorf, Zurich, Switzerland.
2. The submitter prepared the material from
dimethyl adipate following the procedure published by Pickney
3 for the
diethyl ester. The checkers obtained their material by fractional distillation of mixed
carbomethoxy- and carbethoxycyclopentanone available from Arapahoe Chemical Co., Boulder, Colorado.
4. At the end of the reflux period, the reaction mixture is a nonviscous solution containing a white precipitate.
5. The semicarbazone melts at
168–170°.
6.
Lithium iodide dihydrate is available from Fluka A. G., Buchs, S. G., Switzerland. The checkers used the trihydrate and, by means of a
Dean Stark trap4 attached between the flask and the condenser, 1 mole of water was removed via azeotropic distillation with
collidine.
7. In cases where a carbomethoxy group is desired to be selectively cleaved in the presence of a readily hydrolyzed ester group, such as an
acetate of a secondary alcohol, anhydrous
lithium iodide must be employed.
5 In order to avoid partial decomposition of the salt to
iodine, it is best dried by slowly heating it to 150° in a high vacuum. The solubility of anhydrous
lithium iodide in boiling
collidine or
lutidine is slightly less than that of the dihydrate, but it still is adequate for the reaction. In the present case, the use of the anhydrous salt lowers the yield of the
2-benzylcyclopentanone to
67%, and a large amount of a product, believed to be a dimer, boiling around 200° (0.5 mm.) is obtained.
8. For the cleavage of less hindered esters, the lower-boiling
2,6-lutidine (b.p.
143°) can be used as the solvent.
9. The development of a small amount of
iodine is difficult to avoid. The
nitrogen atmosphere is essential to keep this salt decomposition to a minimum.
10. Methyl esters react more rapidly with
lithium iodide than do ethyl esters, which in turn react more rapidly than esters of secondary alcohols. On the other hand,
t-butyl esters are cleaved very readily with a catalytic amount of
lithium iodide.
11. A precipitate remains throughout the reaction.
13. The semicarbazone melts at
204–205°.
3. Discussion
4. Merits of the Preparation
This procedure illustrates a general method for the selective splitting of a carbomethoxy group in the presence of easily hydrolyzed esters of other alcohols, such as the easily hydrolyzed equatorial acetoxy group. The specificity of the reaction is not affected by steric hindrance, and a highly hindered methyl ester can be split in the presence of other less hindered esters of secondary alcohols. Normal alkaline saponification goes in exactly the opposite way.
The present case simply illustrates another utility of the ester cleavage reaction, i.e., the cleavage of a β-keto ester with concomitant decarboxylation under only slightly basic conditions. The method should be particularly applicable to systems which are prone to undergo reverse Claisen reactions.
Copyright © 1921-2002, Organic Syntheses, Inc. All Rights Reserved