Organic Syntheses, CV 6, 625
CARBOXYLATION OF AROMATIC COMPOUNDS: FERROCENECARBOXYLIC ACID
[Ferrocene, carboxy-]
Submitted by Perry C. Reeves
1
Checked by J. J. Mrowca, M. M. Borecki, and William A. Sheppard.
1. Procedure
A.
(2-Chlorobenzoyl)ferrocene. A thoroughly dried,
1-l., three-necked, round-bottomed flask is equipped with a
mechanical stirrer, a
funnel for the addition of air-sensitive solids (Note
1), and a
two-necked adapter holding a
thermometer and a
gas-inlet tube. Throughout the ensuing reaction the system is maintained under positive pressure of dry
nitrogen. The flask is charged with
18.6 g. (0.100 mole) of ferrocene (Note
2),
17.5 g. (0.100 mole) of 2-chlorobenzoyl chloride (Note
3), and
200 ml. of dichloromethane, and the addition funnel contains
14.0 g. (0.105 mole) of anhydrous aluminum chloride. Stirring is begun, and the flask is immersed in an
ice bath. When the solution has been chilled thoroughly, the
aluminum chloride is added in small portions at such a rate that the reaction mixture remains below 5°. The appearance of a deep blue color indicates that the reaction is occurring. This addition requires about 20 minutes, and after its completion stirring is continued for 30 minutes with ice cooling and for 2 hours at room temperature.
The reaction mixture is cooled again in ice, 200 ml. of water is added cautiously, and the resulting two-phase mixture is stirred vigorously for 30 minutes. After transferring the mixture to a
separatory funnel, the layers are separated, and the aqueous layer is extracted with two
50-ml. portions of dichloromethane. The combined
dichloromethane solutions are washed once with 50 ml. of water, twice with
50-ml. portions of 10% aqueous sodium hydroxide, and dried over
magnesium sulfate, filtered and evaporated to dryness at reduced pressure, yielding
30.4–30.9 g. (
94–96%) of
(2-chlorobenzoyl)ferrocene as a viscous, red liquid, which gradually solidifies (Note
4).
B.
Ferrocenecarboxylic acid. A dry,
500-ml., three-necked, round-bottomed flask equipped with a mechanical stirrer and a
reflux condenser topped with a
nitrogen-inlet tube is charged with
250 ml. of 1,2-dimethoxyethane (Note
5) and
46.0 g. (0.411 mole) of potassium tert-butoxide (Note
6). A
nitrogen atmosphere is established in the system, and 2.2 ml. (0.12 mole) of water (Note
6) is added with stirring, producing a slurry, to which the crude
(2-chlorobenzoyl)ferrocene is added. The red solution is stirred and refluxed under
nitrogen. As the reaction proceeds the color fades to tan, and after 1 hour at reflux the reaction mixture is cooled and poured into 1 l. of water. The resulting solution is washed with three
150-ml. portions of diethyl ether, which are combined and back-extracted with two
50-ml. portions of 10% aqueous sodium hydroxide. The aqueous phases are then combined and acidified with concentrated
hydrochloric acid. The precipitate is collected by filtration and air dried, yielding
17.0–19.2 g. (
74–83% from
ferrocene) of
ferrocenecarboxylic acid as an air-stable yellow powder, m.p.
214–216° (dec., (Note
7)).
2. Notes
1. If such a funnel is not available, an
Erlenmeyer flask connected to the reaction flask by a length of thin-walled rubber tubing (Gooch tubing) may be substituted. In this case, the reaction mixture must not be stirred so vigorously that liquid is splashed up into the neck of the flask, which would cause
aluminum chloride to cake there and prevent it from falling into the flask.
2.
Ferrocene was purchased from Strem Chemicals Incorporated, Danvers, Massachusetts.
3.
2-Chlorobenzoyl chloride was purchased from Aldrich Chemical Company, Inc., and used as received with a stated purity of 95%.
4. The crude material contains approximately
5% of unreacted ferrocene. Recrystallization from
heptane affords pure
(2-chlorobenzoyl)ferrocene as scarlet needles, m.p.
99–100°; however, the crude material may be used without purification for Part B.
6.
Potassium tert-butoxide was purchased from Columbia Organic Chemicals Company, Columbia, South Carolina. The molar ratio of
potassium tert-butoxide to water is critical, and the amounts specified represent optimum quantities for cleavage of 0. 10 mole of ketone.
2,3
7. The decomposition point was obtained in a sealed
capillary tube and not corrected. As the solid is heated, it first changes from yellow to brownish red and then decomposes to a dark red liquid. The decomposition temperature of this compound has been reported to be 208.5°,
4 224–225°,
5 and 225–230°.
6
The crude product is suitable for most purposes. It may be recrystallized from
toluene (1 g. in 15–20 ml. of solvent,
80% recovery in the first crop), giving material melting at
220–222° (dec.).
3. Discussion
The carboxylic acids of organometallic systems, important synthetic intermediates, have been prepared by many different synthetic methods.
Ferrocenecarboxylic acid has been studied the most extensively,
7 and the best laboratory syntheses previously reported involve hydrolyses of cyanoferrocene
8 or
S-methylferrocenethiocarbonate.
9
The present synthesis
10 consists of two simple steps, uses readily available and inexpensive starting materials, and produces pure material in high overall yield. It is based on two observations: that nonenolizable ketones may be cleaved to carboxylic acids by
potassium tert-butoxide–water,
2 and that aryl 2-chlorophenyl ketones may be cleaved with loss of the 2-chlorophenyl group, giving only one of the two possible acids.
11 Other compounds prepared by this route include
carboxycyclopentadienyltricarbonylmanganese (
79%)
10 and several substituted benzoic acids:
11 biphenyl-4-carboxylic acid (
64%),
3,4-dimethylbenzoic acid (
57%),
2,4,6-trimethylbenzoic acid (
59%),
3,4-dimethoxybenzoic acid (
73%), and
2,4-dimethoxybenzoic acid (
60%). In cases where the cleavage reaction proceeds in low yield, substitution of
2,6-dichlorobenzoyl chloride for
2-chlorobenzoyl chloride may be helpful. With
thiophene, for example, the yield of carboxylic acid was increased from 10% to 72% by this modification.
11
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