Organic Syntheses, CV 5, 509
Submitted by M. J. Jorgenson and A. F. Thacher
1.
Checked by John J. Miller and William D. Emmons.
1. Procedure
A.
β-Phenylcinnamic acid. A suspension of
8.8 g. (0.20 mole) of a 55.1% sodium hydride dispersion in mineral oil (Note
1) and
300 ml. of 1,2-dimethoxyethane (Note
2) are added to a dry,
1-l., three-necked flask equipped with a
stirrer, a
condenser with
drying tube, and a
pressure-equalizing dropping funnel. The flask is immersed in an
ice bath, and
44.8 g. (0.20 mole) of triethyl phosphonoacetate (Note
3) is added through the
dropping funnel over a 20-minute period. After the addition the solution is stirred at room temperature for 30 minutes, and then
36.4 g. (0.20 mole) of benzophenone is added in one portion. The solution is heated at reflux for 4 days. The two-phase reaction mixture is cooled, and the flask is filled with water. The ester is extracted from the solution with three
100-ml. portions of ether. The ethereal extracts are combined, dried over anhydrous
sodium sulfate, and evaporated to as small a volume as possible on the
steam bath. The resulting mixture of ester and unreacted
benzophenone is added to 140 ml. of water,
45 ml. of dioxane, and
26.4 g. (0.40 mole) of 85% potassium hydroxide in a
500-ml. one-necked flask, and the mixture is refluxed overnight (17 hours). The solution is cooled and extracted with
50 ml. of ether to remove
benzophenone and any unhydrolyzed ester. The aqueous fraction is acidified with
10N sulfuric acid, and the resulting solid product is isolated by filtration, washed with two 50-ml. portions of water, and dried. Recrystallization from
200 ml. of benzene gives
28.3–33.9 g. (
63–75%) of
β-phenylcinnamic acid, m.p.
161–163° (Note
4) and (Note
5).
B.
1,1-Diphenylcyclopropane. A 500-ml. three-necked flask is equipped with a
nitrogen-inlet tube, a condenser, and a dropping funnel. The flask is charged with
100 ml. of dry tetrahydrofuran (Note
6) and
5.13 g. (0.135 mole) of lithium aluminum hydride (Note
1), and the system is purged with dry
nitrogen. To the stirred solution is added dropwise over a period of 15–20 minutes a solution of
20 g. (0.089 mole) of β-phenylcinnamic acid (Note
7) in
100 ml. of tetrahydrofuran. The addition results in an exothermic reaction which causes the solution to reflux. The refluxing is allowed to subside after addition is complete, and then the mixture is carefully reheated to reflux. A mild exotherm occurs a few minutes after reflux is reached. This is easily controlled by removing the heat source or by cooling with ice. After the occurrence of this exothermic reaction, which is accompanied by a color change from rust to deep red, the mixture is heated at the reflux temperature for an additional 2 hours. The mixture is then cooled in an ice bath, and sufficient
10% sulfuric acid (ca. 5 ml.) is carefully
(Caution! Vigorous evolution of hydrogen.) added dropwise to destroy excess
lithium aluminum hydride. Another
100 ml. of 10% sulfuric acid is added after decomposition of the
hydride is complete to dissolve the aluminum salts (Note
8). The acidified solution is worked up immediately (Note
9) by dilution with 200 ml. of water and extraction with one
100-ml. portion and three 50-ml. portions of ether. The combined ethereal extracts are washed with three
50-ml. portions of saturated aqueous sodium bicarbonate. The bicarbonate extracts are combined and washed with
50 ml. of ether, and all the ethereal extracts are combined. The ethereal solution is dried over anhydrous
sodium sulfate, and the
ether is removed at atmospheric pressure. The residue is distilled under reduced pressure to give
10.0–10.7 g. (
57–62%) of
diphenylcyclopropane (Note
10), b.p.
132–134° (10 mm.),
n20D 1.590.
2. Notes
4. About half of the solid is insoluble in the hot
benzene and is removed by filtration.
6.
Tetrahydrofuran is best dried according to the procedure described on
page 976 of this volume.
(Caution! Note warning of danger in drying tetrahydrofuran containing peroxides.) The checkers employed a peroxide-free grade of anhydrous
tetrahydrofuran which is available from Fisher Scientific Co.
7. In the preparation of other phenylcyclopropanes by this method, esters rather than acids were employed. Use of the ester in the present preparation gave a poor yield of product. Since the acid can easily be purified, its use here is also more expedient.
8. The checkers found this amount of acid insufficient to dissolve all of the salts, and an additional
5 ml. of concentrated sulfuric acid was added.
9. In general it has been found that yields of cyclopropanes are lowered if the acidic solutions are permitted to stand before workup.
10. Fractionation is not essential because the main contaminant is high-boiling polymer. The checkers obtained two fractions: b.p. 138–142° (11 mm.), 10.0–10.2 g., 99% pure by vapor-phase chromatography; and b.p. 142–148° (11 mm.), 0.6–0.9 g., 96% pure.
3. Discussion
4. Merits of the Preparation
This procedure illustrates a general method for the preparation of
phenylcyclopropanes from
cinnamic acids, esters, aldehydes, or alcohols.
8 It complements the Simmons-Smith reaction as a general method for the preparation of such
cyclopropanes. It offers advantages over the Simmons-Smith method in cases in which electron-withdrawing substituents in the benzene ring or steric crowding around the double bond lead to low yields in the Simmons-Smith reaction. Also, in the case of possible stereo-isomerism in the starting material or product, the present method leads stereospecifically to a single
cyclopropane. It has the disadvantage that reducible substituents on the benzene ring do not survive the reductive treatment. The present method is an exceptionally simple, one-step preparative process employing starting materials that are commercially available, or readily accessible from aldehydes and ketones via the phosphono ester addition procedure of Wadsworth and Emmons.
9 Cyclopropane formation is particularly facile when electron-withdrawing substituents are present on the aromatic ring or when the β-position is substituted by another aryl group. Alkyl substitution on the double bond also facilitates
cyclopropane formation. The exames recorded in Table I illustrate these effects. An excess of dride is necessary for producing good yields of cyclopropanes.
This preparation is referenced from:
TABLE I PREPARATION OF PHENYLCYCLOPROPANES FROM CINNAMIC ESTERS
|
|
Substituents |
Solvent |
Reflux Time, Hours |
Yield of Cyclopropane, % |
|
R = C6H5, R' = CH3 Ar = C6H5 |
Tetrahydrofuran |
10 |
78 |
R = R' = CH3 Ar = m-CF3C6H4 |
Tetrahydrofuran |
10 |
54 |
R = R' = CH3 Ar = C6H5 |
Dimethoxyethane |
48 |
52 |
R = R' = H Ar = C6H5a |
Dimethoxyethane |
320 |
66b |
R = R' = CH3 Ar = 3,4-Cl2C6H3 |
Tetrahydrofuran |
1 |
45b |
|
a Aldehyde rather than ester was employed; the yield was 28% after 3 days.
|
|
Appendix
Compounds Referenced (Chemical Abstracts Registry Number)
sodium or potassium amide
phenylcyclopropanes
cinnamic acids
cyclopropanes
calcium chloride (10043-52-4)
sulfuric acid (7664-93-9)
acetic acid (64-19-7)
Benzene (71-43-2)
ether (60-29-7)
sodium acetate (127-09-3)
hydrogen (1333-74-0)
sodium bicarbonate (144-55-8)
sodium sulfate (7757-82-6)
nitrogen (7727-37-9)
potassium hydroxide (1310-58-3)
Benzophenone (119-61-9)
calcium oxide
1,1-Diphenylethylene (530-48-3)
cyclopropane (75-19-4)
dioxane (5703-46-8)
Diazomethane (334-88-3)
ethyl diazoacetate (623-73-4)
Tetrahydrofuran (109-99-9)
oxalyl chloride (79-37-8)
lithium aluminum hydride (16853-85-3)
sodium hydride (7646-69-7)
hydride
ethylene glycol dimethyl ether,
1,2-dimethoxyethane (110-71-4)
dimethoxyethane (534-15-6)
1,1-Diphenylcyclopropane,
Cyclopropane, 1,1-diphenyl-,
diphenylcyclopropane (3282-18-6)
triethyl phosphonoacetate (867-13-0)
β-Phenylcinnamic acid (606-84-8)
3,3-diphenylpropyltrimethylammonium iodide
dimethylsulfonium methylide
pyrazoline
Ethyl β-hydroxy-β,β-diphenylpropionate (894-18-8)
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