Org. Synth. 1966, 46, 28
DOI: 10.15227/orgsyn.046.0028
COUMARONE
[Benzofuran]
Submitted by Albert W. Burgstahler and Leonard R. Worden
1.
Checked by Wayland E. Noland, William E. Parham, and Carol Wong.
1. Procedure
A. o-Formylphenoxyacetic acid. A solution of 80.0 g. (2 moles) of sodium hydroxide pellets in 200 ml. of distilled water is added to a mixture of 106 ml. (122 g., 1 mole) of salicylaldehyde (Note 1), 94.5 g. (1 mole) of chloroacetic acid (Note 1) and (Note 2), and 800 ml. of water. The mixture is stirred slowly and heated to boiling. The resulting black solution (Note 3) is heated under reflux for 3 hours (Note 4). The solution is acidified with 190 ml. of concentrated hydrochloric acid (sp. gr. 1.19) and is steam-distilled to remove unchanged salicylaldehyde (40.0–40.5 g.) (Note 5). The residual acidic mixture is cooled to 20°, and the precipitated product is collected on a Büchner funnel and rinsed with water. The light tan solid when dry weighs 99–100 g. (82–83% based on recovered salicylaldehyde), m.p. 130.5–133.0° (Note 6).
B. Coumarone. A mixture of 90.0 g. (0.5 mole) of crude (Note 7), dry o-formylphenoxyacetic acid, 180 g. of anhydrous, powdered sodium acetate, 450 ml. of acetic anhydride, and 450 ml. of glacial acetic acid (Note 8) in a 2-l. flask is heated under gentle reflux with stirring for 8 hours. The hot black solution (total volume ca. 1.2 l.) (Note 3) is poured into 2.5 l. of ice water and extracted with one 600-ml. portion of ether (Note 9). The ether layer is washed with one 600-ml. portion of water and then with several portions of cold dilute 5% sodium hydroxide solution (Note 10) until the aqueous layer is basic. The ether layer is washed successively with water and saturated sodium chloride solution and is partially dried over anhydrous granular sodium sulfate. The ether is removed at water-bath temperature and the product is distilled, b.p. 166.5–168.0° (735 mm.) or 97.5–99.0° (80 mm.). The water-white benzofuran weighs 37.5–40.0 g. (63.5–67.8%, 52–56% overall from salicylaldehyde), n20D 1.5672; λmax 245 (log ε 4.08), 275 (3.45), and 282 mμ (3.48).
2. Notes
1.
Matheson, Coleman and Bell practical grade material was used.
2.
The yield is not increased by use of
bromoacetic acid or
2 moles of chloroacetic acid and an additional mole of
sodium hydroxide.
3.
At no time did the checkers observe a black solution. The color of the solution changed from yellow to red-brown.
4.
The yield is not increased by longer reflux periods.
5.
Removal of unchanged
salicylaldehyde by steam distillation (followed conveniently by testing the distillate with
2,4-dinitrophenylhydrazine reagent) provides a product sufficiently pure for use in the next step. Also, the recovered
salicylaldehyde can be used again without further purification.
6.
Three crystallizations of
36 g. of the crude o-formylphenoxyacetic acid from 360 ml. of water with
10 g. of activated carbon give 18 g. of glistening colorless plates, m.p.
133.0°–133.5°.
7.
Use of purified
o-formylphenoxyacetic acid increases the yield in this step by only 11%.
8.
If no
acetic acid is used,
benzofuran is formed in only
30–31% yield, and
coumarilic acid, m.p.
194–196°, is isolated in about
45% yield.
9.
An additional extraction does not increase the yield appreciably.
10.
About 250 ml. of this solution is required.
3. Discussion
o-Formylphenoxyacetic acid has been prepared previously in
46% yield by alkylation of
salicylaldehyde with
chloroacetic acid2,3 and in unspecified yield by alkylation with
ethyl bromoacetate followed by hydrolysis.
4
Benzofuran is found in coal tar.
5 It has been prepared in
40–46% overall yield from
coumarin by bromination, conversion of the resulting
3,4-dibromocoumarin to
coumarilic acid, and then decarboxylation,
6 and also by passage of
coumarin vapor through an
iron tube at 860°.
7 The method given here is a variation of that described by Rössing,
2 who omitted the addition of
acetic acid (see
(Note 8) above).
Benzofuran also has been prepared by the cyclization of
ω-chloro-o-hydroxystyrene8 or
phenoxyacetaldehyde9 in unspecified low yields and by the cyclization of
phenoxyacetaldehyde diethyl acetal in
9% yield.
10 High-temperature catalytic dehydrocyclization of
o-ethylphenol affords
benzofuran in as much as
59% yield after recycling unchanged
o-ethylphenol.
11
4. Merits of the Preparation
Although the high-temperature catalytic dehydrocyclization of
o-ethylphenol11 gives
benzofuran in fair yield, these conditions are not convenient in the laboratory and cannot be applied easily to functionally substituted
o-formylphenoxyacetic acids. The other methods of preparation give unsatisfactory yields, are unnecessarily lengthy, or require expensive starting materials. The method of Rössing,
2 on which the present procedure is based, gives good yields in its original form only in the case of
o-acylphenoxyacetic acids;
o-formylphenoxyacetic acids give principally the corresponding coumarilic acids. Often these can be decarboxylated only in very poor yield.
12 In the preparation described here,
benzofuran is obtained directly in fair overall yield from readily available and inexpensive starting materials without the necessity of a separate decarboxylation step.
Appendix
Chemical Abstracts Nomenclature (Collective Index Number);
(Registry Number)
o-acylphenoxyacetic acids
o-formylphenoxyacetic acids
hydrochloric acid (7647-01-0)
acetic acid (64-19-7)
ether (60-29-7)
acetic anhydride (108-24-7)
sodium acetate (127-09-3)
sodium hydroxide (1310-73-2)
sodium chloride (7647-14-5)
sodium sulfate (7757-82-6)
chloroacetic acid (79-11-8)
carbon (7782-42-5)
Salicylaldehyde (90-02-8)
2,4-Dinitrophenylhydrazine (119-26-6)
Bromoacetic acid (79-08-3)
Ethyl bromoacetate (105-36-2)
coumarin
3,4-dibromocoumarin (55077-11-7)
Coumarone,
Benzofuran (271-89-6)
phenoxyacetaldehyde (2120-70-9)
phenoxyacetaldehyde diethyl acetal
o-Formylphenoxyacetic acid (6280-80-4)
ω-chloro-o-hydroxystyrene
o-ethylphenol (90-00-6)
Coumarilic acid (496-41-3)
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