Org. Synth. 1944, 24, 69
DOI: 10.15227/orgsyn.024.0069
4-METHYLCOUMARIN
[Coumarin, 4-methyl-]
Submitted by Eugene H. Woodruff
Checked by Nathan L. Drake and Carl Blumenstein.
1. Procedure
In a 5-l. three-necked round-bottomed flask, fitted with a sealed stirrer, dropping funnel, and air condenser, the open end of which is connected to a gas-absorption trap, are placed 188 g. (2 moles) of phenol and 268 g. (2 moles) of ethyl acetoacetate in 300 ml. of dry nitrobenzene (Note 1) and (Note 2). The mixture is heated to 100° by means of an oil bath, stirring is started, and 532 g. (4 moles) of anhydrous aluminum chloride dissolved in 2.1 l. of dry nitrobenzene is added over a period of 30–45 minutes (Note 3). The dropping funnel is then replaced by a thermometer, and the temperature of the solution is raised to 130° and held there 3 hours (Note 4). By this time the evolution of hydrogen chloride will have practically ceased.
The solution is cooled until its temperature is approximately that of the room, and 500 ml. of a mixture of equal parts of concentrated hydrochloric acid and water is added with stirring. The flask is then arranged for steam distillation and heated with a free flame while steam is passed into the reaction mixture until about 200 ml. of distillate is collected (Note 5). While hot, the mixture is placed in a large separatory funnel and the lower aqueous layer removed; the nitrobenzene layer is filtered through a Büchner funnel (Note 6) and (Note 7).
The nitrobenzene is then removed by vacuum distillation using a 2-l. Claisen flask, and the residue in the flask is distilled under diminished pressure; the fraction boiling at 180–195°/15 mm. is collected (Note 8) and (Note 9). The red-yellow oil, which solidifies on cooling, amounts to 128–176 g. (40–55%) and is sufficiently pure for some purposes (Note 10). A nearly white product can be obtained by dissolving the crude product in ether, shaking the ether solution with portions of 5% sodium hydroxide solution until no color appears in the aqueous layer, evaporating the ether, and recrystallizing the residue from a mixture of petroleum ether (b.p. 60–90°, Skellysolve B) and benzene (Note 11). The recrystallized product melts at 83–84°; the recovery is 80–85%.
2. Notes
1.
Methyl acetoacetate has been used but insufficient data have been obtained as to the yield produced.
2.
Commercial
nitrobenzene is dried by distillation under reduced pressure until the distillate is clear. The residue is suitable for use without other treatment.
3.
The
aluminum chloride is added in 25- to 50-g. portions to the
2.1 l. of dry nitrobenzene contained in a
5-l. round-bottomed flask with stirring after each addition. The temperature may rise to 80–90° during the addition; occasional cooling of the flask under running water is necessary. After all the
aluminum chloride has been added, the solution is cooled to room temperature. A small amount of
aluminum chloride may settle to the bottom.
In one instance when the final cooling was omitted the temperature continued to rise and a large amount of hydrogen chloride was evolved. The residue in the flask was a thick paste. Addition of a portion of the paste to water caused nitrobenzene to separate. However, this batch was not suitable for condensation.
4.
Below 100° the condensation does not take place; at 150° tar is formed and no coumarin can be isolated.
5.
Some unchanged ester distils before the
nitrobenzene; its removal aids in the subsequent separation of the two layers.
6.
If a sufficiently large funnel is not available the separation may be done by dividing the solution in portions to suit the funnel available. If too much steam has condensed during the distillation, the aqueous layer may appear on top.
7.
The tarry by-products clog filter paper immediately; a small quantity of filter aid may be used to promote the filtration. If the condensation has been satisfactory only a small amount of material will be retained, and this step may be omitted. Occasionally a considerable amount of lumpy, tarry material is removed; filtration is then more difficult, and the yield is lower. The tar, on distillation, yields no coumarin.
8.
The recovered
nitrobenzene, after being washed with water and dried as in
(Note 2), may be used again. The loss is from 400 to 700 ml.
9.
Considerable tar remains in the distillation flask. The tar is best poured immediately into a flat pan of water or a sink, where it solidifies to a hard brittle mass; that adhering to the walls of the flask is easily removed by adding
100–200 ml. of nitrobenzene to the flask and heating the solvent to boiling under atmospheric pressure.
10.
According to the submitter, when quantities 3 times this size are used, the yield of distilled material is
38–50%.
11.
The ratio of
petroleum ether to
benzene should be 8 to 2.
3. Discussion
4-Methylcoumarin is prepared by the condensation of
phenol and
acetoacetic ester. Concentrated
sulfuric acid1,2 and 73% sulfuric acid have been used.
3,4 The method given here was mentioned by Sethna, Shah, and Shah,
5 and the procedure is adapted from that of the same authors
6 for another coumarin derivative.
Appendix
Chemical Abstracts Nomenclature (Collective Index Number);
(Registry Number)
petroleum ether
acetoacetic ester
sulfuric acid (7664-93-9)
hydrogen chloride,
hydrochloric acid (7647-01-0)
Benzene (71-43-2)
ether (60-29-7)
sodium hydroxide (1310-73-2)
phenol (108-95-2)
aluminum chloride (3495-54-3)
Nitrobenzene (98-95-3)
Ethyl acetoacetate (141-97-9)
4-Methylcoumarin,
Coumarin, 4-methyl- (607-71-6)
Methyl acetoacetate (105-45-3)
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