A Publication
of Reliable Methods
for the Preparation
of Organic Compounds
Annual Volume
Org. Synth. 1960, 40, 43
DOI: 10.15227/orgsyn.040.0043
[Indene, 6,7-dimethoxy-3-methyl-2-carbethoxy-]
Submitted by John Koo1
Checked by John C. Sheehan and J. Iannicelli.
1. Procedure
To 300 g. of polyphosphoric acid (Note 1) precooled to 5° is added 28 g. (0.1 mole) of ethyl α-acetyl-β-(2,3-dimethoxyphenyl)-propionate2 contained in a 400-ml. beaker. The mixture is stirred thoroughly (Note 2) with a strong spatula for 15 minutes. The temperature, which is around 10° at the beginning, increases rapidly and is kept between 20° and 25° by occasionally cooling the beaker in an ice-water bath (Note 3). The deep-yellow reaction paste is then poured immediately into 600 ml. of ice water with thorough stirring and trituration (Note 4), and the beaker is rinsed with small portions of cold water. The product, which separates from the cold water as a colorless precipitate, is extracted with several portions of chloroform (first with 400 ml., then twice with 200 ml., and finally with 100 ml. of this solvent). The combined chloroform extracts are washed successively with 100 ml. of cold water, then once with 100 ml., twice with 50 ml. of 10% sodium bicarbonate solution (Note 5), and finally with 50 ml. of cold water. The chloroform solution is dried over magnesium sulfate and filtered. The chloroform is removed by distillation on a steam bath first at atmospheric pressure and finally under reduced pressure. The residual pale-yellow oil soon solidifies and is practically pure. The yield of ethyl 6,7-dimethoxy-3-methylindene-2-carboxylate is 21.5–22.5 g. (82–86%), m.p. 81–83° (Note 6).
2. Notes
1. Obtained from Victor Chemical Works, Chicago, Illinois.
2. Since the mixture is so viscous, continuous and vigorous hand stirring is necessary.
3. After the reaction starts, the temperature should be checked every few minutes and kept between 20° and 25°, which is the most favorable temperature.
4. Careful stirring and trituration are necessary to ensure the complete decomposition of every drop of the yellow paste.
5. According to the submitter, acidification of the combined sodium bicarbonate washings with 10% hydrochloric acid yields a colorless precipitate of 6,7-dimethoxy-3-methylindene-2-carboxylic acid, which is collected by filtration, washed, and dried; yield, 3.4–3.9 g. (14–16%); m.p. 216–218°.
6. Recrystallization from 75 ml. of 60% ethanol gives a 90% recovery of colorless long needles, m.p. 83–85°.
3. Discussion
The method described here is based on the analogous preparation of some other indenes.3

References and Notes
  1. Present address: National Drug Company, Research Laboratories, Philadelphia, Pennsylvania. Work done in the Laboratory of Chemical Pharmacology, National Cancer Institute, National Institutes of Health, Bethesda, Maryland.
  2. E. C. Horning, J. Koo, M. S. Fish, and G. N. Walker, Org. Syntheses, Coll. Vol. 4, 408 (1963).
  3. J. Koo, J. Am. Chem. Soc., 75, 1891 (1953).

Chemical Abstracts Nomenclature (Collective Index Number);
(Registry Number)

polyphosphoric acid

ethanol (64-17-5)

hydrochloric acid (7647-01-0)

chloroform (67-66-3)

sodium bicarbonate (144-55-8)

magnesium sulfate (7487-88-9)


Ethyl 6,7-dimethoxy-3-methylindene-2-carboxylate,
Indene, 6,7-dimethoxy-3-methyl-2-carbethoxy- (5415-54-3)

6,7-dimethoxy-3-methylindene-2-carboxylic acid