Org. Synth. 1962, 42, 100
DOI: 10.15227/orgsyn.042.0100
THIOBENZOYLTHIOGLYCOLIC ACID
[Benzoic acid, dithio-, carboxymethyl ester]
Submitted by Frederick Kurzer and Alexander Lawson
1.
Checked by Max Tishler, G. A. Stein, and W. F. Jankowski.
1. Procedure
A solution of alcoholic caustic potash, prepared by dissolving 59.3 g. of 85% potassium hydroxide (0.90 mole) in 400 ml. of absolute ethanol with warming, is divided into two equal portions, one of which is saturated with hydrogen sulfide at room temperature (Note 1). The recombined solutions are placed in a 1-l. three-necked flask fitted with a Hershberg stirrer (Note 2), a gas delivery tube (Note 3), and a reflux condenser carrying a dropping funnel (Note 4). The air is displaced from the apparatus by passing a stream of nitrogen through the stirred liquid (Note 5). The solution is warmed to approximately 45–50°, and 49 g. (35 ml., 0.25 mole) of benzotrichloride is added dropwise through the condenser from a dropping funnel at a rate to maintain the temperature of the reaction mixture at approximately 60°; this requires 1–1.5 hours (Note 6). The reaction mixture turns deep red soon after the addition is started. When all the benzotrichloride has been added, the stirred deep-red suspension is refluxed gently for 30 minutes. A solution of 33.1 g. (0.35 mole) of chloroacetic acid in 200 ml. of water, neutralized with 29.4 g. (0.35 mole) of solid sodium bicarbonate, is next rapidly added through the condenser, the stirred mixture heated to boiling as rapidly as possible and refluxed (Note 5) for 5 minutes.
The resulting brownish red suspension is added to 750–1000 g. of ice contained in a 2-l. beaker (Note 7) and the turbid orange solution slowly acidified (to Congo red) with good stirring (Note 8) by the addition of approximately 50 ml. (Note 9) of concentrated hydrochloric acid. The deep-scarlet crystalline precipitate is collected at the pump after 30 minutes at 0° and rinsed with small quantities of water.
The air-dried product is crystallized by dissolving it in chloroform (approximately 120 ml.), followed by dilution of the filtered boiling liquid (Note 10) with hot petroleum ether (boiling range 60–80°, 60–80 ml.). The crystalline product, which separates rapidly, is collected at 0°, rinsed on the filter with a mixture of chloroform and petroleum ether (1:3), and dried. The yield of magnificent deep-scarlet lustrous prisms, m.p. 127–128°, varies between 28.9 and 30.4 g. (54–57% of the theoretical). Concentration of the combined filtrates and wash liquids under reduced pressure to a small volume (50–80 ml.) yields an additional small quantity (1.5–3.0 g., 3–6%) of material of satisfactory purity, m.p. 121–124°.
2. Notes
1.
Saturation is complete when a slow stream of gas is passed through the solution during 2.5–3 hours. The initially turbid liquid generally clears and remains nearly colorless during this process.
The checkers on several occasions obtained a small amount of a flocculent precipitate that most probably was potassium carbonate.
2.
The checkers used a
Trubore stirrer with a Teflon paddle.
3.
The delivery tube is fitted to allow the stream of
nitrogen to enter as far under the surface of the liquid as possible without obstructing the operation of the stirring device.
4.
The checkers used a
pressure-equalizing dropping funnel.
5.
The passage of
nitrogen is continued throughout the experiment.
6.
The exothermic nature of the reaction maintains the temperature of the mixture between 50° and 60°, depending upon the rate of the addition of the
benzotrichloride.
7.
The checkers used a
3-l., wide-necked, round-bottomed flask equipped with a
mechanical stirrer.
8.
Some unmelted ice should remain during the acidification, which is carried out slowly at 0°, to prevent the separation of the crude material in the form of an oil.
9.
The checkers found that
25–30 ml. of concentrated hydrochloric acid was sufficient.
10.
The submitters filtered the solution rapidly with suction through a preheated
Büchner funnel. The checkers found that the product often crystallized too rapidly and plugged the filter. As a result, the crude product was dissolved in an excess of
chloroform (160–175 ml.), then filtered, and the excess solvent evaporated before dilution with light
petroleum ether. In some cases, no filtration was necessary because the
chloroform solution was clear.
3. Discussion
Thiobenzoylthioglycolic acid has been prepared by the interaction of
potassium dithiobenzoate and alkali
chloroacetate.
2,3,4 The required intermediate,
dithiobenzoic acid, has been obtained from
phenylmagnesium bromide and
carbon disulfide,
2,3,5 or by the condensation of
benzaldehyde and hydrogen polysulfides,
2,6 or most conveniently by treatment of
benzotrichloride with
potassium hydrogen sulfide.
2,4,7 The last procedure has been adapted here to afford improved yields.
4. Merits of Preparation
Thiobenzoylthioglycolic acid is a useful thiobenzoylating agent,
2,3,4,8,9,10,11,12 and the resulting products find application for the synthesis of various heterocycles. These applications of
thiobenzoylthioglycolic acid have recently been reviewed.
13
Appendix
Chemical Abstracts Nomenclature (Collective Index Number);
(Registry Number)
petroleum ether
ethanol (64-17-5)
potassium carbonate (584-08-7)
hydrochloric acid (7647-01-0)
chloroform (67-66-3)
sodium bicarbonate (144-55-8)
hydrogen sulfide (7783-06-4)
nitrogen (7727-37-9)
benzaldehyde (100-52-7)
chloroacetic acid,
chloroacetate (79-11-8)
potassium hydroxide (1310-58-3)
benzotrichloride (98-07-7)
carbon disulfide (75-15-0)
potassium hydrogen sulfide (1310-61-8)
Phenylmagnesium bromide (100-58-3)
Thiobenzoylthioglycolic acid
Benzoic acid, dithio-, carboxymethyl ester (942-91-6)
potassium dithiobenzoate
dithiobenzoic acid
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