Organic Syntheses, CV 5, 642
Submitted by C. Frisell and S.-O. Lawesson
1.
Checked by R. M. Scribner, C. G. McKay, and B. C. McKusick.
1. Procedure
A.
2-t-Butoxythiophene. A dry
1-l. three-necked flask is fitted with a
mechanical stirrer (Note
1), a
reflux condenser having a take-off attachment, and a
250-ml. dropping funnel with a pressure-equalizing side tube.
2 A
nitrogen-inlet tube is connected to the top of the condenser, and a T-tube branch of this is led to a
mercury valve. The latter consists of a U-tube the bend of which is just filled with
mercury.
Ten grams (0.41 g. atom) of magnesium turnings (Note
2) is placed in the flask and covered with
200 ml. of dry ether.
Ten milliliters of a solution of 65.2 g. (0.40 mole) of 2-bromothiophene in 60 ml. of dry ether is added, the Grignard reaction is started by gently warming the reaction flask, and the remainder of the solution is added dropwise during 45 minutes. The mixture is stirred for 3.5 hours, the last 15 minutes under reflux. The Grignard reagent is cooled to 0–5° by immersing the flask in ice water.
t-Butyl perbenzoate (62 g., 56 ml., 0.32 mole) (Note
3) in
100 ml. of dry ether is added dropwise during 45 minutes to the stirred ice-cooled mixture. The reaction mixture is stirred overnight, poured into ice water, and acidified with concentrated
hydrochloric acid. The two phases are separated, and the water phase is twice extracted with
ether. The combined
ether solutions are extracted with three
60-ml. portions of 2N sodium hydroxide solution (Note
4), washed until neutral with water, dried over anhydrous
sodium sulfate, and transferred to a distillation flask equipped with a Vigreux column.
Caution! The ether extract should not be distilled unless a test shows that peroxides are absent (Note 5). The
ether is distilled off at atmospheric pressure, and the residual oil is distilled under reduced pressure to give
35–38 g. (
70–76%) of
2-t-butoxythiophene, b.p.
64–66°/13 mm.,
nD20 1.4991.
B.
2-Hydroxythiophene. The
2-t-butoxythiophene obtained in Step A is placed in a distillation flask equipped with a
short Vigreux column and a
capillary inlet for
nitrogen, and
0.1 g. of p-toluenesulfonic acid is added. The apparatus is placed in an
oil bath at 155°. Decomposition begins immediately. After 5–10 minutes the oil bath is removed, and the distillation assembly is connected to a
water pump (Note
6).
2-Hydroxythiophene is distilled under reduced pressure,
nitrogen gas being drawn through the capillary during the whole procedure (Note
7).
2-Hydroxythiophene is collected at
91–93°/13 mm.; yield
20–23 g. (
89–94%);
nD20 1.5613 (Note
8).
2. Notes
1. Although a
mercury seal is preferable, a rubber tube lubricated with
glycerol is an adequate seal.
3.
t-Butyl perbenzoate is supplied by Lucidol Division, Wallace and Tiernan, Inc., Buffalo, New York, and Light and Co., Colnbrook, Bucks, England.
4. Acidification of the basic solution gives
29–32 g. (
80–88%) of
benzoic acid if the reaction has proceeded properly.
5. To make a peroxide test, place a few milligrams of
sodium iodide, a trace of
ferric chloride, and
2–3 ml. of glacial acetic acid in a test tube and carefully add
1–2 ml. of the ether solution. When unconsumed perbenzoate is present, a yellow ring is immediately formed between the two phases.
If this test indicates the presence of peroxide, the extract should not be concentrated and distilled until it has been extracted first with a solution of potassium iodide in acetic acid to remove peroxide and then with aqueous sodium thiosulfate to remove iodine.
6. The decomposition is considered to be complete when the pressure is constant.
3. Discussion
4. Merits of the Preparation
The first step of the procedure illustrates a general way of preparing aryl
t-butyl ethers.
4,6 The second step is the best way to prepare
2-hydroxythiophene, inasmuch as the yield is good and
t-butyl perbenzoate is a readily available perester that is relatively stable. The same procedure has been used to convert several other haloaromatic compounds to hydroxyaromatic compounds in good yield
4 and is probably quite general.
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