Organic Syntheses, CV 5, 1064
Submitted by J. Bornstein and J. E. Shields
1.
Checked by Rosetta McKinley and R. E. Benson.
1. Procedure
Caution! This reaction should be carried out in a
good hood because
hydrogen is evolved and
o-xylylene dibromide is a powerful lachrymator (Note
6).
A
1-l. three-necked flask is fitted with an efficient stirrer (Note
1),
thermometer,
condenser, and a
pressure-equalizing dropping funnel that carries an inlet for admission of dry nitrogen. The entire apparatus is dried by warming with a soft flame as a brisk stream of
nitrogen is passed through the system. The flow of
nitrogen is reduced to a slow stream, and in the cooled flask are placed
18.9 g. (0.42 mole) of 53% sodium hydride dispersed in mineral oil (Note
2) and
60 ml. of purified dimethylformamide (Note
3). The mixture is stirred at room temperature and a solution of
34.2 g. (0.20 mole) of p-toluenesulfonamide (Note
4) in
100 ml. of purified dimethylformamide is added dropwise over a period of 1 hour. The resulting suspension is stirred at room temperature for 1 hour and then at 60° for an additional hour (Note
5).
A solution of
52.8 g. (0.20 mole) of o-xylylene dibromide (Note
6) in
300 ml. of purified dimethylformamide is added dropwise with stirring at such a rate as to maintain a temperature of 60–70° (Note
7). Subsequently the reaction mixture is stirred at room temperature for 3 hours and then poured into 600 ml. of ice water in a
2-l. Erlenmeyer flask. After standing at room temperature overnight the product is collected by suction filtration, pressed on the funnel, and washed twice with 100-ml. portions of water. The crude product is air-dried on filter paper for 2–3 hours and is then dissolved in
1.2 l. of boiling 95% ethanol. The solution is filtered through a heated funnel, and the filtrate is refrigerated overnight. The crystals are collected on a Buchner funnel and washed on the funnel with
100 ml. of cold 95% ethanol. The product is dried over
phosphorus pentoxide in a
vacuum desiccator. The yield of white crystals of
2-(p-tolylsulfonyl)dihydroisoindole is
41–46 g. (
75–84%), m.p.
174–175° (dec.).
2. Notes
1. Either a
paddle-type sealed stirrer or a heavy-duty magnetic stirrer is suitable.
2.
Sodium hydride was obtained from Metal Hydrides Division of Ventron Corporation, Beverly, Massachusetts.
3.
Dimethylformamide, b.p. 152–154°, purchased from Matheson, Coleman and Bell, was stirred for 5 minutes with solid
potassium hydroxide, decanted, shaken briefly with lime, filtered, and distilled.
5. It is necessary to maintain vigorous stirring at this stage to prevent excessive foaming due to the evolution of
hydrogen.
7. Control of the temperature at this point is critical; a deeply colored product is obtained if the temperature is allowed to exceed 70°. The addition of the dibromide requires about 1 hour.
3. Discussion
4. Merits of the Preparation
This is the most practical procedure for the preparation of
2-(p-tolylsulfonyl)dihydroisoindole. It is superior to earlier ones
2,3 because it is more convenient and affords considerably higher yields (
ca. 80% versus
ca. 45%).
This preparation is referenced from:
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