Checked by Max Tishler and George Purdue.
1. Procedure
In a
3-l. three-necked round-bottomed flask, fitted with a
sealed stirrer, a
dropping funnel, and a
reflux condenser, is placed
80 g. (1.1 moles) of dimethylformamide (Note
1). The flask is immersed in an
ice bath, and the internal temperature is maintained at 10–20°, while
169 g. (1.1 moles) of phosphorus oxychloride is added through the dropping funnel over a period of 15 minutes. An exothermic reaction occurs with the formation of the
phosphorus oxychloride-dimethylformamide complex. The ice bath is removed, and the mixture is stirred for 15 minutes (Note
2).
The ice bath is replaced, and
250 ml. of ethylene dichloride is added to the mixture. When the internal temperature has been lowered to 5°, a solution of
67 g. (1.0 mole) of freshly distilled pyrrole in 250 ml. of ethylene dichloride is added through a clean dropping funnel to the stirred, cooled mixture over a period of 1 hour. After the addition is complete, the ice bath is replaced with a heating mantle, and the mixture is stirred at the reflux temperature for 15 minutes, during which time there is copious evolution of
hydrogen chloride.
The mixture is then cooled to 25–30°, and to it is added through the dropping funnel a solution of
750 g. (5.5 moles) of sodium acetate trihydrate (Note
3) in about 1 l. of water, cautiously at first, then as rapidly as possible. The reaction mixture is again refluxed for 15 minutes, vigorous stirring being maintained all the while (Note
4).
The cooled mixture is transferred to a
3-l. separatory funnel, and the
ethylene dichloride layer is removed. The aqueous phase is extracted three times with a total of about
500 ml. of ether. The
ether and
ethylene chloride solutions are combined and washed with three
100-ml. portions of saturated aqueous sodium carbonate solution, which is added cautiously at first to avoid too rapid evolution of
carbon dioxide. The non-aqueous solution is then dried over anhydrous
sodium carbonate, the solvents are distilled, and the remaining liquid is transferred to a
Claisen flask and distilled from an
oil bath under reduced pressure (Note
5). The aldehyde boils at
78° at 2 mm.; there is very little fore-run and very little residue. The yield of crude
2-pyrrolealdehyde is
85–90 g. (
89–95%), as an almost water-white liquid which soon crystallizes. A sample dried on a clay plate melts at
35–40°. The crude product is purified by dissolving in boiling
petroleum ether (b.p.
40–60°), in the ratio of 1 g. of crude
2-pyrrolealdehyde to 25 ml. of solvent, and cooling the solution slowly to room temperature, followed by refrigeration for a few hours. The pure aldehyde is obtained from the crude in approximately
85% recovery. The over-all yield from
pyrrole is
78–79% of pure
2-pyrrolealdehyde, m.p.
44–45°.
2. Notes
1. The
dimethylformamide is available as technical grade DMF from the Grasselli Chemicals Department of E. I. duPont de Nemours and Company, Wilmington, Delaware.
2. If the ice bath is not removed, the mixture may solidify and must be dissolved by adding solvent and heating slightly. Mixing of the reactants at ice-bath temperature prevents discoloration. Practical grades of materials were used.
3. The use of sufficient
sodium acetate is essential. If the acidic reaction products are not neutralized, the yield drops to as low as 15–20% of badly discolored product which cannot be readily purified.
4. Efficient stirring must be maintained to keep the two phases in close contact. Hydrolysis is not complete if the mixture is not heated.
5. The use of a
wide-bore condenser and a
simple receiver, without a stopcock, is preferable. Usually the product does not solidify at once, but occasionally it crystallizes during distillation. The use of a fraction cutter is not necessary or advisable.
3. Discussion
Copyright © 1921-2002, Organic Syntheses, Inc. All Rights Reserved