Organic Syntheses, Coll. Vol. 4, p.915 (1963); Vol. 31, p.108 (1951).
The reaction is carried out in a 500-ml. three-necked round-bottomed flask fitted with ground-glass joints
and equipped with a thermometer
, a mechanical stirrer
, a dropping funnel
, and a calcium chloride tube
. In the flask are placed 135 g. (1.0 mole) of N-methylformanilide (Note 1)
and 153 g. (91 ml., 1.0 mole) of phosphorus oxychloride
, and the mixture is allowed to stand for 30 minutes (Note 2)
. Mechanical stirring is then begun, and the flask is immersed in a cold-water bath
while 92.4 g. (1.1 moles) of thiophene
is added at such a rate that the temperature is maintained at 25–35° (Note 3)
. After the addition is complete, the reaction mixture is stirred 2 hours longer at the same temperature and is then allowed to stand at room temperature for 15 hours. The dark, viscous solution is poured into a vigorously stirred mixture of 400 g. of cracked ice and 250 ml. of water. The aqueous layer is separated and extracted with three 300-ml. portions of ether
. The ether
extracts are combined with the organic layer and washed twice with 200-ml. portions of dilute hydrochloric acid (Note 4)
to remove all traces of N-methylaniline (Note 5)
. These aqueous washings are in turn extracted with 200 ml. of ether
, and the ether
extract is added to the ether
solution of the product. The combined ether
extracts are washed twice with 200-ml. portions of saturated sodium bicarbonate
solution (Note 6)
, then with 100 ml. of water, and finally are dried over anhydrous sodium sulfate
. The yellow oil obtained by concentrating the ether
solution is distilled from a 100-ml. flask
fitted with a satisfactory column (Note 7)
. The yield of 2-thiophenecarboxaldehyde
boiling at 97–100°/27 mm.
1.5893, is 80–83 g.
). The product darkens on standing.
Directions for preparing this intermediate have been published.2
The temperature of the mixture rises slowly to 40–45°, and a color change from yellow to red also occurs.
If the temperature is allowed to exceed 35°, a lower yield of aldehyde results.
This solution is prepared by mixing 50 g. of concentrated hydrochloric acid
and 400 ml. of water. The aldehyde has appreciable solubility in strongly acidic solutions.
The original aqueous layer and the acidic extracts are combined, cooled, and made strongly alkaline with 450 ml. of 40% sodium hydroxide
solution. The liberated N-methylaniline
is extracted with three 200-ml. portions of ether
. The ether
extracts are combined, washed with 100 ml. of water, dried over anhydrous sodium sulfate
, and concentrated. Distillation of the residue from a 200-ml. flask
equipped with an 11-cm. Vigreux column
gives 95.6 g.
) of N-methylaniline
boiling at 96–100°/27 mm.
Care must be taken in adding the bicarbonate solution, as vigorous foaming occurs until neutralization is complete.
The submitters used an 11-cm. Vigreux column; the checkers employed a 10-in. column
of the same type.
The present procedure is a modification of a previously described method.11
This preparation is referenced from:
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