Organic Syntheses, CV 4, 626
Submitted by Ernest L. Eliel and Milton T. Fisk
1.
Checked by James Cason, Mary S. Nakata, and William G. Dauben.
1. Procedure
To
200 ml. of glacial acetic acid in a
1-l. round-bottomed flask is added slowly, with cooling in an
ice bath,
151 ml. (54 g. of dimethylamine, 1.2 moles) of 40% aqueous dimethylamine solution, followed by
90 ml. (36 g. of formaldehyde, 1.2 mole) of 37% aqueous formaldehyde (formalin) solution. The flask is removed from the ice bath and equipped with a
reflux condenser, through which
82 g. (90 ml., 1 mole) of 2-methylfuran (Note
1) is added all at once. Upon gentle swirling of the flask, an exothermic reaction may set in spontaneously; if it does not, the flask is heated on a
steam bath until reaction commences. In any event, the spontaneous reaction is allowed to proceed without further external heating. When it ceases, the reaction mixture is heated on a steam bath for another 20 minutes, cooled, and without delay poured into a cold solution of
250 g. of sodium hydroxide (Note
2) in 800 ml. of water.
The reaction mixture is steam-distilled until the distillate is only faintly alkaline (Note
3). To the distillate is added
sodium hydroxide (Note
2) to the extent of 10 g. for each 100 ml. of distillate. The strongly alkaline solution is cooled and extracted with two
300-ml. portions of ether. The combined
ether layers are dried over
25 g. of solid potassium hydroxide (Note
4), decanted, and concentrated. The residue is distilled under reduced pressure; the yield of
5-methylfurfuryldimethylamine boiling at
62–63°/13 mm. is
96–106 g. (
69–76%),
nD25 1.4616–1.4620.
2. Notes
1. The submitters used
du Pont 2-methylfuran. Since the stabilizer contained in this material inhibits the reaction, it should be removed before use. The liquid is stored over solid
potassium hydroxide (10 g. for each
100 ml. of 2-methylfuran) for 24 hours, decanted, and stored over the same amount of fresh
potassium hydroxide at least overnight. A more rapid but less convenient method of removing the stabilizer is to extract the liquid with
10% aqueous potassium hydroxide until the extracts are only faintly colored.
3. The steam distillate amounts to 2–3 l.
4. If a large aqueous phase appears, the amine should be decanted and dried further over a fresh portion of
potassium hydroxide pellets.
3. Discussion
The first preparation of 5-methylfurfurylamines by the Mannich reaction was by Holdren and Hixon.
2 The present modification has been published
3 without the stem-distillation step, which facilitates separation of the product.
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