Organic Syntheses, Coll. Vol. 3, p.305 (1955); Vol. 23, p.30 (1943).
In a 500-ml. round-bottomed flask
attached to a reflux condenser
are placed 60 g. (58.5 ml., 0.5 mole) of acetophenone (Note 1)
, 52.7 g. (0.65 mole) of dimethylamine hydrochloride
, and 19.8 g. (0.22 mole) of paraformaldehyde
. After the addition of 1 ml. of concentrated hydrochloric acid
(sp. gr. 1.19) in 80 ml. of 95% ethanol
, the mixture is refluxed on a steam bath
for 2 hours (Note 2)
. The yellowish solution is filtered, if it is not clear (Note 3)
and (Note 4)
, and is transferred to a 1-l. wide-mouthed Erlenmeyer flask
. While still warm, it is diluted by the addition of 400 ml. of acetone (Note 5)
, allowed to cool slowly to room temperature, and then chilled overnight in the refrigerator
. The large crystals are filtered and washed with 25 ml. of acetone
. After it has been dried for 2.5 hours at 40–50°, this crude product weighs 72–77 g
) and melts at 138–141° (Note 6)
and (Note 7)
; it is suitable for many reactions.
It may be recrystallized by dissolving it in 85–90 ml. of hot 95% ethanol
and slowly adding 450 ml. of acetone
to the solution. The recovery is about 90%
. The purified material, dried at 70°, melts at 155–156° (Note 8)
and (Note 9)
The reaction mixture, which at first forms two layers, soon becomes homogeneous, and the paraformaldehyde
The filtration must be done rapidly, preferably through a preheated funnel. Any material that crystallizes in the receiver
is brought into solution again by warming on the steam bath.
Alternatively, the reaction mixture may be cooled at once and the solid product removed. The filtrate is successively concentrated and chilled three times, each crop of crystals being rinsed with acetone
. For example, in a run using 480 g. of acetophenone
, the amounts obtained were 297
, and 16 g.
respectively, and 42 g.
from the acetone
washings, making a total of 500 g.
, or 66%
of the theoretical amount.
The material is somewhat hygroscopic and holds traces of water tenaciously. The melting point is lowered by the presence of moisture; a preliminary shrinking is usually observed.
After it has been dried for an additional 4 hours, the product melts at 152–153°
. The product melts at this same temperature after it has been kept for 60 hours in a vacuum desiccator
, except that then there is no preliminary shrinking.
These directions are applicable equally well for runs of larger size.
The procedure described is an example of a general reaction,1,2
the Mannich reaction, a review of which, from the experimental point of view, has been published.3
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