Submitted by Nathan Levin and Walter H. Hartung.
Checked by C. F. H. Allen and J. VanAllan.
1. Procedure
A 500-ml. three-necked round-bottomed flask is provided with a small dropping funnel, a sealed mechanical stirrer, a reflux condenser connected to a gas-absorption trap, and a hydrogen chloride delivery tube which extends to the bottom of the flask.
In the reaction flask are placed
15.4 g. (0.1 mole) of phenacyl chloride (Note
1) and
100 ml. of dry ether. The stirrer is started, and, after the solid has dissolved, anhydrous
hydrogen chloride (Note
2) is introduced at the rate of 2–3 bubbles per second.
Ten and three-tenths grams (11.8 ml., 0.1 mole) of freshly distilled n-butyl nitrite1 (Note
3) is then admitted from the dropping funnel in 0.5- to 1-ml. portions. After addition of the first portion of nitrite the reaction mixture becomes orange-brown, and after several minutes, light yellow; at this point a second portion of nitrite is added and a similar color change takes place, whereupon a third portion is added; further additions are made until all the
butyl nitrite has been added. The reaction mixture warms up, and the
ether begins to reflux gently (Note
4). After all the nitrite has been added (about 30 minutes is required), stirring and addition of
hydrogen chloride are continued an additional 15 minutes. At this point, the solution will have practically ceased boiling and will have assumed an orange color.
The reaction mixture is allowed to stand for 1–2 hours (or overnight, if more convenient); after this interval the solution will have assumed a clear, pale yellow color. The condenser is then set for downward distillation, stirring is resumed, and the solvent is removed by distillation from a
steam bath (Note
5). After nearly all the
ether has been removed, the distillation is continued under reduced pressure (40–50 mm.) until no further appearance of crystals is noted. The residue, which consists of yellow crystals of the crude product, is then allowed to stand until dry in a
vacuum desiccator which contains concentrated
sulfuric acid,
soda lime, and anhydrous
calcium chloride (Note
6).
The dried product is then recrystallized from
30–35 ml. of a 1:3 mixture of boiling benzene and carbon tetrachloride (Note
7). The yield of snow-white crystals is
15–15.7 g. (
82–86%); the recrystallized product melts at
131–132° and is sufficiently pure for synthetic purposes. A second recrystallization gives a product which melts at
132–133° (Note
8) and (Note
9).
2. Notes
1. Commercial
phenacyl chloride may be used; if unavailable the chloride may be prepared in
85–88% yield by a Friedel-Crafts reaction, using
234 g. (265 ml., 3 moles) of dry benzene and
79.5 g. (53 ml., 0.70 mole) of chloroacetyl chloride, in the presence of
103 g. (0.77 mole) of powdered anhydrous aluminum chloride; the product distils at
120–125°/4 mm. and melts at
56–57°.
Phenacyl chloride is a strong lachrymator and vesicant; it should be handled with care.
3. Any alkyl nitrite may be employed. The submitters preferred the use of
isopropyl nitrite, since the low boiling point of the
isopropyl alcohol formed facilitates its removal.
A mixture of
147 g. (80 ml., 1.5 moles) of concentrated sulfuric acid (sp. gr. 1.84), 60 ml. of water, and
180 g. (230 ml., 3 moles) of 97% isopropyl alcohol, previously cooled to 0°, is added to a solution of
227.7 g. (3.3 moles) of 97% sodium nitrite in 1 l. of water, cooled to −5°. About 2 hours is required for the addition of the alcohol solution, during which time the temperature of the reaction mixture is maintained at −2° to 0°. The product may be isolated and purified as described under
butyl nitrite. After drying over
15–20 g. of anhydrous sodium sulfate, the nitrite is distilled from a steam bath using a
20-cm. column. Practically all the
isopropyl nitrite distils at
39–40°/745 mm. as a pale yellow oil; the yield of product is
191 g. (
71.4%).
Isopropyl nitrite, when stored in a
refrigerator, has been found to be much more stable than
butyl nitrite.
4. The rate of stirring must be kept fairly constant since an abrupt increase in speed may cause the
ether to reflux at an undesirably rapid rate. The rate of addition of the nitrite is also governed by the rate of the refluxing.
5. The recovered
ether may be employed without purification as the solvent in a subsequent run.
7. This is most conveniently done by dissolving the chloride in the
benzene and then diluting.
8. This procedure works equally well in 0.5-mole runs.
9. This procedure, with minor changes, may be applied to various nuclear-substituted phenacyl chlorides. The yields vary from 74% to 92%.
2,3
3. Discussion
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