Organic Syntheses, Coll. Vol. 3, p.191 (1955); Vol. 24, p.25 (1944).
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.
); 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)
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
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.
). Isopropyl nitrite
, when stored in a refrigerator
, has been found to be much more stable than butyl nitrite
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.
The recovered ether
may be employed without purification as the solvent in a subsequent run.
This is most conveniently done by dissolving the chloride in the benzene
and then diluting.
This procedure works equally well in 0.5-mole runs.
This procedure, with minor changes, may be applied to various nuclear-substituted phenacyl chlorides. The yields vary from 74% to 92%.2,3
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