Organic Syntheses, Coll. Vol. 5, p.266 (1973); Vol. 49, p.27 (1969).
A. 2-Chlorocyclooctanone oxime hydrochloride
. In a 2-l. three-necked, round-bottomed flask
, fitted with a mechanical stirrer
, a gas inlet tube
, and a tube fitted with a thermometer
and a calcium chloride tube
, is placed 55 g. (0.50 mole) of freshly distilled cyclooctene
and 600 ml. of trichloroethylene
. The solution is cooled with ice water to 5°, and 36 g. (0.55 mole) of nitrosyl chloride (Note 1)
and excess of hydrogen chloride
gas (about 400–600 ml. per minute) are bubbled into the solution, keeping the reaction temperature between 5–10°. The solution gradually becomes light reddish brown. The addition of nitrosyl chloride
should be carried out in about 1.5 hours. After completion of the addition of nitrosyl chloride
, hydrogen chloride
gas is bubbled in for another 15 minutes. A light brown oily material is obtained after evaporation of the solvent under an aspirator pressure below 35° (Note 2)
by using an efficient rotatory evaporator
. On cooling this product in a refrigerator, 107.2 g.
) of crude 2-chlorocyclooctanone oxime hydrochloride
is obtained as a solid.
B. 2-Methoxycyclooctanone oxime
. In a 500-ml., three-necked, round-bottomed flask
, fitted with a mechanical stirrer, a dropping funnel
, and a reflux condenser
equipped with a calcium chloride tube, is placed a solution of 53.5 g. (0.252 mole) of crude 2-chlorocyclooctanone oxime hydrochloride
in 250 ml. of methanol
. While cooling the vessel with running water, 60.7 g. of triethylamine (0.60 mole)
is added dropwise during 40 minutes. The reaction temperature is kept below 50° and the reaction is continued for 30 minutes with stirring. After removal of methanol
under reduced pressure using an efficient rotatory evaporator, a light brown semisolid is obtained; it is treated with 200 ml. of ether
and 200 ml. of water to effect complete solution. The ether
layer is separated and the aqueous layer is further extracted twice with ether
. The combined ether
solution is washed with saturated sodium chloride
and dried over sodium sulfate
. Removal of ether
affords 42.8 g.
of crude 2-methoxycyclooctanone oxime (Note 3)
as a brown oil.
C. Beckmann fission of 2-methoxycyclooctanone oxime.
In a 500-ml., three-necked, round-bottomed flask
equipped with a mechanical stirrer, a dropping funnel, and a calcium chloride tube is placed a suspension of 62.5 g. (0.30 mole) of phosphorus pentachloride (Note 4)
in 150 ml. of absolute ether
, and the reaction vessel is cooled with ice. A solution of 42.8 g. of crude 2-methoxycyclooctanone oxime (0.25 mole)
in 100 ml. of absolute ether
is added over 30 minutes with vigorous stirring and the reaction is continued for 50 minutes at 5°. The reaction mixture, which becomes a transparent reddish brown solution (Note 5)
, is poured with mechanical stirring into 500 g. of ice in a 2-l. beaker
. Stirring is continued for 1.5 hours at 5° (Note 6)
. The ether
layer is separated and the aqueous layer is extracted with methylene chloride
three times. The combined organic extracts are neutralized with dilute sodium carbonate
solution and dried over sodium sulfate (Note 7)
. Removal of the solvent below 40° affords a reddish brown oil which is distilled to give 29.6 g.
) of 7-cyanoheptanal (Note 8)
, b.p. 109–115° (0.3 mm.) n26D
= 1.4456. The 2,4-dinitrophenylhydrazone
has m.p. 74–75°
after recrystallization from ethanol
Solid nitrosyl chloride
stored in a dry-ice box
is quickly melted by warming, and as rapidly as possible the liquid nitrosyl chloride
is weighed into a flask contained in a hood
. Nitrosyl chloride
is simply allowed to volatilize into the reaction from this flask under ambient conditions; rapid addition of nitrosyl chloride
causes a decrease of the yield of α-chlorooxime
. It may sometimes be necessary to control the rate of addition by cooling the nitrosyl chloride
container with ice water.
A very small amount of excess of phosphorus pentachloride
is sometimes observed at the bottom of the reaction vessel.
If necessary, the temperature is kept at 5–10° by adding ice occasionally.
If the solution is acidic, the yield of ω-cyanoaldehyde is diminished by the occurrence of aldo condensation.
Although this distilled product, a pale yellow oil, is pure enough to use for most purposes, pure 7-cyanoheptanal
, a colorless oil, is obtained by redistillation, b.p. 85–87° (0.013 mm.)
ω-Cyanoaldehydes are not easily accessible by other routes but are interesting synthetic intermediates,4
since the two terminal function groups are in different oxidation states which readily allow separate modification or elaboration.5,6
The general applicability of the method described herein allows the synthesis of a wide variety of ω-cyanoaldehydes from available cycloolefins.
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