In a
3-l. three-necked flask fitted with a
calcium chloride drying tube, a
nitrogen-inlet tube, and a
sealed mechanical stirrer are placed
54.0 g. (1.00 mole) of commercial, anhydrous sodium methoxide (Note
1) and
2 l. of anhydrous ether. The flask is purged with dry
nitrogen and cooled in an
ice bath. The inlet tube is replaced by an
addition funnel containing a solution of
123 g. (1.10 moles) of 2-methylcyclohexanone (Note
2) and
81.4 g. (1.10 moles) of ethyl formate (Note
3). The solution is added rapidly, dropwise, and at the end of the addition the funnel is replaced by the nitrogen-inlet tube. After 15 minutes the ice bath is removed, and the mixture is stirred for 12 hours at room temperature. The thick suspension is filtered by suction, and the filter cake is washed with anhydrous
ether, care being taken to protect the product from atmospheric moisture (Note
4). The solid salt is dried in a
vacuum oven at
ca. 70°, powdered (Note
5), and stored in a tightly capped bottle.
Sodio-2-formyl-6-methylcyclohexanone, a cream-colored powder, is obtained in
80–85% (
130–138 g.) yield (Note
6).
In a
1-l. three-necked flask equipped with a
dry ice-acetone condenser and a sealed mechanical stirrer is placed
700 ml. of commercial, anhydrous, liquid ammonia. To the stirred
ammonia is added a small piece of
potassium metal.
(Caution! Care should be exercised in handling potassium metal, since it is extremely reactive and it ignites on contact with water, atmospheric moisture, or alcohol. It should be manipulated under toluene or xylene, and blotted with filter paper before addition.) After the appearance of a blue color a few crystals of
ferric nitrate hydrate (ca. 0.1 g.) are added, followed by small pieces of freshly cut
potassium metal until 7.0 g. (0.18 g. atom) has been added. After all the
potassium has been converted to the amide (Note
7),
24.9 g. (0.154 mole) of sodio-2-formyl-6-methylcyclohexanone is added carefully through a
powder funnel (Note
8). After 1 hour a solution of
28.2 g. (0.21 mole) of n-butyl bromide (Note
9) in
50 ml. of anhydrous ether is added dropwise from an addition funnel. The mixture is stirred for 3 hours, and then the dry ice-acetone condenser is replaced by a
water condenser. A
steam bath is placed under the flask, and the
ammonia is evaporated (
Caution!) as
400 ml. of anhydrous ether is added. When the
ammonia has been removed and the
ether has refluxed for 5 minutes, 100 g. of ice is added, followed by 300 ml. of water. When the solid has dissolved, the layers are separated, and the ethereal layer is extracted twice with cold water. The combined aqueous extracts are placed in a
1-l. round-bottomed flask, and
6.4 g. of sodium hydroxide is added. The flask is warmed briefly to remove dissolved
ether from the solution. The flask is equipped with an
efficient condenser, and the mixture is refluxed until an enol test is no longer obtained (6–8 hours) (Note
10) and (Note
11). The mixture is cooled and extracted with three
200-ml. portions of ether. The combined ethereal extracts are washed with dilute
hydrochloric acid and dried over anhydrous
magnesium sulfate. The
ether is evaporated, and the residue is distilled under reduced pressure to give
14–19 g. (
54–74%) of
2-n-butyl-2-methylcyclohexanone, b.p.
116–118° (20 mm.) (Note
12).