A
300-ml., three-necked flask (Note
1), equipped with a
magnetic stirring bar,
thermometer,
pressure-equalizing dropping funnel fitted with septum inlet adapter (Note
2), and
reflux condenser fitted with a hose adapter leading to a mineral oil bubbler (Note
3), is charged with
10.0 ml. (0.100 mole) of borane–methyl sulfide complex (Note
4) and
30 ml. of tetrahydrofuran (Note
5) and (Note
6). The flask is immersed in an
ice-water bath as
27.2 g. (31.7 ml., 0.200 mole) of (+)-α-pinene (Note
7) is added dropwise at 0–3° to the well-stirred reaction mixture over a period of 15 minutes. The
(−)-diisopinocampheylborane [(−)-di-3-pinanylborane] precipitates as a white solid as the reaction proceeds. Following addition, the reaction mixture is stirred for 3.5 hours at 0°. Under a slow stream of
nitrogen, the outlet hose adapter on the reflux condenser is connected with rubber vacuum hose to a
vacuum trap which is then cooled in an
acetone–dry ice bath. The
dimethyl sulfide and
tetrahydrofuran are bulb-to-bulb vacuum-distilled (0.1 mm.) with the reaction flask in a room temperature
water bath. When only a dry, white solid residue remains, the vacuum is released with
nitrogen. The flask is again placed under a slight positive pressure of
nitrogen. The solid is slurried in
36 ml. of tetrahydrofuran (Note
5) at room temperature. An additional
4.08 g. (4.76 ml., 0.030 mole) of (+)-α-pinene (Note
7) is added. The resulting slurry is stirred at room temperature for 5 minutes and then stored under
nitrogen in a closed system in a cold room at 4° for 3 days (Note
8). The flask is then removed from the cold room and immersed in an ice-water bath. Under a slow stream of
nitrogen, the outlet adapter on the reflux condenser is again connected to the mineral oil bubbler. The excess hydride is destroyed by the slow, dropwise addition of
8 ml. of methanol (Note
9), followed by the addition in one portion of
36.6 ml. of 3 M aqueous sodium hydroxide. The
borinic acid intermediate is now oxidized by the dropwise addition of
24 ml. of 30% aqueous hydrogen peroxide (Note
10) to the well-stirred reaction mixture at 35° ± 3° (Note
11). After the
hydrogen peroxide addition is complete, the ice-water bath is replaced with a warm-water bath and the reaction mixture is stirred for one hour at 50–55° (Note
12) and then cooled to room temperature. The aqueous layer is saturated with
sodium chloride and
50 ml. of diethyl ether is added. The upper organic layer is removed, and the aqueous layer is extracted with two
100-ml. portions of ether. The organic layer and extracts are combined, dried over
anhydrous potassium carbonate, filtered, and concentrated to an oil on a
rotary evaporator at 60° (15 mm.) (Note
13). The crude product is fractionally distilled using a
30-cm. column packed with glass helices, giving
24.7 g. (
80%) of
(−)-isopinocampheol, b.p.
60–65° (0.1 mm.) (Note
14). The distillate crystallizes completely in the receiver, m.p.
49–55°, 97.5% purity by GC,
[α]19D −34.3° (C, 20 in
ethanol) (Note
15). Slurrying 4.7 g. in
2.3 ml. of pentane at room temperature, cooling to −78°, collecting on a filter, and air drying gives
3.8 g. of crystalline
(−)-isopinocampheol, m.p.
52–55°, purity 99.2% by GC,
[α]19D −34.9° (C, 20 in
ethanol).