A dry,
500-ml., two-necked flask containing
6.75 g. (0.0500 mole) of N,N-dimethyl-p-toluidine (Note
1) and
175 ml. of anhydrous hexane (Note
2) is fitted with a
Teflon-coated magnetic stirring bar, a
pressure-equalizing dropping funnel capped with a
rubber septum, and a
nitrogen inlet tube. The reaction vessel is flushed with
nitrogen, and a static
nitrogen atmosphere is maintained within the apparatus for the remainder of the reaction sequence. A solution of
8.8 g. (0.076 mole of N,N,N',N'-tetramethylethylenediamine (Note
3) in
40 ml. of anhydrous hexane is added to the dropping funnel, followed by a
hexane solution containing
0.076 mole of n-butyllithium (Note
4). The resulting solution, which becomes warm as the organolithium-diamine complex forms, is allowed to stand for 15 minutes, then added to the reaction mixture, dropwise and with stirring over 15–20 minutes. The resulting bright yellow, turbid reaction mixture is stirred at room temperature for 4 hours longer before a solution of
13.8 g. (0.0758 mole) of benzophenone (Note
5) in
40 ml. of anhydrous diethyl ether is added to the reaction mixture, dropwise and with stirring over 20 minutes. The resulting, deep-green solution is stirred for an additional 20 minutes, then poured into a vigorously stirred solution of
12 g. (0.20 mole) of acetic acid in 30 ml. of ether (Note
6). After the reaction solution has been successively extracted with 50 ml. of water and four
50-ml. portions of 5% hydrochloric acid, the aqueous extracts are combined (Note
7) and made basic with aqueous
10% sodium hydroxide. The alkaline mixture is heated to boiling and maintained at this temperature until the escaping vapor is no longer basic to moistened pHydrion paper (Note
8). The mixture is then cooled, and the white solid product which separates is collected on a
Büchner funnel and washed with three 20-ml. portions of water. The crude product (m.p.
142–168°) is recrystallized from
250 ml. of 3 : 1 (v/v) hexane-ethyl acetate, giving
6.6–8.2 g. of the amino alcohol product as colorless prisms, m.p.
168–171°. Concentration of the mother liquors gives an additional
0.8–1.2 g. of product, m.p.
167–169°, for a total yield of
7.8–9.0 g. (
49–57%). Although the product is sufficiently pure for most purposes, a second recrystallization from
hexane-
ethyl acetate raises the melting point to
169.5–172° (Note
9).