Organic Syntheses, CV 7, 451
Submitted by George A. Olah and Massoud Arvanaghi
1.
Checked by David Heiler and Martin F. Semmelhack.
1. Procedure
Magnesium (2.88 g, 0.12 mol),
300 mL of anhydrous tetrahydrofuran (Note
1), and
10 mg of iodine are placed in a
1-L, three-necked, round-bottomed flask fitted with a stirrer, dropping funnel with a pressure-equalizing tube, and a reflux condenser connected to a
nitrogen flow line.
Nitrogen is passed through the solvent for 15 min and a constant flow of
nitrogen is maintained throughout the reaction. A solution of
14.06 g (0.1 mol) of (2-chloroethyl)benzene (Note
2) in
50 mL of tetrahydrofuran is placed in the
dropping funnel. About 2 mL of this solution is added to the reaction mixture and the reaction is initiated by gently heating the flask (with a heat gun). Once the reaction has started, as evidenced by the disappearance of
iodine color, the rest of the
(2-chloroethyl)benzene solution is added dropwise at such a rate that a gentle reflux is maintained throughout the addition. The resulting solution is stirred for an additional 1 hr at 23°C, followed by heating at reflux for 8 hr. The reaction vessel is cooled to 0°C and a solution of
13.56 g (0.12 mol) of N-formylpiperidine (Note 3) in 50 mL of dry tetrahydrofuran is added dropwise (Note
4). The mixture is brought to 23°C and stirred for another 15 min.
The reaction mixture is quenched by the addition of 25 mL of ice water and slowly acidified to pH 2 with
75 mL of 3 N hydrochloric acid. The organic layer is separated and the aqueous layer is extracted with three
75-mL portions of ether. The extracts are combined with the original
ether layer, washed successively with 50 mL of water, two
50-mL portions of aqueous 10% sodium bicarbonate, and
50 mL of saturated sodium chloride solution, and dried over anhydrous
magnesium sulfate. After the
magnesium sulfate is removed by filtration, the solvent is removed at aspirator vacuum on a
rotary evaporator and the residue is distilled through a short column to give
8.8–10.2 g (
66–76%) of
3-phenylpropionaldehyde, bp
87°C (1.0 mm) (Note
5),(Note
6),(Note
7).
2. Notes
2. The
(2-chloroethyl)benzene was purchased from Eastman Organic Chemicals and used without further purification.
3.
N-Formylpiperidine was obtained from Reilly Tar and Chemicals or from Aldrich Chemical Company and used without further purification.
4. Too rapid addition of
N-formylpiperidine should be avoided as it can result in a cake-like solid that hinders mixing of the reaction mixture. Efficient stirring is crucial to optimum yields.
6. The spectral properties of the product are as follows:
13C NMR (CDCl
3) δ: 27.9 (t, -CH
2-CH
2-CHO), 45.1 (t, -CH
2-CHO), 126.1 (d,
para), 128.2 (d,
ortho), 128.5 (d,
meta), 140.2 (s,
ipso), 201.4 (d, -CHO);
1H NMR (CDCl
3) δ: 2.77 (m, -CH
2-CHO); 2.95 (m, -CH
2-CH
2-CHO), 7.16–7.33 (m, aromatic), 9.80 (t, -CHO); IR cm
−1: 2700, 1710.
3. Discussion
This preparation is referenced from:
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