反応手順
Under nitrogen atmosphere 100 grams of Darocur 1173 (2-hydroxy-2-methyl-1-phenylpropan-1-one) was placed in 2 L of dry chloroform. After the mixture was cooled to 0° C., 480 grams of anhydrous AlCl3 and 55 grams of paraformaldehyde powder were successively added and the resultant mixture was vigorously stirred at 60° C. overnight for 14 hrs (note that HCl gas released from the reaction was neutralized by 2N NaOH solution). An additional portion of 55 grams of paraformaldehyde was added at this point and the reaction was stirred at this temperature for another 12 hrs. The mixture was cooled to room temperature, and under vigorous stirring poured into 3 L of water. The organic layer thus separated was collected, and the aqueous layer was extracted with 1 L of dichloromethane for three times. The combined chloroform and dichloromethane layer was next dried over anhydrous Na2SO4, filtered, and concentrated. The residue was loaded onto silica gel column and gradient eluted by mixtures of hexane/ethyl acetate (V/V=15/1 to 12/1) to give the intermediate 1-(3-(chloromethyl)phenyl)-2-hydroxy-2-methylpropan-1-one as a light-yellow oil (77.4% yield), and four other by-products A-D (22.6% combined yield). Characterization data for compound A (11.7% yield): 1H NMR (CDCl3, ppm): 8.01 (s, 2H), 7.63 (s, 1H), 4.63 (s, 4H), 3.78 (s, 1H), 1.62 (s, 6H); 13C NMR (CDCl3, ppm): 203.7, 138.5, 135.0, 132.7, 129.7, 76.7, 45.2, 28.3; Compound B (2.6% yield): 1H NMR (CDCl3, ppm): 7.93 (s, 2H), 7.82 (s, 2H), 7.43 (s, 2H), 4.60 (s, 4H), 4.12 (s, 2H), 3.82 (s, 2H), 1.59 (s, 12H); Compound C (3.1% yield): 1H NMR (CDCl3, ppm): 7.89 (dd, 2H), 7.86 (s, 2H), 7.42-7.40 (m, 4H), 4.10 (s, 2H), 4.05 (s, 2H), 1.60 (s, 12H); 13C NMR (CDCl3, ppm): 204.7, 140.8, 134.2, 133.4, 130.1, 128.7, 127.8, 76.5, 41.5, 28.4; Compound D (4.9% yield): 1H NMR (CDCl3, ppm): 10.06 (s, 1H), 8.54 (s, 1H), 8.31 (d, 1H, J=7.5 Hz), 8.06 (d, 1H, J=7.6 Hz), 7.62 (dd, 1H, J=7.5 Hz, J=7.6 Hz), 3.89 (s, 1H), 1.61 (s, 6H); 13C NMR (CDCl3, ppm): 203.4, 191.9, 136.0, 135.5, 135.3, 132.6, 131.5, 128.9, 77.0, 27.9.
