5-Chloromethyl-2-hydroxybenzaldehyde (2a):
This compound was synthesized from salicylaldehyde according to the classical chloromethylation procedure modified with catalyst ZnCl2, and hydrogen chloride gas atmosphere. In a typical synthesis, (17.5 g, 160 mmol) of salicylaldehyde was treated with 24 ml of 37% aqueous formaldehyde and (1.2 g, 8.8 mmol) of ZnCl2 in 100 ml of concentrated hydrochloric acid. The mixture was stirred at room temperature under HC1g atmosphere (HC1g was generated in another system, connected to the reaction vessel, by dropping concentrated H2SO4 slowly on to solid NaCl) for 24 h. The white solid that separated from the reaction mixture was filtered, re-dissolved in diethyl ether, and the combined organic phases were washed several times with milli-Q water, till pH = 7 for washing liquor, and then dried over sodium sulfate. Volatiles were distilled off, under inert atmosphere, and the resulting white crude residue was filtered and further recrystallized from n-hexane to furnish 5-chloromethyl-2-hydroxybenzaldehyde as white-colored needles (15.2 g, 62.0 % yield). FT-IR (ATR, cm-1): 3240 (m, br, ν OH), 3120 (m, br, νasym CH, Ph), 3050 (m, br, νsym CH, Ph), 2876 (m, sh, ν CH2), 1659 (vs, sh, ν C=O), 1578, 1489, 1437 (s, sh, ν C=Carom + ν C-H bend), 1338 (m, sh, ν CH2), 1252 (s, sh, ν CH2Cl), 1150 (s, sh, ν HCC, Ph), 772 (s, sh, ν C–Cl). 1H NMR (200 MHz, CDCl3) δ (ppm): 11.07 (s, 1H, Ph-OH) 9.90 (s, 1H, Ph-HC=O), 7.59-7.55 (m, 2H, 2 x Ph-H), 7.02–6.98 (d, 1H, JHH = 8.34 Hz, Ph-H), 4.60 (s, 2H, CH2-Ph). 13C NMR (500 MHz, CDCl3) δ (ppm): 196.02 (HC=O), 160.90 (C-OH), 137.22 (C, Ph), 133.64 (CH, Ph), 129.86 (CH, Ph), 120.34 (C, Ph), 118.72 (CH, Ph), 45.28 CH2-phen