Structural Identification of Products from the Chloromethylation of Salicylaldehyde

Abstract

In the functionalization of salicylaldehyde to give 5-(chloromethyl)salicylaldehyde, two byproducts [5-(hydroxymethyl)salicylaldehyde and 5,5′-methylenebis(salicylaldehyde)] were also isolated. ­Detailed characterizations and structural analyses of all three products by single-crystal X-ray diffraction, multinuclear NMR spectroscopy, high-resolution mass spectrometry, and IR spectroscopic techniques are presented and discussed. A strategy is presented for the preferential isolation of the two byproducts through column chromatography.

Key words

salicylaldehyde - chloromethylation - chloromethylsalicyl­aldehyde - crystal structure - hydroxymethylsalicylaldehyde - methylene­bissalicylaldehyde

• References and Notes

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• 19 5-(Chloromethyl)salicylaldehyde [2; 5-(Chloromethyl)-2-hydroxybenzaldehyde] Salicylaldehyde (15 g, 0.1228 mol) and 30% aq formaldehyde (5 mL) were added to a stirred solution of concd HCl (100 mL) at 0 °C in an ice bath, and the mixture was allowed to warm to r.t. After 24 h, the mixture was again cooled to 0 °C, and the solid that precipitated out was washed with 5% aq NaHCO₃ (30 mL), collected by filtration, and dried in air. The resulting mixture (12 g) was dissolved in Et₂O (50 mL), and 2 was recovered by evaporation of the solvent from an open beaker in a fume hood. Further purification was achieved by washing with hexane and crystallization from Et₂O to give a white powder; yield: 10.8 g (0.0619 mol, 50%); mp 84–86 °C (lit.¹⁸ 85–86 °C). IR (ATR, air): 1649, 1581, 1476, 1283 cm^–1. ¹H NMR (400 MHz, DMSO-d ₆): δ = 4.75 (s, 2 H), 7.01 (d, J = 8.66 Hz, 1 H), 7.58 (dd, J = 8.51/2.30 Hz, 1 H), 7.72 (d, J = 2.29 Hz, 1 H), 10.26 (s, 1 H), 10.90 (s, 1 H). ¹³C NMR (100 MHz, DMSO-d ₆): δ = 45.71, 117.75, 122.17, 128.80, 129.12, 136.95, 160.73, 190.72. Anal. Calcd for ­C₈H₇ClO₂·⅛H₂O: C, 55.59; H, 4.23; Found: C, 55.29; H, 3.9.
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• 23 CCDC 1862047, 1862048, and 1862049 contain the supplementary crystallographic data for compounds 2–4, respectively. The data can be obtained free of charge from The Cambridge Crystallographic Data Centre via www.ccdc.cam.ac.uk/getstructures. Tables of selected data collection and refinement information, bond lengths and angles, and hydrogen-bonding interactions are also available in the Supporting Information.
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