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.

Salicylaldehydes Derived from 5-Chloromethyl-2-hydroxybenzaldehyde – Synthesis and Reactions

“…Chloromethylation of salicylaldehyde has been first reported more than 120 years ago, 28 but a practical synthesis for 5-(chloromethyl)salicylaldehyde has been described only approximately fifty years later. 29 Despite being widely used, the Blanc reaction of salicylaldehyde is known to have a series of shortcomings such as poor reproducibility or broad range of reported yields, which could stem from the co-existence in the final reaction mixture of the target product, of the intermediate carbinol and various side products which could potentially convert into one another under the employed reaction condition, 25 and even from the presence of 3-chloromethylsalicylaldehyde as a by-product of chloromethylation. 30 From an experimental point of view, chloromethylation of salicylaldehyde has been usually performed with formalin, in concentrated aqueous HCl as reaction medium, at room temperature, with reaction times extending up to 48 h. Occasionally, the use of zinc chloride 31 or sulfuric acid 32 as catalysts has been reported.…”

Synthesis and Structure of an Aqueous Stable Europium-Based Metal–Organic Framework with Ratiometric Fluorescence Sensing for Phosphate and Luminescence Quenching for Salicylaldehyde

“…Salicylaldehyde is an extremely versatile fine chemical product, which is widely used in the synthesis of pesticides, medicines, fragrances, chelating agents, dye intermediates, etc. 22 Salicylaldehyde is also used in the electroplating industry as a brightener and leveling agent, and low concentrations of salicylaldehyde are often used as a preservative in flavors and fragrances because of its potent ability to reduce bacterial activity. However, it is volatile, is unsafety to the human body, and pollutes air and water bodies, and thus, it is very important to be quickly detected.…”