Organic chemistry: Methanol and its metabolites

Methanol poisoning is a medical emergency. Methanol is converted to formic acid via formaldehyde, with formic acid being the toxic metabolite that causes damage to the optic nerves leading to permanent blindness.

Oral ingestion of methanol-containing mixtures require immediate medical attention. Once ingested, peak serum levels occur within 30-90 minutes. Methanol is metabolized in the liver in sequential steps to formaldehyde first by hepatic alcohol dehydrogenase, then to formic acid by formaldehyde dehydrogenase and then finally detoxified as carbon dioxide. The slow conversion of formic acid to carbon dioxide forms the basis of methanol toxicity.

In the laboratory, methanol can be converted to formic acid via a series of chemical transformations. The chemical process is summarized in the schematic presented in Figure 1. A student proposes to replicate this chemical pathway and performs two trials but obtains varied results.

Trial 1: At the beginning of the experiment, the student mistakenly uses isopropyl alcohol ((CH3)2CHOH) instead of methanol. He succeeds in converting isopropyl alcohol to an unknown substance using pyridinum cholochromate (PCC, C5H6NCrO3Cl) in dichloromethane (CH2Cl2) solvent (this is the same procedure for formaldehyde formation from methanol). However, this unknown substance demonstrates different properties than what he expects from formaldehyde.

Trial 2: The student follows the same protocol with PCC and dichloromethane (as in Trial 1), but with the proper starting reagent of methanol and successfully forms formaldehyde. He proceeds to add Tollen's reagent (Ag2O dissolved in aqueous NH3) to the formaldehyde, successfully yielding formic acid.

Citation: International Programme on Chemical Safety. (2002, May). Methanol. Retrieved from: http://www.inchem.org/documents/pims/chemical/pim335.htm.