Question

What information about the progress of the synthesis of acetaminophen could be inferred from the TLC?

Answer 1

Acetaminophen can be synthesized via traditional one or two­step syntheses but three step syntheses are not as common. To begin the synthesis, an electrophilic aromatic substitution on phenol with nitric acid was completed to create p­nitrophenol. P­Nitrophenol was then hydrogenated using an iron catalyst to produce p­aminophenol. Benzene, the solvent in this reaction, is typically discarded, although in this synthesis it was kept as a recyclable solvent, thus maximizing our atom economy. Benzene was separated and characterized by Nuclear Magnetic Resonance (NMR) and Infrared Spectroscopy (IR) to be pure and reusable. P­aminophenol was selectively acetylated using acetic anhydride and the reaction was completed within 10 minutes compared to other protocol using chloroform as the acylated reagent which would have taken 15 hours.

experiment :

Acetonitrile was added to phenol (0.401g, 4.27mmol) until it completely dissolved. Nitric acid (0.269g, 4.27mmol) was then added to the solution. A solution of cetrimonium bromide (0.389g, 1.067mmol) was added and the reaction mixture was stirred at room temperature for two hours. A color change and thin layer chromatography (TLC) analysis indicated that the reaction had reached completion. The acetonitrile was evaporated by being rotovapped. The product was diluted with dichloromethane and washed with water (3 x 5 ml). The organic layer was dried over anhydrous sodium sulfate, and dichloromethane was removed. Silica­gel chromatography with ethyl acetate:hexane (3:7) was used to purify and collect the crude product, p­nitrophenol. The solution was then rotovapped and allowed to sit overnight for orange crystals to form. The final yielded 50.1mg of major product with a percent yield of 35.7%. IR: 3342 cm-­1 (O­H stretch), 3119­2921 cm-­1 (C­H aromatic stretch), 2851 cm-­1 (C­Hstretch), 1589­1331 cm-­1(N­O nitro stretch).