Production of Biomass‐Derived p‐Hydroxybenzamide: Synthesis of p‐Aminophenol and Paracetamol

• Published in: ChemSusChem 2024-04, Vol.17 (8), p.e202400234-n/a
• Main Authors: Karlen, Steven D., Timokhin, Vitaliy I., Sener, Canan, Mobley, Justin K., Runge, Troy, Ralph, John
• Format: Article
• Language: English
• Subjects: Acetaminophen - chemical synthesis; Acetaminophen - chemistry; amination; Aminophenol; Aminophenols - chemistry; Analgesics; Aniline; Benzamides - chemical synthesis; Benzamides - chemistry; Biomass; Bioplastics; Chemistry Techniques, Synthetic; Esters; green chemistry; Hofmann rearrangement; INORGANIC, ORGANIC, PHYSICAL, AND ANALYTICAL CHEMISTRY; Liquid-liquid extraction; Parabens - chemistry; Raw materials; rearrangement; Renewable energy sources; Renewable resources
• ISSN: 1864-5631; 1864-564X
• DOI: 10.1002/cssc.202400234

As we work to transition the modern society that is based on non‐renewable chemical feedstocks to a post‐modern society built around renewable sources of energy, fuels, and chemicals, there is a need to identify the renewable resources and processes for converting them to platform chemicals. Herein, we explore a strategy for utilizing the p‐hydroxybenzoate in biomass feedstocks (e. g., poplar and palm trees) and converting it into a portfolio of commodity chemicals. The targeted bio‐derived product in the first processing stage is p‐hydroxybenzamide produced from p‐hydroxybenzoate esters found in the plant. In the second stage a continuous reaction process converts the p‐hydroxybenzamide to p‐aminophenol via the Hofmann rearrangement and recovers the unreacted p‐hydroxybenzamide. In the third stage the p‐aminophenol can be acetylated to form paracetamol, which is readily isolated by liquid/liquid extraction at >95 % purity and an overall p‐hydroxybenzamide‐to‐paracetamol process yield of ~90 %. We explore how utilization of protecting groups alters the challenges in this process and expands the portfolio of possible products to include p‐(methoxymethoxy)aniline and N‐acetyl‐p‐(methoxymethoxy)aniline. These target compounds could become value‐added renewably‐sourced platform chemicals that could be used to produce biodegradable plastics, pigments, and pharmaceuticals. Paracetamol can be produced from p‐hydroxybenzamide at >95 % purity in 90 % yield. Aqueous ammonia treatment of poplar or oil palm empty fruit bunches forms p‐hydroxybenzamide. Under continuous processing conditions, a Hofmann rearrangement converts p‐hydroxybenz‐amide to p‐aminophenol, then liquid/liquid extraction combined with acid/base chemistry and acetylation purifies, forms, and isolates paracetamol.