An efficient method for demethylation of aryl methyl ethers

doi:10.1016/j.tetlet.2008.04.070

Tetrahedron Letters

Volume 49, Issue 25, 16 June 2008, Pages 4054-4056

https://doi.org/10.1016/j.tetlet.2008.04.070 Get rights and content

Abstract

A new efficient method for demethylation of aryl methyl ethers using iodocyclohexane in DMF under reflux condition is described.

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Acknowledgments

We are grateful for financial support from National Science Foundation of China (0801031005), Chinese National Programs for High Technology Research and Development (0604071005 and 0704051005), the New Drug Basic Research Program of the Shanghai Institute of Materia Medica (07G603B005).

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The selective demethylation of aryl methyl ethers is a reaction of high relevance both in the context of deprotection in organic syntheses as well as in the modification of lignin and lignin-derived chemicals. The resulting vicinal diol or triol configurations originating from guaiacyl or synapyl lignin moieties are particularly relevant for adhesive properties, while other positions are applicable for condensation polymerization. Throughout the years, a plethora of methods have been developed to efficiently cleave the particularly stable aryl methyl bond. This review provides, on the one hand, a comprehensive overview of conventional approaches associated with the field of organic chemistry, with a focus on recently developed methods with a focus on aspects of green chemistry. On the other hand, acid- and base-catalyzed as well as (hydro)thermal methods are discussed as well as the occurrence of demethylation reactions under metal-catalyzed hydrotreatment conditions, which, however, proved to be the most environmentally friendly principle. While the different chemical approaches are first presented for the conversion of selected model compounds, a subsequent section presents the application of these methods to lignin. The selective cleavage of aryl methyl ether moieties of lignin to increase the amount of phenolic hydroxyl groups has recently gained considerable attention, and research can benefit from the emerging knowledge gained from the new approaches on model compound demethylation. In sum, we provide a multi-faceted and critical overview of demethylation strategies to obtain phenol and catechol moieties from the renewable lignin and related compounds.
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Lignin, as a natural antioxidant, shows great potential in food engineering and medicine. However, the inherent macromolecular structure, high polydispersity, and few phenolic hydroxy seriously limit its antioxidant activity. In this work, a mild iodocyclohexane demethylation for highly improving the antioxidant activity of lignin was proposed. The results showed –OCH₃ content exhibited an almost linear decrease as a function of treating time, and the demethylation and cleavage of β–aryl ether bonds prompt an obvious increase in phenolic hydroxyl content (4.01 mmol/g) and a significant decline in aliphatic hydroxyl (∼0.03 mmol/g). Meanwhile, attributing to the fragmentation of β–O–4, β–β, and β–5 substructures, the polydispersity of lignin molecular weight decreases from 2.7 to 2.2. As a result, the formed catechol-typed lignin showed an outstanding antioxidant activity, with the radical (DPPH·) scavenging index (inverse of concentration for 50% of maximal effect (EC₅₀) value) over 2 000 mL/mg, much superior to the commercial antioxidants (< 500 mL/mg). Further structure-activity relationship analysis implied that the Ph–OH/–OCH₃ ratio might act as a key factor influencing the antioxidant activity of lignin. This mild demethylation demonstrates a facile and effective method for highly enhancing the antioxidant activity of lignin and makes the catechol-typed lignin a green and promising product for practical use in food, medicine, and pharmacy.
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Ultra-pure water (18.2 MΩ-cm) from water purification system (ELGA, Lane End, UK) were used to prepare all buffers including sodium bicarbonate buffer (pH 8.5, 50 mM) and phosphate buffer (pH 7.4, 0.01 M). According to previous studies, with some modification, the methyl ester and aromatic ether of mitragynine were modified and conjugated to protein (Limsuwanchote et al., 2014; Zuo et al., 2008). The immunogen was prepared separately for the mitragynine conjugates to cBSA (i.e., MG-22-cBSA and MG-9-cBSA) and the plate coating was prepared separately for the mitragynine conjugates to OVA (i.e, MG-22-OVA and MG-9-OVA).
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An efficient method for demethylation of aryl methyl ethers

Abstract

Graphical abstract

Section snippets

Acknowledgments

J. Org. Chem.

J. Org. Chem.

Tetrahedron Lett.

J. Org. Chem.

J. Org. Chem.

Org. Lett.