Synthesis methods of 3'-hydroxyacetophenone

General Description

3’-Hydroxyacetophenone is a chemical compound (figure 1) and it is a component of castoreum, the exudate from the castor sacs of the mature beaver [1]. It is used in the synthesis and preparation of chalcones and flavonoids as anti-tuberculosis agents, as well as antileishmanial chaocones [2]

Figure 1 The appearance of 3’-Hydroxyacetophenone

Synthetic Methods

There are a lot of synthesis routes for 3'-Hydroxyacetophenone preparation. Such as 3'-Methoxyacetophenone prepared 3'-Hydroxyacetophenone by microwave-assisted demethylation of methyl aryl ethers using an ionic liquid with ~94% yield [3].  The direct and selective synthesis of phenols from aryl/heteroaryl halides and KOH has been achieved through the use of highly active monophosphine-based catalysts derived from Pd2dba3 and ligands L1 or L2 and the biphasic solvent system 1, 4-dioxane/H₂O, so m-Bromoacetophenone prepared 3'-Hydroxyacetophenone also with ~98% yield [4].  

Yingwei Zhang and coworkers [5] developed a synthesis method, which includes the steps (scheme 1) that 3-hydroxybenzoic acid is subjected to hydroxyl protection through an esterification or etherification reaction, then a chloroformylation reaction and an alkylation reaction are conducted, finally hydrolysis is conducted, and the 3-hydroxyacetophenone is obtained. According to the method, raw materials are cheap, easy to obtain and wide in source, high-temperature and high-pressure operation does not exist, equipment requirement is low, and equipment investment is low; peroxide, heavy nitride and the like do not exist, and high safety is achieved; compared with a nitration-iron powder reduction-diazotization route commonly adopted in the nation, the synthesis method has huge environment-friendly advantages. Besides, according to the method, the amount of wastewater is less than 5% that of an original process, the total route yield is 90% [5].

Scheme 1 Synthesis method of 3'-Hydroxyacetophenone

Xinhua Shao developed another preparation technology of high purity 3-hydroxyacetophenone comprises the following steps of: adding 38 weight portions of 3-nitroacetophenone and 37 weight portions of water into a reaction vessel, adding an iron powder to react for 10 hours, adding methanol with stirring, centrifuging a precipitate for removing water to obtain 3-aminoacephenone, pouring the 3-aminoacephenone into a diazonium kettle; adding sulfuric acid, slowly adding a sodium nitrite aqueous solution into the diazonium kettle to produce 3-diazo sulfate acetophenone, adding 3-diazo sulfate acetophenone into a hydrolysis kettle, and finally drying to obtain the pure product 3-hydroxyacetophenone. The method has advantages of simple technology, high yield of the product and high purity. By reasonable design of the reaction steps and adjustment of a charging order, the application amount of strong acid is greatly reduced; in addition, by the addition of a certain amount of methanol in the reaction, the process of the reaction can be accelerated, and the synthesis quality can be raised. According to statistics, the overall yield of the technology can reach over 92%; compared with other production technologies, the technology enables the product cost to decrease by more than 40% and is environmentally friendly [6].

References

[1] https://en.wikipedia.org/wiki/3-Hydroxyacetophenone

[2] www.chemicalbook.com › ChemicalProductProperty_EN_CB1407158

[3] J Park, J Chae, Microwave-assisted demethylation of methyl aryl ethers using an ionic liquid, Synlett, 2010, # 11 p. 1651 – 1656

[4] KW Anderson et. al., The selective reaction of aryl halides with KOH: synthesis of phenols, aromatic ethers, and benzofurans, Journal of the American Chemical Society, 2006, vol. 128, # 33 p. 10694 – 10695

[5] Ying-wei Zhang et. al., 3-hydroxyacetophenone synthesis method, CN105967986A

[6] Xinhua Shao, Preparation technology of high purity 3-hydroxyacetophenone, CN102249884B