JP-2026076114-A - Method for producing hydroxybenzoic acid crystals

Abstract

[Problem] To provide a method for producing hydroxybenzoic acid crystals with suppressed discoloration. [Solution] A method for producing hydroxybenzoic acid crystals, comprising the steps of: adjusting the pH of an aqueous solution containing hydroxybenzoic acid derived from a microbial culture medium to 1.0 to 6.5; contacting the aqueous solution with an adsorbent; and crystallizing the hydroxybenzoic acid under conditions of pH 3.0 to 6.5. [Selection Diagram] None

Inventors

• 望月 佳
• 野場 将宏
• 入江 裕

Assignees

• 花王株式会社

Dates

Publication Date

20260511

Application Date

20251001

Priority Date

20241023

Claims (5)

1. A method for producing hydroxybenzoic acid crystals, comprising the steps of: adjusting the pH of an aqueous solution containing hydroxybenzoic acid derived from a microbial culture medium to 1.0 to 6.5; contacting the aqueous solution with an adsorbent; and crystallizing the hydroxybenzoic acid under conditions of pH 3.0 to 6.5.
2. A method for producing hydroxybenzoic acid crystals according to claim 1, comprising crystallizing an aqueous solution containing hydroxybenzoic acid by cooling it at a temperature of 1°C/min or less.
3. A method for producing hydroxybenzoic acid crystals according to claim 1 or 2, wherein the amount of adsorbent used is 0.1 to 10% by mass relative to the aqueous solution containing hydroxybenzoic acid.
4. A method for producing hydroxybenzoic acid crystals according to claim 1 or 2, wherein the content of hydroxybenzoic acid in the aqueous solution containing hydroxybenzoic acid before crystallization is less than 15% by mass.
5. A method for producing hydroxybenzoic acid crystals according to claim 1 or 2, wherein the adsorbent is activated carbon.

Description

This invention relates to a method for producing hydroxybenzoic acid crystals. Hydroxybenzoic acid is a type of aromatic hydroxycarboxylic acid, a compound in which one hydroxyl group and one carboxyl group are bonded to a benzene ring. Hydroxybenzoic acid has three isomers, differing in the relative positions of the hydroxyl and carboxyl groups. Hydroxybenzoic acid is used as a food preservative, additive, and raw material for pharmaceuticals. Hydroxybenzoic acid has been industrially produced for many years by an organic chemical synthesis method known as the Kolbe-Schmidt reaction. However, due to environmental concerns and safety issues, recent developments have focused on developing hydroxybenzoic acid production processes using fermentation methods with microorganisms. For example, Patent Document 1 reports that a culture medium containing hydroxybenzoic acid was obtained through a bioprocess using plant-derived sugars and microorganisms, followed by concentration of the culture medium, and then recovery of hydroxybenzoic acid crystals from the concentrate by crystallization. International Publication No. 2020/196424 [Method for producing hydroxybenzoic acid crystals] The present invention provides a method for producing hydroxybenzoic acid crystals, comprising the steps of: adjusting the pH of an aqueous solution containing hydroxybenzoic acid derived from a microbial culture medium to 1.0 to 6.5; contacting the aqueous solution with an adsorbent; and crystallizing the hydroxybenzoic acid under conditions of pH 3.0 to 6.5. The present invention provides hydroxybenzoic acid crystals with suppressed discoloration. The reason why the discoloration of the hydroxybenzoic acid crystals is suppressed by the present invention is not clear, but it is presumed that one of the factors is improved separation between the crystallization mother liquor and the crystals during filtration after crystallization, as higher pH yields crystals with larger particle sizes and fewer defects. (Hydroxybenzoic acid) Hydroxybenzoic acid exists in three isomers: o-, m-, and p-. These can be denoted as 2-hydroxybenzoic acid, 3-hydroxybenzoic acid, and 4-hydroxybenzoic acid, respectively. In this invention, hydroxybenzoic acid may be any of these isomers, or a mixture of any two or three of the isomers. This invention is more preferably used for the crystallization of p-4-hydroxybenzoic acid. In the present invention, the aqueous solution containing hydroxybenzoic acid is an aqueous solution derived from a microbial culture medium. Fermentation production methods for hydroxybenzoic acid using microorganisms are well known and can be achieved by combining known biosynthesis techniques from carbon sources such as glucose, and the starting materials may be other than sugars. For example, International Publication No. 2012/081084 describes a method for producing salicylic acid (2-hydroxybenzoic acid) from phthalic acid, Japanese Patent Publication No. Hei 7-184671 describes a method for producing 3-hydroxybenzoic acid from isophthalic acid, and Japanese Patent Publication No. 2004-215586 describes a method for producing 4-hydroxybenzoic acid from toluene or benzoic acid. The microorganism may be a wild-type strain, a mutant strain, or a mutant strain in which mutations such as insertion, substitution, or deletion of the base sequence have occurred through various genetic manipulations. It may also be a microorganism to which the ability to produce hydroxybenzoic acid has been conferred by known artificial modifications. For example, microorganisms capable of producing hydroxybenzoic acid include the genera Escherichia, Rhodococcus, Acinetobacter, Bradyrhizobium, Corynebacterium, Pseudomonas, Rhodopseudomonas, Sinorhizobium, and Brevibacterium. Examples of microorganisms include those belonging to the genera *m*, *Novosphingobium*, *Ralstonia*, *Nocardioidaceae*, *Microbacterium*, *Streptomyces*, *Amycolatopsis*, *Kineococcus*, *Pantoea*, *Klebsiella*, and *Arthrobacter*. The culture medium used for culturing microorganisms capable of producing hydroxybenzoic acid preferably contains, as culture materials, a carbon source, an inorganic nitrogen source, or an organic nitrogen source, as well as other necessary organic trace nutrients that the microorganisms can utilize. Examples of carbon sources include sugars (glucose, sucrose, maltose, etc.), organic acids, dextran, soluble starch, methanol, and the like. Examples of inorganic or organic nitrogen sources include ammonium salts, nitrates, various amino acids, corn steep liquor, tryptone, peptone, casein, yeast extract, meat extract, soybean meal, potato extract, and the like. It may also contain inorganic salts (such as sodium chloride, calcium chloride, sodium dihydrogen phosphate, potassium dihydrogen phosphate, dipotassium hydrogen phosphate, magnesium chloride, magnesium sulfate, and manganese sulfate), vitamins, and antibiotics (such as tetracycline, neomycin, kanamycin, spectino