Preparation background and overview of 4-hydroxymethylbenzeneboronic acid
4-Hydroxymethylphenylboronic acid is a type of substituted phenylboronic acid with superior performance. This kind of phenylboronic acid shows a more superior binding ability to sugar substances in neutral aqueous solution. 4-Hydroxymethylphenylboronic acid ligand has a very low acid dissociation constant (pKa) and strong binding ability to cis-dihydroxy compounds, and can specifically enrich cis-dihydroxy compounds under neutral and acidic conditions. Compounds such as nucleosides and glycoproteins. In addition, 4-hydroxymethylphenylboronic acid has a high retention capacity and is suitable for high-throughput analysis of various complex biological samples, which effectively solves the problems currently faced by boron affinity materials.
Preparation and application of 4-hydroxymethylbenzeneboronic acid
Due to the strong binding ability and excellent water solubility of 4-hydroxymethylphenylboronic acid, this type of substituted phenylboronic acid has even better ability to bind carbohydrates in aqueous solution than Wulff type phenylboronic acid. 4-Hydroxymethylphenylboronic acid has shown superior performance to other types of substituted boronic acids in the recognition of carbohydrates under neutral conditions and is widely used as an affinity ligand to recognize glycoproteins, such as TF‑antibodies and HI viruses. gp‑120 in . In addition, 4-hydroxymethylphenylboronic acid is also widely used as an enzyme inhibitor, such as an antivertebral agent. The boric acid of 4-hydroxymethylphenylboronic acid may be a good solution to the problems mentioned above regarding boron affinity materials.
Preparation of 4-hydroxymethylbenzeneboronic acid
The first step is the synthesis of 4-hydroxymethylphenylboronic acid pinacol ester
Place 10.02g of methyl 4-bromomethylbenzoate, 13.00g of pinacol diboron, 1.28g of potassium acetate, [1,1′-bis(diphenylphosphine)ferrocene]palladium dichloride Put 0.095 g into a 100 ml three-necked flask, vacuum it and fill it with nitrogen. Add 30 ml of dioxane in a nitrogen atmosphere and react at 100°C for 12 hours. After cooling to room temperature, basic magnesium carbonate was added, 50 ml of ethyl acetate and 50 ml of water were added, the organic layer was separated, washed twice with water and once with brine, and dried over anhydrous magnesium sulfate. After filtration, the solvent was concentrated to remove, and the residue was separated by column chromatography. The eluent was (EtOAc:Hexane=1:50, v/v). The white solid obtained was 4-hydroxymethylphenylboronic acid pinacol ester. Yield 92%.
The second step of synthesis of 4-hydroxymethylbenzeneboronic acid
Weigh 1.12 g of the product obtained in the first step and dissolve it in 30 ml of carbon tetrachloride, then add 0.81 g of N-bromosuccinimide and 0.036 g of azobisisobutyronitrile, and heat to reflux for 4 hours. , after cooling to room temperature, the reaction solution was washed twice with water, once with brine, and dried over anhydrous magnesium sulfate. After filtration, the solvent was removed under reduced pressure, and the obtained crude product was dissolved in 50 ml of diethyl ether. The diethyl ether phase was extracted three times with 15% potassium hydroxide, and the obtained aqueous phases were combined. In an ice bath, use hydrochloric acid to adjust the pH of the water phase to 1 under magnetic stirring. A white precipitate will precipitate. Collect the white solid obtained, wash it with an appropriate amount of chloroform, and dry it under vacuum to obtain a white solid, which is 4-hydroxymethylbenzene. Boric acid 0.45 g, yield 62%.