Overview of the preparation method of 2-thiopheneboronic acid
As an important reaction intermediate, 2-thiopheneboronic acid is widely used in the fields of medicine, chemical industry, and materials. Expanding the synthesis of new thiopheneboronic acids has great practical significance in the synthesis and screening of drugs and organic materials. In addition, thiophene boronic acid derivatives also have high added value. Studying the efficient preparation and synthesis of thiophene boronic acid has great practical significance, both from the potential development significance and from the perspective of generation.
Preparation method of 2-thiopheneboronic acid Preparation method
⑴ Mix 3-thiophenecarbaldehyde, p-toluenesulfonic acid monohydrate, ethylene glycol, and toluene, reflux and dehydrate, then cool to room temperature, and then extract once with 0.5 to 2.0 times its volume of saturated sodium bicarbonate aqueous solution. , respectively obtain organic phase A and aqueous phase; the aqueous phase is extracted twice with an equal volume of ethyl acetate to obtain organic phase B; after the organic phase A and the organic phase B are combined, 5% by mass of the After drying with 15% anhydrous sodium sulfate, filtering to remove the desiccant, and spinning to dryness, a crude product of 2-(3-thienyl)-1,3-dioxolane is obtained; the 2-(3-thienyl)-1,3-dioxolane crude product is obtained; )-1,3-dioxolane crude product is eluted with a petroleum ether-dichloromethane mixture of 1000 to 3000 times its mass to obtain 2-(3-thienyl)-1,3-dioxolane; The molar ratio of the 3-thiophenecarbaldehyde to the p-toluenesulfonic acid monohydrate is 95:1~105:1; the molar ratio of the 3-thiophenecarboxaldehyde to the ethylene glycol is 1:6~1: 8; The ratio of the 3-thiophenecarboxaldehyde to the toluene is 1mol:1.0 L~1mol:10 L;
(2) After the 2-(3-thienyl)-1,3-dioxolane is replaced with nitrogen three times, anhydrous tetrahydrofuran is injected, the temperature is cooled to -70℃~-50℃, and the temperature is maintained at -65℃~ Add n-butyl lithium dropwise within 10 minutes at -50°C; keep the temperature for 10 to 30 minutes after completion, then add pinacol isopropoxy borate dropwise for reaction, and naturally warm to room temperature after 30 minutes, then add aqueous ammonium chloride solution A quenching reaction is performed to obtain a crude 2-thiopheneboronic acid product. The crude 2-thiopheneboronic acid product is extracted three times with an equal volume of ethyl acetate, and the organic phase C is combined; the organic phase C is treated with 5% to 15% of its mass anhydrous solution. Dry the sodium sulfate and spin it to dryness. Add dichloromethane to completely dissolve it, and add petroleum ether until no solid is precipitated. Finally, when the dichloromethane and remaining petroleum ether are evaporated at 25~35°C, the 2-thiophene boric acid solid begins to precipitate. The single-mouth bottle after rotary evaporation was frozen at -5°C for 5 hours and then filtered with suction to obtain white solid 2-thiopheneboronic acid; the 2-(3-thienyl)-1,3-dioxolane and the anhydrous The ratio of tetrahydrofuran is 1mol:0.5L~1mol:2.5L; the molar ratio of n-butyllithium and the 2-(3-thienyl)-1,3-dioxolane is 1:1~ 1.5:1; the molar ratio of the isopropoxyboronic acid pinacol ester and the 2-(3-thienyl)-1,3-dioxolane is 1:1~1:1.125.
Preparation method of 2-thiopheneboronic acid:
Hydroxymethylbenzeneboronic acid
The reflux dehydration reaction conditions in step (1) refer to a temperature of 100~140°C and a time of 6~10 h.
The spin-drying conditions in step ⑴ and step ⑵ both refer to a temperature of 35~45°C.
The step (1) 3-(pyrrolidin-2-yl)pyridine petroleum ether-dichloromethane mixture refers to a solution obtained by mixing petroleum ether and dichloromethane in a volume ratio of 2:1 to 5:1 .
Reference materials
[1]Fu Zhenfang. Biginelli reaction catalyzed by 2-thiopheneboronic acid and synthesis of cyanidefen[D]. Zhejiang University of Technology, 2012.
[2] Song Jinran. Research on the synthesis and HPLC detection method of 2-thiopheneboronic acid and 1-naphthaleneboronic acid [D]. 2012.
