Preparation background and overview of 2-naphthaleneboronic acid
2-Naphthaleneboronic acid is an important intermediate in organic boronic acids. There are three main synthesis routes for 2-naphthylboronic acid, namely Grignard reagent method, organolithium method, and dinaphthylmercury method. Since the price of 2-bromonaphthalene is relatively low, it is more suitable to use the Format reagent method.
The Grignard reagent method is to react 2-bromonaphthalene with magnesium in tetrahydrofuran solvent to form a Grignard reagent at the reflux temperature, then cool it to a low temperature of -78°C, add the borate ester dropwise, and slowly increase the temperature after the addition. After reaching room temperature and hydrolyzing with hydrochloric acid, 2-naphthaleneboronic acid was obtained with a yield of 77%. Another commonly used method is the organolithium synthesis method. 2-Bronaphthalene is first reacted with organolithium and then with borate ester using tetrahydrofuran as the solvent at low temperature -78°C. After hydrolysis, 2-naphthaleneboronic acid is obtained. Organolithium is n-butyllithium or isobutyllithium, and borate esters include trimethylborate and lithium propyl triisometaborate. The synthesis method of 2-naphthylboronic acid is to use 2-bromonaphthalene as raw material, synthesize naphthyl Grignard reagent through Grignard reagent method, and then react with borate ester to generate 2-naphthaleneboronic acid.
2-Naphthylboronic acid
Preparation of 2-naphthaleneboronic acid
Preparation method 1 of 2-naphthaleneboronic acid:
Tetrahydrofuran can be used if the water content is below 100ppm. In a 50L glass kettle, add 415g of magnesium chips, replace the nitrogen, measure the oxygen content to be less than 200ppm, and introduce low-flow argon gas. A solution of 150g 2-bromonaphthalene, 2000mL tetrahydrofuran and 20g iodine was added to the kettle to initiate. After successful initiation, adjust the water bath temperature to keep the reaction temperature at (55±5)°C. Pump in a solution of 3.3kg 2-bromonaphthalene (total 2-bromonaphthalene 3.45kg, 16.66mol) and 26000mL tetrahydrofuran (total 28000mLTHF), and complete the addition in about 3 hours. After the addition is completed, keep the reaction temperature at 60°C, take a sample for 3 hours, add a small amount of water, and take the upper organic phase for analysis to prove that 2-bromonaphthalene is completely reacted, then cool to 20-30°C. After the 100L glass kettle is cooled to -40°C, transfer the Grignard reagent from the bottom of the 50L glass kettle to the 100L glass kettle. After the transfer is completed, it is protected by argon gas and cooled to -30°C. Add 2450 mL of trimethyl borate (21.57 mol) dropwise into the three-necked flask through a constant pressure dropping funnel, keeping the temperature at (-25°C plus ultrafine calcium carbonate 2)°C. Complete the drops in about 3 hours, and keep the reaction for 3 hours. Naturally raise the temperature to 20°C, slowly add 11L 8% cold hydrochloric acid, and stir for 1 hour. Let stand and separate the organic layer. Extract the aqueous layer with ethyl acetate (3×5000mL) and combine the organic phases. The solvent was evaporated from the organic phase under reduced pressure and then refined to obtain 2.075kg of white powder 2-naphthylboronic acid. The purity is 99.1% and the yield is 72.4%.
Preparation method two of 2-naphthaleneboronic acid:
Grids were prepared by slowly adding dropwise 2-bromonaphthalene (0.05m) in sodium-dried diethyl ether (50ml) to magnesium chips (0.05m) in sodium-dried diethyl ether (50ml). Riyadh reagent. The reaction can be accelerated by adding a few iodine crystals.
Cool trimethylborate (0.05m) or tri-n-butylborate (0.05m) in sodium-dried diethyl ether to -70°C and maintain the borate solution at -70°C And add Grignard reagent dropwise within 2 hours with continuous stirring.
The reaction mixture was warmed to room temperature overnight and then hydrolyzed by dropwise addition of cold dilute sulfuric acid (10%, 50 ml). The diethyl ether layer was separated and the aqueous layer was extracted with diethyl ether. The diethyl ether containing fractions were combined and the solvent was removed. The residue is made distinctly basic and any methanol and butanol so formed are removed. The alkaline solution is acidified and cooled and the resulting 2-naphthaleneboronic acid crystals are removed by filtration. The combined boric acid crystals were recrystallized from distilled water.
