Application of 4-tolueneboric acid_Kain Industrial Additive

Background and Overview

4-Tolueneboronic acid is a carboxylic acid derivative that can be used in suzuki reactions.

Preparation^[4]

Add treated Mg strips (2.15g, 90mmol), 2 grains of iodine into a 250ml double-necked flask, protect with nitrogen, and evacuate 3 times. Slowly add the anhydrous THF solution of the compound p-toluobenzene (compound 1, 60mmol) with a syringe under heating conditions. After the reaction is initiated, it is in a reflux state. Continue to add the remaining solution. After the addition, the reflux reaction is completed for 5 hours to obtain the solution of p-bromotoluene. Grignard reagent (compound 2), after cooling to room temperature, transfer the reaction device to a low-temperature reactor, adjust the temperature to -20°C, and add anhydrous THF solution of trimethyl borate (9.36g, 90mmol) with a syringe after 5 minutes. , after the addition, react at room temperature for 3 hours, then add 100 ml of 2 mol/L HCl solution for hydrolysis reaction, and detect the reaction with TLC. After the reaction is complete, THF is removed under reduced pressure, the aqueous phase is extracted three times with ethyl acetate, the extracted organic phases are combined, the organic phase is washed with water and saturated brine until neutral, then dried over anhydrous sodium sulfate, suction filtered, and the filtrate is reduced to The solvent was removed by pressure and recrystallized from absolute ethanol to obtain 4.66 g of 4-tolueneboronic acid (compound 3), with a yield of 57%.

Apply^[1-3]

1. Used in the synthesis of 2-cyano-4’-methylbiphenyl

2-Cyano-4′-methylbiphenyl, also known as Sartanbiphenyl, is a key intermediate in the preparation of Sartan antihypertensive drugs. 2-Cyano-4′-Methylbiphenyl is currently synthesized The general method is the Suzuki coupling reaction between o-chlorobenzonitrile and p-methylboronic acid. This reaction has the advantages of mild reaction conditions, high yield, and economical and easy availability of raw materials. It is widely used in chemical industry, medicine, pesticides and other fields.

CN201510776200.0 provides a preparation method of 2-cyano-4’-methylbiphenyl with low cost and high yield. The Suzuki coupling reaction of o-chlorobenzonitrile and 4-tolueneboronic acid is carried out in the presence of a reaction solvent and a catalyst, the catalyst is polystyrene-triphenylphosphine supported palladium, the reaction solvent is EtOH/H2O, The volume ratio of EtOH/H2O is 4:1 to 1:4; perform the following steps in sequence:

1), add o-chlorobenzonitrile, 4-tolueneboric acid and alkali to the reaction solvent, heat to reflux, then add a catalyst to react under reflux conditions; The molar ratio is 1:1.25, and the molar ratio of o-chlorobenzonitrile and alkali is 1:2; 41.4 mg of catalyst is used for every 10 mmol o-chlorobenzonitrile;

2). Use TLC to detect the reaction process. After the reaction is completed (TLC detects that the reaction solution o-chlorobenzonitrile disappears), perform suction filtration to obtain the filtrate and filter cake respectively; add water to the filtrate, and wash the resulting organic phase with saturated brine. Then it was dried with anhydrous sodium sulfate and separated by column chromatography to obtain 2-cyano-4′-methylbiphenyl.

2. Used to prepare 4-methyl-4’-fluoro-benzophenone

Benzophenone series products are organic fine chemical products with a wide range of uses. Due to the different types, quantities and positions of the substituent groups on both ends of the carbonyl ring, the benzophenone series family members have many members. This series of fine chemical products has been widely used in fields such as medicine, pesticides, dyes, plastics, coatings, daily chemicals and electronic chemicals.

CN201610379782.3 provides a preparation method of 4-methyl-4′-fluoro-benzophenone. The raw materials are cheap and easy to obtain, the reaction conditions are mild, the production cost is low, the safety is high, the operation is simple, and it has good development prospects. In order to achieve the above purpose, a preparation method of 4-methyl-4′-fluoro-benzophenone is designed, which includes the following steps: adding p-fluorobenzoic acid and 4-tolueneboronic acid in a reaction bottle, and adding a catalyst, and then Add an appropriate amount of alkali, additives and Boc-acid anhydride, and finally add tetrahydrofuran as the solvent, use the “one-pot method” to react at room temperature, and obtain 4-methyl-4′-fluoro-benzophenone after separation. Compared with the existing technology, the present invention provides a green, low production cost and high safety synthesis method for preparing 4-methyl-4′-fluoro-benzophenone, using p-fluorobenzoic acid, 4 – Tolueneboronic acid is used as raw material, tetrahydrofuran is used as solvent, and catalyst, alkali, additives and Boc-acid anhydride are added, and the “one-pot method” is used to react at room temperature for 15-24 hours to finally synthesize 4-methyl-4′- Fluoro-benzophenone, its raw materials are cheap and easy to obtain, the reaction conditions are mild, and the operation is simple.��It has good development prospects and potential industrial application prospects, and is worthy of promotion and application.

3. Efficient synthesis of bisphenol F as an auxiliary catalyst

Bisphenol F (BPF for short) is a new chemical raw material developed in the 1980s. It is a bisphenol compound formed by the condensation of phenol and formaldehyde. Its chemical name is dihydroxydiphenylmethane. , is a mixture of three isomers: 4,4′-, 2,4′- and 2,2′-. Compared with other bisphenol compounds, bisphenol F has unique properties, among which 4,4’-dihydroxydiphenylmethane has the best performance. The products synthesized with its participation have significant improvements in heat resistance, moisture resistance, insulation, especially processing (operation) and mechanical properties, so they can meet the needs of high solid coatings, electronic grade epoxy resins, castings and casting moldings. , flame retardant materials and other special performance requirements, it is mainly used as modifier and stabilizer of low viscosity epoxy resin, polycarbonate raw material, polyester resin, phenolic resin and information recording paper additives. Bisphenol F products have good market development and application prospects.

CN201410190309.1 provides a new method for efficiently synthesizing bisphenol F using 4-tolueneboronic acid as an auxiliary catalyst, including the following process steps:

(1) Add phenol and phosphoric acid into the reaction vessel at a molar ratio of 5:1 to 4:1, stir evenly at 45°C, add toluene as the solvent (1-2M), and add 0.1% 4-tolueneboric acid at the same time As an auxiliary catalyst, slowly add 37% formaldehyde aqueous solution and heat the reaction to 40-90°C. The reaction temperatures are: 40°C, 50°C, 60°C, 70°C, 80°C, and 90°C. DMF and dioxane can also be used as solvents for the reaction. The reaction time is 3-10 hours.

(2) Layer the reaction liquid obtained in step (1). The obtained water layer is a co-catalytic system of phosphoric acid and 4-tolueneboric acid, and the oil layer is reacted in situ to react the crude product. The crude product obtained from the reaction is rotary evaporated to recover toluene, and the remaining phenol is recovered by vacuum distillation. The remaining product is simply recrystallized once with the recovered toluene to obtain pure 4,4′-dihydroxydiphenylmethane (bisphenol F ).

Main reference materials

[1] CN201510776200.0 Preparation method of 2-cyano-4’-methylbiphenyl

[2] CN201610379782.3 A preparation method of 4-methyl-4’-fluoro-benzophenone

[3] CN201410190309.1 A new method for efficiently synthesizing bisphenol F with boric acid as an auxiliary catalyst

[4] CN201410437921.4 A kind of N,6 diphenylpyrimidine-4-amine Bcr-Abl inhibitor and its preparation method and application