Preparation method of 2-iodobenzyl bromide and its application in organic synthesis_Kain Industrial Additive

Background and overview^[1]

2-Bromomethyl-4-fluorobenzene can be used as an intermediate for pharmaceutical and chemical synthesis. If 2-iodobenzyl bromide is inhaled, move the patient to fresh air; if there is skin contact, take off contaminated clothing, rinse the skin thoroughly with soap and water, and seek medical attention if you feel uncomfortable; if there is eye contact, , you should separate your eyelids, rinse with running water or saline, and seek medical attention immediately; if ingested, rinse your mouth immediately, do not induce vomiting, and seek medical attention immediately.

Structure

Apply^[1]

2-Bromomethyl-4-fluorobenzene can be used as an intermediate for pharmaceutical and chemical synthesis. Such as the synthesis of 1-(3-en-butyl)-2-iodobenzene derivatives. 1-(3-ene-butyl)-2-iodobenzene derivatives have important application value in organic synthesis. They can perform intermolecular cross-coupling reactions with organometallic reagents of halocarbons, and can also perform intramolecular reactions. Heck reaction, and at the same time, its own free radical cyclization reaction is carried out under the action of a catalyst. Such compounds are relatively expensive or have not been commercialized. There are studies using allyl bromide Grignard reagent to cross-couple benzyl bromide or to add aromatic aldehydes. The resulting product has a high yield and is easy to separate (without separation and purification). The generated 1-(3-ene- Butyl)-2-iodobenzenes can also be further modified. The specific synthesis of 1-(3-en-butyl)-2-iodobenzene (3) is as follows: slowly drop into 30 mL of anhydrous THF solution containing 2-iodobenzyl bromide (4.0 g, 13.5 mmol). Add allyl magnesium bromide (17.5 mmol, 24.7 mL) in diethyl ether, heat the reaction solution to reflux and react overnight. TLC shows that the raw materials are completely reacted. The reaction solution was carefully quenched with 5% HCl by mass, extracted with ethyl acetate, the organic phase was washed with saturated brine, dried over anhydrous sodium sulfate, and the organic phase was concentrated without column separation to obtain 3.3 g of colorless oil 3 ( 1-(3-en-butyl)-2-iodobenzene), yield 96%.

Preparation ^[1]

Synthesis of 2-iodobenzyl bromide: PBr3 (2.85 mL, 30 mmol) was slowly added to 40 mL of anhydrous dichloromethane solution containing compound 1 (o-iodobenzyl alcohol, 3.51 g, 15 mmol). , the reaction solution was stirred at room temperature for 16 h. TLC showed that the raw materials reacted completely. The reaction solution was concentrated under vacuum conditions. The oil obtained by concentration was washed with saturated NaHCO3 solution. The aqueous phase was extracted with dichloromethane, dried over anhydrous sodium sulfate, and the organic phase was concentrated to obtain 4.0 g colorless crystals of 2-iodine. Benzyl bromide, yield 90%.

Main reference materials

[1] Dong Zhibing, Gao Fan, Cao Qiang, et al. Synthesis of substituted iodobenzenes with distal double bonds [J]. Journal of Wuhan Institute of Technology, 2017, 39(1): 40.