Background and overview[1]
Colorless transparent liquid. Molecular weight 171.04. Melting point -39.8℃. Boiling point 183.7℃. Relative density 1.4099 (20/4℃). Refractive index 1.5510. Flash point 60℃. Miscible with ethanol, ether and benzene, but insoluble in water. Toxic! It is obtained by diazotization and reduction of 3-bromo-4-aminotoluene. Meta-bromotoluene itself is toxic. It is more toxic than toluene. It is anesthetic and can poison the nerve center. It is irritating and irritates the skin and mucous membranes. Therefore, it must be strictly controlled during preparation. Currently, there are some problems in the industrial production of m-bromotoluene. It has problems such as low yield, low purity and serious pollution, and the production process is relatively complex and difficult to meet human needs.
Purpose[2-4]
Meta-bromotoluene is mainly used as a raw material for organic synthesis; as a solvent; as a pharmaceutical raw material to produce drugs for the treatment of joint pain. Examples of its application are as follows:
1) Used for the total synthesis of DTNB, including: nitration step: adding mixed acid dropwise to m-bromotoluene to obtain 2-nitro-5-bromotoluene; oxidation step: adding 2 to 2-nitro-5-bromotoluene -8wt% potassium permanganate solution to obtain 2-nitro-5-bromo-benzoic acid; vulcanization step: dissolve the 2-nitro-5-bromo-benzoic acid obtained in the oxidation step with water and adjust the pH to >3.5 , stir and heat to 45-55°C, add sodium sulfide aqueous solution in batches, keep warm for 2 hours, adjust pH <1 with hydrochloric acid, collect precipitates, and obtain DTNB. The total synthesis method of DTNB has a short synthesis route and strong production controllability. The total yield of the synthesis process is more than 35%, the cost is low, and it is easy for industrial production.
2) Used to synthesize a kind of 3-carboxyphenylboronic acid, involving the field of organic synthesis technology, using m-bromotoluene as the starting material, first reacting with magnesium chips and iodine to form a Grignard reagent, and then reacting with boric acid trisulfide Methyl ester is borated to produce m-tolueneboronic acid, which is then oxidized by potassium permanganate under alkaline conditions to produce 3-carboxybenzeneboronic acid. The invention uses cheap and easily available m-bromotoluene as the starting material, and prepares 3-carboxyphenylboronic acid through Grignard reaction, boration reaction and oxidation reaction. The operation is simple, and the average purity of the product 3-carboxyphenylboronic acid reaches 99.3 %, the average total yield reaches 50%, ensuring the yield and purity of the product on the basis of low cost, thus being suitable for industrial production.
3) Used to prepare a cinnamate derivative. The preparation method of cinnamate derivatives includes reacting formate and propargyl bromide in anhydrous acetonitrile under the catalysis of sodium hydride to obtain a white solid product; reacting the white solid product with phenylacetylenyl bromide or substituted phenylacetylenyl bromide Under the catalysis of Pd(PPh3)2Cl2/CuI, use triethylamine as a base and react in anhydrous acetonitrile to obtain a light brown solid product; under the conditions of 90-110°C, react the light brown solid product with m-bromotoluene. The reaction of o-bromocinnamic acid gives cinnamic acid ester derivatives. The present invention provides the generation of a series of new cinnamate derivatives. Compared with ordinary cinnamic acid ester derivatives, the cinnamic acid ester derivatives prepared in the present invention have polycyclic rings, and their structures are more complex and diverse, and will also show broader use prospects in chemical production and clinical medicine.
Preparation[5]
A production process for the synthesis of m-bromotoluene, which is characterized by: including the following process steps,
a. Add 620-630kg of 95% ethanol into the reaction kettle, and turn on the stirrer to stir.
b. Weigh 360-370kg of concentrated sulfuric acid and 240-260kg of 3-bromo-aminomethylbenzene, add them to the reaction kettle in step a and turn on the frozen brine to cool, and continue stirring until the mixture is evenly stirred.
c. Weigh 140-150kg of sodium nitrite and 250-270kg of water and mix to prepare a solution for later use.
d. When the temperature in the reaction kettle drops to 10°C in step b, put the mixed solution prepared in step c into the reaction kettle, keep the temperature ≤ 10°C, and continue to stir the reaction for 20 minutes.
e. Weigh 35kg of copper powder, wash it with diethyl ether and add it to the reaction kettle in step d.
f. Turn on the steam for heating to release nitrogen, and keep the temperature at 40-60°C for 20 minutes. Then increase the temperature to 80-100°C and continue the reaction until no bubbles overflow and the liquid changes from reddish brown to reddish brown. After turning yellow, the reaction ends. .
g. Add 2000L water to step f, then directly introduce water vapor for distillation, and then collect the distillate in the oil-water separator until no oil is produced, stop distillation, and let the distillate stand for 1 hour , separate into layers and take out the water phase.
h. Wash the oil phase in step g twice with 100L of 10.0% sodium hydroxide solution, then wash once with 100L of 5.0% sodium carbonate solution, and then separate the water phase.
i. Dry the treated oil phase in step h with anhydrous calcium chloride and then filter it to remove the solid matter, and then pump the remaining liquid into the rectification kettle for rectification to obtain a colorless The product is the finished product of m-bromotoluene, which is packaged and stored in warehouse.
Main reference materials
[1] Concise Dictionary of Fine Chemicals
[2] CN201711494442.6 A total synthesis method of DTNB
[3] CN201710331153.8 A preparation method of 3-carboxyphenylboronic acid
[4] CN201410728360.3 A cinnamate derivative and its preparation method
[5] CN201410243050.2 A production process for the synthesis of m-bromotoluene
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