Background and overview[1][3]
Boron trifluoride complex is a highly active catalyst that can be used in a variety of organic synthesis reactions, especially in the synthesis process of cephalosporin antibacterial drugs. Due to the introduction of boron trifluoride complex That is to say, the reaction time of the original product is shortened, and the yield of the original product is greatly increased. The catalytic effect of boron trifluoride acetonitrile complex is better than that of boron trifluoride etherate complex, so boron trifluoride acetonitrile complex has broad market prospects.
Boron trifluoride acetonitrile complex is mainly used as a catalyst for organic reactions. It is an important raw material for the preparation of boron halides, elemental boron, borane, sodium borohydride and other borides. It is also used for the production of boron hydrogen high-energy fuel and extraction The basic raw material of isotopes can also be used as a curing agent for epoxy resin.
Preparation[1]
The current preparation method of boron trifluoride acetonitrile complex is: react 20% fuming sulfuric acid, boron anhydride, and fluorite at a mass ratio of 9:1:3 at 130°C to generate boron trifluoride. The gas is then passed into acetonitrile for complexation. The finished product is an acetonitrile solution of boron trifluoride acetonitrile complex. The content of boron trifluoride is generally about 20wt%. It is difficult to accurately measure during use, and solid boron trifluoride The boron trifluoride content in the acetonitrile complex is high and the complexation is complete, which is easy to measure. In order to obtain the solid boron trifluoride acetonitrile complex, it is necessary to ensure that the boron trifluoride acetonitrile complex in acetonitrile reaches a certain purity and concentration. In order to solve the problem that the boron trifluoride content in the boron trifluoride acetonitrile complex solution is low and difficult to be used in a metered manner, CN201210594334.7 provides a preparation method of a solid boron trifluoride acetonitrile complex.
Add sulfur trioxide, boric acid and anhydrous hydrofluoric acid into the gas generator at a weight ratio of 4:1:1, react at 18°C for 15 hours, and use a vacuum pump to evacuate the trifluoride Boron gas, vacuum degree is 0.07MPa. The exported boron trifluoride gas enters the purification kettle filled with concentrated sulfuric acid for purification. The gauge pressure of the purification kettle is 0.2MPa.
The purified boron trifluoride gas enters the complexing kettle, which is filled with acetonitrile. The mass ratio of the filling amount of acetonitrile to the boron trifluoride gas produced by each kettle in the gas generating kettle is 4:6. The complexing reaction temperature was 20°C, and the reaction time was 12 hours.
The complexing reaction liquid circulates between the complexing kettle and the filter. The filter temperature is 8°C lower than the temperature of the complexing kettle. At this temperature, the reaction liquid becomes a supersaturated solution and crystals precipitate; the reaction after crystallization The liquid is returned to the complexation kettle for further complexation, and the crystals are collected and dried in a centrifuge to obtain solid boron trifluoride acetonitrile complex. The product is white crystal, in which the content of boron trifluoride is 60wt%.
Testing method for boron trifluoride content: weigh 1.5g of sodium fluoride, place it in a crucible that has been dried to constant weight, and put it into an electric dry bath to dry for 3 hours. The drying temperature is 180°C. Precision Weigh it as M1, add 15ml of third-grade water to dissolve, then add 0.5000±0.0002g of sample, and accurately weigh it as M2. Place the crucible in an electric dry bath to dry for 3 hours, and the drying temperature is 180°C. Take it out and transfer it to a desiccator to cool to room temperature, and accurately weigh it as M3.
Calculation formula: Content %=[（M3‑M1）/M2]×100%
In the formula: M1‑‑‑‑‑‑‑empty crucible, weight of sodium fluoride in g
M2‑‑‑‑‑‑‑‑Sample weight g
M3‑‑‑‑‑‑‑‑Total weight g of the crucible after drying
This content is converted into a boron trifluoride acetonitrile complex purity of about 99.85%. It can be seen that the degree of complexation is very high and there are very few impurities.
Apply[2-3]
CN201410650034.5 discloses a preparation method of cefotiam hydrochloride, which is a second-generation injectable antibiotic. It includes: using 7-ACA and DMMT as raw materials, using boron trifluoride acetonitrile complex as the catalyst, and using acetonitrile as the reaction solvent to perform a condensation reaction to prepare a 7-ACMT reaction solution; this reaction solution does not require separation and purification of 7-ACMT, and can be directly After adding water and adjusting the alkali, perform a “one-pot” acylation reaction with ATC·HCl; after the acylation reaction liquid is acidified and organic solvent extracted to separate organic impurities, a hydrophilic solvent is added to precipitate high-purity cefotiam hydrochloride. The invention carries out the two-step reaction in one step, improves equipment usage efficiency and labor efficiency, reduces labor intensity, increases product yield and reduces production costs while ensuring product quality. In the present invention, all impurity separation operations are performed after the acylation reaction, thereby reducing product losses caused by the intermediate separation operation and ensuring product purity.
CN201711182027.7 discloses a new synthesis process for 7-ACT. 7-ACT, also known as 7-aminoceftriazoline, is an intermediate for the synthesis of ceftriaxone sodium. It includes the following steps: (1) After mixing acetonitrile and boron trifluoride acetonitrile complex, add 7-ACA and triazine ring, and stir the reaction at 10 to 20°C until the 7-ACA residue is ≤0.5%, it is regarded as The reaction is complete; (2) Lower the reaction solution to 0-10°C, add 0-10°C purified water, and hydrolyze; (3) Add ethyl acetate for extraction and then add ethyl acetate to the water layer for secondary extraction; (4) Take water Add alkali dropwise to the layer at 0 to 10°C to adjust the pH to 3.4 to 3.6. After the dropwise addition, stir and grow the crystals at 0 to 10°C for 2 hours; (5) Filter, wash twice and dry to obtain 7-ACT. Utilizing the synthesis process of the present invention, 7-ACT products with good crystal size can be obtained. The products are white crystals, the purity can reach more than 99.5%, and the mass yield can reach more than 125%.
Main reference materials
[1][中National invention] CN201210594334.7 Preparation method and application of solid boron trifluoride acetonitrile complex
[2]CN201410650034.5 Preparation method of cefotiam hydrochloride
[3]New synthesis process of CN201711182027.77-ACT
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