Contents Table
1. Product introduction
Bronopol is a new type of bromine-based bactericidal preservative. In the past, it was mainly used as a cosmetic preservative. Used as a fungicide in pesticides and medicine. It is currently widely used in many countries.
There are two main methods to produce bronopol. The first method is to brominate nitromethane and then hydroxyl methylation reaction. The characteristic of this method is that the intermediate product is stable and easy to separate, but the yield is low. The second method is the hydroxymethylation of nitromethane followed by the bromination reaction. The intermediate is directly brominated without separation, which is easy to operate, simple equipment, low production cost and convenient for industrial production.
However, nitromethane has three active hydrogens. In addition to nitropropanediol, a small amount of nitroethanol and 2-nitro-2-hydroxy-1,3-propanediol were also formed during condensation with formaldehyde. Nitropropanediol is very unstable and its separation process is very difficult. Direct bromination without separation results in poor product purity and requires some post-processing work. Therefore, the purity of the product can be affected in the actual production.
This experiment mainly studies the post-treatment process of bronopol in the synthetic method of bronopol condensation followed by bromination. The purpose is to improve the purity of products.
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2. Experiment
2.1 Raw materials and instruments
The experimental raw materials include: paraformaldehyde, bromide chloride, nitroethane, sodium hydroxide.
Experimental instruments include: constant temperature and constant pressure drop funnel, stirring rod, drop funnel, thermometer, refrigeration system, four-mouth flask, rotary evaporator, etc.
2.2 Principle of product synthesis reaction
Salt formation: ΝaΟΗ+CΗ3ΝΟ2→[CΗ2ΝΟ2]Νa+Η2Ο
Bromination: [CΗ2ΝΟ2]Νa+BrCl→CΗ2BrΝΟ2+ΝaCl
2.3 Technical route of product synthesis
(1) At -10 ℃, the bromine chloride was produced by reacting chlorine gas with 50% bromine methanol solution;
(2) At -10 ℃, put 11 mL of nitromethane solution into a four-necked flask to cool down, mix 36 mL of 20% sodium hydroxide solution and 20 mL of water solution, then slowly drop into the nitromethane solution, control the reaction temperature from -10 ℃ to -5 ℃, and stir for 10 min after the drop is added;
(3) Add 37% formaldehyde solution to the above reaction solution for condensation reaction. Control the reaction temperature at 0 ℃ ~ 2 ℃, and stir for 2 hours after the drop is added;
(4) Add 20 ml of 50% bromine chloride methanol solution (volume ratio) to the above reaction solution for bromination reaction, control the reaction temperature at 5 ℃ – 7 ℃, the color of the solution changes from milky white to dark brown, then to colorless, and then to light yellow is the end of the reaction. After the addition is complete, stir for 15 min;
(5) the reaction finished liquid decompression distillation, separation, to obtain crude products;
(6) Use water as solvent, recrystallize 2 times, dry and get bronopol product.
2.4 Product purification process principle
The purification of bronopol mainly comes from the separation and recrystallization process of the finished liquid after the reduced pressure distillation.
The separation mainly adopts the principle of similarity and solubility. “similarity” means that the solute and solvent are similar in structure; “solubility” means that the solute and solvent are mutually soluble. The solubility of bronopol in organic solvents is greater than that in water, and the product is extracted from it.
Recrystallization means that the solubility of solid organics in solvents is closely related to temperature. The solubility of the solvent is different for the purified substance and impurities. The purified material can be separated from the supersaturated solution. The solubility of impurities in solvents is extremely small. Then the saturated solution is filtered and removed, so as to achieve the purpose of purification.
2.5 Product purification process
The organic phase is extracted and separated with ether solution to separate water-soluble impurities from the product, and then the ether is evaporated to obtain a crude product; Using methanol and dichloromethane as solvent, the bromonitrol product was obtained by column chromatography, judging the end point with chromogenic agent, recrystallizing once and drying. The specific process is as follows:
(1) Adding ether for extraction. After the reaction product was distilled under reduced pressure, 20 mL of ether solution was added, and stirred at low temperature for several minutes, so that bromonitroalcohol was completely dissolved in the ether solution, and after standing for 10 min, the ether solution was separated, and then the ether was distilled out to obtain a white product.
(2) Column chromatography separation. Dissolve the crude product with methanol and dichloromethane at a ratio of 1: 20, pass through ф Ф5 cm×30 cm silica gel column, separate impurities in by-products, and use phosphomolybdic acid as color developer to judge the end point, thus obtaining a relatively pure product.
(3) Recrystallization and drying. Keep the filtrate at 60 ℃ and distill under reduced pressure. When crystallization just appears, stop heating and let it cool slowly. After all the crystals are precipitated out, the solid products are separated by the pumping and filtering device, and then placed in the electric air blast oven to dry the high purity products under the set temperature conditions.
2.6 Product analysis and assay method
High performance liquid chromatography (HPLC) is used as the method of product analysis and testing.
3. Experimental results and discussion
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4. Conclusion
After the synthesis of bronopol by bromine chloride method, the product contains a large number of impurities that need to be removed. The experimental method of extracting and separating the crude product first, then removing the organic impurities by silica gel column chromatography, and finally recrystallizing the crude product was used to purify the synthesized product, which can increase the content of the product from 80% to 97.8%, thus achieving the purpose of purifying the product and improving the quality of the product used. The product can be purified from 80% to 97.8%, thus improving the quality of the product, and expanding the range of application.