3-Nitrobenzaldehyde is an organic substance with the chemical formula of c7h5no3. It is a light yellow or quasi white crystal. Soluble in alcohol, ether, chloroform, benzene and acetone, almost insoluble in water. Capable of steam distillation. It can be used as a pharmaceutical intermediate of nitrendipine, nimodipine and nicardipine or as a dye.
M-nitrobenzaldehyde is an important chemical intermediate, which is widely used in synthetic medicine, dyes and active agents. M-nitrobenzaldehyde is in great demand at home and abroad, so it is of great significance to study and improve the preparation process of m-nitrobenzaldehyde. Used as dye, photosensitive material and intermediate of nitrendipine, nimodipine and nicardipine; This product is an intermediate of organic synthesis, such as medicine, dye, surfactant, etc. In the pharmaceutical industry, it is used to synthesize calcium iodopronate, iodophoric acid, m-hydroxylamine bitartrate, nimodipine, nicardipine, nitrendipine, nilodipine, etc.; It is used as an intermediate in the organic synthesis of dyes, surfactants and pharmaceuticals. In the pharmaceutical industry, it is used in the production of calcium iodopronate, iodofophanic acid, calcium cholesteride, M-hydroxy bitartaric acid, nifedipine, etc.
The synthetic methods of M - nitrobenzaldehyde can be divided into direct nitration and Indirect nitrification. Direct nitration takes benzaldehyde as raw material and nitrates with mixed acid, potassium nitrate and sodium nitrate. The yield of the product is about 60%. Due to the large amount of ortho nitrification by-products, the yield of the target product is low and the separation of the product is difficult. At present, the production process of m-nitrobenzaldehyde mostly adopts direct nitration. Indirect nitration method is to protect the aldehyde group first and then nitration. For example, organic amines such as isopropylamine are used to protect the aldehyde group, and then remove the aldehyde protection reagent to prepare m-nitrobenzaldehyde. When m-nitrobenzaldehyde is synthesized by indirect nitration with organic amine as aldehyde protecting reagent, because the steric hindrance effect of imino group is greater than that of aldehyde group, the amount of ortho nitration product can be reduced, so as to improve the yield and purity of the target product.
In this experiment, m-nitrobenzaldehyde was synthesized by indirect nitration with ammonia water as aldehyde protecting reagent. The technological conditions of condensation and nitration were studied. The purity of m-nitrobenzaldehyde prepared by this method can reach 99.8%, which can meet the needs of drug production.
Reaction principle: two molecules of ammonia condense with three molecules of benzaldehyde to form triphenyl formaldehyde diamine (tbda) with greater steric hindrance effect, which can make the meta selectivity of nitration products higher; Nitration products can be rapidly hydrolyzed to m-nitrobenzaldehyde under acidic conditions. The reaction formula is as follows:
3-Nitrobenzaldehyde experimental method and steps:
1.3.1 tbda is prepared with agitator and dropping funnel Three 250ml ports of thermometer
Add 53 g of benzaldehyde to the flask, cool it to 10 C with ice water bath, drop 90ml of ammonia water with a mass fraction of 25%, raise the temperature to 40 C after dropping, keep the temperature for 12 hours, then cool it to room temperature, filter, wash and dry it to get 49.1 g of white tbda, with a yield of 98.7%.
1.3.2 nitrification reaction
Add 258.1 g of concentrated sulfuric acid with a mass fraction of 98% to a 250 ml three port flask equipped with a stirrer, a dropping funnel and a thermometer, cool it to 10 C with an ice water bath, slowly add tbda under stirring, slowly add 83.0 g of concentrated nitric acid with a mass fraction of 97% after dissolution, control the dropping acceleration rate to maintain the reaction temperature at 10~15 C, and continue stirring at room temperature for 2 hours after dropping. After the reaction, pour the nitration product into 500 g crushed ice, stir for 0.5 h, filter, wash the filter cake with sodium carbonate solution to neutral, and then wash it with water for several times. After drying, 64.4 g of light yellow crude m-nitrobenzaldehyde is obtained, with a yield of 86 3%。
1.3.3 recrystallization
Add 64.4 g of crude m-nitrobenzaldehyde to a 250 ml three port flask equipped with a stirrer, a reflux condenser and a thermometer, and then add 185 ml of petroleum ether toluene mixed solvent (volume ratio: 1.5:1). After heating and dissolving, add activated carbon to decolorize. After refluxing for 10 minutes, filter while hot, cool the filter solution to 5 C, and then dry the filter cake after filtration to obtain 57.8g of white glossy m-nitrobenzaldehyde crystal with a purity of 99 8%, and the yield was 89.7%. The solvent can be recycled and reused. After condensation, nitration and recrystallization, the total yield of m-nitrobenzaldehyde was 76 4%。
Downstream products: m-Hydroxybenzaldehyde -- > 3-Chlorobenzaldehyde -- > iodophoric acid -- > (+ / -) - 4 - (3-nitrophenyl) - 2,6-dimethyl-1,4-dihydropyridine-3,5-dicarboxylate methoxyethyl ester isopropyl ester -- > nicardipine -- > 3 - (3-nitrophenyl) propionic acid -- > 2,6-dimethyl-4 - (3-nitrophenyl) -1,4-dihydro-3,5-pyridinedioic acid methyl ethyl ester -- > m-nitrocinnamic acid -- > m-aminobenzaldehyde, polymer -- > 3-nitrobenzyl -- > 2[(3-nitrophenyl) methylene] butyric acid
Upstream raw materials: ethanol -- > ethyl acetate -- > sulfuric acid -- > methylene chloride -- > petroleum ether -- > nitric acid -- > carbon tetrachloride -- > N-bromosuccinimide -- > benzaldehyde -- > dibenzoyl peroxide -- > potassium nitrate -- > 3-nitrotoluene -- > nitro compounds
Store in a cool and ventilated warehouse. Keep away from kindling and heat sources. It should be stored separately from oxidants, acids, alkalis and edible chemicals, and should not be mixed. Equip with corresponding varieties and quantities of fire-fighting equipment. Appropriate materials shall also be prepared to contain the leakage. 25kg cardboard barrels (lined with double-layer plastic bags) are used for packaging. They are stored in a cool and dry place, and the containers are sealed away from strong oxidants and strong alkalis.