Background and overview[1]
4-Chloropropiophenone is an aromatic asymmetric ketone compound. It is a white crystalline solid with a melting point of 34-37°C. 4-Chloropropiophenone is an important intermediate that plays a structural role. Mainly used as a pharmaceutical intermediate for the synthesis of new weight loss drug rimonabant (N-(piperidine)-5-(4-chlorophenyl)-1-(2,4-dichlorophenyl)-4- Methyl-IH-pyrazole-3carboxamide) key intermediates α-bromo-4-chloropropiophenone and 4-(4-chlorophenyl)-3-methyl-2,4-dioxobutyric acid Ethyl ester; can also be used as fine chemical raw materials for the synthesis of fine chemical products containing p-chlorobenzene ring structures in the molecules. It can also be used as other pharmaceutical and pesticide intermediates.
Preparation[1]
In a four-neck reaction bottle equipped with an electric stirrer, a reflux condenser and a thermometer, add 15.65g of p-chlorobenzoic acid, 51.8g of propionic acid, and 2.5g of catalyst in sequence. After adding the materials, start stirring and control the condensation reaction temperature. The temperature is about 140°C. The condensation reaction is carried out by stirring for 12 hours. The excess propionic acid is distilled out. The temperature continues to rise until carbon dioxide gas begins to escape at 280°C. The decarboxylation reaction is carried out at a temperature of 280°C-285°C, while using 95 % ethanol solution absorbs the escaping carbon dioxide gas and the distilled liquid. After 2 hours of decarboxylation reaction, the reaction will stop when no liquid distills out in the four-port reactor. Then it is cooled and crystallized to obtain 4-chloropropiophenone product, 4-chloropropiophenone. The yield of phenylacetone reaches 86.45%, and the melting point is 34-37°C.
Apply[2-3]
Rimonabant is a new type of weight loss drug, and α-bromo-4-chloropropiophenone is the key intermediate in the synthesis of rimonabant. CN201110155228.4 discloses a method for preparing the pharmaceutical intermediate α-bromo-4-chloropropiophenone. It uses 4-chloropropiophenone and liquid bromine as raw materials and reacts in the presence of a catalyst to prepare α-bromo-4-chloropropiophenone. -Chloropropiophenone. The invention synthesizes α-bromo-4-chloropropiophenone, has a simple separation and purification process, short reaction time, high product purity, product yield of more than 97%, low energy consumption, low environmental pollution and low cost, and is suitable for industrialized production. Ideal craftsmanship.
CN201610864147 discloses a kind of thifenacet and its preparation method. thifenfen is an insecticide (acaricide). Using 4-chloropropiophenone as the starting material, it reacts with n-butyl nitrite at a mass ratio of 70:47 to form a ketoxime, which is then hydrogenated and reduced to 2-amino-1-p-chlorophenylpropanol hydrochloride. , 2-amino-1-p-chlorophenylpropanol hydrochloride reacts directly with carbon disulfide to synthesize trans-5-(4-chlorophenyl)-4-methyl-2-thiothiazolidinone, and then reacts with hydrogen peroxide Oxidation produces 5-(4-chlorophenyl)-4-methyl-2-oxothiazolidinone, which is the same and different again Cyclohexyl cyanate undergoes an addition reaction to obtain the final product thifenacet. The preparation method adopted in the present invention is suitable for industrial production, simplifies the process flow, improves the reaction yield, reduces the difficulty of synthesis, reduces the formation of by-products, reduces environmental pollution problems during the preparation process, and reduces production costs.
Main reference materials
[1] [Chinese invention] CN201010153442.1 A preparation method of 4-chloropropiophenone
[2] [Chinese invention] CN201110155228.4 A preparation method of pharmaceutical intermediate α-bromo-4-chloropropiophenone
[3] CN201610864147.4 A kind of thioxenone and its preparation method
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