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Method for synthesizing chloramphenicol from 4-chloro-benzaldehyde

A synthesis method and technology of chloramphenicol are applied in chemical instruments and methods, preparation of organic compounds, organic chemistry and other directions, which can solve the problems of increased production cost and three wastes, long synthetic route of chloramphenicol, etc. The effect of easy availability of raw materials and short synthetic route

Active Publication Date: 2012-04-04
WUHAN WUYAO SCI & TECH
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  • Abstract
  • Description
  • Claims
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Problems solved by technology

[0006] As can be seen from the above, the synthesis route of chloramphenicol is long at present, because the theoretical maximum yield of splitting is only 50%, calculated in terms of ethylbenzene, the actual yield of domestic production is about 30%, which makes the production cost and the three wastes increase. The aluminum propoxide reduction process also produces a large amount of three wastes that are difficult to handle, so finding a more economical synthesis method is always a challenge

Method used

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  • Method for synthesizing chloramphenicol from 4-chloro-benzaldehyde
  • Method for synthesizing chloramphenicol from 4-chloro-benzaldehyde
  • Method for synthesizing chloramphenicol from 4-chloro-benzaldehyde

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Embodiment 1

[0033] Embodiment 1 (1R, 2R)-1 of the preparation of-2-nitro-1-(4-chlorophenyl)-1,3-propanediol

[0034] 1.8 g of Cu(OTf) 2 (0.50mmol), 2.4 grams of 2,6-bis[(S)-4-isopropyl-1-phenyl-4,5-dihydro-1H-2-imidazolyl]pyridine (5.2mmol) and 40 ml Add 1,4-dioxane into a 250 ml single-necked flask, replace the air inside with nitrogen and keep the nitrogen flow constant. At room temperature, stir magnetically for 2 hours and cool with an ice bath, then add 7.0 g of 4-chlorobenzaldehyde in sequence (50mmol), 45.5 grams of 2-nitroethanol (500mmol) and N-methylmorpholine (0.54 milliliters, 5.0mmol), the reaction solution was stirred in an ice bath at 0~5°C for about 24 hours, and no raw material was detected by thin-plate chromatography After 4-chlorobenzaldehyde spots, then the volatile solvent was removed by distillation under reduced pressure, the catalyst was removed by silica gel filtration, and the filtrate was concentrated to obtain 10.6 grams of product, the yield was 91.8%, and t...

Embodiment 2

[0035] Example 2 Preparation of (1R, 2R)-2-nitro-1-(4-chlorophenyl)-1,3-propanediol 2

[0036] 0.8 g of Cu(OTf) 2 (0.50mmol), 0.8 gram of rhodium acetate, 1.2 gram of 2,6-bis[(S)-4-isopropyl-1-phenyl-4,5-dihydro-1H-2-imidazolyl]pyridine (5.2 mmol) and 20 milliliters of 1,4-dioxane were added in a 250 milliliter single-necked flask, and the nitrogen flow was kept constant after replacing the air inside with nitrogen. At room temperature, magnetically stirred for 2 hours and then cooled with an ice bath, and then added 7.0 grams of 4-Chlorobenzaldehyde (50mmol), 45.5 grams of 2-nitroethanol (500mmol) and 0.15 grams of picoline, the reaction solution was stirred in an ice bath at 4°C for about 20 hours, and no raw material 4-chlorobenzaldehyde was detected by thin-plate chromatography After spotting, the volatile solvent was then distilled off under reduced pressure, the catalyst was removed by silica gel filtration, and the filtrate was concentrated to obtain 10.9 grams of prod...

Embodiment 3

[0037] Example 3 Preparation of (1R, 2R)-2-nitro-1-(4-chlorophenyl)-1,3-propanediol 3

[0038] 1.8 g of Cu(OTf) 2(0.50mmol), 2.4 grams of 2,6-bis[(S)-4-isopropyl-1-phenyl-4,5-dihydro-1H-2-imidazolyl]pyridine (5.2mmol) and 40 ml Add 1,4-dioxane into a 250 ml single-necked flask, replace the air inside with nitrogen and keep the nitrogen flow constant. At room temperature, stir magnetically for 2 hours and cool in an ice bath, then add 6.0 g of 4-bromobenzaldehyde in turn , 45.5 grams of 2-nitroethanol (500mmol) and N-methylmorpholine (0.54 milliliters, 5.0mmol), the reaction solution was stirred in an ice bath at 4°C for about 30 hours, and no raw material 4-chlorobenzaldehyde was detected by thin plate chromatography After spotting, the volatile solvent was then distilled off under reduced pressure, the catalyst was removed by silica gel filtration, and the filtrate was concentrated to obtain 9.6 grams of product, with a yield of 86.2%. The e.e value of HPLC was 92.9%. 1H), ...

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Abstract

The invention relates to a method for synthesizing a broad spectrum antibiotic, namely, chloramphenicol. The method comprises the following steps of: synthesizing (1R,2R)-2-nitro-1-(4-chlorophenyl)-1,3-propanediol by using 4-chlorobenzaldehyde and 2-nitroethylalcohol as raw materials in the presence of a chiral catalyst, and performing catalytic hydrogenation to obtain (1R,2R)-2-amino-1-(4-chlorophenyl)-1,3-propanediol; and performing dichloro acetylization and nitro substitution on the intermediate to obtain the chloramphenicol. By the method, the common chiral resolution and aluminum isopropoxide reduction in the industry at present can be avoided, three wastes are reduced, and the raw materials and reagents are cheap and readily available; 4-chlorobenzaldehyde is selected as a raw material, nitro substitution is adopted, and the generation of byproducts in nitration reaction is reduced; moreover, the method comprises a few synthesizing steps, the yield is high, and the method is more suitable for industrial production.

Description

technical field [0001] The invention relates to a preparation method of a compound, in particular to a method for synthesizing chloramphenicol from 4-chlorobenzaldehyde. Background technique [0002] Chlorotoxin is a broad-spectrum antibiotic, mainly used for typhoid bacillus, Shigella, meningococcus, pneumococcus infection, and can also be used for rickettsial infection. Although it has many side effects such as inhibition of bone marrow hematopoietic function, causing coarse cells and thrombocytopenia or aplastic anemia, it is still the drug of choice for the treatment of typhoid fever. [0003] Chloramphenicol is white or slightly yellow-green needle-like, long flaky crystals or crystalline powder. Bitter. The melting point is 149-153°C. Soluble in organic solvents such as methanol, ethanol and acetone, slightly soluble in water. Specific rotation [α] D 25 =+18.5~+21.5° (absolute ethanol). [0004] There are many reports about the synthetic route of chloramphenicol...

Claims

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Application Information

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Patent Type & Authority Applications(China)
IPC IPC(8): C07C233/18C07C231/12
Inventor 杨尚金皮金红朱毅冯珂潘季红郭亚兵谢国范
Owner WUHAN WUYAO SCI & TECH
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