Method for synthesizing chloramphenicol from nitromethane

A technology of chloramphenicol and nitro, which is applied in the field of compound preparation, can solve the problems of production cost, increase of three wastes, and long synthesis route of chloramphenicol, and achieve the effect of cheap raw materials, easy availability of raw materials, and high total yield

Active Publication Date: 2012-04-04
WUHAN WUYAO SCI & TECH
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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 nitromethane
  • Method for synthesizing chloramphenicol from nitromethane
  • Method for synthesizing chloramphenicol from nitromethane

Examples

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Embodiment 1

[0035] 1 of the preparation of embodiment 1 (R)-2-nitro-1-(4-chlorophenyl) ethanol

[0036] 1.8 g copper trifluoromethanesulfonate Cu(OTf) 2 (0.50mmol), 2.4 grams of ligand {2,6-bis[(S)-4-isopropyl-1-phenyl-4,5-dihydro-1H-2-imidazolyl]pyridine} (5.2mmol ) and 40 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 in the inside with nitrogen gas. After magnetic stirring for 2 hours, 7.0 grams of p-chlorobenzaldehyde ( 50mmol), 30.6 grams of nitromethane (500mmol) and N-methylmorpholine (0.54 milliliters, 5.0mmol), the reaction solution was stirred in ice-bath cooling for 24 hours, and after thin plate chromatography detected no raw material p-chlorobenzaldehyde spots, Then the volatile solvent is removed by distillation under reduced pressure, the catalyst is removed by silica gel filtration, and the filtrate is concentrated to obtain 9.0 grams of product, the yield is 90%, and the HPLC ...

Embodiment 2

[0037] The 2 of the preparation of embodiment 2 (R)-2-nitro-1-(4-chlorophenyl)ethanol

[0038] In a 100 ml single-necked flask, add 0.5 g of 1-[2-(4S)-4-R-4,5-dihydro-2-oxazoline-ethyl]piperidine, 0.09 g of trifluoromethanesulfonate Copper (CuOTf) 2, 40 milliliters of anhydrous dimethyl sulfoxide, keep the nitrogen flow constant after replacing the air inside with nitrogen, cool with ice bath after magnetic stirring for 3 hours, add 7.0 grams of p-chlorobenzaldehyde (50mmol) successively , 30.6 grams of nitromethane (500mmol) and N-methylmorpholine (0.54 milliliters, 5.0mmol), the reaction solution was stirred in ice-bath cooling for 24 hours, after thin-plate chromatography detected no raw material p-chlorobenzaldehyde spots, then subtracted The volatile solvent was removed by distillation under pressure, the catalyst was removed by silica gel filtration, and the filtrate was concentrated to obtain 9.1 grams of product, with a yield of 91%, and the HPLC measurement e.e value ...

Embodiment 3

[0039] Example 3 Preparation of (1R, 2R)-2-nitro-1-(4-chlorophenyl)-1,3-propanediol 1

[0040] Add 40 ml of 1,4-dioxane into a 250 ml single-necked flask, replace the air inside with nitrogen to keep the nitrogen flow constant, stir magnetically and add 1.2 g of paraformaldehyde (40 mmol), 8.0 g of (R)-2 -Nitro-1-(4-chlorophenyl)ethanol (40mmol) and N-methylmorpholine (0.44 milliliters, 4mmol), the reaction solution was stirred in ice-bath cooling for 24 hours, and no raw material (R )-2-nitro-1-(4-chlorophenyl)ethanol spots, the volatile solvent was distilled off under reduced pressure, purified by silica gel filtration, and the filtrate was concentrated to obtain 4.0 g of the product, with a yield of 86%. 1 H NMR (acetone-d 6 )δ: 3.71(s, 1H), 3.85(m, 1H), 4.12(m, 1H), 4.52(m, 1H), 4.79(m, 1H), 5.01(d, J=8.7Hz, 1H), 7.15-7.26 (m, 4H).

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Abstract

The invention relates to a method for synthesizing a broad spectrum antibiotic of chloramphenicol. The method comprises the following steps of: synthesizing (R)-2-nitro-1-(4-chlorophenyl)ethanol by using p-chlorobenzaldehyde and nitromethane as raw materials in the presence of a chiral catalyst; reacting with formaldehyde to obtain (1R,2R)-2-nitro-1-(4-chlorophenyl)-1,3-propanediol, and performing catalytic hydrogenation to obtain (1R,2R)-2-amino-1-(4-chlorophenyl)-1,3-propanediol; and performing nitro substitution and dichloro acetylization 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, the raw materials and reagents are cheap and readily available, 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 nitromethane. 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, but th...

Claims

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Application Information

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Patent Type & Authority Applications(China)
IPC IPC(8): C07C233/18C07C231/02
Inventor 杨尚金冯珂朱毅皮金红潘季红郭亚兵谢国范
Owner WUHAN WUYAO SCI & TECH
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