Method for synthesizing chloramphenicol

A synthesis method and technology of chloramphenicol, applied in chemical instruments and methods, preparation of organic compounds, organic chemistry, etc., can solve the problems of production cost, increase of three wastes, and long synthesis route of chloramphenicol, and achieve cheap raw materials, Raw materials are easily available and the total yield is high

Active Publication Date: 2014-07-16
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

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  • Method for synthesizing chloramphenicol
  • Method for synthesizing chloramphenicol
  • Method for synthesizing chloramphenicol

Examples

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Embodiment 1

[0031] 1 of the preparation of embodiment 1 (R)-2-nitro-1-phenylethanol

[0032] 0.9 g of copper trifluoromethanesulfonate Cu(OTf)2 (0.25 mmol), 1.2 g of ligand {2,6-bis[(S)-4-isopropyl-1-phenyl-4,5-bis Hydrogen-1H-2-imidazolyl]pyridine} (2.6mmol) and 20ml of 1,4-dioxane were added to a 100ml single-necked flask, and the nitrogen flow was kept constant after replacing the air inside with nitrogen. After magnetic stirring for 2 hours, Cool in an ice bath, add 2.7 grams of benzaldehyde (25mmol), 15 grams of nitromethane (250mmol) and N-methylmorpholine (0.27 milliliters, 2.5mmol) successively, and the reaction solution was stirred in an ice bath for 24 hours. After the chromatographic detection of no raw material benzaldehyde 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 4.3 grams of product, with a yield of 97%, and the e.e value was 97% as deter...

Embodiment 2

[0033] The 2 of the preparation method of embodiment 2 (R)-2-nitro-1-phenylethanol

[0034] 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 For copper (CuOTf), replace the air inside with nitrogen and keep the nitrogen flow constant. After 3 hours of magnetic stirring, cool in an ice bath, add 2.7 g of benzaldehyde (2 mol) and 15 g of nitromethane (6 mol) to anhydrous di A mixture was formed in methyl sulfoxide, and then the reaction solution was stirred in an ice bath for 12 hours. After thin-plate chromatography detected no raw material benzaldehyde spots, 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 The product was 4.2 grams, the yield was 92%, and the e.e value determined by HPLC was 97%.

Embodiment 3

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

[0036] Add 20 ml of 1,4-dioxane into a 100 ml single-necked flask, replace the air inside with nitrogen and keep the nitrogen flow constant, stir magnetically and add 0.75 g of paraformaldehyde (25 mmol), 4.2 g of (R)-2 -Nitro-1-phenylethanol (25mmol) and N-methylmorpholine (0.27 ml, 2.5mmol), the reaction solution was stirred in an ice bath for 24 hours, no raw material (R)-2- was detected by thin plate chromatography After the nitro-1-phenylethanol spots, then the volatile solvent was removed by distillation under reduced pressure, purified by silica gel filtration, and the filtrate was concentrated to obtain 4.2 grams of product, with a yield of 85%, 1H NMR (acetone-d6) δ: 3.46 (ddd, J=3.2, 7.9, 12.0Hz, 1H), 3.70(s, 1H), 3.90(ddd, J=6.5, 9.2, 12.0Hz, 1H), 4.19~4.23(m, 2H), 4.84(ddd, J= 3.2, 9.2, 9.2Hz, 1H), 5.08 (d, J = 9.2Hz, 1H), 5.03~5.11 (m, 1H), 7.31~7.48 (m, 5H). 13C NMR (acetone-d6) δ: 61...

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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 (R)-2-nitro-1-benzylcarbinol by using benzaldehyde and nitromethane as raw materials in the presence of a chiral catalyst; reacting with formaldehyde to obtain (1R,2R)-2-nitro-1-benzyl-1,3-propanediol, and performing hydrogenation reduction to obtain (1R,2R)-2-amino-1-benzyl-1,3-propanediol; and performing dichloro acetylization and nitration on the (1R,2R)-2-amino-1-benzyl-1,3-propanediol 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 synthesis method of a compound, in particular to a synthesis method of a broad-spectrum antibiotic chloramphenicol. 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, bu...

Claims

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Application Information

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Patent Type & Authority Patents(China)
IPC IPC(8): C07C233/18C07C231/12
Inventor 杨尚金冯珂朱毅杨波郭婷婷赵涛涛谢国范
Owner WUHAN WUYAO SCI & TECH
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