CN112574040B - Synthesis method of ethyl 2, 3-dichloro-4-nitrobenzoate - Google Patents
Synthesis method of ethyl 2, 3-dichloro-4-nitrobenzoate Download PDFInfo
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- CN112574040B CN112574040B CN202110116838.7A CN202110116838A CN112574040B CN 112574040 B CN112574040 B CN 112574040B CN 202110116838 A CN202110116838 A CN 202110116838A CN 112574040 B CN112574040 B CN 112574040B
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- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07C—ACYCLIC OR CARBOCYCLIC COMPOUNDS
- C07C201/00—Preparation of esters of nitric or nitrous acid or of compounds containing nitro or nitroso groups bound to a carbon skeleton
- C07C201/06—Preparation of nitro compounds
- C07C201/12—Preparation of nitro compounds by reactions not involving the formation of nitro groups
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- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07C—ACYCLIC OR CARBOCYCLIC COMPOUNDS
- C07C201/00—Preparation of esters of nitric or nitrous acid or of compounds containing nitro or nitroso groups bound to a carbon skeleton
- C07C201/06—Preparation of nitro compounds
- C07C201/08—Preparation of nitro compounds by substitution of hydrogen atoms by nitro groups
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Abstract
The invention belongs to the technical field of medical intermediates, and particularly relates to a synthetic method of 2, 3-dichloro-4-ethyl nitrobenzoate. The invention provides a synthetic method of 2, 3-dichloro-4-ethyl nitrobenzoate, which provides a synthetic route for the synthetic method of 2, 3-dichloro-4-ethyl nitrobenzoate, and the synthetic route is short, reasonable in design, simple in operation and easy to control, and meanwhile, the yield and the purity of the prepared 2, 3-dichloro-4-ethyl nitrobenzoate product are high.
Description
Technical Field
The invention belongs to the technical field of medical intermediates, and particularly relates to a synthetic method of 2, 3-dichloro-4-ethyl nitrobenzoate.
Background
The synthesis method of the compound 2, 3-dichloro-4-ethyl nitrobenzoate and related derivatives have wide application in medicinal chemistry and organic synthesis. At present, the synthesis method of 2, 3-dichloro-4-ethyl nitrobenzoate is only reported in documents. Therefore, it is necessary to develop a synthesis method which has easily available raw materials, convenient operation, easy control of reaction, proper overall yield and suitability for industrial production.
Disclosure of Invention
The technical problems to be solved by the invention are as follows: aiming at the problems, the synthesis method of the 2, 3-dichloro-4-ethyl nitrobenzoate is provided.
In order to solve the technical problems, the invention adopts the following technical scheme:
a synthetic method of 2, 3-dichloro-4-ethyl nitrobenzoate comprises the following chemical formula:
the synthesis method comprises the following steps:
(1) adding the compound A and concentrated sulfuric acid into a reactor, dripping 65% nitric acid by mass at 0-2 ℃, heating, and reacting to obtain a compound B;
(2) mixing the compound B, pyridine and water, heating, adding potassium permanganate, preserving heat, and reacting to obtain a compound C;
(3) and mixing the compound C and thionyl chloride, heating to 60-65 ℃, reacting, removing thionyl chloride, adding ethanol, heating to 80-85 ℃, and reacting to obtain a compound D, namely ethyl 2, 3-dichloro-4-nitrobenzoate.
In the step (1), the mass ratio of the compound A to 65% by mass of nitric acid is 10: 7-9, and the solid-liquid g/mL ratio of the compound A to concentrated sulfuric acid is 1: 5.
In the step (2), the mass ratio of the compound B to the potassium permanganate is 1: 2-5, and the ratio of the compound B to pyridine to water = g: mL: mL is 1:10: 20-25.
The ratio of the compound C, thionyl chloride and ethanol = g: mL: mL in the step (3) is 1:5: 10-15.
Compared with other methods, the method has the beneficial technical effects that:
(1) the invention provides a synthetic method of 2, 3-dichloro-4-ethyl nitrobenzoate, which provides a synthetic route for the synthetic method of 2, 3-dichloro-4-ethyl nitrobenzoate;
(2) the synthetic method of the ethyl 2, 3-dichloro-4-nitrobenzoate provided by the invention is short in route, reasonable in design, simple to operate and easy to control;
(3) the yield and the purity of the 2, 3-dichloro-4-ethyl nitrobenzoate product prepared by the method are high.
Detailed Description
A synthetic method of 2, 3-dichloro-4-ethyl nitrobenzoate comprises the following steps:
(1) taking materials according to the mass ratio of the compound A to 65% nitric acid of 10: 7-9 and the solid-liquid g/mL ratio of the compound A to concentrated sulfuric acid of 1:5, adding the compound A and the concentrated sulfuric acid into a reactor, dripping the 65% nitric acid of the mass fraction at 0-2 ℃, heating to 25-35 ℃, and reacting for 24-26 hours to obtain a compound B;
(2) taking materials according to the mass ratio of the compound B to the potassium permanganate of 1: 2-5, and the mass ratio of the compound B to pyridine to water = g: mL: 20-25, mixing the compound B, the pyridine and the water, heating to 85-90 ℃, adding the potassium permanganate, preserving heat, and reacting for 23-26 h to obtain a compound C;
(3) taking a material according to the ratio of 1:5: 10-15 of compound C, thionyl chloride and ethanol = g: mL: mL, mixing the compound C and the thionyl chloride, heating to 60-65 ℃, reacting for 3-5 h, removing the thionyl chloride, adding ethanol, heating to 80-85 ℃, and reacting for 22-25 h to obtain a compound D, namely the 2, 3-dichloro-4-ethyl nitrobenzoate.
Example 1
A synthetic method of 2, 3-dichloro-4-ethyl nitrobenzoate comprises the following steps:
(1) adding 10g of compound A and 50mL of concentrated sulfuric acid into a reactor, dropwise adding 7g of nitric acid with the mass fraction of 65% at the temperature of 2 ℃, heating to 35 ℃, reacting for 26h, detecting by TLC, slowly pouring the reaction solution into 1000mL of ice water after the reaction of the raw materials is finished, extracting with ethyl acetate (800 mL of 2), concentrating an organic phase, mixing a sample with silica gel, and passing through a column to obtain 12g of yellow solid, namely compound B, wherein the yield is 93.7%, and the purity is 98.2%;
(2) mixing 1g of compound B, 10mL of pyridine and 20mL of water, heating to 90 ℃, adding potassium permanganate, preserving heat, reacting for 26h, detecting by TLC, reacting part of raw materials, filtering while hot, washing with hot water, extracting unreacted raw materials (250 mL x 2) by ethyl acetate, concentrating an aqueous phase to remove pyridine, dropwise adding 4M hydrochloric acid into residues to adjust the pH to about 3, extracting by ethyl acetate, and concentrating an organic phase to obtain 1.05g of yellow oily matter, namely compound C, wherein the yield is 91.7%, and the purity is 96.3%;
(3) mixing 1g of the compound C with 5mL of thionyl chloride, heating to 65 ℃, reacting for 5h, removing thionyl chloride, adding 10mL of ethanol, heating to 85 ℃, reacting for 25h, detecting by TLC, concentrating, removing ethanol, mixing silica gel with a sample to obtain an off-white solid, namely 1.06g of the compound D, namely the 2, 3-dichloro-4-ethyl nitrobenzoate, wherein the yield is 94.7%, and the purity is 98.9%.
1H NMR（CDCl3）: 7.74(d, J=8.4Hz, 1H), 7.68(d, J=8.4Hz, 1H), 4.41(q, J=7.2Hz, 1H), 1.40(t, J=7.2Hz, 1H)。
Example 2
A synthetic method of 2, 3-dichloro-4-ethyl nitrobenzoate comprises the following steps:
(1) adding 10g of compound A and 50mL of concentrated sulfuric acid into a reactor, dropwise adding 7g of nitric acid with the mass fraction of 65% at 0 ℃, heating to 25 ℃, reacting for 24h, detecting by TLC, slowly pouring the reaction solution into 1000mL of ice water after the reaction of the raw materials is finished, extracting with ethyl acetate (800 mL x 2), concentrating an organic phase, mixing a sample with silica gel, and passing through a column to obtain 12.1g of yellow solid, namely compound B, 94.6%, wherein the purity is 97.5%;
(2) mixing 1g of compound B, 10mL of pyridine and 20mL of water, heating to 85 ℃, adding potassium permanganate, preserving heat, reacting for 23h, detecting by TLC (thin layer chromatography), allowing part of raw materials to react, filtering while hot, washing with hot water, extracting unreacted raw materials (250 mL. about.2) by ethyl acetate, concentrating an aqueous phase to remove pyridine, dropwise adding 4M hydrochloric acid into residues to adjust the pH to about 3, extracting by ethyl acetate, and concentrating an organic phase to obtain 1.04g of yellow oily matter, namely compound C, wherein the yield is 90.8%, and the purity is 98.2%;
(3) mixing 1g of the compound C and 5mL of thionyl chloride, heating to 60 ℃, reacting for 3h, removing thionyl chloride, adding 10mL of ethanol, heating to 80 ℃, reacting for 22h, detecting by TLC, concentrating, removing ethanol, mixing silica gel with a sample to obtain an off-white solid, namely 1.1g of the compound D, namely the 2, 3-dichloro-4-ethyl nitrobenzoate, wherein the yield is 98.3%, and the purity is 95.2%.
1H NMR（CDCl3）: 7.74(d, J=8.4Hz, 1H), 7.68(d, J=8.4Hz, 1H), 4.41(q, J=7.2Hz, 1H), 1.40(t, J=7.2Hz, 1H)。
Claims (4)
1. A synthetic method of 2, 3-dichloro-4-ethyl nitrobenzoate is characterized in that the chemical formula of the method is as follows:
the synthesis method comprises the following steps:
(1) adding the compound A and concentrated sulfuric acid into a reactor, dripping 65% nitric acid by mass at 0-2 ℃, heating, and reacting to obtain a compound B;
(2) mixing the compound B, pyridine and water, heating, adding potassium permanganate, preserving heat, and reacting to obtain a compound C;
(3) and mixing the compound C and thionyl chloride, heating to 60-65 ℃, reacting, removing thionyl chloride, adding ethanol, heating to 80-85 ℃, and reacting to obtain a compound D, namely ethyl 2, 3-dichloro-4-nitrobenzoate.
2. The synthesis method of ethyl 2, 3-dichloro-4-nitrobenzoate according to claim 1, wherein in the step (1), the mass ratio of the compound A to nitric acid with a mass fraction of 65% is 10: 7-9, and the solid-liquid g/mL ratio of the compound A to concentrated sulfuric acid is 1: 5.
3. The synthesis method of ethyl 2, 3-dichloro-4-nitrobenzoate according to claim 1, wherein the mass ratio of the compound B to potassium permanganate in the step (2) is 1: 2-5, and the ratio of the compound B to pyridine to water = g: mL: mL is 1:10: 20-25.
4. The method for synthesizing ethyl 2, 3-dichloro-4-nitrobenzoate according to claim 1, wherein the ratio of compound C, thionyl chloride and ethanol = g: mL: mL in step (3) is 1:5: 10-15.
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| CN112250599A (en) * | 2020-11-24 | 2021-01-22 | 阿里生物新材料（常州）有限公司 | Synthesis method of 4-bromo-2-cyano-3-fluorobenzoic acid methyl ester |
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Patent Citations (6)
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| CN111606845A (en) * | 2020-07-20 | 2020-09-01 | 阿里生物新材料（常州）有限公司 | Synthesis method of 4-chloro-6-fluoropyridine-2-alcohol |
| CN111646922A (en) * | 2020-07-21 | 2020-09-11 | 阿里生物新材料（常州）有限公司 | Synthetic method of 2- (4-bromo-2-cyano-6-fluorophenyl) acetic acid |
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