CN104557623A - Preparation method of 4-amino-6-(trichloroethenyl)-1, 3-benzene disulfonamide - Google Patents
Preparation method of 4-amino-6-(trichloroethenyl)-1, 3-benzene disulfonamide Download PDFInfo
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- CN104557623A CN104557623A CN201310500911.6A CN201310500911A CN104557623A CN 104557623 A CN104557623 A CN 104557623A CN 201310500911 A CN201310500911 A CN 201310500911A CN 104557623 A CN104557623 A CN 104557623A
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Abstract
The invention discloses a preparation method of a veterinary drug 4-amino-6-(trichloroethenyl)-1, 3-benzene disulfonamide. The preparation method comprises the following steps: using m-nitrobenzaldehyde as a raw material, and performing condensation reaction, chlorination reaction, elimination reaction reduction reaction, sulfonation reaction and ammoniation reaction to obtain 4-amino-6-(trichloroethenyl)-1, 3-benzene disulfonamide, wherein a catalyst used in the condensation reaction is cesium carbonate; an iridium complex is used as a catalyst in the reduction reaction. The cesium carbonate is used as the catalyst in the condensation reaction and the iridium complex is used as the catalyst in the reduction reaction, so that the whole reaction process is speeded up, and the prepared veterinary drug is good in quality and high in yield.
Description
Technical field
The present invention relates to a kind of preparation method of veterinary medicine, be specifically related to a kind of 4-amino-6--(trichloro-vinyl) preparation method of-1,3-benzene two sulfanilamide (SN), belong to field of medicine preparation.
Background technology
4-amino-6--(trichloro-vinyl)-1,3-benzene two sulfanilamide (SN) can suppress the degrading enzyme of glucose, and block the main energy sources of liver fluke, and play but worm effect.Further research display, 4-amino-6--(trichloro-vinyl)-1,3-benzene two sulfanilamide (SN) energy competitive inhibition 8-phosphoglyceride kinases and phosphoglyceride mutase, blocking glucose oxidase is acetate and propionic salt.In addition, 4-amino-6--(trichloro-vinyl)-1,3-benzene two sulfanilamide (SN) can also suppress adenosine triphyosphate (ATP) level of liver fluke.Subcutaneous injection 4-amino-6--(trichloro-vinyl)-1,3-benzene two sulfanilamide (SN), after administration 24h, reach maximum plasma concentration level, in administration after 21 days, Plasma Concentration maintains treatment level.
For benzene sulfa drugs through a large amount of chemical research and biological test results, prove 4-amino-6-trieline-1,3-benzene N4-sulfanilyl sulfanilamide (4-Amino-6-Trichloroethenyl-1,3-Benzenedisulphonamide) is the most effective to expeling Fasciolidae fluke.Its dosage is 10 milligrams and 15 milligrams calf and sheep per kilogram of body weight, is 97% and 92% to virgin worm anthelmintic efficiency; At ox, sheep per kilogram of body weight single administration 3.75 milligrams.Adult in body can be driven away to the greatest extent.
4-amino-6--(the trichloro-vinyl that data at home and abroad is reported)-1,3-benzene two sulfanilamide (SN) synthetic information is fewer, be that raw material is through reaction preparation 4-amino-6--(trichloro-vinyls such as condensation, chlorination, cancellation, reduction, sulfonation, chlorination, ammonifications usually with m-nitrobenzaldehyde in prior art)-1,3-benzene two sulfanilamide (SN) crude product, 4-amino-6--(trichloro-vinyl has been synthesized again through refining)-1,3-benzene two sulfanilamide (SN).In the reaction of each step, there is combined coefficient lower, the shortcomings such as the cycle is long.
Summary of the invention
The object of this invention is to provide a kind of process safety environmental protection, quality product height synthesis 4-amino-6--(trichloro-vinyl) method of-1,3-benzene two sulfanilamide (SN).Reaction mechanism of the present invention is:
The technical solution realizing the object of the invention is: a kind of 4-amino-6--(trichloro-vinyl)-1, the preparation method of 3-benzene two sulfanilamide (SN), take m-nitrobenzaldehyde as raw material, 4-amino-6--(trichloro-vinyl is obtained after condensation reaction, chlorination reaction, elimination reaction, reduction reaction, sulfonation reaction, aminating reaction)-1,3-benzene two sulfanilamide (SN), the catalyzer adopted in described condensation process is the one in cesium carbonate; Iridium complex catalyzer is adopted in described reduction reaction.
Further, in described condensation reaction, the consumption of cesium carbonate is raw material m-nitrobenzaldehyde 3-5wt%.
Further, in described reduction reaction, iridium complex catalyzer is [Cp*IrCl
2]
2(Cp*=pentamethylcyclopentadienyl).
Further, the consumption of described iridium complex catalyzer is the 0.5-1wt% of erasure.
Advantage of the present invention: have employed cesium carbonate in the condensation reaction as catalyzer, adopts iridium complex as catalyzer in reduction reaction, accelerates process and the productive rate of whole reaction mechanism.
Embodiment
A kind of 4-amino-6--(trichloro-vinyl)-1, the preparation method of 3-benzene two sulfanilamide (SN), its preparation process is: at-10 ~-20 DEG C, m-nitrobenzaldehyde and chloroform are bathed in DMF, add cesium carbonate, be cooled to and carry out condensation reaction between-10 ~-20 DEG C, after chlorination, cancellation, obtain 3 one trichloro-vinyl oil of mirbane, then add iridium complex catalyzer and carry out reduction reaction, 4-amino-6--(trichloro-vinyl is obtained finally by after chlorosulfuric acid, ammonification, purification)-1,3-benzene two sulfanilamide (SN).
Embodiment 1
M-nitrobenzaldehyde 30g and chloroform 15ml is bathed in 120mlDMF, be cooled to-10 ~-20 DEG C, cesium carbonate 0.9g dissolves in methyl alcohol 20ml, drip under passing into condition of nitrogen gas,-15 ~-20 DEG C of insulations are transferred in 200mL toluene and 20mL30% hydrochloric acid soln for 2-3 hour, branch vibration layer, organic layer washed with water, branch vibration layer; Organic layer is purified with after sodium bicarbonate washing, drier, and obtain condenses, yield is 88%; By condenses after chlorination reaction, elimination reaction, 50g elimination products methanol-water is made solvent and makes reductive agent with iron in acid condition, 0.25g iridium complex [Cp*IrCl
2]
2make catalyzer, obtain dark red liquid at normal temperatures through reduction reaction, productive rate is 92%, and last reduzate obtains 4-amino-6--(trichloro-vinyl after chlorosulfuric acid, ammonification, purification)-1,3-benzene two sulfanilamide (SN).
Embodiment 2
M-nitrobenzaldehyde 30g and chloroform 15ml is bathed in 120mlDMF, be cooled to-10 ~-20 DEG C, cesium carbonate 1.5g dissolves in methyl alcohol 20ml, drip under passing into condition of nitrogen gas,-15 ~-20 DEG C of insulations are transferred in 200mL toluene and 20mL30% hydrochloric acid soln for 2-3 hour, branch vibration layer, organic layer washed with water, branch vibration layer; Organic layer is purified with after sodium bicarbonate washing, drier, and obtain condenses, yield is 90%; By condenses after chlorination reaction, elimination reaction, 50g elimination products methanol-water is made solvent and makes reductive agent with iron in acid condition, 0.5g iridium complex [Cp*IrCl
2]
2make catalyzer, obtain dark red liquid at normal temperatures through reduction reaction, productive rate is 96%, and last reduzate obtains 4-amino-6--(trichloro-vinyl after chlorosulfuric acid, ammonification, purification)-1,3-benzene two sulfanilamide (SN).
Embodiment 3
M-nitrobenzaldehyde 30g and chloroform 15ml is bathed in 120mlDMF, be cooled to-10 ~-20 DEG C, cesium carbonate 1.2g dissolves in methyl alcohol 20ml, drip under passing into condition of nitrogen gas,-15 ~-20 DEG C of insulations are transferred in 200mL toluene and 20mL30% hydrochloric acid soln for 2-3 hour, branch vibration layer, organic layer washed with water, branch vibration layer; Organic layer is purified with after sodium bicarbonate washing, drier, and obtain condenses, yield is 89%; By condenses after chlorination reaction, elimination reaction, 50g elimination products methanol-water is made solvent and makes reductive agent with iron in acid condition, 0.4g iridium complex [Cp*IrCl
2]
2make catalyzer, obtain dark red liquid at normal temperatures through reduction reaction, productive rate is 90%, and last reduzate obtains 4-amino-6--(trichloro-vinyl after chlorosulfuric acid, ammonification, purification)-1,3-benzene two sulfanilamide (SN).
Claims (4)
1. a 4-amino-6--(trichloro-vinyl)-1, the preparation method of 3-benzene two sulfanilamide (SN), it is characterized in that taking m-nitrobenzaldehyde as raw material, 4-amino-6--(trichloro-vinyl is obtained after condensation reaction, chlorination reaction, elimination reaction, reduction reaction, sulfonation reaction, aminating reaction)-1,3-benzene two sulfanilamide (SN), the catalyzer adopted in described condensation process is the one in cesium carbonate; Iridium complex catalyzer is adopted in described reduction reaction.
2. 4-amino-6--(trichloro-vinyl according to claim 1) preparation method of-1,3-benzene two sulfanilamide (SN), it is characterized in that the consumption of cesium carbonate in described condensation reaction is raw material m-nitrobenzaldehyde 3-5wt%.
3. 4-amino-6--(trichloro-vinyl according to claim 1) preparation method of-1,3-benzene two sulfanilamide (SN), it is characterized in that in described reduction reaction, iridium complex catalyzer is [Cp*IrCl
2]
2.
4. 4-amino-6--(trichloro-vinyl according to claim 1) preparation method of-1,3-benzene two sulfanilamide (SN), it is characterized in that the consumption of described iridium complex catalyzer is the 0.5-1wt% of erasure.
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| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| CN201310500911.6A CN104557623A (en) | 2013-10-23 | 2013-10-23 | Preparation method of 4-amino-6-(trichloroethenyl)-1, 3-benzene disulfonamide |
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| CN201310500911.6A CN104557623A (en) | 2013-10-23 | 2013-10-23 | Preparation method of 4-amino-6-(trichloroethenyl)-1, 3-benzene disulfonamide |
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Cited By (2)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN107868024A (en) * | 2017-10-25 | 2018-04-03 | 浙江海正药业股份有限公司 | Crystal formation of MK-401 and its production and use |
| CN113773235A (en) * | 2021-08-20 | 2021-12-10 | 北大方正集团有限公司 | Synthesis method of clorsulon |
-
2013
- 2013-10-23 CN CN201310500911.6A patent/CN104557623A/en active Pending
Non-Patent Citations (2)
| Title |
|---|
| ALESSANDRO ZANARDI，ET AL: "One-Pot Preparation of Imines from Nitroarenes by a Tandem Process with an Ir–Pd Heterodimetallic Catalyst", 《CHEM.EUR.J.》 * |
| 杨典文: "三氟甲磺酸镱在有机合成中的应用以及氯舒隆的合成研究", 《万方数据硕士论文库》 * |
Cited By (3)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN107868024A (en) * | 2017-10-25 | 2018-04-03 | 浙江海正药业股份有限公司 | Crystal formation of MK-401 and its production and use |
| CN113773235A (en) * | 2021-08-20 | 2021-12-10 | 北大方正集团有限公司 | Synthesis method of clorsulon |
| CN113773235B (en) * | 2021-08-20 | 2022-06-17 | 北大方正集团有限公司 | Synthesis method of clorsulon |
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Application publication date: 20150429 |