CN102816118A - Catalytic synthesis method of mefenpyr-diethyl - Google Patents
Catalytic synthesis method of mefenpyr-diethyl Download PDFInfo
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- CN102816118A CN102816118A CN2012101945451A CN201210194545A CN102816118A CN 102816118 A CN102816118 A CN 102816118A CN 2012101945451 A CN2012101945451 A CN 2012101945451A CN 201210194545 A CN201210194545 A CN 201210194545A CN 102816118 A CN102816118 A CN 102816118A
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Abstract
The invention discloses a catalytic synthesis method of (RS)-1-(2,4-dichlorophenyl)-5-methyl-2-pyrazol-3,5-dicarboxylate, comprising the following steps of: A, diazotization: a diazo reaction is carried out by the use of 2,4-dichloroaniline, hydrochloric acid and sodium nitrite so as to obtain aniline diazo salt; B, synthesis of chloro-ethyl acetoacetate: chlorination is carried out by the use of ethyl acetoacetate and sulfuric chloride to obtain chloro-ethyl acetoacetate; C, synthesis of 2-chlorine-2-(2,4-dichlorophenylhydrazone)-ethyl glyoxalate: diazo salt obtained from the step A reacts with chloro-ethyl acetoacetate obtained from the step B under the action of a catalyst to obtain 2-chlorine-2-(2,4-dichlorophenylhydrazone)-ethyl glyoxalate; and D, cyclization: a cyclization reaction between 2-chlorine-2-(2,4-dichlorophenylhydrazone)-ethyl glyoxalate obtained from the step C and methyl methacrylate is carried out so as to obtain (RS)-1-(2,4-dichlorophenyl)-5-methyl-2-pyrazol-3,5-dicarboxylate. The method provided by the invention has advantages of simple technology, easily-obtained raw materials and high yield of the product.
Description
Technical field
The invention belongs to the medical compounds field, be specifically related to a kind of (RS)-1-(2,4 dichloro benzene base)-5-antazoline-3,5-diethyl dicarboxylate's process for catalytic synthesis.
Background technology
(RS)-and 1-(2,4 dichloro benzene base)-5-antazoline-3, the 5-diethyl dicarboxylate, its structural formula does
According to EP0635996, be raw material with the 2,4 dichloro aniline; At first make midbody 2,4 dichloro benzene hydrazine, generate azo with ethyl oxalyl chloride again; Obtain 2-chloro-2-(2 with the phosphorus pentachloride chlorination again; 4-dichlorobenzene hydrazone group)-and glyoxylic acid ethyl ester, carry out the Michael addition reaction with Jia Jibingxisuanyizhi then, obtain object with the alkali cyclization again.
This complex process, yield is low.
Summary of the invention
The objective of the invention is to address the above problem, a kind of (RS)-1-(2,4 dichloro benzene base)-5-antazoline-3 is provided; 5-diethyl dicarboxylate's compound method; It comprises with the 2,4 dichloro aniline being starting raw material, and diazotization forms diazonium salt; Reaction obtains 2-chloro-2-(2 with methyl aceto acetate chlorating product chloro ethyl acetoacetate again; 4-dichlorobenzene hydrazone group)-glyoxylic acid ethyl ester, 2-chloro-2-(2,4 dichloro benzene the hydrazone group)-glyoxylic acid ethyl ester that obtains directly and the Jia Jibingxisuanyizhi cyclization obtain object.
The object of the invention can reach through following measure:
(RS)-1-(2,4 dichloro benzene base)-5-methyl-2-pyrazoles-3 is synthesized in a kind of catalysis, 5-diethyl dicarboxylate's method, and it comprises the steps:
A, diazotization: carry out doazo reaction with 2,4 dichloro aniline, hydrochloric acid and Sodium Nitrite, obtain the diazonium salt of aniline, reaction formula is following:
In steps A, use 2,4 dichloro aniline, hydrochloric acid and Sodium Nitrite to carry out the diazonium salt solution that doazo reaction is prepared aniline, its temperature of reaction between-10 ℃～10 ℃, preferred-10 ℃～0 ℃.This reaction solvent is a water.Wherein the mol ratio of 2,4 dichloro aniline and Sodium Nitrite is 1:0.9～1.5.The concentration of the hydrochloric acid that is adopted among the present invention is generally about 36%-38%.
Synthesizing of B, chloro ethyl acetoacetate: carry out chlorination with methyl aceto acetate and sulfuryl chloride and obtain chloro ethyl acetoacetate, reaction formula is following:
In step B; Use methyl aceto acetate and sulfuryl chloride to carry out chlorination and prepare chloro ethyl acetoacetate, wherein the mol ratio of methyl aceto acetate and sulfuryl chloride is 1:0.9～1.1, preferred 1:1～1.05; Temperature of reaction is between-10 ℃～20 ℃, preferred 0 ℃～10 ℃.
C, 2-chloro-2-(2; 4-dichlorobenzene hydrazone group)-and glyoxylic acid ethyl ester synthetic: the chloro ethyl acetoacetate that uses diazonium salt that steps A obtains and step B to obtain reacts under catalyst action and obtains 2-chloro-2-(2; 4-dichlorobenzene hydrazone group)-and glyoxylic acid ethyl ester (formula II), reaction formula is following:
In step C, can directly use diazonium salt solution and chloro ethyl acetoacetate under the catalysis of catalyst acetic acid sodium, reaction obtains 2-chloro-2-(2,4 dichloro benzene hydrazone group)-glyoxylic acid ethyl ester.Employed solvent is selected from alcoholic solvent, water, particular methanol and/or water.Diazonium salt and chloro ethyl acetoacetate mol ratio are 1:0.9～1.2, preferred 1:1～1.1, and catalyst acetic acid sodium usage quantity is 6～10 times of chloro ethyl acetoacetate mole number, and is preferred: 7～9 times; Temperature of reaction is at 0 ℃～40 ℃, and is preferred, 5 ℃～30 ℃.
D, cyclization: the 2-chloro-2-(2 that obtains with step C; 4-dichlorobenzene hydrazone group)-glyoxylic acid ethyl ester (formula II) and Jia Jibingxisuanyizhi carry out ring-closure reaction, obtain (RS)-1-(2,4 dichloro benzene base)-5-antazoline-3; The 5-diethyl dicarboxylate, reaction formula is following:
In step D, use the cyclization under the situation of triethylamine and saleratus catalysis and stopper (on a small quantity) existence of 2-chloro-2-(2,4 dichloro benzene hydrazone group)-glyoxylic acid ethyl ester and Jia Jibingxisuanyizhi to prepare title product; Wherein the mol ratio of 2-chloro-2-(2,4 dichloro benzene hydrazone group)-glyoxylic acid ethyl ester and Jia Jibingxisuanyizhi is 1:1～6, preferred 1:2～4.5; Triethylamine and saleratus add-on are an amount of; Generally speaking, the consumption of triethylamine is 1～10% of said 2-chloro-2-(2,4 dichloro benzene hydrazone group)-glyoxylic acid ethyl ester quality; The consumption of saleratus is said 2-chloro-2-(2; 4-dichlorobenzene hydrazone group)-the glyoxylic acid ethyl ester quality 20～50%, the consumption of stopper is 0.1～1% of said 2-chloro-2-(2,4 dichloro benzene hydrazone group)-glyoxylic acid ethyl ester quality.This step temperature of reaction is in 30 ℃～80 ℃ scopes, and is preferred, 40 ℃～60 ℃.Stopper is phenol stopper or radical type stopper, like 2,5 di tert butyl hydroquinone or Resorcinol etc.
Technology of the present invention is simple, and raw material is easy to get, and product yield is high, is prone to suitability for industrialized production, and the products obtained therefrom quality is high, has avoided using the strong phosphorus pentachloride of the big danger of toxicity.
Embodiment
Embodiment 1, chloro ethyl acetoacetate synthetic
In reaction flask, add the 1mol methyl aceto acetate, open and stir, cooling; Treat that temperature of charge reduces to 0 ℃, begin to drip the 1.05mol sulfuryl chloride, the dropping process remains temperature 0-5 ℃; 2 hours dropping time, after dropwising, be incubated 0.5 hour; To control in the sampling, triethyl is residual≤and 0.2% reaction is end.Be warming up to 80 ℃, be incubated 1 hour.Be chilled under 50 ℃ after insulation finishes, add water 100ml again, stir half a hour after, static layering, the organic layer washing obtains chloro ethyl acetoacetate, content 98%, yield 97% to neutral.
Embodiment 2,2-chloro-2-(2,4 dichloro benzene hydrazone group)-glyoxylic acid ethyl ester synthetic
In reaction flask, drop into hydrochloric acid 350ml and water 400ml, open stirring, drop into 100g2,4-dichlorphenamide bulk powder again, be chilled to (more than 10 ℃) below 0 ℃, begin to drip sodium nitrite in aqueous solution (44g Sodium Nitrite, 100ml water), dripped time 2-2.5 hour.Whole dropping process guarantees that the material temperature is between-5～0 ℃.The diazonium salt that generates is for use.
In another reaction flask, drop into 600ml methyl alcohol and 200ml water, under agitation drop into the 400g sodium-acetate, add 110g chloro triethyl (being chloro ethyl acetoacetate) again.Be cooled to 15 ℃, begin to drip diazonium liquid, about 1 hour of whole dropping time.Drip and finish, then be incubated 3 hours, insulation finishes, discharging, and suction filtration is analyzed, and obtains 2-chloro-2-(2,4 dichloro benzene hydrazone group)-glyoxylic acid ethyl ester 171g, content 95%, yield 94.9%.Fusing point: 98 ℃ of 95 ∽.
Embodiment 3, cyclization
In reaction flask, drop into 500g Jia Jibingxisuanyizhi and 450g (95%) 2-chloro-2-(2; 4-dichlorobenzene hydrazone group)-glyoxylic acid ethyl ester; Add triethylamine 10g and 2 again; 5-di-tert-butyl hydroquinone 2g is warming up to 60 ℃ and begins to drip potassium bicarbonate solution (the 150g saleratus is dissolved in 550mL water), drips off in about 3 hours.Drip and finish, be incubated 2.5 hours, static 30 minutes, tell lower floor's waste water.Begin to heat up, the high vacuum precipitation, precipitation finishes, and adds methyl alcohol 350mL, and cooling treats that temperature arrives-5 ℃, and is centrifugal, obtains the 505g product, content 95.2%, yield 88%.Fusing point: 52 ℃ of 50 ∽.Embodiment 4, chloro ethyl acetoacetate synthetic
In reaction flask, add the 1mol methyl aceto acetate, open and stir, cooling; Treat that temperature of charge reduces to 5 ℃, begin to drip the 1.02mol sulfuryl chloride, the dropping process remains temperature 0-5 ℃; 3 hours dropping time, after dropwising, be incubated 1 hour; To control in the sampling, triethyl is residual≤and 0.2% reaction is end.Be warming up to 80 ℃, be incubated 1 hour.Be chilled under 50 ℃ after insulation finishes, add water 100ml again, stir half a hour after, static layering, the organic layer washing obtains chloro ethyl acetoacetate, content 97.5%, yield 96.8% to neutral.
Embodiment 5,2-chloro-2-(2,4 dichloro benzene hydrazone group)-glyoxylic acid ethyl ester synthetic
In reaction flask, drop into hydrochloric acid 320ml and water 400ml, open stirring, drop into 100g 2,4-dichlorphenamide bulk powder again, be chilled to (more than 10 ℃) below 0 ℃, begin to drip sodium nitrite in aqueous solution (50g Sodium Nitrite, 100ml water), 2 hours dropping time.Whole dropping process guarantees that the material temperature is between-5～0 ℃.The diazonium salt that generates is for use.
In another reaction flask, drop into 600ml methyl alcohol and 200ml water, under agitation drop into the 450g sodium-acetate, add 120g chloro triethyl again.Be cooled to 15 ℃, begin to drip diazonium liquid, about 1 hour of whole dropping time.Drip and finish, then be incubated 3 hours, insulation finishes, discharging, and suction filtration is analyzed, and obtains 2-chloro-2-(2,4 dichloro benzene hydrazone group)-glyoxylic acid ethyl ester 169g, content 95.5%, yield 95.1%.Fusing point: 98 ℃ of 95 ∽.
Embodiment 6, cyclization
In reaction flask, drop into 600g Jia Jibingxisuanyizhi and 450g (95%) 2-chloro-2-(2; 4-dichlorobenzene hydrazone group)-glyoxylic acid ethyl ester; Add triethylamine 18g and Resorcinol 2g again; Be warming up to 60 ℃ and begin to drip potassium bicarbonate solution (the 160g saleratus is dissolved in 550mL water), dripped off in about 3 hours.Drip and finish, be incubated 2.5 hours, static 30 minutes, tell lower floor's waste water.Begin to heat up, the high vacuum precipitation, precipitation finishes, and adds methyl alcohol 350mL, and cooling treats that temperature arrives-5 ℃, and is centrifugal, obtains the 509g product, content 95.6%, yield 90.1%.Fusing point: 52 ℃ of 50 ∽.
Claims (10)
1. (RS)-1-(2,4 dichloro benzene base)-5-methyl-2-pyrazoles-3 is synthesized in a catalysis, and 5-diethyl dicarboxylate's method is characterized in that comprising the steps:
A, diazotization: carry out doazo reaction with 2,4 dichloro aniline, hydrochloric acid and Sodium Nitrite, obtain the diazonium salt of aniline,
Synthesizing of B, chloro ethyl acetoacetate: carry out chlorination with methyl aceto acetate and sulfuryl chloride and obtain chloro ethyl acetoacetate,
Synthesizing of C, 2-chloro-2-(2,4 dichloro benzene hydrazone group)-glyoxylic acid ethyl ester: the chloro ethyl acetoacetate that diazonium salt that the use steps A obtains and step B obtain reacts under catalyst action and obtains 2-chloro-2-(2,4 dichloro benzene hydrazone group)-glyoxylic acid ethyl ester,
D, cyclization: 2-chloro-2-(2,4 dichloro benzene the hydrazone group)-glyoxylic acid ethyl ester and the Jia Jibingxisuanyizhi that obtain with step C carry out ring-closure reaction, obtain (RS)-1-(2,4 dichloro benzene base)-5-antazoline-3, the 5-diethyl dicarboxylate,
2. method according to claim 1 is characterized in that in the steps A, and the temperature of doazo reaction is-10 ℃～10 ℃, and reaction solvent is a water.
3. method according to claim 1 is characterized in that in the steps A, and the mol ratio of 2,4 dichloro aniline and Sodium Nitrite is 1:0.9～1.5.
4. method according to claim 1 is characterized in that among the step B that the mol ratio of methyl aceto acetate and sulfuryl chloride is 1:0.9～1.1, and chlorination reaction temperature is-10 ℃～20 ℃.
5. method according to claim 4 is characterized in that among the step B that the mol ratio of methyl aceto acetate and sulfuryl chloride is 1:1～1.05, and chlorination reaction temperature is 0 ℃～10 ℃.
6. method according to claim 1 is characterized in that among the step C that said catalyzer is a sodium-acetate; The solvent that reacts among the step C is selected from alcoholic solvent or water, and temperature of reaction is 0 ℃～40 ℃.
7. method according to claim 6 is characterized in that among the step C that the solvent of reaction is methyl alcohol and/or water, and temperature of reaction is 5 ℃～30 ℃.
8. method according to claim 6 is characterized in that among the step C that the mol ratio of diazonium salt and chloro ethyl acetoacetate is 1:0.9～1.2, and catalyst acetic acid sodium usage quantity is 6～10 times of chloro ethyl acetoacetate molar weight.
9. method according to claim 1 is characterized in that among the step D, 2-chloro-2-(2,4 dichloro benzene hydrazone group)-glyoxylic acid ethyl ester and Jia Jibingxisuanyizhi under the catalysis of triethylamine and saleratus with stopper in the presence of ring-closure reaction; The mol ratio of said chlorine hydrazone and Jia Jibingxisuanyizhi is 1:1～6; Said stopper is phenol stopper or radical type stopper; The ring-closure reaction temperature is 30 ℃～80 ℃.
10. method according to claim 1 is characterized in that among the step D, and the mol ratio of 2-chloro-2-(2,4 dichloro benzene hydrazone group)-glyoxylic acid ethyl ester and Jia Jibingxisuanyizhi is 1:2～4.5; The quality of triethylamine is 1～10% of said 2-chloro-2-(2,4 dichloro benzene hydrazone group)-glyoxylic acid ethyl ester quality, and the quality of saleratus is 20～50% of said 2-chloro-2-(2,4 dichloro benzene hydrazone group)-glyoxylic acid ethyl ester quality; The quality of stopper is 0.1～1% of said 2-chloro-2-(2,4 dichloro benzene hydrazone group)-glyoxylic acid ethyl ester quality, and said stopper is 2,5 di tert butyl hydroquinone or Resorcinol; The ring-closure reaction temperature is 40 ℃～60 ℃.
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Cited By (7)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN103833550A (en) * | 2014-03-25 | 2014-06-04 | 杜承贤 | Preparation method for organic intermediate 2-chloroacetoacetic acid ethyl ester |
| WO2017092466A1 (en) * | 2015-12-02 | 2017-06-08 | Rotam Agrochem International Company Limited | Novel form of mefenpyr-diethyl,process for preparation and use thereof |
| CN110003107A (en) * | 2019-04-28 | 2019-07-12 | 东华大学 | A kind of synthetic method of mefenpyrdiethyl |
| CN110724144A (en) * | 2019-10-16 | 2020-01-24 | 江苏艾科姆检测有限公司 | Pyrazolidone impurity, preparation method and application |
| CN111592493A (en) * | 2020-05-30 | 2020-08-28 | 上海赫腾精细化工有限公司 | Preparation method of mefenpyr-diethyl |
| CN112409203A (en) * | 2019-08-23 | 2021-02-26 | 帕潘纳(北京)科技有限公司 | Method for simultaneously synthesizing phenylhydrazine salt and pyruvic acid or glyoxylic acid |
| CN113429347A (en) * | 2021-04-29 | 2021-09-24 | 江苏永凯化学有限公司 | Preparation method of high-purity mefenpyr-diethyl |
Citations (4)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN1051078C (en) * | 1989-11-30 | 2000-04-05 | 赫彻斯特股份公司 | Pyrazolinyl compounds for preventing crop from detriment of herbicides |
| CN1269791A (en) * | 1997-09-09 | 2000-10-11 | 赫彻斯特-舍林农业发展有限公司 | Method for preparing 1-phenylpyrrazolin-3-carboxylic acid derivatives |
| CN1721414A (en) * | 2005-06-15 | 2006-01-18 | 浙江大学 | Process for synthesizing 2-p-trifluoro toluene-4-methyl-5-thiazolyl ethyl formate |
| EP1947088A1 (en) * | 2007-01-17 | 2008-07-23 | Laboratorios del Dr. Esteve S.A. | Substituted pyrazoline compounds with ACAT inhibition activity, their preparation and use as medicaments |
-
2012
- 2012-06-13 CN CN2012101945451A patent/CN102816118A/en active Pending
Patent Citations (4)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN1051078C (en) * | 1989-11-30 | 2000-04-05 | 赫彻斯特股份公司 | Pyrazolinyl compounds for preventing crop from detriment of herbicides |
| CN1269791A (en) * | 1997-09-09 | 2000-10-11 | 赫彻斯特-舍林农业发展有限公司 | Method for preparing 1-phenylpyrrazolin-3-carboxylic acid derivatives |
| CN1721414A (en) * | 2005-06-15 | 2006-01-18 | 浙江大学 | Process for synthesizing 2-p-trifluoro toluene-4-methyl-5-thiazolyl ethyl formate |
| EP1947088A1 (en) * | 2007-01-17 | 2008-07-23 | Laboratorios del Dr. Esteve S.A. | Substituted pyrazoline compounds with ACAT inhibition activity, their preparation and use as medicaments |
Non-Patent Citations (2)
| Title |
|---|
| NORBERT DE KIMPE: "A Convenient Synthesis of 1-Chloro-2-allkanones", 《SYNTHESIS》, no. 2, 28 February 1987 (1987-02-28), pages 188 - 190 * |
| V.S. MATIICHUK ETAL: "Molecular design of pyrazolo[3,4-d]pyridazines", 《RUSSIAN JOURNAL OF ORGANIC CHEMISTRY》, vol. 44, no. 9, 1 September 2008 (2008-09-01), pages 1352 - 1361 * |
Cited By (10)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN103833550A (en) * | 2014-03-25 | 2014-06-04 | 杜承贤 | Preparation method for organic intermediate 2-chloroacetoacetic acid ethyl ester |
| WO2017092466A1 (en) * | 2015-12-02 | 2017-06-08 | Rotam Agrochem International Company Limited | Novel form of mefenpyr-diethyl,process for preparation and use thereof |
| US9809555B2 (en) | 2015-12-02 | 2017-11-07 | Rotam Agrochem International Company Limited | Form of mefenpyr-diethyl, a process for its preparation and use of the same |
| CN110003107A (en) * | 2019-04-28 | 2019-07-12 | 东华大学 | A kind of synthetic method of mefenpyrdiethyl |
| CN110003107B (en) * | 2019-04-28 | 2022-09-16 | 东华大学 | Synthetic method of mefenpyr-diethyl |
| CN112409203A (en) * | 2019-08-23 | 2021-02-26 | 帕潘纳(北京)科技有限公司 | Method for simultaneously synthesizing phenylhydrazine salt and pyruvic acid or glyoxylic acid |
| CN110724144A (en) * | 2019-10-16 | 2020-01-24 | 江苏艾科姆检测有限公司 | Pyrazolidone impurity, preparation method and application |
| CN111592493A (en) * | 2020-05-30 | 2020-08-28 | 上海赫腾精细化工有限公司 | Preparation method of mefenpyr-diethyl |
| CN111592493B (en) * | 2020-05-30 | 2021-11-09 | 上海赫腾精细化工有限公司 | Preparation method of mefenpyr-diethyl |
| CN113429347A (en) * | 2021-04-29 | 2021-09-24 | 江苏永凯化学有限公司 | Preparation method of high-purity mefenpyr-diethyl |
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Application publication date: 20121212 |