CN104059020A - Preparation method for 1-aryl-5-hydroxy pyrazol - Google Patents
Preparation method for 1-aryl-5-hydroxy pyrazol Download PDFInfo
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- CN104059020A CN104059020A CN201410298552.5A CN201410298552A CN104059020A CN 104059020 A CN104059020 A CN 104059020A CN 201410298552 A CN201410298552 A CN 201410298552A CN 104059020 A CN104059020 A CN 104059020A
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- hydroxypyrazoles
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- methyl acrylate
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- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D231/00—Heterocyclic compounds containing 1,2-diazole or hydrogenated 1,2-diazole rings
- C07D231/02—Heterocyclic compounds containing 1,2-diazole or hydrogenated 1,2-diazole rings not condensed with other rings
- C07D231/10—Heterocyclic compounds containing 1,2-diazole or hydrogenated 1,2-diazole rings not condensed with other rings having two or three double bonds between ring members or between ring members and non-ring members
- C07D231/14—Heterocyclic compounds containing 1,2-diazole or hydrogenated 1,2-diazole rings not condensed with other rings having two or three double bonds between ring members or between ring members and non-ring members with hetero atoms or with carbon atoms having three bonds to hetero atoms with at the most one bond to halogen, e.g. ester or nitrile radicals, directly attached to ring carbon atoms
- C07D231/18—One oxygen or sulfur atom
- C07D231/20—One oxygen atom attached in position 3 or 5
- C07D231/22—One oxygen atom attached in position 3 or 5 with aryl radicals attached to ring nitrogen atoms
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Abstract
The invention discloses a preparation method for 1-aryl-5-hydroxy pyrazol. According to the preparation method, the 1-aryl-5-hydroxy pyrazol is prepared by reaction of aryl hydrazine or hydrochloride of the aryl hydrazine and methoxy methyl acrylate in a solvent, and the chemical reaction formula is as shown in the specification. The preparation method for 1-aryl-5-hydroxy pyrazol is simple, has few reaction steps, is easy to operate, has the product yield greater than 50%, which is much higher than that of the prior art, uses the raw materials of wide source, and is applicable to industrial production.
Description
Technical field
The present invention relates to the preparation method of 1-aryl-5-hydroxypyrazoles.Be specifically related to prepare taking the hydrochloride of aryl hydrazines or aryl hydrazines and methoxy-methyl acrylate as raw material the method for 1-aryl-5-hydroxypyrazoles.
Background technology
1-aryl-5-hydroxypyrazoles and derivative thereof, there is extensive and important purposes, be the intermediate of Multiple Pesticides, medicinal activity compound, patent WO2010135536 discloses the derivative of class 1-aryl-5-hydroxypyrazoles in the application reducing in blood uric acid level; The application of the derivative that patent US2004057588 discloses class 1-aryl-5-hydroxypyrazoles on treating AIDS; The application of the derivative that patent WO2008023235 discloses class 1-aryl-5-hydroxypyrazoles on thrombus treatment.
About synthesizing of 1-aryl-5-hydroxypyrazoles, probably there is following synthetic method at present:
One, aryl hydrazines and diethyl ethoxymethylenemalonate obtain 1-aryl-5-hydroxypyrazoles through cyclization, decarboxylation two steps.The method obtains 1-phenyl-5-hydroxypyrazoles with two step total recoverys 36%.
Two, aryl hydrazines and the cyclization of 3,3-dimethoxy methyl propionate obtain 1-aryl-5-hydroxypyrazoles.The method obtains 1-(the chloro-4-aminomethyl phenyl of 2-)-5-hydroxypyrazoles with 24% yield.
Summary of the invention
The object of the invention is to prepare the problems such as the method product yield of 1-aryl-5-hydroxypyrazoles is not high in order to overcome prior art, provide a kind of hydrochloride that adopts aryl hydrazines or aryl hydrazines in solvent, to react the method for preparing 1-aryl-5-hydroxypyrazoles with methoxy-methyl acrylate.
Chemical equation is as follows:
In formula, n represents the integer of 1-3, and R is hydrogen atom or halogen atom, nitro, cyano group, alkoxyl group, alkyl, trihalogenmethyl.
Solvent of the present invention is one or more mixtures in methyl alcohol, ethanol, n-propyl alcohol, Virahol, propyl carbinol, isopropylcarbinol, the trimethyl carbinol, and the feed ratio of solvent and methoxy-methyl acrylate is volume (mL) with mmole (mmol) than 0.2～200 ︰ 1; The molar ratio of described aryl hydrazines or the hydrochloride of aryl hydrazines and methoxy-methyl acrylate is 1 ︰ 0.7～1.4.; Temperature of reaction is 40 DEG C of temperature that reflux to reaction solvent, and the reaction times is 1～240h.
The preparation method of 1-aryl-5-hydroxypyrazoles provided by the invention, technique is simple, reactions steps is few, easy to operate, product yield > 50%, far above prior art, raw material sources are extensive, are applicable to suitability for industrialized production.
Embodiment
Below in conjunction with embodiment, the invention will be further described.
Embodiment 1
In three mouthfuls of reaction flasks, add 17.9g (100mmol) p-hydrochloride, 11.6g (100mmol) methoxy-methyl acrylate, 100mL methyl alcohol.Be warming up to back flow reaction about 6 hours, reaction solution is quantitative by liquid chromatography, 1-rubigan-5-hydroxypyrazoles yield 81.3%.
Embodiment 2
In three mouthfuls of reaction flasks, add 10.8g (100mmol) phenylhydrazine, 11.6g (100mmol) methoxy-methyl acrylate, 100mL methyl alcohol.Be warming up to back flow reaction about 6 hours, reaction solution is quantitative by liquid chromatography, 1-phenyl-5-hydroxypyrazoles yield 85.7%.
Embodiment 3
In three mouthfuls of reaction flasks, add 15.3g (100mmol) 2-nitrophenyl hydrazine, 11.6g (100mmol) methoxy-methyl acrylate, 100mL methyl alcohol.Be warming up to 40 DEG C of reactions about 6 hours, reaction solution is quantitative by liquid chromatography, and 1-is to nitre phenyl-5-hydroxypyrazoles yield 52.6%.
Embodiment 4
In three mouthfuls of reaction flasks, add 21.2g (100mmol) 3-trifluoromethyl phenyl hydrazine hydrochloride, 11.6g (100mmol) methoxy-methyl acrylate, 100mL methyl alcohol.Be warming up to back flow reaction about 6 hours, reaction solution is quantitative by liquid chromatography, 1-(3-trifluoromethyl)-5-hydroxypyrazoles yield 64.8%.
Embodiment 5
In three mouthfuls of reaction flasks, add 17.5g (100mmol) 4-methoxyphenyl hydrazine hydrochloride, 11.6g (100mmol) methoxy-methyl acrylate, 100mL methyl alcohol.Be warming up to back flow reaction about 6 hours, reaction solution is quantitative by liquid chromatography, 1-(4-p-methoxy-phenyl)-5-hydroxypyrazoles yield 79.3%.
Embodiment 6
In three mouthfuls of reaction flasks, add 20.1g (100mmol) 4-tertiary butyl hydrazinobenzene hydrochloride salt, 11.6g (100mmol) methoxy-methyl acrylate, 100mL methyl alcohol.Be warming up to back flow reaction about 6 hours, reaction solution is quantitative by liquid chromatography, 1-(4-tert-butyl-phenyl)-5-hydroxypyrazoles yield 84.1%.
Embodiment 7
In three mouthfuls of reaction flasks, add 1.77g (10mmol) 5-fluoro-2-methylbenzene hydrazonium salt hydrochlorate, 1.16g (10mmol) methoxy-methyl acrylate, 10mL methyl alcohol.Be warming up to back flow reaction about 6 hours, reaction solution is quantitative by liquid chromatography, 1-(5-fluoro-2-methylbenzene base)-5-hydroxypyrazoles yield 75.9%.
Embodiment 8
In three mouthfuls of reaction flasks, add 1.70g (10mmol) 4-cyano group hydrazinobenzene hydrochloride salt, 1.16g (10mmol) methoxy-methyl acrylate, 10mL methyl alcohol.Be warming up to back flow reaction about 6 hours, reaction solution is quantitative by liquid chromatography, 1-(5-cyanogen-2-aminomethyl phenyl)-5-hydroxypyrazoles yield 64.2%.
Embodiment 9
In three mouthfuls of reaction flasks, add 17.9g (100mmol) p-hydrochloride, 11.6g (100mmol) methoxy-methyl acrylate, 100mL methyl alcohol.Be warming up to 40 DEG C of reactions about 240 hours, reaction solution is quantitative by liquid chromatography, 1-rubigan-5-hydroxypyrazoles yield 72.4%.
Embodiment 10
In three mouthfuls of reaction flasks, add 17.9g (100mmol) p-hydrochloride, 11.6g (100mmol) methoxy-methyl acrylate, 100mL ethanol.Be warming up to 40 DEG C of reactions about 1 hour, reaction solution is quantitative by liquid chromatography, 1-rubigan-5-hydroxypyrazoles yield 43.6%.
Embodiment 11
In three mouthfuls of reaction flasks, add 17.9g (100mmol) p-hydrochloride, 11.6g (100mmol) methoxy-methyl acrylate, 20mL methyl alcohol.Heat up 40 DEG C to back flow reaction about 6 hours, reaction solution is quantitative by liquid chromatography, 1-rubigan-5-hydroxypyrazoles yield 51.1%.
Embodiment 12
In three mouthfuls of reaction flasks, add 17.9g (100mmol) p-hydrochloride, 11.6g (100mmol) methoxy-methyl acrylate, 20mL methyl alcohol.Heat up 40 DEG C to back flow reaction about 6 hours, reaction solution is quantitative by liquid chromatography, 1-rubigan-5-hydroxypyrazoles yield 51.1%.
Embodiment 13
In three mouthfuls of reaction flasks, add 1.79g (10mmol) p-hydrochloride, 1.16g (10mmol) methoxy-methyl acrylate, 2000mL methyl alcohol.Heat up 40 DEG C to back flow reaction about 6 hours, reaction solution is quantitative by liquid chromatography, 1-rubigan-5-hydroxypyrazoles yield 82.5%.
Embodiment 14
In three mouthfuls of reaction flasks, add 17.9g (100mmol) p-hydrochloride, 16.2g (140mmol) methoxy-methyl acrylate, 30mL n-propyl alcohol, 30mL Virahol, 30mL propyl carbinol, 30mL isopropylcarbinol.Be warming up to 55 DEG C of reactions about 6 hours, reaction solution is quantitative by liquid chromatography, 1-rubigan-5-hydroxypyrazoles yield 74.3%.
Embodiment 15
In three mouthfuls of reaction flasks, add 17.9g (100mmol) p-hydrochloride, 8.1g (70mmol) methoxy-methyl acrylate, 100mL isopropylcarbinol.Be warming up to 60 DEG C of reactions about 6 hours, reaction solution is quantitative by liquid chromatography, 1-rubigan-5-hydroxypyrazoles yield 64.4%.
Embodiment 16
In three mouthfuls of reaction flasks, add 17.9g (100mmol) p-hydrochloride, 11.6g (100mmol) methoxy-methyl acrylate, the 100mL trimethyl carbinol.Be warming up to back flow reaction about 6 hours, reaction solution is quantitative by liquid chromatography, 1-rubigan-5-hydroxypyrazoles yield 79.1%.
Embodiment 17
In three mouthfuls of reaction flasks, add 17.9g (100mmol) p-hydrochloride, 8.1g (70mmol) methoxy-methyl acrylate, 100mL propyl carbinol.Be warming up to 60 DEG C of reactions about 40 hours, reaction solution is quantitative by liquid chromatography, 1-rubigan-5-hydroxypyrazoles yield 66.4%.
Embodiment 18
In three mouthfuls of reaction flasks, add 17.9g (100mmol) p-hydrochloride, 11.6g (100mmol) methoxy-methyl acrylate, 30mL methyl alcohol, 30mL ethanol.Be warming up to back flow reaction about 80 hours, reaction solution is quantitative by liquid chromatography, 1-rubigan-5-hydroxypyrazoles yield 80.8%.
Embodiment 19
In three mouthfuls of reaction flasks, add 17.9g (100mmol) p-hydrochloride, 11.6g (100mmol) methoxy-methyl acrylate, 30mL methyl alcohol, the 30mL trimethyl carbinol, 100mL propyl carbinol.Be warming up to back flow reaction about 160 hours, reaction solution is quantitative by liquid chromatography, 1-rubigan-5-hydroxypyrazoles yield 81.2%.
Claims (2)
1. a preparation method for 1-aryl-5-hydroxypyrazoles, is characterized in that the hydrochloride of aryl hydrazines or aryl hydrazines and methoxy-methyl acrylate react in solvent to obtain 1-aryl-5-hydroxypyrazoles, and reaction equation is:
In formula, n represents the integer of 1-3, and R is hydrogen atom or halogen atom, nitro, cyano group, alkoxyl group, alkyl, trihalogenmethyl, and described solvent is one or more mixtures in methyl alcohol, ethanol, n-propyl alcohol, Virahol, propyl carbinol, isopropylcarbinol, the trimethyl carbinol.
2. the preparation method of 1-aryl-5-hydroxypyrazoles according to claim 1, the feed ratio that it is characterized in that solvent and methoxy-methyl acrylate is volume (mL) with mmole (mmol) than 0.2～200 ︰ 1; The molar ratio of described aryl hydrazines or the hydrochloride of aryl hydrazines and methoxy-methyl acrylate is 1 ︰ 0.7～1.4.; Temperature of reaction is 40 DEG C of temperature that reflux to reaction solvent, and the reaction times is 1～240h.
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Cited By (1)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN109320457A (en) * | 2018-10-12 | 2019-02-12 | 凯莱英医药化学（阜新）技术有限公司 | The preparation method and device of hydroxypyrazoles |
Citations (4)
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|---|---|---|---|---|
| CN1330639A (en) * | 1998-11-19 | 2002-01-09 | 巴斯福股份公司 | Method for producing 1-substituted 5-or 3-hydroxypyrazoles |
| CN101774972A (en) * | 2010-02-02 | 2010-07-14 | 浙江大学 | Method for synthesizing methoxyacrylate compound |
| CN101959882A (en) * | 2007-12-27 | 2011-01-26 | 第一三共株式会社 | Imidazole carbonyl compound |
| CN102030710A (en) * | 2010-11-23 | 2011-04-27 | 浙江大学 | Method for synthesizing 14 C-labeled compound of pyraoxystrobin serving as bactericide |
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Patent Citations (4)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN1330639A (en) * | 1998-11-19 | 2002-01-09 | 巴斯福股份公司 | Method for producing 1-substituted 5-or 3-hydroxypyrazoles |
| CN101959882A (en) * | 2007-12-27 | 2011-01-26 | 第一三共株式会社 | Imidazole carbonyl compound |
| CN101774972A (en) * | 2010-02-02 | 2010-07-14 | 浙江大学 | Method for synthesizing methoxyacrylate compound |
| CN102030710A (en) * | 2010-11-23 | 2011-04-27 | 浙江大学 | Method for synthesizing 14 C-labeled compound of pyraoxystrobin serving as bactericide |
Non-Patent Citations (1)
| Title |
|---|
| PALWINDER SINGH,ET AL.: "Synthesis of pyrazole-based hybrid molecules: Search for potent multidrug resistance modulators", 《BIOORGANIC & MEDICINAL CHEMISTRY》 * |
Cited By (1)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN109320457A (en) * | 2018-10-12 | 2019-02-12 | 凯莱英医药化学（阜新）技术有限公司 | The preparation method and device of hydroxypyrazoles |
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