CN101838816B - Method for electrochemically preparing 5,5'-dihydroxyl-4,4'-dipyrazole compound - Google Patents
Method for electrochemically preparing 5,5'-dihydroxyl-4,4'-dipyrazole compound Download PDFInfo
- Publication number
- CN101838816B CN101838816B CN201010145334XA CN201010145334A CN101838816B CN 101838816 B CN101838816 B CN 101838816B CN 201010145334X A CN201010145334X A CN 201010145334XA CN 201010145334 A CN201010145334 A CN 201010145334A CN 101838816 B CN101838816 B CN 101838816B
- Authority
- CN
- China
- Prior art keywords
- dihydroxyl
- alkyl
- current density
- double pyrazole
- anode
- Prior art date
- Legal status (The legal status is an assumption and is not a legal conclusion. Google has not performed a legal analysis and makes no representation as to the accuracy of the status listed.)
- Expired - Fee Related
Links
- ZEKDAUBTCAMDLA-UHFFFAOYSA-N Cc(c(-c(c(C)n[n]1-c(cc2)ccc2OC)c1O)c1O)n[n]1-c(cc1)ccc1OC Chemical compound Cc(c(-c(c(C)n[n]1-c(cc2)ccc2OC)c1O)c1O)n[n]1-c(cc1)ccc1OC ZEKDAUBTCAMDLA-UHFFFAOYSA-N 0.000 description 1
Landscapes
- Electrolytic Production Of Non-Metals, Compounds, Apparatuses Therefor (AREA)
Abstract
The invention discloses a method for electrochemically preparing 5,5'-dihydroxyl-4,4'-dipyrazole compound. In the method, 5-pyrazolone is taken as raw material, and alkali halide is used as supporting electrolyte in alcohol solvent, electrolysis is carried out by taking metal electrodes as an anode and a cathode in an electrolytic cell at reaction temperature of 10 DEG C below zero to40 DEG C and current density of 3-8mA/cm<2>,and the 5,5'-dihydroxyl-4,4'-dipyrazole compound as shown in the following formula (I) is obtained after 0.2-2faraday/molar of electric quantity passes through, wherein R1 represents-H, aryl or C1-5 alkyl; and R2 represents-H, C1-5 alkyl, C5-7 naphthenic base, benzyl, naphthyl and substituted or unsubstituted phenyl. The method adopts common industrial reagent and conventional production conditions, has mild reaction conditions, simple operation and high yield, uses cheap electrode material which is easily obtained, and is easy for mass production.
Description
Technical field
The invention belongs to the synthetic field of medicine, be specifically related to 5,5 '-dihydroxyl-4, the electrochemical preparation method of 4 '-double pyrazole compounds.
Background technology
Active oxygen is a kind of very active oxygen carrier, and it participates in intravital each kinds of oxidation reaction.Active oxygen comprises hydroxyl radical free radical, superoxide anion, singlet oxygen, hydrogen peroxide, peroxidase free radical and alkoxy free group etc.
In recent years, the result of study in fields such as biology, medical science and pharmacology shows that intravital various physiological activity is relevant with intravital free radical with active oxygen.Ultraviolet radiation, radioactive rays, atmospheric pollution, oxygen, lipid peroxidation, metal ion, ischemia-reperfusion, all formation of active oxygen and free radical in the possibility inductor.Consequent active oxygen and free radical can be induced various reactions in vivo, as the blood fat peroxidation, and protein denaturation, thus nucleic acid decomposition etc. cause diseases such as cerebral ischemia, heart disease, digestive system, tumour, aging or inflammation.Therefore, the external nothing of this active oxygen and free radical wound detects to have and helps study the reason that this disease produces, and provides the medical information of usefulness.
5,5 '-dihydroxyl-4,4 '-double pyrazole compounds can be caught active oxygen or free radical effectively, thereby can be as prevention and treatment cerebral ischemia, heart disease, digestive system, tumour, the medicine of aging or inflammation or as the detection reagent of active oxygen or free radical.
5,5 '-dihydroxyl-4,4 '-double pyrazole compounds generally are to be raw material with the 5-pyrazolone, take place under the effect of oxygenant that oxidative coupling reaction prepares.People such as Obara (US patent 6121305,2000) are catalyzer with the tin anhydride, and the hydrogen peroxide of excessive triple 30% is an oxygenant, this compounds of preparation under nitrogen protection, and productive rate is lower than 50%.People such as Azev (Chemistry ofHeterocyclic Compounds, 2003,39,1478-1486) then with 3,6-phenylbenzene-1,2,4-triazine-4-oxide compound is that oxygenant prepares 5,5 '-dihydroxyl-1,1 '-phenylbenzene-4,4 '-double pyrazole and 5,5 '-dihydroxyl-1,1 '-two p-nitrophenyls-4,4 '-double pyrazole, productive rate are respectively 28% and 18%.The oxide compound that above preparation method uses sometimes is difficult for obtaining, and perhaps uses deleterious catalyzer tin anhydride and unsettled hydrogen peroxide, and it is dealt with improperly and can set off an explosion.In addition, above preparation method's productive rate is low, and reaction needed is carried out under nitrogen protection, complicated operation.
Summary of the invention
The purpose of this invention is to provide 5,5 '-dihydroxyl-4, the electrochemical preparation method of 4 '-double pyrazole compounds.
Provided by the present invention 5,5 '-dihydroxyl-4, the electrochemical preparation method of 4 '-double pyrazole compounds, its step is that the 5-pyrazolone of representing with formula (II) is a raw material, in alcoholic solvent, be supporting electrolyte with the alkali metal halide, in electrolyzer, be that anode and negative electrode carry out electrolysis with the metal electrode, temperature of reaction-10～40 ℃, current density 3～8mA/cm
2, behind the electric weight by 0.2～2 faraday/mole, obtain 5 of formula (I) expression, 5 '-dihydroxyl-4,4 '-double pyrazole compounds,
Wherein, R
1Expression-H, aryl or C
1～5Alkyl; R
2Expression-H, C
1～5Alkyl, C
5～7Cycloalkyl, benzyl, naphthyl, replace or do not have the phenyl of replacement.
Above-mentioned alcoholic solvent preferred alcohol.
The preferred Sodium Bromide of above-mentioned alkali metal halide.
Above-mentioned electrolyzer is a single compartment electrolytic cell.
Preferred platinum of above-mentioned anode or carbon-point.
The preferred iron of above-mentioned negative electrode.
Preferred 0 ℃ of above-mentioned temperature of reaction.
Preferred 4～the 7mA/cm of above-mentioned current density
2, preferred especially 5mA/cm
2
The preferred 1.0 faraday/moles of the above-mentioned electric weight that passes through.
Preparation method's of the present invention reaction formula is as follows:
Compared with prior art, beneficial effect of the present invention is: adopted electrochemical production first 5,5 '-dihydroxyl-4,4 '-double pyrazole compounds.The inventive method is used industrial general agents and conventional working condition, and the reaction conditions gentleness is simple to operate; obviously improved productive rate; electrode materials is cheap and easy to get simultaneously, can carry out under the galvanostatic conditions in simple single compartment electrolytic cell, thereby be easy to large-scale production.In the reaction process with electronics as oxygenant, need not use deleterious tin anhydride, also be a kind of production process of cleaning.
Embodiment
Embodiment 1:5,5 '-dihydroxyl-3,3 '-dimethyl-4, the preparation of 4 '-double pyrazole
With 3-methyl-5-pyrazolone 98mg (1mmol), methyl alcohol 15mL and Sodium Bromide 100mg join single compartment electrolytic cell, are anode with the carbon-point, and iron staff is a negative electrode, and under 10 ℃, current density is 6mAcm
-2, by termination reaction behind the electric weight of 1.5 faraday/moles, obtain 5,5 '-dihydroxyl-3,3 '-dimethyl-4,4 '-double pyrazole.Its yield is 51%.
1H?NMR(400MHz，DMSO-d
6)：δ2.09(s，6H，-CH
3)，10.3(br，2H)，11.27(bs，2H).
13C?NMR(100MHz，DMSO-d
6)：δ10.76，78.02，138.40，158.21.
Embodiment 2:5,5 '-dihydroxyl-3,3 '-dimethyl-4, the preparation of 4 '-double pyrazole
Supporting electrolyte is a sodium iodide, and other step is with embodiment 1, and its yield is 26%.
Embodiment 3:5,5 '-dihydroxyl-3,3 '-dimethyl-4, the preparation of 4 '-double pyrazole
Solvent is an ethanol, and other step is with embodiment 1, and its yield is 61%.
Embodiment 4:5,5 '-dihydroxyl-3,3 '-dimethyl-4, the preparation of 4 '-double pyrazole
Anode is a platinized platinum, and other step is with embodiment 3, and its yield is 63%.
Embodiment 5:5,5 '-dihydroxyl-3,3 '-dimethyl-4, the preparation of 4 '-double pyrazole
Temperature is 0 ℃, and other step is with embodiment 4, and its yield is 74%.
Embodiment 6:5,5 '-dihydroxyl-3,3 '-dimethyl-1,1 '-phenylbenzene-4, the preparation of 4 '-double pyrazole
Raw material is 1-phenyl-3-methyl-5-pyrazolone, and other step is with embodiment 5, and its yield is 57%.
1H?NMR(400MHz，CDCl
3)：δ2.67(s，6H，-CH
3)，7.25(t，J＝7.2Hz，1H，Ar-H)，7.44(t，J＝7.6Hz，2H，Ar-H)，7.45(d，J＝8.0Hz，2H，Ar-H).
Embodiment 7:5,5 '-dihydroxyl-3,3 '-dimethyl-1,1 '-two rubigan-4, the preparation of 4 '-double pyrazole
Raw material is 1-(4-chlorine) phenyl-3-methyl-5-pyrazolone, and other step is with embodiment 5, and its yield is 62%.
1H?NMR(400MHz，CDCl
3)：δ2.61(s，6H，-CH
3)，7.47(d，J＝8.8Hz，4H，Ar-H)，7.69(d，J＝8.8Hz，4H，Ar-H).
Embodiment 8:5,5 '-dihydroxyl-3,3 '-dimethyl-1,1 '-two p-methylphenyls-4, the preparation of 4 '-double pyrazole
Raw material is 1-(4-methyl) phenyl-3-methyl-5-pyrazolone, and other step is with embodiment 5, and its yield is 39%.
1H?NMR(400MHz，Acetone-d
6)：δ2.31(s，6H，-CH
3)，2.58(s，6H，-CH
3)，7.23(d，J＝8.0Hz，4H，Ar-H)，7.48(d，J＝8.0Hz，4H，Ar-H).
Embodiment 9:5,5 '-dihydroxyl-3,3 '-dimethoxy-1,1 '-two p-methylphenyls-4, the preparation of 4 '-double pyrazole
Raw material is 1-(4-methyl) phenyl-3-methyl-5-pyrazolone, and other step is with embodiment 5, and its yield is 60%.
1H?NMR(400MHz，CDCl
3)：δ2.66(s，6H，-CH
3)，3.84(s，6H，-OCH
3)，6.97(d，J＝6.4Hz，4H，Ar-H)，7.73(d，J＝7.2Hz，4H，Ar-H).
Claims (10)
1.5,5 '-dihydroxyl-4, the electrochemical preparation method of 4 '-double pyrazole compounds, the step that it is characterized in that this method is that the 5-pyrazolone of representing with formula (II) is a raw material, in alcoholic solvent, be supporting electrolyte with the alkali metal halide, in electrolyzer, be that anode and negative electrode carry out electrolysis with the metal electrode, temperature of reaction-10～40 ℃, current density 3～8mA/cm
2, behind the electric weight by 0.2～2 faraday/mole, obtain 5 of formula (I) expression, 5 '-dihydroxyl-4,4 '-double pyrazole compounds,
Wherein, R
1Expression-H, aryl or C
1～5Alkyl; R
2Expression-H, C
1～5Alkyl, C
5～7Cycloalkyl, benzyl, naphthyl, replace or do not have the phenyl of replacement.
2. according to the method for claim 1, it is characterized in that described alcoholic solvent is an ethanol.
3. according to the method for claim 1, it is characterized in that described alkali metal halide is a Sodium Bromide.
4. according to the method for claim 1, it is characterized in that described electrolyzer is a single compartment electrolytic cell.
5. according to the method for claim 1, it is characterized in that described anode is a platinum.
6. according to the method for claim 1, it is characterized in that described negative electrode is an iron.
7. according to the method for claim 1, it is characterized in that described temperature of reaction is 0 ℃.
8. according to the method for claim 1, it is characterized in that described current density is 4～7mA/cm
2
9. method according to Claim 8 is characterized in that described current density is 5mA/cm
2
10. according to the method for claim 1, it is characterized in that the electric weight that passes through is 1.0 faraday/moles.
Priority Applications (1)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| CN201010145334XA CN101838816B (en) | 2010-04-09 | 2010-04-09 | Method for electrochemically preparing 5,5'-dihydroxyl-4,4'-dipyrazole compound |
Applications Claiming Priority (1)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| CN201010145334XA CN101838816B (en) | 2010-04-09 | 2010-04-09 | Method for electrochemically preparing 5,5'-dihydroxyl-4,4'-dipyrazole compound |
Publications (2)
| Publication Number | Publication Date |
|---|---|
| CN101838816A CN101838816A (en) | 2010-09-22 |
| CN101838816B true CN101838816B (en) | 2011-09-07 |
Family
ID=42742485
Family Applications (1)
| Application Number | Title | Priority Date | Filing Date |
|---|---|---|---|
| CN201010145334XA Expired - Fee Related CN101838816B (en) | 2010-04-09 | 2010-04-09 | Method for electrochemically preparing 5,5'-dihydroxyl-4,4'-dipyrazole compound |
Country Status (1)
| Country | Link |
|---|---|
| CN (1) | CN101838816B (en) |
Families Citing this family (4)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN103436911B (en) * | 2013-09-05 | 2015-11-25 | 北京工业大学 | The electrochemical catalysis synthetic method of ethylenimine compounds |
| EP2985364A1 (en) * | 2014-08-14 | 2016-02-17 | Basf Se | Process for preparing alcohols by electrochemical reductive coupling |
| CN109321939B (en) * | 2018-10-15 | 2020-08-21 | 北京工业大学 | Electrochemical synthesis method of thiazole compound |
| CN114990591B (en) * | 2022-07-21 | 2024-02-20 | 河南师范大学 | Method for synthesizing chiral acyclic nucleoside compound by electrochemical asymmetric dihydroxylation reaction |
Family Cites Families (2)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| JPH10306077A (en) * | 1997-05-07 | 1998-11-17 | Daiichi Rajio Isotope Kenkyusho:Kk | Bipyrazole derivative, and medicine and reagent consisting essentially thereof |
| CN1285589C (en) * | 2004-12-25 | 2006-11-22 | 浙江工业大学 | Heterocyclic compound containing double pyrazole, preparing method and its use |
-
2010
- 2010-04-09 CN CN201010145334XA patent/CN101838816B/en not_active Expired - Fee Related
Also Published As
| Publication number | Publication date |
|---|---|
| CN101838816A (en) | 2010-09-22 |
Similar Documents
| Publication | Publication Date | Title |
|---|---|---|
| CN101838816B (en) | Method for electrochemically preparing 5,5'-dihydroxyl-4,4'-dipyrazole compound | |
| CN110616439B (en) | Method for synthesizing 4-sulfonic acid substituted isoquinolone derivative through electrochemical oxidation | |
| CN113073348A (en) | Method for electrochemically synthesizing tazobactam key intermediate | |
| CN102503829A (en) | Preparation methods for sitagliptin intermediates | |
| CN111910208A (en) | Electrochemical synthesis method of 3-thiophenyl quinolinone | |
| JPS60243293A (en) | Manufacture of m-hydroxybenzyl alcohol | |
| CN108505063A (en) | A kind of electrochemical preparation method of N- (3,5- dimethyl -4- hydroxy phenyls) acetamide | |
| Ikegami et al. | Photosensitive cyclomer formation of 1, 1'-(1, 2-ethanediyl) bis (pyridinyl) diradical and its derivatives | |
| CN101775613B (en) | Electrochemical synthesis method for preparing halogenated hydantoin | |
| CN107445900A (en) | A kind of benzimidazole part with chiral carbon, benzimidazole metal complex and its preparation method and application | |
| CN101078129B (en) | Formiate ion liquid compound and its preparing method and application | |
| KR20220160642A (en) | Solutions of TEMPO-derivatives for use as electrolytes in redox-flow batteries | |
| KR20220161419A (en) | Solutions of TEMPO-derivatives for use as electrolytes in redox-flow batteries | |
| Ravichandran et al. | Indirect reduction of p-nitroaniline to p-phenylenediamine at a Ti/TiO 2 electrode | |
| CN115919817B (en) | Gem diselenide compound and its synthesis method and application | |
| US6419814B1 (en) | Methods for electrochemical synthesis of organoiodonium salts and derivatives | |
| JPS60110887A (en) | Manufacture of alpha-alkylated acetic acid derivative | |
| JPS6342712B2 (en) | ||
| CN114539197B (en) | Synthesis method of 3-fluoroalkyl substituted chromone derivative | |
| Khaleghi et al. | Electrochemical oxidation of catechol in the presence of an aromatic amine in aqueous media | |
| JPH03107490A (en) | Preparation of aminobenzyl alcohol | |
| US4624757A (en) | Electrocatalytic method for producing quinone methides | |
| JPS61271250A (en) | Production of substituted tropic acid | |
| US3836440A (en) | Process for the manufacture of phenylhydrazine | |
| JPS63157891A (en) | Production of m-hydroxybenzyl alcohol |
Legal Events
| Date | Code | Title | Description |
|---|---|---|---|
| C06 | Publication | ||
| PB01 | Publication | ||
| C10 | Entry into substantive examination | ||
| SE01 | Entry into force of request for substantive examination | ||
| C14 | Grant of patent or utility model | ||
| GR01 | Patent grant | ||
| C17 | Cessation of patent right | ||
| CF01 | Termination of patent right due to non-payment of annual fee |
Granted publication date: 20110907 Termination date: 20130409 |