CN105085439A - Preparation method for epoxiconazole intermediate - Google Patents
Preparation method for epoxiconazole intermediate Download PDFInfo
- Publication number
- CN105085439A CN105085439A CN201510543066.XA CN201510543066A CN105085439A CN 105085439 A CN105085439 A CN 105085439A CN 201510543066 A CN201510543066 A CN 201510543066A CN 105085439 A CN105085439 A CN 105085439A
- Authority
- CN
- China
- Prior art keywords
- compound
- organic solvent
- preparation
- reaction
- epoxiconazole intermediate
- 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.)
- Granted
Links
Classifications
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D301/00—Preparation of oxiranes
- C07D301/02—Synthesis of the oxirane ring
- C07D301/03—Synthesis of the oxirane ring by oxidation of unsaturated compounds, or of mixtures of unsaturated and saturated compounds
- C07D301/14—Synthesis of the oxirane ring by oxidation of unsaturated compounds, or of mixtures of unsaturated and saturated compounds with organic peracids, or salts, anhydrides or esters thereof
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D303/00—Compounds containing three-membered rings having one oxygen atom as the only ring hetero atom
- C07D303/02—Compounds containing oxirane rings
- C07D303/12—Compounds containing oxirane rings with hydrocarbon radicals, substituted by singly or doubly bound oxygen atoms
- C07D303/14—Compounds containing oxirane rings with hydrocarbon radicals, substituted by singly or doubly bound oxygen atoms by free hydroxyl radicals
Abstract
The invention relates to a preparation method for an epoxiconazole intermediate. The epoxiconazole intermediate is 2-methyl methanesulfonate-2-(4-fluorophenyl)-3-(2-chlorphenyl)-epoxyethane. According to the preparation method provided by the invention, fluorophenylethanal and o-chlorobenzaldehyde are taken as materials, the epoxiconazole intermediate is prepared by addition, epoxidation, reduction and nucleophilic substitution reactions, novel solid acid-base catalyst is adopted in the reaction process, the process of the method is simple, the cost is low, the three types of wastes are less, both the content and yield of the target product are high, and the preparation method for the epoxiconazole intermediate is suitable for industrial production.
Description
Technical field
The present invention relates to a kind of preparation method of epoxiconazole intermediate 2-methyl mesylate base-2-(4-fluorophenyl)-3-(2-chloro-phenyl-)-oxyethane.
Background technology
Epoxiconazole is a kind of novel, wide spectrum, lasting period long triazole bactericidal agent, and being developed nineteen eighty-three by BASF Aktiengesellschaft, is C-14 demethylation enzyme inhibitors in sterol biosynthesis, has protection and therapeutic action concurrently.Suitable for crop wheat, barley, paddy rice, beet, rape, leguminous crop, vegetables, grape and apple etc., under recommended dose to crop safety, without poisoning.
Epoxiconazole intermediate 2-methyl mesylate base-2-(4-fluorophenyl)-3-(2-chloro-phenyl-)-oxyethane is the key intermediate of synthesizing fungicide epoxiconazole, and its structural formula is as follows:
With the route of 2-methyl mesylate base-2-(4-fluorophenyl)-3-(2-chloro-phenyl-)-polyethylene oxide intermediate synthesis epoxiconazole compared to the route of other intermediates, there is the advantages such as yield is high, easy and simple to handle, mild condition.In the present invention with fluorophenylethanal and o-chlorobenzaldehyde for raw material, obtain through addition, epoxidation, reduction, nucleophilic substitution reaction, reaction process have employed novel solid acid base catalysator, reduce costs, reduce waste liquid, avoid using the hazardous agents such as Grignard reagent, safe and reliable, be applicable to suitability for industrialized production.
Summary of the invention
The present invention proposes a kind of preparation method of brand-new epoxiconazole intermediate 2-methyl mesylate base-2-(4-fluorophenyl)-3-(2-chloro-phenyl-)-oxyethane, with fluorophenylethanal and o-chlorobenzaldehyde for raw material, obtain through addition, epoxidation, reduction, nucleophilic substitution reaction, reaction process have employed novel solid acid base catalysator, be convenient to be separated, excellent catalytic effect.
A preparation method for epoxiconazole intermediate, the structural formula that described epoxiconazole intermediate is is:
It is characterized in that: described preparation method comprises the following steps of carrying out successively:
Step (1), fluorophenylethanal, o-chlorobenzaldehyde and sodium hydroxide react in presence of organic solvent, and obtain compound (1) through aftertreatment after reaction terminates, the structural formula of described compound (1) is:
Step (2), the compound (1) step (1) obtained and Peracetic Acid are reacted under the existence of solid acid catalyst and organic solvent, obtain compound (2) through aftertreatment after reaction terminates, the structural formula of described compound (2) is:
Step (3), the compound (2) that step (2) obtained carry out reduction reaction under the existence of reductive agent and organic solvent, obtain compound (3) through aftertreatment after reaction terminates, the structural formula of described compound (3) is:
Step (4), the compound (3) step (3) obtained and Methanesulfonyl chloride react under the existence of alkaline catalysts and organic solvent, obtain described epoxiconazole intermediate after reaction terminates through aftertreatment.
Preferably, in step (1), the molar ratio of described fluorophenylethanal, described o-chlorobenzaldehyde, described sodium hydroxide is 1:1 ~ 2:1 ~ 1.5.
Further preferably, in step (1), the molar ratio of described fluorophenylethanal, described o-chlorobenzaldehyde, described sodium hydroxide is 1:1 ~ 1.5:1 ~ 1.5.
Preferably, in step (2), described compound (1) and the molar ratio of described Peracetic Acid are 1:0.9 ~ 2.
Further preferably, in step (2), described compound (1) and the molar ratio of described Peracetic Acid are 1:0.9 ~ 1.5.
Preferably, in step (4), described compound (3) and the molar ratio of described Methanesulfonyl chloride are 1:0.9 ~ 1.2.
Preferably, the temperature of reaction of step (1) is 0 DEG C ~ 40 DEG C, the temperature of reaction of step (2) is 30 DEG C ~ 65 DEG C, and the temperature of reaction of step (3) is 0 DEG C ~ 15 DEG C, and the temperature of reaction of step (4) is 0 DEG C ~ 25 DEG C.
Preferably, in step (2), described solid acid catalyst is HPW/MCM-41.
Preferably, in step (3), described reductive agent is sodium borohydride.
Preferably, in step (4), described alkaline catalysts is calcium oxide.
Preferably, step (1) is in step (4), and described organic solvent is methyl alcohol.
Preferably, the embodiment of described preparation method is as follows:
Step (1), add described fluorophenylethanal, described o-chlorobenzaldehyde, described sodium hydroxide and described organic solvent in the reactor, stirring reaction 4 ~ 5 hours, remove described organic solvent through underpressure distillation after reaction terminates, obtain described compound (1);
Step (2), add described compound (1), described Peracetic Acid, described solid acid catalyst and described organic solvent in the reactor, be heated to backflow, react 5 ~ 6 hours, through filtering described solid acid catalyst after reaction terminates, then the organic solvent described in removed under reduced pressure and described Peracetic Acid, obtain described compound (2);
Step (3), add described compound (2) and the organic solvent described in part in the reactor, described reductive agent is dissolved in remaining described organic solvent and forms mixed solution, then described mixed solution is added drop-wise in described reactor, after dripping, stirring reaction 3 ~ 4 hours, reaction terminate after through washing after separatory, the organic solvent then described in removed under reduced pressure, obtains described compound (3);
Step (4), in reactor, add described compound (3), described organic solvent and described alkaline catalysts, stir, then in reactor, described Methanesulfonyl chloride is dripped, after being added dropwise to complete, stirring reaction 1 ~ 2 hour, through filtering described alkaline catalysts after reaction terminates, then through washing, removing described organic solvent, obtain described epoxiconazole intermediate.
Reaction equation of the present invention is as follows:
Owing to adopting above technical scheme, the present invention has the following advantages compared with other techniques:
Preparation method of the present invention is the variation route of synthesis epoxiconazole intermediate 2-methyl mesylate base-2-(4-fluorophenyl)-3-(2-chloro-phenyl-)-oxyethane, its technique is relatively simple, and raw material is easy to get, with low cost, operating process agents useful for same and medicine toxicity relatively low, compare ordinary method route short, mild condition, the three wastes are few, total recovery is high, therefore synthesize cost significantly low, the content of target product is high simultaneously, is well suited for suitability for industrialized production.
Embodiment
Below in conjunction with specific embodiment, the present invention is described in further details.Should be understood that these embodiments are for illustration of ultimate principle of the present invention, principal character and advantage, and the present invention is not limited by the following examples.The implementation condition adopted in embodiment can do further adjustment according to specific requirement, and not marked implementation condition is generally the condition in normal experiment.
Embodiment 1
2-methyl mesylate base-2-(4-fluorophenyl)-3-(2-the chloro-phenyl-)-process for making ethylene oxide of the present embodiment has following steps:
(1) in reaction flask, fluorophenylethanal 13.8 grams is added successively, o-chlorobenzaldehyde 14.1 grams, solvent methanol 30 grams, 4 grams, sodium hydroxide, stirring reaction 4 hours at normal temperature 25 DEG C, underpressure distillation precipitation, obtains 25.6 g of compound (1), the wherein content 92.1% of compound (1), yield 90.8%.
(2) in reaction flask, add the finished product 25.6 grams of step (1) gained, solvent methanol 30 grams, Peracetic Acid 6.9 grams, catalyzer HPW/MCM-410.7 gram, be heated to backflow, react 5 hours.Reaction terminates rear solids removed by filtration catalyzer, and solvent and Peracetic Acid are sloughed in decompression, obtain 24.8 g of compound (2), wherein the content 91.5% of compound (2), yield 91.5%.
(3) in reaction flask, add the finished product 24.8 grams of step (2) gained, solvent methanol 25 grams, 0.9 gram of sodium borohydride is dissolved in 10 grams of methyl alcohol, be added drop-wise in reaction flask at about 10 DEG C, drip rear continuation stirring 3 hours, separatory after washing, decompression precipitation, obtain 21.7 g of compound (3), wherein the content 91.3% of compound (3), yield 88.9%.
(4) in reaction flask, add the finished product 21.7 grams of step (3) gained, solvent methanol 20 grams, 0.6 gram, solid catalyst calcium oxide, stirs, less than 10 DEG C drip Methanesulfonyl chloride 8.5 grams, drip off rear continuation stirring 1 hour, Filtration of catalyst, washing, precipitation, obtain 24.4 g of compound (4), wherein the content 92.7% of compound (4), yield 90.5%.
Product m.p:110-112 DEG C.
1hNMR (600MHz, DMSO-d
6): δ 7.70-7.12 (m, 8H), 4.19 (s, 1H), 3.8 (m, 2H), 3.16 (s, 3H) .MS:m/z=356.8 (M
+) .Anal.calcdfor (C16H14ClFO4S): C, 71.56; H, 3.70; Found:C, 71.36; H, 3.65.
Embodiment 2
2-methyl mesylate base-2-(4-fluorophenyl)-3-(2-the chloro-phenyl-)-process for making ethylene oxide of the present embodiment has following steps:
(1) in reaction flask, fluorophenylethanal 13.8 grams is added successively, o-chlorobenzaldehyde 16.92 grams, solvent methanol 40 grams, 4.5 grams, sodium hydroxide, stirring reaction 5 hours at 30 DEG C, underpressure distillation precipitation, obtains 25.6 g of compound (1), the wherein content 92.5% of compound (1), yield 91.2%.
(2) in reaction flask, add the finished product 25.6 grams of step (1) gained, solvent methanol 30 grams, Peracetic Acid 7.5 grams, catalyzer HPW/MCM-410.9 gram, be heated to backflow, react 5 hours.Reaction terminates rear solids removed by filtration catalyzer, and solvent and Peracetic Acid are sloughed in decompression, obtain 25.4 g of compound (2), wherein the content 91.0% of compound (2), yield 92.8%.
(3) in reaction flask, add the finished product 25.4 grams of step (2) gained, solvent methanol 25 grams, 1.0 grams of sodium borohydrides are dissolved in 15 grams of methyl alcohol, be added drop-wise in reaction flask at about 10 DEG C, drip rear continuation stirring 4 hours, separatory after washing, decompression precipitation, obtain 22.7 g of compound (3), wherein the content 91.6% of compound (3), yield 89.4%.
(4) in reaction flask, add the finished product 22.7 grams of step (3) gained, solvent methanol 30 grams, 0.8 gram, solid catalyst calcium oxide, stirs, less than 10 DEG C drip Methanesulfonyl chloride 8.5 grams, drip off rear continuation stirring 1 hour, Filtration of catalyst, washing, precipitation, obtain 26.5 g of compound (4), wherein the content 92.1% of compound (4), yield 91.6%.
Embodiment 3
2-methyl mesylate base-2-(4-fluorophenyl)-3-(2-the chloro-phenyl-)-process for making ethylene oxide of the present embodiment has following steps:
(1) in reaction flask, fluorophenylethanal 13.8 grams is added successively, o-chlorobenzaldehyde 18.0 grams, solvent methanol 30 grams, 5 grams, sodium hydroxide, stirring reaction 5 hours at normal temperature 25 DEG C, underpressure distillation precipitation, obtains 25.6 g of compound (1), the wherein content 92.3% of compound (1), yield 90.8%.
(2) in reaction flask, add the finished product 25.6 grams of step (1) gained, solvent methanol 30 grams, Peracetic Acid 8.0 grams, catalyzer HPW/MCM-411.0 gram, be heated to backflow, react 6 hours.Reaction terminates rear solids removed by filtration catalyzer, and solvent and Peracetic Acid are sloughed in decompression, obtain 25.4 g of compound (2), wherein the content 91.7% of compound (2), yield 93.0%.
(3) in reaction flask, add the finished product 25.4 grams of step (2) gained, solvent methanol 25 grams, 1.0 grams of sodium borohydrides are dissolved in 15 grams of methyl alcohol, be added drop-wise in reaction flask at about 10 DEG C, drip rear continuation stirring 3 hours, separatory after washing, decompression precipitation, obtain 22.4 g of compound (3), wherein the content 90.7% of compound (3), yield 86.5%.
(4) in reaction flask, add the finished product 22.4 grams of step (3) gained, solvent methanol 30 grams, 0.9 gram, solid catalyst calcium oxide, stirs, less than 10 DEG C drip Methanesulfonyl chloride 9.0 grams, drip off rear continuation stirring 2 hours, Filtration of catalyst, washing, precipitation, obtain 25.4 g of compound (4), wherein the content 92.5% of compound (4), yield 90.4%.
Claims (10)
1. a preparation method for epoxiconazole intermediate, the structural formula of described epoxiconazole intermediate is:
,
It is characterized in that: described preparation method comprises the following steps of carrying out successively:
Step (1), fluorophenylethanal, o-chlorobenzaldehyde and sodium hydroxide react in presence of organic solvent, and obtain compound (1) through aftertreatment after reaction terminates, the structural formula of described compound (1) is:
;
Step (2), the compound (1) step (1) obtained and Peracetic Acid are reacted under the existence of solid acid catalyst and organic solvent, and obtain compound (2) through aftertreatment after reaction terminates, the structural formula of described compound (2) is:
;
Step (3), the compound (2) that step (2) obtained carry out reduction reaction under the existence of reductive agent and organic solvent, and obtain compound (3) through aftertreatment after reaction terminates, the structural formula of described compound (3) is:
;
Step (4), the compound (3) step (3) obtained and Methanesulfonyl chloride react under the existence of alkaline catalysts and organic solvent, obtain described epoxiconazole intermediate after reaction terminates through aftertreatment.
2. the preparation method of epoxiconazole intermediate according to claim 1, is characterized in that: in step (1), and the molar ratio of described fluorophenylethanal, described o-chlorobenzaldehyde, described sodium hydroxide is 1:1 ~ 2:1 ~ 1.5.
3. the preparation method of epoxiconazole intermediate according to claim 1, is characterized in that: in step (2), and described compound (1) and the molar ratio of described Peracetic Acid are 1:0.9 ~ 2.
4. the preparation method of epoxiconazole intermediate according to claim 1, is characterized in that: in step (4), and described compound (3) and the molar ratio of described Methanesulfonyl chloride are 1:0.9 ~ 1.2.
5. the preparation method of epoxiconazole intermediate according to claim 1, it is characterized in that: the temperature of reaction of step (1) is 0 DEG C ~ 40 DEG C, the temperature of reaction of step (2) is 30 DEG C ~ 65 DEG C, and the temperature of reaction of step (3) is 0 DEG C ~ 15 DEG C, and the temperature of reaction of step (4) is 0 DEG C ~ 25 DEG C.
6. the preparation method of epoxiconazole intermediate according to claim 1, is characterized in that: in step (2), and described solid acid catalyst is HPW/MCM-41.
7. the preparation method of epoxiconazole intermediate according to claim 1, is characterized in that: in step (3), and described reductive agent is sodium borohydride.
8. the preparation method of epoxiconazole intermediate according to claim 1, is characterized in that: in step (4), and described alkaline catalysts is calcium oxide.
9. the preparation method of epoxiconazole intermediate according to claim 1, is characterized in that: step (1) is in step (4), and described organic solvent is methyl alcohol.
10. according to the preparation method of the epoxiconazole intermediate described in claim 1 to 9, it is characterized in that: the embodiment of described preparation method is as follows:
Step (1), add described fluorophenylethanal, described o-chlorobenzaldehyde, described sodium hydroxide and described organic solvent in the reactor, stirring reaction 4 ~ 5 hours, remove described organic solvent through underpressure distillation after reaction terminates, obtain described compound (1);
Step (2), add described compound (1), described Peracetic Acid, described solid acid catalyst and described organic solvent in the reactor, be heated to backflow, react 5 ~ 6 hours, through filtering described solid acid catalyst after reaction terminates, then the organic solvent described in removed under reduced pressure and described Peracetic Acid, obtain described compound (2);
Step (3), add described compound (2) and the organic solvent described in part in the reactor, described reductive agent is dissolved in remaining described organic solvent and forms mixed solution, then described mixed solution is added drop-wise in described reactor, after dripping, stirring reaction 3 ~ 4 hours, reaction terminate after through washing after separatory, the organic solvent then described in removed under reduced pressure, obtains described compound (3);
Step (4), in reactor, add described compound (3), described organic solvent and described alkaline catalysts, stir, then in reactor, described Methanesulfonyl chloride is dripped, after being added dropwise to complete, stirring reaction 1 ~ 2 hour, through filtering described alkaline catalysts after reaction terminates, then through washing, removing described organic solvent, obtain described epoxiconazole intermediate.
Priority Applications (1)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| CN201510543066.XA CN105085439B (en) | 2015-08-31 | 2015-08-31 | A kind of preparation method of epoxiconazole intermediate |
Applications Claiming Priority (1)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| CN201510543066.XA CN105085439B (en) | 2015-08-31 | 2015-08-31 | A kind of preparation method of epoxiconazole intermediate |
Publications (2)
| Publication Number | Publication Date |
|---|---|
| CN105085439A true CN105085439A (en) | 2015-11-25 |
| CN105085439B CN105085439B (en) | 2018-03-16 |
Family
ID=54566859
Family Applications (1)
| Application Number | Title | Priority Date | Filing Date |
|---|---|---|---|
| CN201510543066.XA Active CN105085439B (en) | 2015-08-31 | 2015-08-31 | A kind of preparation method of epoxiconazole intermediate |
Country Status (1)
| Country | Link |
|---|---|
| CN (1) | CN105085439B (en) |
Cited By (1)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN107952425A (en) * | 2017-12-27 | 2018-04-24 | 高军 | A kind of preparation method of antitumor drug NVP-BEZ235 intermediates |
Citations (6)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| US4920232A (en) * | 1987-07-10 | 1990-04-24 | Basf Aktiengesellschaft | α,β-substituted acroleins |
| WO2002094817A1 (en) * | 2001-05-18 | 2002-11-28 | Basf Aktiengesellschaft | Method for the purification of triazolylmethylepoxides |
| WO2002094818A1 (en) * | 2001-05-18 | 2002-11-28 | Basf Aktiengesellschaft | Method for the production of triazolylmethylepoxides |
| WO2005056548A1 (en) * | 2003-12-11 | 2005-06-23 | Cheminova A/S | Enantiomerically pure epoxiconazole and its use as crop protection agent |
| CN102378760A (en) * | 2009-02-05 | 2012-03-14 | 巴斯夫欧洲公司 | Method for producing hydroxymethyl diphenyloxiranes and corresponding 1-azolylmethyl-1,2-diphenyloxiranes |
| CN104356097A (en) * | 2014-10-20 | 2015-02-18 | 中国科学院广州能源研究所 | Preparation method of microbial oil-based epoxide |
-
2015
- 2015-08-31 CN CN201510543066.XA patent/CN105085439B/en active Active
Patent Citations (6)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| US4920232A (en) * | 1987-07-10 | 1990-04-24 | Basf Aktiengesellschaft | α,β-substituted acroleins |
| WO2002094817A1 (en) * | 2001-05-18 | 2002-11-28 | Basf Aktiengesellschaft | Method for the purification of triazolylmethylepoxides |
| WO2002094818A1 (en) * | 2001-05-18 | 2002-11-28 | Basf Aktiengesellschaft | Method for the production of triazolylmethylepoxides |
| WO2005056548A1 (en) * | 2003-12-11 | 2005-06-23 | Cheminova A/S | Enantiomerically pure epoxiconazole and its use as crop protection agent |
| CN102378760A (en) * | 2009-02-05 | 2012-03-14 | 巴斯夫欧洲公司 | Method for producing hydroxymethyl diphenyloxiranes and corresponding 1-azolylmethyl-1,2-diphenyloxiranes |
| CN104356097A (en) * | 2014-10-20 | 2015-02-18 | 中国科学院广州能源研究所 | Preparation method of microbial oil-based epoxide |
Non-Patent Citations (3)
| Title |
|---|
| DIRK HOEGAERTS ET AL.: "Heterogeneous tungsten-based catalysts for the epoxidation of bulky olefins", 《CATALYSIS TODAY》 * |
| 李金林等: "烯烃环氧化催化剂的种类和特征", 《中南民族学院学报（自然科学版）》 * |
| 江才鑫等: "氟环唑的合成综述", 《浙江化工》 * |
Cited By (2)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN107952425A (en) * | 2017-12-27 | 2018-04-24 | 高军 | A kind of preparation method of antitumor drug NVP-BEZ235 intermediates |
| CN107952425B (en) * | 2017-12-27 | 2020-05-08 | 四川协力制药股份有限公司 | Preparation method of antitumor drug NVP-BEZ235 intermediate |
Also Published As
| Publication number | Publication date |
|---|---|
| CN105085439B (en) | 2018-03-16 |
Similar Documents
| Publication | Publication Date | Title |
|---|---|---|
| CN103282344B (en) | Method for preparation of ketoxime compound and method for preparation of alkoxy-mine hydrochloride | |
| Fringuelli et al. | Cobalt (II) chloride-catalyzed chemoselective sodium borohydride reduction of azides in water | |
| CN108341776A (en) | The technique for synthesizing Chlorquinaldol | |
| WO2006001493A1 (en) | Method for producing (z)-1-phenyl-1-diethylaminocarbonyl-2-aminomethyl cyclopropane hydrochloride | |
| JP2018529655A (en) | Process for preparing 1,4-bis (ethoxymethyl) cyclohexane | |
| CN101381389A (en) | Chemical synthesis method of 5,7-diene steroids compounds | |
| Zolfigol et al. | H5IO6/KI: A new combination reagent for iodination of aromatic amines, and trimethylsilylation of alcohols and phenols through in situ generation of iodine under mild conditions | |
| CN101100450A (en) | Method for preparing ethylsulfonyl acetonitrile | |
| CN105085439A (en) | Preparation method for epoxiconazole intermediate | |
| CN108101868B (en) | 4-vinyl epoxy cyclohexane and preparation method thereof | |
| Xu et al. | Hot water as a mild Brønsted acid catalyst in ring opening reactions of epoxides | |
| WO1999029699A1 (en) | Process for producing toluene derivatives | |
| EP2035465A2 (en) | Method for deprotecting aryl or alkyl sulfonamides of primary or secondary amines | |
| CN113816874A (en) | Process method for synthesizing 4-cyano-2-fluorobenzyl alcohol | |
| CN111892547A (en) | Synthesis method of prothioconazole intermediate | |
| CN111072745A (en) | Preparation method of 6-methylene-7-ketocholic acid | |
| Zolfigol et al. | HIO3/KI: A new combination reagent for iodination of aromatic amines and trimethylsilylation of alcohols and phenols through in situ generation of iodine under mild conditions | |
| JP3282357B2 (en) | Piperonal manufacturing method | |
| CN113754602B (en) | Synthesis method of 5, 5-dimethyl-4, 5-dihydro-isoxazole-3-one | |
| JP6754131B2 (en) | Method for producing a coupling product of an organic compound having a leaving group and an organoboron compound | |
| CN114805176A (en) | Preparation method of 6, 6-dimethyl-3-azabicyclo [3.1.0] hexane | |
| JP2016169192A (en) | Method of producing 7-octenyl halide | |
| CN117624151A (en) | Preparation method of losartan potassium degradation impurity | |
| CN110292948B (en) | Application of imines-functionalized imidazole chloride salt as catalyst in preparation of aromatic heterocyclic formate compounds | |
| JP2004182607A (en) | Method for producing 4-chloro-3-hydroxybutyronitrile |
Legal Events
| Date | Code | Title | Description |
|---|---|---|---|
| C06 | Publication | ||
| PB01 | Publication | ||
| C10 | Entry into substantive examination | ||
| SE01 | Entry into force of request for substantive examination | ||
| GR01 | Patent grant | ||
| GR01 | Patent grant |