CN114394915A - Preparation method of 2-cyanobenzaldehyde and derivatives thereof - Google Patents
Preparation method of 2-cyanobenzaldehyde and derivatives thereof Download PDFInfo
- Publication number
- CN114394915A CN114394915A CN202210291637.5A CN202210291637A CN114394915A CN 114394915 A CN114394915 A CN 114394915A CN 202210291637 A CN202210291637 A CN 202210291637A CN 114394915 A CN114394915 A CN 114394915A
- Authority
- CN
- China
- Prior art keywords
- cyanobenzaldehyde
- derivatives
- reaction
- purity
- halogenated
- 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
- C07C—ACYCLIC OR CARBOCYCLIC COMPOUNDS
- C07C253/00—Preparation of carboxylic acid nitriles
- C07C253/30—Preparation of carboxylic acid nitriles by reactions not involving the formation of cyano groups
-
- Y—GENERAL TAGGING OF NEW TECHNOLOGICAL DEVELOPMENTS; GENERAL TAGGING OF CROSS-SECTIONAL TECHNOLOGIES SPANNING OVER SEVERAL SECTIONS OF THE IPC; TECHNICAL SUBJECTS COVERED BY FORMER USPC CROSS-REFERENCE ART COLLECTIONS [XRACs] AND DIGESTS
- Y02—TECHNOLOGIES OR APPLICATIONS FOR MITIGATION OR ADAPTATION AGAINST CLIMATE CHANGE
- Y02P—CLIMATE CHANGE MITIGATION TECHNOLOGIES IN THE PRODUCTION OR PROCESSING OF GOODS
- Y02P20/00—Technologies relating to chemical industry
- Y02P20/50—Improvements relating to the production of bulk chemicals
- Y02P20/584—Recycling of catalysts
Landscapes
- Chemical & Material Sciences (AREA)
- Organic Chemistry (AREA)
- Chemical Kinetics & Catalysis (AREA)
- Organic Low-Molecular-Weight Compounds And Preparation Thereof (AREA)
Abstract
A preparation method of 2-cyanobenzaldehyde and derivatives thereof belongs to the field of preparation of pharmaceutical intermediates, and comprises the steps of sequentially adding a palladium catalyst, a ligand and an acid-binding agent into a reaction solvent, then adding o-halogenated benzonitrile and derivatives thereof and paraformaldehyde, stirring and heating to 80-110 ℃, reacting for 6-24 hours, and carrying out aftertreatment to obtain the high-purity 2-cyanobenzaldehyde and derivatives thereof. The preparation method disclosed by the invention is green and environment-friendly, the utilization rate of the starting raw materials is higher, the reaction yield is higher, and the reaction conditions are mild; avoids using high-toxicity and high-risk reaction materials such as chlorine, cyanide and the like used in the prior art; the yield of the 2-cyanobenzaldehyde and the derivatives thereof prepared by the method provided by the invention is 74.2-91.9% in terms of o-halogenated cyanobenzene and the derivatives thereof, and the purity of the 2-cyanobenzaldehyde and the derivatives thereof can reach 97.54-99.45%.
Description
Technical Field
The invention particularly relates to a preparation method of a drug intermediate 2-cyanobenzaldehyde and a derivative thereof, belonging to the field of synthesis of drug intermediates.
Background
2-cyanobenzaldehyde is an important intermediate of hydralazine hydrochloride which is a medicine for treating hypertension, and the synthetic methods of o-cyanobenzaldehyde in the existing domestic and foreign literature reports mainly comprise the following steps:
the method comprises the following steps: taking 2-methylbenzonitrile as a raw material, and carrying out a double substitution reaction in the presence of chlorine to generate o-cyano dichlorobenzyl; then reacting with organic alkali sodium methoxide to generate 2-cyanobenzaldehyde dimethyl acetal, and finally hydrolyzing with hydrochloric acid to obtain o-cyanobenzaldehyde. The method is discussed in fine petrochemical engineering vol.25(2), 2008, 32-34, and the synthesis process is roughly as follows:
the method is a main industrial method at present, but in the first step of generating the o-cyanobenzyl dichloride, toxic gas chlorine is used as a reaction medium, the reaction temperature is high, and in the reaction, materials with high toxicity such as phosphorus trichloride and benzoyl peroxide are used, so that the method has great pollution to the environment and has great potential safety hazard in the production process.
The method 2 comprises the following steps: 2-methyl benzonitrile is taken as a raw material, NBS is taken as a bromization reagent to carry out substitution reaction, and o-cyano-dibromo-benzyl is generated; then reacting with silver nitrate reagent to directly generate o-cyanobenzaldehyde. The yield of the route is high. The method is described in "A Tandem Elimination-Cyclization-Suzuki Approach: effective One-Pot Synthesis of Functionalized (Z) -3- (arylmethyl) isoindolin-1-ones", J. org. chem. Vol. 73, number 18, 2008, 7361-One 7364, and the process is roughly:
the method avoids the use of chlorine, but in the first step, in the process of preparing the o-cyanobenzyl dibromide, environmentally-unfriendly carbon tetrachloride is used for dissolving, NBS is used as a bromination reagent, and a large amount of waste residues are generated; moreover, the reaction is a free radical reaction, the reaction at the initiation stage is violent, the amplification production is not well controlled, and the method is extremely dangerous; in addition, the expensive silver nitrate reagent is used in the process of preparing o-cyanobenzaldehyde in the second step, and the production cost is overhigh.
The method 3 comprises the following steps: the o-chlorobenzaldehyde is used as a raw material, zinc cyanide is used as a cyanation reagent, and the o-chlorobenzaldehyde is generated by reaction under the conditions of a metal catalyst, a ligand and organic alkali. This method is described in CN108623495A, "General and Mill Nickel-catalysis corporation of Aryl/Heteroaryl Chlorides with Zn (CN)2: Key rolls of DMAP", Organic Letters, 2017, vol 19, # 8, p 2118-:
the method has a short route, but a cyanation reagent zinc cyanide (which reacts with carbon dioxide in humid air to release highly toxic hydrogen cyanide gas) used in the reaction process is a highly toxic tube product, has great potential safety hazard in the production and use processes, and has low reaction yield.
In the prior art, reagents such as chlorine and phosphorus trichloride with high toxicity are used in the route 1, the reaction conditions are harsh, and potential safety hazards exist; the bromination reaction in the route 2 is a free radical reaction, the reaction in the initiation stage is violent, potential safety hazards exist in the industrial process, and carbon tetrachloride is used as a solvent, so that the method is not environment-friendly. The cyanide used in the route 3 is used as a reactant, and potential safety hazards exist in the amplification production process.
Disclosure of Invention
Aiming at the defects in the prior art, the invention provides a preparation method of 2-cyanobenzaldehyde and derivatives thereof, which realizes the following purposes: the method for preparing the environment-friendly, green and environment-friendly 2-cyanobenzaldehyde and the derivatives thereof is developed, the yield is high, and the purity of the prepared 2-cyanobenzaldehyde and the derivatives thereof is high.
In order to realize the purpose, the invention adopts the following technical scheme:
a method for preparing 2-cyanobenzaldehyde and derivatives thereof is characterized in that o-halogenated cyanobenzene and derivatives thereof react with paraformaldehyde in a reaction solvent under the combined action of a palladium catalyst, a ligand and an acid-binding agent to generate the 2-cyanobenzaldehyde and the derivatives thereof, wherein the reaction equation is as follows:
the following is a further improvement of the above technical solution:
sequentially adding a palladium catalyst, a ligand and an acid-binding agent into a reaction solvent, and then adding o-halogenated benzonitrile and derivatives thereof and paraformaldehyde; stirring and heating to 80-110 ℃, reacting for 6-24 hours, and performing post-treatment to obtain high-purity 2-cyanobenzaldehyde and derivatives thereof;
the o-halogenated benzonitrile and the derivative thereof are one of 2-bromobenzonitrile, 2-chlorobenzonitrile and 3-methyl-2-bromobenzonitrile;
the 2-cyanobenzaldehyde and the derivative thereof are one of 2-cyanobenzaldehyde and 2-methyl-6-cyanobenzaldehyde;
the molar ratio of the o-halogenated benzonitrile, the derivative of the o-halogenated benzonitrile and the paraformaldehyde is 1: 1-3;
the molar weight of the palladium catalyst added is 1-5% of that of the o-halogenated benzonitrile and the derivatives thereof;
the molar weight of the added ligand is 2-10% of that of the o-halogenated benzonitrile and the derivatives thereof;
the molar weight of the acid-binding agent is 1-2 times of that of the o-halogenated benzonitrile and the derivatives thereof;
the reaction solvent is one of toluene and xylene;
the palladium catalyst is Pd (TFA)2、Pd(OAC)2、PdI2、Pd(OH)2One of (1);
the ligand is one of 4, 5-bis (diphenylphosphino) -9, 9-dimethyl xanthene (xanthphos), bis (2-diphenylphosphinophenyl) ether (DPEphos) and 1, 2-bis (diphenylphosphino) ethane (DPPE);
the acid-binding agent is one of potassium carbonate, potassium bicarbonate and potassium hydroxide;
the post-treatment comprises the following specific operations: after the reaction is finished, cooling to room temperature, filtering, extracting and washing the filtrate for 2-3 times (50-80 ml/time) by using saturated salt water, adding 3.0-6.0 g of activated carbon into the filtrate after extraction and washing, stirring for 1-2 h at room temperature for decolorization, filtering by using a Bush funnel after decolorization is finished, removing the activated carbon, removing toluene by using a rotary evaporator to obtain crude products of 2-cyanobenzaldehyde and derivatives thereof, recrystallizing by using toluene, and drying to obtain the high-purity 2-cyanobenzaldehyde and derivatives thereof.
The reaction mechanism of this reaction is as follows:
compared with the prior art, the invention has the following beneficial effects:
1. the preparation method disclosed by the invention is green and environment-friendly, the utilization rate of the starting raw materials is higher, the reaction yield is higher, and the reaction conditions are mild;
2. the preparation method avoids using high-toxicity and high-risk reaction materials such as chlorine, cyanide and the like used in the prior art;
3. by adopting the method, the yield of the prepared 2-cyanobenzaldehyde and the derivatives thereof can reach 74.2-91.9% and the purity can reach 97.54-99.45% in terms of the o-halogenated cyanobenzene and the derivatives thereof.
Detailed Description
The following description of the preferred embodiments of the present invention is provided for the purpose of illustration and description, and is in no way intended to limit the invention.
Example 1: preparation method of 2-cyanobenzaldehyde
600ml of toluene were placed in a 1L three-necked reaction flask, and Pd (TFA) was added thereto, followed by stirring2 1.99g (0.006mol), 5.79g (0.01mol) of 4, 5-bis-diphenylphosphine-9, 9-dimethylxanthene, 41.46g (0.30mol) of potassium carbonate, 36.40g (0.2mol) of 2-bromobenzonitrile, 12.00g (0.4mol) of paraformaldehyde(ii) a The reaction mixture was heated to 100 ℃ and reacted for 12 h. After the reaction is finished, cooling to room temperature and filtering; extracting and washing the filtrate for 3 times by using saturated saline water (the using amount of the saturated saline water is 60 ml/time), adding 4.0g of activated carbon into the filtrate after extraction and washing, stirring for 1.5h at room temperature for decolorization, filtering by using a Bush funnel after the decolorization is finished, removing the activated carbon, removing toluene by using a rotary evaporator to obtain a brown yellow solid 2-cyanobenzaldehyde crude product, recrystallizing the crude product by using toluene, and drying to obtain the high-purity 2-cyanobenzaldehyde.
In example 1, 24.7g of high-purity 2-cyanobenzaldehyde was obtained, the yield of 2-cyanobenzaldehyde was 91.9% and the liquid-phase purity was 97.54%, based on 2-bromobenzonitrile.
Example 2: preparation method of 2-cyanobenzaldehyde
600ml of toluene were placed in a 1L three-necked reaction flask, and Pd (TFA) was added thereto, followed by stirring2 0.66g (0.002mol), 1.59g (0.004mol) of 1, 2-bis (diphenylphosphino) ethane, 20.02g (0.20mol) of potassium hydrogencarbonate, 27.51g (0.2mol) of 2-chlorobenzonitrile, 6.00g (0.2mol) of paraformaldehyde; the reaction mixture is heated to 80 ℃ and is reacted for 6 hours under the condition of heat preservation. After the reaction is finished, cooling to room temperature and filtering; extracting and washing the filtrate for 2 times by using saturated saline water (the using amount of the saturated saline water is 50 ml/time), adding 3.0g of activated carbon into the filtrate after extraction and washing, stirring for 1 hour at room temperature for decolorization, filtering by using a Bush funnel after the decolorization is finished, removing the activated carbon, removing toluene by using a rotary evaporator to obtain a brown yellow solid 2-cyanobenzaldehyde crude product, recrystallizing the crude product by using toluene, and drying to obtain the high-purity 2-cyanobenzaldehyde.
In example 2, 19.7g of high-purity 2-cyanobenzaldehyde was obtained, and the yield of 2-cyanobenzaldehyde was 74.2% and the liquid-phase purity was 98.81%, based on 2-bromobenzonitrile.
Example 3: preparation method of 2-cyanobenzaldehyde
600ml of toluene were placed in a 1L three-necked reaction flask, and Pd (OAC) was added thereto, followed by stirring2 2.25g (0.01mol), 11.57g (0.02mol) of 4, 5-bis-diphenylphosphine-9, 9-dimethylxanthene and 55.28g (0.40mol) of potassium carbonate, 36.40g (0.2mol) of 2-bromobenzonitrile, 18.0g (0.6mol) of paraformaldehyde; the reaction mixture is heated to 110 ℃, and the reaction is carried out for 24 hours under the condition of heat preservation. The reaction is finishedCooling to room temperature, and filtering; extracting and washing the filtrate for 3 times by using saturated saline water (the using amount of the saturated saline water is 80 ml/time), adding 6.0g of activated carbon into the filtrate after extraction and washing, stirring for 2 hours at room temperature for decolorization, filtering by using a Bush funnel after decolorization is finished, removing the activated carbon, removing toluene by using a rotary evaporator to obtain a brown yellow solid 2-cyanobenzaldehyde crude product, recrystallizing the crude product by using toluene, and drying to obtain the high-purity 2-cyanobenzaldehyde.
In example 3, 21.3g of high-purity 2-cyanobenzaldehyde was obtained, and the yield of 2-cyanobenzaldehyde was 80.3% and the liquid-phase purity was 98.90% based on 2-bromobenzonitrile.
Example 4: preparation method of 2-cyanobenzaldehyde
600ml of toluene is added into a 1L three-mouth reaction flask, stirring is started, and PdI is sequentially added23.60g (0.01mol), 2.15g (0.004mol) of bis (2-diphenylphosphinophenyl) ether, 33.17g (0.24mol) of potassium carbonate, 36.40g (0.2mol) of 2-bromobenzonitrile, 12.0g (0.4mol) of paraformaldehyde; the reaction mixture is heated to 100 ℃ and is reacted for 16h under the condition of heat preservation. After the reaction is finished, cooling to room temperature and filtering; extracting and washing the filtrate for 2 times by using saturated saline water (the using amount of the saturated saline water is 70 ml/time), adding 5.0g of activated carbon into the filtrate after extraction and washing, stirring for 2 hours at room temperature for decolorization, filtering by using a Bush funnel after decolorization is finished, removing the activated carbon, removing toluene by using a rotary evaporator to obtain a brown yellow solid 2-cyanobenzaldehyde crude product, recrystallizing the crude product by using toluene, and drying to obtain the high-purity 2-cyanobenzaldehyde.
In example 4, 23.0g of high-purity 2-cyanobenzaldehyde was obtained, and the yield of 2-cyanobenzaldehyde was 86.9% and the liquid-phase purity was 99.12% based on 2-bromobenzonitrile.
Example 5: preparation method of 2-methyl-6-cyanobenzaldehyde
600ml of toluene were placed in a 1L three-necked reaction flask, and Pd (OH) was added thereto in order with stirring2 1.40g (0.01mol), Xantphos11.6g (0.02mol), potassium hydroxide 14.03g (0.25mol), 3-methyl-2-bromobenzonitrile 39.21g (0.2mol), paraformaldehyde 12.0g (0.4 mol); the reaction mixture is heated to 110 ℃, and the reaction is carried out for 14 hours under the condition of heat preservation. After the reaction is finished, cooling to room temperature and filtering; the filtrate was extracted and washed with saturated brine for 2 times (amount of saturated brine)70 ml/time), adding 5.0g of activated carbon into the filtrate after extraction and washing, stirring for 2h at room temperature for decolorization, filtering by using a Bush funnel after decolorization is finished, removing the activated carbon, removing toluene by using a rotary evaporator to obtain a brown yellow solid crude product of 2-methyl-6-cyanobenzaldehyde, recrystallizing the crude product by using toluene, and drying to obtain the high-purity 2-methyl-6-cyanobenzaldehyde.
In example 5, 25.8g of high purity 2-methyl-6-cyanobenzaldehyde was obtained, and the yield of 2-methyl-6-cyanobenzaldehyde was 88.4% and the liquid-phase purity was 99.45% based on 3-methyl-2-bromobenzonitrile.
Claims (2)
1. A method for preparing 2-cyanobenzaldehyde and derivatives thereof is characterized in that: sequentially adding a palladium catalyst, a ligand and an acid-binding agent into a reaction solvent, and then adding o-halogenated benzonitrile and derivatives thereof and paraformaldehyde; stirring and heating to 80-110 ℃, reacting for 6-24 hours, and performing post-treatment to obtain high-purity 2-cyanobenzaldehyde and derivatives thereof;
the molar ratio of the o-halogenated benzonitrile, the derivative of the o-halogenated benzonitrile and the paraformaldehyde is 1: 1-3;
the molar weight of the palladium catalyst added is 1-5% of that of the o-halogenated benzonitrile and the derivatives thereof;
the molar weight of the added ligand is 2-10% of that of the o-halogenated benzonitrile and the derivatives thereof;
the molar weight of the acid-binding agent is 1-2 times of that of the o-halogenated benzonitrile and the derivatives thereof;
the o-halogenated benzonitrile and the derivative thereof are one of 2-bromobenzonitrile, 2-chlorobenzonitrile and 3-methyl-2-bromobenzonitrile;
the 2-cyanobenzaldehyde and the derivative thereof are one of 2-cyanobenzaldehyde and 2-methyl-6-cyanobenzaldehyde;
the reaction solvent is toluene;
the palladium catalyst is Pd (TFA)2、Pd(OAC)2、PdI2、Pd(OH)2One of (1);
the ligand is one of 4, 5-bis (diphenylphosphino) -9, 9-dimethyl xanthene, bis (2-diphenylphosphinophenyl) ether and 1, 2-bis (diphenylphosphino) ethane;
the acid-binding agent is one of potassium carbonate, potassium bicarbonate and potassium hydroxide.
2. The process for producing 2-cyanobenzaldehyde and derivatives thereof according to claim 1, wherein:
the post-treatment comprises the following specific operations: after the reaction is finished, cooling to room temperature, filtering, extracting and washing the filtrate for 2-3 times by using saturated saline solution, wherein the dosage of the saturated saline solution is 50-80 ml each time, adding 3.0-6.0 g of activated carbon into the filtrate after extraction and washing, stirring for 1-2 h at room temperature for decolorization, filtering to remove the activated carbon, evaporating to remove toluene to obtain crude products of 2-cyanobenzaldehyde and derivatives thereof, recrystallizing with toluene, and drying to obtain the high-purity 2-cyanobenzaldehyde and derivatives thereof.
Priority Applications (1)
Application Number | Priority Date | Filing Date | Title |
---|---|---|---|
CN202210291637.5A CN114394915B (en) | 2022-03-24 | 2022-03-24 | Preparation method of 2-cyanobenzaldehyde and derivatives thereof |
Applications Claiming Priority (1)
Application Number | Priority Date | Filing Date | Title |
---|---|---|---|
CN202210291637.5A CN114394915B (en) | 2022-03-24 | 2022-03-24 | Preparation method of 2-cyanobenzaldehyde and derivatives thereof |
Publications (2)
Publication Number | Publication Date |
---|---|
CN114394915A true CN114394915A (en) | 2022-04-26 |
CN114394915B CN114394915B (en) | 2022-06-07 |
Family
ID=81235107
Family Applications (1)
Application Number | Title | Priority Date | Filing Date |
---|---|---|---|
CN202210291637.5A Active CN114394915B (en) | 2022-03-24 | 2022-03-24 | Preparation method of 2-cyanobenzaldehyde and derivatives thereof |
Country Status (1)
Country | Link |
---|---|
CN (1) | CN114394915B (en) |
Cited By (1)
Publication number | Priority date | Publication date | Assignee | Title |
---|---|---|---|---|
CN116143701A (en) * | 2023-02-22 | 2023-05-23 | 吴桥县六合德利化工有限责任公司 | Method for recycling waste residues generated in production of cyanobenzyl chloride |
Citations (6)
Publication number | Priority date | Publication date | Assignee | Title |
---|---|---|---|---|
JP2004002220A (en) * | 2002-05-31 | 2004-01-08 | Dainippon Ink & Chem Inc | Benzonitrile derivative and method for producing the same |
JP2004043425A (en) * | 2002-05-20 | 2004-02-12 | Nippon Soda Co Ltd | Method for producing n-acyl amino acids |
JP2004277338A (en) * | 2003-03-14 | 2004-10-07 | Nippon Soda Co Ltd | Method for producing n-acylamino acid |
EP1721892A1 (en) * | 1998-05-28 | 2006-11-15 | Showa Denko Kabushiki Kaisha | Method for producing cyanophenyl derivatives |
US20090287013A1 (en) * | 2008-05-13 | 2009-11-19 | Morrison Christopher F | Process for preparing substituted 7-cyano quinone methides |
CN114394906A (en) * | 2022-03-24 | 2022-04-26 | 中孚药业股份有限公司 | Preparation method of agomelatine intermediate |
-
2022
- 2022-03-24 CN CN202210291637.5A patent/CN114394915B/en active Active
Patent Citations (6)
Publication number | Priority date | Publication date | Assignee | Title |
---|---|---|---|---|
EP1721892A1 (en) * | 1998-05-28 | 2006-11-15 | Showa Denko Kabushiki Kaisha | Method for producing cyanophenyl derivatives |
JP2004043425A (en) * | 2002-05-20 | 2004-02-12 | Nippon Soda Co Ltd | Method for producing n-acyl amino acids |
JP2004002220A (en) * | 2002-05-31 | 2004-01-08 | Dainippon Ink & Chem Inc | Benzonitrile derivative and method for producing the same |
JP2004277338A (en) * | 2003-03-14 | 2004-10-07 | Nippon Soda Co Ltd | Method for producing n-acylamino acid |
US20090287013A1 (en) * | 2008-05-13 | 2009-11-19 | Morrison Christopher F | Process for preparing substituted 7-cyano quinone methides |
CN114394906A (en) * | 2022-03-24 | 2022-04-26 | 中孚药业股份有限公司 | Preparation method of agomelatine intermediate |
Non-Patent Citations (4)
Title |
---|
KISHORE NATTE,等: "Palladium-Catalyzed Carbonylations of Aryl Bromides using Paraformaldehyde: Synthesis of Aldehydes and Esters", 《ANGEW. CHEM. INT. ED.》, 28 July 2014 (2014-07-28), pages 10090 - 10094 * |
VELU SADHASIVAM,等: "PdO nanoparticles supported on triazole functionalized porous triazine polymer as an efficient heterogeneous catalyst for carbonylation of aryl halides", 《APPL ORGANOMETAL CHEM.》, 21 June 2019 (2019-06-21), pages 4994 * |
李广利等: "氯化镁催化苯酚一步法合成水杨醛", 《精细石油化工进展》, no. 04, 28 July 2013 (2013-07-28), pages 43 - 47 * |
汪元博等: "酯化氧化法合成水杨醛工艺", 《化学工业与工程》, no. 01, 30 January 2007 (2007-01-30), pages 32 - 35 * |
Cited By (1)
Publication number | Priority date | Publication date | Assignee | Title |
---|---|---|---|---|
CN116143701A (en) * | 2023-02-22 | 2023-05-23 | 吴桥县六合德利化工有限责任公司 | Method for recycling waste residues generated in production of cyanobenzyl chloride |
Also Published As
Publication number | Publication date |
---|---|
CN114394915B (en) | 2022-06-07 |
Similar Documents
Publication | Publication Date | Title |
---|---|---|
CN111978263B (en) | Preparation method of fampicin and intermediate thereof | |
JP2009526826A (en) | Process for producing substituted biphenyls | |
CN110903248B (en) | Synthesis method of 5-chloro-4-aminopyridazine | |
CN114394915B (en) | Preparation method of 2-cyanobenzaldehyde and derivatives thereof | |
CN111349049B (en) | Favipiravir and synthesis process of intermediate thereof | |
CN108358760B (en) | Application of metalate/palladium compound catalytic reduction system in debenzylation reaction and deuteration reaction | |
JPH01104045A (en) | Manufacture of 2,5-bis(2,2,2-trifluoroethoxy)- n-(2-piperidylmethyl)benzamide | |
CN101981007A (en) | Method for purification of pyridine, and method for production of chlorinated pyridine | |
CN102197016A (en) | Process for the preparation of benzonorbornenes | |
AU2018389809B2 (en) | A process for the preparation of crisaborole | |
CN108530301B (en) | Synthetic method of 2,4, 6-trifluorobenzylamine | |
KR20140131817A (en) | Manufacturing process of phenylenediamine having recyclability of iodine | |
CN113429256A (en) | Preparation method of bifenthrin insecticide intermediate | |
CN110818621B (en) | Simple preparation method of 2, 3-dichloropyridine | |
KR20020061111A (en) | Process for the Preparation of Trifluoromethyl-Substituted Biphenylcarboxylic Acids and Novel Trichloromethyl- and Trifluoromethyl-Substituted Biphenylcarbonitriles | |
CN110872225A (en) | Preparation method of Barosavir intermediate | |
US6979749B2 (en) | Catalytic process for the production of 3,3′, 4,4′-tetraminobiphenyl | |
JP4570057B2 (en) | Process for producing arylpyridine derivatives | |
CN108947950A (en) | A kind of preparation method of native malt phenol | |
CN107400083A (en) | A kind of preparation method of 3 [2 (3 chlorphenyl) ethyl] 2 pyridine carbonitriles | |
CN113336780B (en) | Preparation method of 2-formyl-4- (4-cyanophenoxy) phenylboronic acid pinacol ester | |
CN114195690B (en) | Preparation method of vinyl aryl thioether compound | |
CN111039796A (en) | Novel synthesis method of 4' -chloro-2-aminobiphenyl | |
CN110240545B (en) | Preparation method of 2- (5-fluoro-2, 4-dinitrophenoxy) acetic acid | |
JP2008007503A (en) | Method for producing 4-methylpyrazole-5-carboxylic ester |
Legal Events
Date | Code | Title | Description |
---|---|---|---|
PB01 | Publication | ||
PB01 | Publication | ||
SE01 | Entry into force of request for substantive examination | ||
SE01 | Entry into force of request for substantive examination | ||
GR01 | Patent grant | ||
GR01 | Patent grant |