Author: Jessica.F

Electric Literature of 194853-86-6, As we all know, there are many different methods for the synthesis of a compound, and people can choose the synthesis method that suits their own laboratory according to the actual situation. 194853-86-6 name is 4-Fluoro-2-(trifluoromethyl)benzonitrile, This compound is widely used in many fields, so it is necessary to find a new synthetic route. The downstream synthesis method of this compound is introduced below.

COMPARATIVE EXAMPLE A This example illustrates the preparation of 4-[(1S, 4S)-4-Hydroxy-1- 0 methylpentyloxy]-2-trifluoromethylbenzonitrile, using a strong base under anhydrous conditions, as described in co-pending United States patent application serial number 11/053,010.A 10 L, jacketed ChemGlass reactor was fitted with a mechanical stirrer, nitrogen sweep line, and NesLab chiller. The vessel was purged with nitrogen for 5 15 minutes and then charged with 61 g (1.5 mol) of sodium hydride (60% in mineral oil) and 2.0 L of tetrahydrofuran (1THF”). The suspension was stirred and cooled to 6.5C and then a solution of 180.3 g (1.53 mol) of (2S,5S)-(+)-2,5- hexanediol in 1.0 L of THF was added, in 4 portions, over 35 minutes. The mixture became very thick and 1.0 L of THF was added about halfway through Q the addition in order to facilitate better stirring. The maximum internal temperature observed was 14.4C. The suspension was stirred for 30 minutes and then 288.1 g (1 .52 mol) of 4-fluoro-2-(trifluoromethyl)benzonitrile was added. The mixture was further diluted with another 1.0 L of THF and then warmed to room temperature and allowed to stir overnight (a clear solution was obtained after 30 minutes). HPLC analysis at the 21 hour point showed a 48:45 mixture of the expected product (3) to the bis-alkylated byproduct (4). Water (3.0 L) and ethyl acetate (4.0 L) were added and the layers separated. The organic layer was washed with 2 x 2.0 L of water and 1 x 2.0 L of brine. The aqueous layers were back-extracted with 2.0 L of ethyl acetate and then the organic layers were combined and evaporated at the Rotavap. The residue was twice dissolved in 1.0 L of 2-propanol and evaporated at the Rotavap (to remove water). The crude product was twice purified by flash chromatography on silica gel using dichloromethane/methanol. A third chromatography column (Biotage system) was carried out using ethyl acetate/hexanes. The purified target was isolated as 149.8 g (34%) of an oil. The material assayed at >99% purity (a/a, HPLC) and had a proton NMR spectrum consistent with structure.

At the same time, in my other blogs, there are other synthetic methods of this type of compound, 4-Fluoro-2-(trifluoromethyl)benzonitrile, and friends who are interested can also refer to it.

Reference:
Patent; WARNER-LAMBERT COMPANY LLC; WO2006/136910; (2006); A1;,
Nitrile – Wikipedia,
Nitriles – Chemistry LibreTexts

Synthetic Route of 117482-84-5, In the chemical reaction process, reaction time, type of solvent, can easily affect the result of the reaction, thereby determining the yield and properties of the reaction product. An updated downstream synthesis route of 117482-84-5 as follows.

Anhydrous p-toluene sulfonic acid (10 g, 52.57 mmol) was melted at 120 C and 3-amino-4-methoxy benzoic acid methyl ester (3.88 g, 21.44 mmol) obtained in step 1 of Preparation Example 1 and 3-chloro-4-fluorobenzonitrile (5.0 g, 32.14 mol) were added thereto and stirred at 160 C for 8 hours. The resulting solution was cooled to room temperature and the reaction was stopped by adding NaHCO3 thereto. The resulting mixture was extracted with ethyl acetate, the extract was dried over MgSO4 and concentrated under a reduced pressure. The resulting residue was purified by silica gel column chromatography to obtain the title compound (3.24 g, 9.62 mmol) in a yield of 45 %. 1H NMR (CDCl3): delta 7.96-7.95 (1H, m), 7.76-7.73 (2H, m), 7.60 (1H, bs), 7.17-7.11 (1H, m), 6.93 (1H, d), 3.85 (3H, s), 3.84 (3H, d) MW: 336

According to the analysis of related databases, 117482-84-5, the application of this compound in the production field has become more and more popular.

Reference:
Patent; CRYSTALGENOMICS, INC.; YUYU INC.; WO2004/65370; (2004); A1;,
Nitrile – Wikipedia,
Nitriles – Chemistry LibreTexts

1080-74-6, name is 2-(3-Oxo-2,3-dihydro-1H-inden-1-ylidene)malononitrile, belongs to nitriles-buliding-blocks compound, is considered to be a conventional heterocyclic compound, which is widely used in drug synthesis. The chemical synthesis route is as follows. 1080-74-6

General procedure: Compound 4 (400 mg, 0.47 mmol) and INCN (458 mg, 2.36 mmol) were dissolved in anhydrous chloroform (CF, 25 mL) and 0.3 mL of pyridine was slowly injected into mixture solution. Thereaction was stirred under a nitrogen atmosphere at 65 C for 12 h. Subsequently, the reaction vessel was cooled to room temperature and extracted with chloroform several times. The extracted organic layer were dried over MgSO4, filtered, and evaporated to obtain a residue. The mixture compound was then purified with column chromatography using chloroform to afford a dark solid.

Statistics shows that 1080-74-6 is playing an increasingly important role. we look forward to future research findings about 2-(3-Oxo-2,3-dihydro-1H-inden-1-ylidene)malononitrile.

Reference:
Article; Lee, Seong Lim; Kim, Hee Su; Ha, Jong-Woon; Park, Hea Jung; Hwang, Do-Hoon; Bulletin of the Korean Chemical Society; vol. 41; 2; (2020); p. 143 – 149;,
Nitrile – Wikipedia,
Nitriles – Chemistry LibreTexts

Application of 1735-53-1, In the next few decades, the world population will flourish. As the population grows rapidly and people all over the world use more and more resources, all industries must consider their environmental impact. 1735-53-1, name is 4-Bromo-3-(trifluoromethyl)benzonitrile belongs to nitriles-buliding-blocks compound, it is a common compound, a new synthetic route is introduced below.

Example 485A/-(5-(6-(4-cvano-2-(trifluoromethyl)phenyl)imidazori ,2-blpyridazin-2-yl)-2- methylphenvDpivalamideA 200 mL flask is charged with 2-(4-methyl-3-pivalamidophenyl)imidazo[1 ,2-6]pyridazin-6- ylboronic acid (1 1 .4 g, 0.0325 mol), 4-bromo-3-(trifluoromethyl)benzonitrile (10.16 g, 0.04 mol), K2C03 (8.98 g, 0.065 mol), palladium acetate (0.510 g, 2.28 mmol), 2- dicyclohexylphosphino-2′,6′-dimethoxy-1 , 1 ‘-biphenyl (1.868 g, 4.55 mmol) and a solution of isopropanol-water (3:1 , 80 mL). The mixture is degassed by bubbling N2 through and heated at 90 C for 5 hours. The mixture is then cooled and filtered through celite, concentrated and purified by silica gel chromatography (0-100% EtOAc in CH2CI2). The desired fractions are combined and stirred for 24 hours with QuadraSil MP (a mercaptopropyl bound silica gel, 20 g) to scavenge the palladium, filtered and concentrated to give desired title compound (7.5 g). LCMS (m/z) = 478.6 [M+H]+, fR = 2.97 min.

In the field of chemistry, the synthetic routes of compounds are constantly being developed and updated. I will also mention this compound in other articles, 4-Bromo-3-(trifluoromethyl)benzonitrile, other downstream synthetic routes, hurry up and to see.

Reference:
Patent; PAMLICO PHARMACEUTICAL INC.; ATKINSON, Robert N.; OMMEN, Andy J.; VEAL, James M.; HUANG, Kenneth H.; SMITH, Emilie, D.; WO2012/88411; (2012); A1;,
Nitrile – Wikipedia,
Nitriles – Chemistry LibreTexts

These common heterocyclic compound, 21524-39-0, name is 2,3-Difluorobenzonitrile, its traditional synthetic route has been very mature, but the traditional synthetic route has various shortcomings, such as complicated route, low yield, poor purity, etc, below Introduce a new synthetic route. Formula: C7H3F2N

A mixture of 3 -methyl- lH-pyrazole-4-carboxylic acid ethyl ester (1.25 g, 8.1 1 mmol), potassium carbonate (1.68 g, 12.16 mmol), 2,3-difluorobenzonitrile (1.08 mL, 9.73 mmol) in dimethylformamide (12 mL) is heated at 100C with the aid of a magnetic stirred. After 2.5 hr. the reaction mixture is treated with water and extracted with ethyl acetate. The organic layer is decanted, washed with brine, dried over magnesium sulfate and the solvent evaporated under reduced pressure to give 2.3 g of l-(2-cyano-6-fluoro- phenyl)-3 -methyl- lH-pyrazole-4-carboxylic acid ethyl ester (this compound is contaminated with the other pyrazole regioisomer in a ratio 75:25). MS (m/z): 274 (M+1). A capped vial is charged with ethyl l-(2-cyano-6-fluoro-phenyl)-3-methyl- pyrazole-4-carboxylate (1.97 g, 7.21 mmol) (contaminated with the other pyrazole regioisomer in a ratio of 75:25, 1,2-ethanediamine, N-methyl- (6 mL, 68.02 mmol) and phosphorus pentasulfide (229 mg, 1,01 mmol) and the mixture is stirred at 1 10C for 30 min and then allow to reach rt. Solvent is evaporated in vacuo and the residue purified by normal phase Isco chromatography using dichloromethane/2M ammonia in methanol from 95/5 to 85/15 as eluent to yield 2.1 1 g of ethyl l-[2-fluoro-6-(l-methyl-4,5- dihydroimidazol-2-yl)phenyl]-3-methyl-pyrazole-4-carboxylate (contaminated with the other pyrazole regioisomer in a ratio 75:25). MS (m/z): 331 (M+1).

The synthetic route of 2,3-Difluorobenzonitrile has been constantly updated, and we look forward to future research findings.

Reference:
Patent; ELI LILLY AND COMPANY; BENITO COLLADO, Ana Belen; DIAZ BUEZO, Nuria; JIMENEZ-AGUADO, Alma Maria; LAFUENTE BLANCO, Celia; MARTINEZ-GRAU, Maria Angeles; PEDREGAL-TERCERO, Concepcion; TOLEDO ESCRIBANO, Miguel Angel; WO2011/60217; (2011); A1;,
Nitrile – Wikipedia,
Nitriles – Chemistry LibreTexts

Researchers who often do experiments know that organic synthesis is a process of preparing more complex target molecules from simple raw materials through one or more chemical reactions. Generally, it requires fewer steps, and cheap raw materials. 90110-98-8, name is 3-Bromo-4-(hydroxymethyl)benzonitrile, A new synthetic method of this compound is introduced below., COA of Formula: C8H6BrNO

A solution of compound B (211 mg, 1.0 mmol) and triisopropyl borate (282 mg, 1.5 mmol) in anhydrous THF (10 mL) at N2 atmosphere was cooled to -78C. n- BuLi (0.9 mL, 2.25 mmol) was added dropwise at -78C. Then the mixture was allowed to warm to room temperature and stirr at room temperature for 1 h. The mixture was qunched with IN HCl and extracted with ethyl acetate (25 mL*3). The combined organic layers were washed with brine (20 mL), dried (Na2SO4) and concentrated under vacuum. The residue was purified by column chromatography (eluting with CH3OH and EtOAc =1 :1) on silica gel to give the desired compound C as a yellow solid (80 mg, 50 %).1H NMR (300 MHz, CDCl3): delta 9.50 (s, IH), 8.08 (s, IH), 7.83-7.92 (m, IH), 7.61-7.66 (m, IH), 5.06 (s, 2H). LC-MS: 160 (M + I)+.

The basis of chemical reaction formula synthesis, the synthesis route is composed of some specific reactions and combined according to certain logical thinking. We look forward to the emergence of more reaction modes in the future.

Reference:
Patent; ANACOR PHARMACEUTICALS, INC.; JACOBS, Robert; ORR, Matthew; WRING, Stephen; CHEN, Daitao; ZHOU, Huchen; DING, Dazhong; FENG, Yiqing; YE, Long; HERNANDEZ, Vincent, S.; ZHANG, Yong-Kang; PLATTNER, Jacob J.; WO2010/45503; (2010); A1;,
Nitrile – Wikipedia,
Nitriles – Chemistry LibreTexts

Electric Literature of 19179-31-8, As we all know, there are many different methods for the synthesis of a compound, and people can choose the synthesis method that suits their own laboratory according to the actual situation. 19179-31-8 name is 3,5-Dimethoxybenzonitrile, This compound is widely used in many fields, so it is necessary to find a new synthetic route. The downstream synthesis method of this compound is introduced below.

Adding 0.02 equivalents of anhydrous copper sulfate and 4.0 equivalents of potassium t-butoxide to a 25 mL Schlenk reaction tube, drying in vacuum for 15 minutes, and sequentially adding 1,4-dioxane 1.5 mL and t-butanol 1 mL under argon atmosphere, 3,5-dimethoxybenzonitrile 5.0 equivalents,1 mmol of 1-(phenylthio)benzyl-2-iodobenzene was placed in the reaction tube after adding polytetrafluoroethylene stopper was placed into an oil bath of the reaction 100 C for 4 h. After the reaction is completed, the solvent is removed by filtration, and the solvent is separated by column chromatography. The eluent is petroleum ether/dichloromethane/ethyl acetate (v:v:v=20:10:1) to give a yellow liquid as 2-(3,5-dimethoxyphenyl)-3-(phenylthio)-1H-indole. The yield was 98%

At the same time, in my other blogs, there are other synthetic methods of this type of compound, 3,5-Dimethoxybenzonitrile, and friends who are interested can also refer to it.

Reference:
Patent; University of Science and Technology of China; Kang Yanbiao; Shan Xianghuan; (12 pag.)CN108863894; (2018); A;,
Nitrile – Wikipedia,
Nitriles – Chemistry LibreTexts

Some common heterocyclic compound, 859855-53-1, name is 3-Amino-4-fluorobenzonitrile, molecular formula is C7H5FN2, traditional synthetic route has been very mature, but the traditional synthetic route has various shortcomings, such as complicated route, low yield, poor purity, etc, below Introduce a new synthetic route. Computed Properties of C7H5FN2

Intermediate 28: (4-Fluoro-3-(pyrrolidin-l-yl)phenyl)methanamineStep 1: 4-Fluoro-3-(pyrrolidin-l-yl)benzonitrile3-Amino-4-fluorobenzonitrile (0.5 g, 3.67 mmol), 1 ,4-dibromobutane (0.439 ml, 3.67 mmol), sodium carbonate (0.779 g, 7.35 mmol) and toluene (3 ml) were added into a microwave vial. The resulting mixture was heated by microwave irradiation at 140 C for 2 hours. 1 ,4-dibromobutane (0.5 ml, 4.18 mmol) was added and the reaction mixture was irradiated at 140 C and at 160 C until the reaction had clearly stopped. The reaction mixture was diluted with dichloromethane and washed twice with water. The organic phase was dried over Na2S04, filtered and evaporated. The crude product was purified by column chromatography. 0.221 g of the title compound was obtained. NMR (400 MHz, CDC13) delta ppm 1.96 – 2.00 (m, 4 H) 3.39 – 3.48 (m, 4 H) 6.84 (dd, 1 H) 6.89 – 6.94 (m, 1 H) 6.96 – 7.04 (m, 1 H)

These compound has a wide range of applications. It is believed that with the continuous development of the source of the synthetic route 859855-53-1, its application will become more common.

Reference:
Patent; ORION CORPORATION; ARVELA, Riina; HOLM, Patrik; PIETIKAeINEN, Pekka; ROSLUND, Mattias; VAeISAeNEN, Emilia; WOHLFAHRT, Gerd; WO2012/152983; (2012); A1;,
Nitrile – Wikipedia,
Nitriles – Chemistry LibreTexts

These common heterocyclic compound, 50670-64-9, name is 5-Amino-2-methylbenzonitrile, its traditional synthetic route has been very mature, but the traditional synthetic route has various shortcomings, such as complicated route, low yield, poor purity, etc, below Introduce a new synthetic route. HPLC of Formula: C8H8N2

Add a solution of sodium nitrile (2.1 g, 31 mmol) in water (15 mL) drop wise at 5 C to a stirred solution of 5-amino-2-methylbenzonitrile (4.0 g, 31 mmol) in 33% sulfuric acid (45 mL) and keep the temperature below 5 C. In a separate flask, add concentrated sulfuric acid (30 mL) cautiously to a stirred solution of sodium sulfate (21.7 g, 153 mmol) in water (15 mL) and heat the mixture to reflux. Add the prepared diazonium solution to the re fluxing mixture in portions and continue refluxing for 2 hours. Cool the mixture slowly to room temperature and stir overnight. Extract the mixture with ethyl acetate (2 x 100 mL) and wash the combined organic extracts with water (2 x 150 mL) and 10% NaOH water solution (3 x 100 mL). Acidify the combined NaOH extracts with concentrated HC1 and then extract with ethyl acetate (2 x 200 mL). Dry the organic extracts over Na2S04 and concentrate under reduced pressure to give the title compound as a yellow solid (2.4 g, 60%): ES/MS (m/z) 134 (M+H), which is used directly without further purification.

The synthetic route of 5-Amino-2-methylbenzonitrile has been constantly updated, and we look forward to future research findings.

Reference:
Patent; ELI LILLY AND COMPANY; LILLY CHINA RESEARCH AND DEVELOPMENT CO., LTD.; LIU, Kevin Kun-Chin; XIE, Yinong; WU, Liang; ZHOU, Guoqiang; WO2015/89800; (2015); A1;,
Nitrile – Wikipedia,
Nitriles – Chemistry LibreTexts

These common heterocyclic compound, 57381-37-0, name is 2-Bromo-5-chlorobenzonitrile, its traditional synthetic route has been very mature, but the traditional synthetic route has various shortcomings, such as complicated route, low yield, poor purity, etc, below Introduce a new synthetic route. Product Details of 57381-37-0

To a solutionof 2-bromo-5-chlorobenzonitrile (20 g, 93 mmol) in THF (200 mL) was added cyclopropylmagnesiumbromide (558 mL, 279 mmol) at 0 C. The resulting reaction – 151 -mixture was stirred at 0-5 C for 5 hours before MeOH (100 mL) was added and stirring continued at room temperature for 15 min. NaBH4 (7.1 g, 186 mmol) was added subsequently and the reaction mixture was stirred at room temperature overnight. Water was added and reaction mixture was exacted with AcOEt (300 mL x 3). The combined organic layers were concentrated in vacuo to give a crude product which was then purified by chromatography to give (2-bromo-5-chlorophenyl)(cyclopropyl)methanamine (8.2 g, yield 34%).

The synthetic route of 2-Bromo-5-chlorobenzonitrile has been constantly updated, and we look forward to future research findings.

Reference:
Patent; F. HOFFMANN-LA ROCHE AG; AEBI, Johannes; AMREIN, Kurt; CHEN, Wenming; HORNSPERGER, Benoit; KUHN, Bernd; LIU, Yongfu; MAERKI, Hans P.; MAYWEG, Alexander V.; MOHR, Peter; TAN, Xuefei; WANG, Zhanguo; ZHOU, Mingwei; WO2013/79452; (2013); A1;,
Nitrile – Wikipedia,
Nitriles – Chemistry LibreTexts