Month: September 2021

Electric Literature of 133116-83-3, Each compound has different characteristics, and only by selecting the characteristics of the compound suitable for a specific situation can the compound be applied on a large scale. 133116-83-3, name is 2-Fluoro-6-(trifluoromethyl)benzonitrile, This compound has unique chemical properties. The synthetic route is as follows.

To a solution of 2-fluoro-6-(trifluoromethyl)benzonitrile (1.0 g, 5.29 mmol) and K2C03 (1.46 g, 10.58 mmol) in DMF (5 mL) was added 2-(trimethylsilyl)ethanethiol (1.01 ml, 6.35 mmol). The mixture was stirred at room temperature for 4 hours. The TLC indicated complete consumption of starting material. The mixture was filtered and evaporated to dryness in vacuo. The crude was adsorbed onto silica gel, and purified by hexane and ethyl acetate to afford the desired compound. LC/MS [M+H]+:304.

The chemical industry reduces the impact on the environment during synthesis 2-Fluoro-6-(trifluoromethyl)benzonitrile. I believe this compound will play a more active role in future production and life.

Reference:
Patent; MERCK SHARP & DOHME CORP.; MANDAL, Mihir; TANG, Haifeng; XIAO, Li; SU, Jing; LI, Guoqing; YANG, Shu-Wei; PAN, Weidong; TANG, Haiqun; DEJESUS, Reynalda; HICKS, Jacqueline; LOMBARDO, Matthew; CHU, Hong; HAGMANN, William; PASTERNAK, Alex; GU, Xin; JIANG, Jinlong; DONG, Shuzhi; DING, Fa-Xiang; LONDON, Clare; BISWAS, Dipshikha; YOUNG, Katherine; HUNTER, David, N.; ZHAO, Zhiqiang; YANG, Dexi; WO2015/112441; (2015); A1;,
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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. 10406-25-4 name is 4-(Aminomethyl)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. 10406-25-4

General procedure: Under nitrogen atmosphere, a Schlenk tube was sequentially charged with cyclicdiaryliodonium salt (1.0 equiv), copper catalyst A1 or A2 (5.0 mol%), Na2CO3 (3.0 equiv) anddichloromethane (0.05 M). After the mixture was chilled to proper temperature, the appropriateamine (1.2 equiv) was added and stirred for the time indicated in the experimental procedures.The reaction mixture was filtered through a plug of celite with ethyl acetate. The filtrate wasconcentrated under reduced pressure, and the residue was purified by column chromatographyon silica gel to deliver the corresponding product.

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

Reference:
Article; Zhao, Kun; Duan, Longhui; Xu, Shibo; Jiang, Julong; Fu, Yao; Gu, Zhenhua; Chem; vol. 4; 3; (2018); p. 599 – 612;,
Nitrile – Wikipedia,
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Some common heterocyclic compound, 34667-88-4, name is 2-Fluoro-4-nitrobenzonitrile, molecular formula is C7H3FN2O2, 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 34667-88-4

Methyl 3-amino-6-nitrobenzothiophene-2-carboxylate: Methyl thioglycolate (0.08 mL, 0.85 mmol) was added to a solution of 2-fluoro-4-nitrobenzonitrile (145 mg, 0.87 mmol), and triethylamine (0.14 mL, 1.0 mmol) in acetonitrile (20 mL) stirred under nitrogen at 25° C. After 3 hours further triethylamine (0.28 mL, 2.0 mmol) was added to the solution, which was stirred at 25° C. for a further 16 hours. The solvent was removed under reduced pressure to give a brown residue, which upon trituration with chloroform precipitated methyl 3-amino-6-nitrobenzothiophene-2-carboxylate (103 mg, 54percent) as a red brown solid, mp 228.5-229.5° C. 1H NMR (DMSO-d6): delta 8.87 (d, J=2.0 Hz, 1H), 8.32 (d, J=9.0 Hz, 1H), 8.15 (dd, J=8.8, 2.0 Hz, 1H), 7.26 (brs, 2H), 3.77 (s, 3H). Mass Spectrum (CI): 253 (100, MH+), 252 (52, M+).

These compound has a wide range of applications. It is believed that with the continuous development of the source of the synthetic route 34667-88-4, its application will become more common.

Reference:
Patent; Warner-Lambert Company; US6344459; (2002); B1;,
Nitrile – Wikipedia,
Nitriles – Chemistry LibreTexts

Adding a certain compound to certain chemical reactions, such as: 29509-06-6, name is 4-Methyl-3-oxopentanenitrile, belongs to nitriles-buliding-blocks compound, can increase the reaction rate and produce products with better performance than those obtained under traditional synthetic methods. Here is a downstream synthesis route of the compound 29509-06-6, Product Details of 29509-06-6

Sodium hydride (60%, 11.52 g, 287 mmol) in a round bottomflask was cooled using an ice-water bath and kept under nitrogenatmosphere on a Schlenk line. Anhydrous acetonitrile (15.0 mL,287 mmol) and 9.0 mL of anhydrous DMSO were added to the flaskand the mixture was stirred for 30 min. Methyl isobutyrate(33.0 mL, 29.3 g, 287 mmol) was added to the reaction mixture.After stirring for approximately 2 h, the reaction mixture turnedinto a thick white solid. The excess NaH in the reaction mixturewas quenched by slow addition of deionized water. NH4Cl(30.7 g) was added to fully protonate the product, which immediatelygave a milky white suspension. The product was thenextracted three times (150 mL each) with ethyl acetate. All organiclayers were combined and washed with NaCl brine. The organiclayer was dried over anhydrous MgSO4 and filtered. To this solutionwas added 16.0 ml (13.1 g, 110 mmol) of DMF-DMA and thereaction was stirred for 18 h, after which the solvent was removedunder reduced pressure and the product (2-isobutyryl-3-dimethylaminoacrylonitrile) purified by column chromatographyusing CHCl3 as the mobile phase. The solvent was removed andthe product dissolved in 50 mL of methanol. Hydrazine hydrate(8.0 mL, 78 mmol) was added and the reaction stirred overnight.Solvent was removed under reduced pressure and the productpurified by column chromatography using 50:50 ethyl acetate/hexanes to give 2e as a light yellow powder (5.86 g, 43.4 mmol,15% yield based on acetonitrile).

If you are interested in these compounds, you can also browse my other articles.Thank you for taking the time to read this article. I hope you enjoyed it.

Reference:
Article; Kadel, Lava R.; Kromer, John R.; Moore, Curtis E.; Eichhorn, David M.; Polyhedron; vol. 125; (2017); p. 206 – 218;,
Nitrile – Wikipedia,
Nitriles – Chemistry LibreTexts

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,
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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,
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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,
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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