Category: nitriles-buliding-blocks

133116-83-3, 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. 133116-83-3 name is 2-Fluoro-6-(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.

2-Fluoro-6-(trifluoromethyl)benzonitrile (10 g, 0.053 mol) was warmed at 40C in 200 ml of anhydrous methylamine in an autoclave for 2 days. The excess methylamine was allowed to evaporate and the resulting grey solid was dissolved in 200 ml of methylene chloride together with 4-aminopyridine (0.1 g, 0.001 mol) and triethylamine (3.3 ml, 0.026 mol). To the chilled solution was slowly added ethyl malonyl chloride (8.8 g, 0.060 mol). The solution was stirred for 4 hours and then worked up to give a yellowish syrup. The syrup was dissolved in 100 ml of anhydrous ethanol, and sodium methoxide (5.4 g, 0.10 mol) was added. After 1 hour, the solvent was removed and the residue worked up with methylene chloride and water. The quinoline derivative formed was carefully dried and suspended in 250 ml of chilled anhydrous tetrahydrofuran. Sodium hydride (4 g, 0.125 mol) was slowly added and then methyl iodide (10 ml, 0.15 mol). The mixture was heated under reflux for 6 hours, quenched with water and worked up with diethyl ether. The solvents were removed and the residue (17.3 g) was dissolved in a mixture of ethanol (50 ml) and conc. hydrochloric acid (10 ml). The solution was warmed at 45C overnight, cooled and the precipitate was collected to give 8 g of the title compound, yield 48 %. 1H NMR delta (CDCl3) delta 1.46 (3H, t), 3.68 (3H, s), 4.50 (2H, q), 7.58 (1H, m), 7.71 (2H, m), 15.0(1H, s).

At the same time, in my other blogs, there are other synthetic methods of this type of compound, 2-Fluoro-6-(trifluoromethyl)benzonitrile, and friends who are interested can also refer to it.

Reference:
Patent; Active Biotech AB; EP1095021; (2003); B1;,
Nitrile – Wikipedia,
Nitriles – Chemistry LibreTexts

50712-68-0, 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. 50712-68-0, name is 4-Chloro-2-methylbenzonitrile, A new synthetic method of this compound is introduced below.

2-(bromomethyl)-4-chlorobenzonitrileInto a 50-mL round-bottom flask, was placed a mixture of 4-chloro-2-methylbenzonitrile (1 g, 6.60 mmol, 1.00 equiv), CCl4 (15 mL), NBS (1.29 g, 7.25 mmol, 1.10 equiv) and BPO (50 mg, 0.20 mmol, 0.03 equiv). The resulted solution was stirred for 16 h at 80 C. The reaction mixture was cooled to 25 C. Then it was washed with 3¡Á15 mL of water. The organic phase was dried over anhydrous sodium sulfate and concentrated under vacuum. The residue was purified by a silica gel column and eluted with ethyl acetate/ hexane (1:50). This resulted in 0.45 g (30%) of 2-(bromomethyl)-4-chlorobenzonitrile as a light yellow solid. LC-MS (ESI) m/z: Calculated for C8H5BrClN: 228.9. found: 230 [M+H]+.

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; Global Blood Therapeutics, Inc.; Li, Zhe; Xu, Qing; Yu, Chul; Yee, Calvin; Gwaltney,, II, Stephen L.; Metcalf, Brian W.; Richards, Steven; Lardy, Matthew A.; Setti, Lina; Sham, Hing; US2015/315198; (2015); A1;,
Nitrile – Wikipedia,
Nitriles – Chemistry LibreTexts

Some common heterocyclic compound, 453565-55-4, name is 5-Fluoroisophthalonitrile, molecular formula is C8H3FN2, 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. 453565-55-4

Example 15 To a solution of 1-(3-hydroxyphenyl)ethanol (69 mg) in 1-methyl-2-pyrrolidinone under a nitrogen atmosphere was added sodium hydride (60% in oil, 44 mg). The mixture was stirred at 20 C. for 10 minutes then 5-fluoroisophthalonitrile (0.161 g) was added and the mixture heated at 100 C. for 0.5 hour then at 150 C. for a further 0.5 hour. The cooled mixture was diluted (ethyl acetate), washed (water), dried over magnesium sulphate, evaporated and purified by dry column chromatography on silica (eluent dichloromethane/isohexane) to yield 1-(3,5-dicyanophenoxy)-3-[1-(3,5-dicyanophenoxy)ethyl]benzene (Compound 89, 84 mg), NMR (300 MHz, CDCl3) 7.56 (1H, t); 7.45-7.38 (2H, m); 7.32 (2H, d); 7.24 (2H, d); 7.22-7.18 (1H, m); 6.98 (1H, t); 6.92 (1H, dd); 5.29 (1H, quartet); 1.66 (3H, d).

These compound has a wide range of applications. It is believed that with the continuous development of the source of the synthetic route 453565-55-4, its application will become more common.

Reference:
Patent; Cornell, Clive; Cramp, Michael Colin; Gingell, Michael; Westaway, Susan; US2003/181334; (2003); A1;,
Nitrile – Wikipedia,
Nitriles – Chemistry LibreTexts

1558-82-3,Some common heterocyclic compound, 1558-82-3, name is Ethyl N-cyanoacetimidate, molecular formula is C5H8N2O, 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.

Intermediate 33Preparation of N’-cyano-N-(cyanomethyl)-N-methylacetimidamideTo a solution of ethyl N-cyanoacetimidate (1.12 g; 10 mmol) in ethanol (20 mL) was add 2-(methylamino)acetonitrile (0.736 g; 10.5 mmol) and the reaction mixture was stirred at room temperature for 24 h. The volatiles were removed under reduced pressure and the 1.36 g (100%) of the crude white solid were dried and used without further purification. ESI/APCI(+): 137 (M+H).

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

Reference:
Patent; KATHOLIEKE UNIVERSITEIT LEUVEN; US2012/316161; (2012); A1;,
Nitrile – Wikipedia,
Nitriles – Chemistry LibreTexts

17626-40-3, name is 3,4-Diaminobenzonitrile, 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. 17626-40-3

A solution of 1 (557.5 mg, 2.5 mmol), 3, 4-diaminobenzonitrile (332.5 mg, 2.5 mmol), and benzoquinone (270.2 mg, 2.5 mmol) in ethanol (40 mL) was allowed to reflux under nitrogen for overnight. The reaction mixture was distilled off under reduced pressure. The residue was triturated with ether and filtered off to afford 2 in 90%, mp >340 C.’H NMR (DMSO-d6) ; J 7.20 (d, J = 8.4 Hz, 1 H), 7.68 (d, J = 8.4 Hz, 1 H), 7.86-7. 98 (m, 6H), 8.28 (s, 1 H), 8.57 (s, 1H), 12.80 (brs, 1H), 13.65 (brs, 1H). 13C NMR ; No. 158. 4, 153. 9,143. 5,132. 9, 131.0, 129.3, 126.7, 125.7, 119.7, 118.9, 118.1, 112.8, 109.4, 104.5. MS (m/z, rel. int. ); 336 (M+, 100), 307 (25), 280 (5), 164 (10). High resolution calcd. for C21H12N4O ms 336. 10111. Observed 336.10189. Anal. (C21H12N4O-0.25H2O) C, H, N.

Statistics shows that 17626-40-3 is playing an increasingly important role. we look forward to future research findings about 3,4-Diaminobenzonitrile.

Reference:
Patent; UNIVERSITY OF NORTH CAROLINA AT CHAPEL HILL; GEORGIA STATE UNIVERSITY RESEARCH FOUNDATION, INC.; WO2005/40132; (2005); A1;,
Nitrile – Wikipedia,
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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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403-54-3, Adding some certain compound to certain chemical reactions, such as: 403-54-3, name is 3-Fluorobenzonitrile, 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 403-54-3.

General procedure: To an oven-dried 15 mL sealed tube were added 2-aminophenylmethanol 1 (0.425 mmol), benzonitrile 2(0.25 mmol), Ru cat. b (1.94 mg, 1 mol%), and KOtBu (14.02 mg, 0.5equiv) intamyl alcohol (1 mL) under an air atmosphere. The sealedtube was capped and heated at 130C for 2 h. The reaction mixturewas cooled down to room temperature and directly concentratedunder vacuum. The crude mixture was puried by preparative thin-layer-chromatography (petroleum ether/ethyl acetate 20/1) togive the desired product 3 or 4.

Chemical properties determine the actual use. Each compound has specific chemical properties and uses. We look forward to more synthetic routes in the future to expand reaction routes of 403-54-3.

Reference:
Article; Wan, Xiao-Min; Liu, Zi-Lin; Liu, Wan-Qing; Cao, Xiao-Niu; Zhu, Xinju; Zhao, Xue-Mei; Song, Bing; Hao, Xin-Qi; Liu, Guoji; Tetrahedron; vol. 75; 18; (2019); p. 2697 – 2705;,
Nitrile – Wikipedia,
Nitriles – Chemistry LibreTexts

185147-08-4, The chemical industry reduces the impact on the environment during synthesis 185147-08-4, name is 4-Fluoro-3-methylbenzonitrile, I believe this compound will play a more active role in future production and life.

7.00 g (51.8 mmol) 4-fluoro-3-methyl-benzonitrile are heated to 110¡ã C. together with 1-N-methyl-[1,4]diazepan for 1 week with stirring. After evaporation i. vac. the residue is separated on aluminium oxide (eluant: dichloromethane) and the corresponding fractions are again purified on silica gel (eluting gradient: dichloromethane/methanol 100:1->9:1). Yield: 1.70 g (14percent) C14H19N3 (229.33) Mass spectrum: (M+H)+=230 Rf value: 0.25 (silica gel; dichloromethane/methanol=9:1)

The chemical industry reduces the impact on the environment during synthesis 4-Fluoro-3-methylbenzonitrile. I believe this compound will play a more active role in future production and life.

Reference:
Patent; Boehringer Ingelheim International GmbH; US2005/203078; (2005); 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. 79463-77-7, name is Diphenyl N-cyanocarbonimidate, A new synthetic method of this compound is introduced below., 79463-77-7

6.1 To a solution of 4-(2-keto-1-benzimidazolinyl)piperidine (1.3 g; 5.98 mmol) in acetonitrile was added diphenyl N-cyanocarbonimidate (1.56 g; 6.55 mmol; 1.1 equiv). The reaction mixture was stirred at 60 C. for 48 h under nitrogen atmosphere and then concentrated under reduced pressure. The crude product was suspended in ethyl acetate (50 mL) and a saturated aqueous solution of sodium bicarbonate (50 mL) and stirred overnight at room temperature. The solid was collected by filtration and dried to give N-cyano-4-(2-oxo-2,3-dihydro-benzoimidazol-1-yl)-piperidine-1-carboximidic acid phenyl ester (1.85 g; 85%) as a white solid.

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; Icagen, Inc.; US2003/171360; (2003); A1;,
Nitrile – Wikipedia,
Nitriles – Chemistry LibreTexts

17216-62-5, 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. 17216-62-5, name is Diethyl 2-(2-cyanoethyl)malonate, A new synthetic method of this compound is introduced below.

241 kg of the above intermediate, 1200 kg of isopropyl alcohol and 28 kg of catalyst Raney Co were placed in a 2-liter stainless steel autoclave. After replacing the air in the kettle with hydrogen,Press the hydrogen pressure to 25kg/cm2, turn on the stirring, and slowly raise the temperature to 70 C with jacketed steam.Above, the oxygen inhalation reaction begins to exotherm. At this point, turn on the cooling water to cool.The reaction temperature was controlled to rise smoothly to 90-100 C, and the introduction of hydrogen gas was controlled to stabilize the pressure at 35-40 kg/cm 2 .After 4.5 hours, the hydrogen absorption was stopped and the reaction was continued at 100 C, 35 kg / cm 2 for 1 hour.The material in the autoclave was cooled to 44 C with cooling water, and after the residual hydrogen pressure was vented,Press the material to the filter with N2 gas.The Raney Co catalyst was recovered by filtration under N2 gas protection.The filtrate was introduced into a 2000 liter glass-line distillation crystallization kettle, and heated under stirring.The solvent isopropanol was distilled off. Then add 660 kg of petroleum ether while stirring for 0.5 hour.The crystals are gradually cooled, and the stirring is intermittently started to prevent the product from being easily discharged from the bottom of the kettle after agglomeration. After the completion of the crystallization, the mixture was centrifuged and dried to give 184 kg of a white solid. The content of HPLC detection was 99.6%, and the hydrogenation reaction yield was 96.4%.The total yield of the two-step reaction was 79.2%.

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; Shanghai Jingwei Chemical Technology Co., Ltd.; Yao Husheng; Zhao Zhulin; Zhang Ming; Chen Bo; (6 pag.)CN108484484; (2018); A;,
Nitrile – Wikipedia,
Nitriles – Chemistry LibreTexts