Category: nitriles-buliding-blocks

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

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

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

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

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;,
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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;,
Nitrile – Wikipedia,
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Reference of 145689-34-5,Some common heterocyclic compound, 145689-34-5, name is 2-(2,3-Difluorophenyl)acetonitrile, molecular formula is C8H5F2N, 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.

(35′,5^-3-Amino-5-(23-difluorophenyl)-l-(2,2,2-trifluoroethyl piperidin-2-one hydrochloride; Step A: Ethyl 4-cvano-4-f2,3-difluorophenyl)butanoate; To a mixture of (2,3-difluorophenyl)acetonitrile (40.5 g, 265 mmol), ethyl acrylate (24 mL, 221 mmol), and hydroquinone (50 mg, 0.45 mmol) was added OH (2 M in MeOH, 2.0 mL, 4.0 mmol) and the resulting mixture was heated at 160 C for 16 h and then allowed to cool to ambient temperature. The crude mixture was purified by silica gel chromatography, eluting with a gradient of hexanes: EtOAc – 100:0 to 50:50, to give the title compound. MS: miz = 207.9 (M – OEt).

These compound has a wide range of applications. It is believed that with the continuous development of the source of the synthetic route 2-(2,3-Difluorophenyl)acetonitrile, its application will become more common.

Reference:
Patent; MERCK SHARP & DOHME CORP.; BELL, Ian, M.; BELARDI, Justin; WO2012/129013; (2012); A1;,
Nitrile – Wikipedia,
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Related Products of 103146-25-4,Some common heterocyclic compound, 103146-25-4, name is 4-(4-(Dimethylamino)-1-(4-fluorophenyl)-1-hydroxybutyl)-3-(hydroxymethyl)benzonitrile, molecular formula is C20H23FN2O2, 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.

To a stirred solution [OF RACEMIC 4- [4-DIMETHYLAMINO-1- (4-FLUORO-PHENYL)-1-HYDROXY-] [BUTYL]-3-HYDROXYMETHYL-BENZONITRILE] (0,29 mmol, 100 mg) and vinylbutyrate (0,29 mmol, [37 L)] in anhydrous toluene (2,925 ml) is added Novozymes 435, (0,2 mg) and 1,1 eq. Carboxylic acid. The reaction is heated to 40 degrees celcius and followed by HPLC. The enzyme is filtered off and washed with a small amount of toluene. The combined organic phases are evaporated in vacuo and subsequently analyzed on super critical fluid chromatography. Result is shown in table 19.

These compound has a wide range of applications. It is believed that with the continuous development of the source of the synthetic route 4-(4-(Dimethylamino)-1-(4-fluorophenyl)-1-hydroxybutyl)-3-(hydroxymethyl)benzonitrile, its application will become more common.

Reference:
Patent; H. LUNDBECK A/S; WO2004/14821; (2004); A1;,
Nitrile – Wikipedia,
Nitriles – Chemistry LibreTexts

Electric Literature of 7251-09-4, 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. 7251-09-4, name is 4-Amino-2-methoxybenzonitrile, This compound has unique chemical properties. The synthetic route is as follows.

A suspension of 6-chloro-7-hydroxy-2-oxo-l,2-dihydroquinoline-3- carbaldehyde (58.0 mg, 0.259 mmol) and 4-amino-2-methoxybenzonitrile (48.0 mg, 0.324 mmol) in DCM (4.0 mL) was treated with acetic acid (0.07 mL, 1.223 mmol) and stirred 10 minutes. Sodium triacetoxyborohydride (84.0 mg, 0.396 mmol) was added. The mixture was stirred at room temperature overnight. The mixture was diluted with EtOAc (50 mL), washed with water (2×50 mL) and brine (50 mL), dried (Na2S04), filtered, and evaporated under reduced pressure. The residue was dissolved in methanol, treated with silica gel, and evaporated. The material was chromatographed by Biotage MPLC (10 g silica gel column) with 20 to 100% EtOAc in hexanes to provide the title compound 1-57 (18.6 mg, 0.052 mmol, 20.2 % yield) as a peach-coloured solid. 1H NMR (300 MHz, DMSO-d6): delta ppm 11.82 (s, 1 H), 10.89 (s, 1 H), 7.70 (s, 1 H), 7.63 (s, 1 H), 7.28 (d, J=8.50 Hz, 1 H), 7.12 (dd, J=6.00, 6.00 Hz, 1 H), 6.91 (s, 1 H), 6.32 (d, J=1.76 Hz, 1 H), 6.22 (dd, J=8.60, 1.60 Hz, 1 H), 4.17 (d, J=5.60 Hz, 2 H), 3.78 (s, 3 H). LCMS (Method 4): Rt 1.17 min., m/z 356.1 [M+H]+.

The chemical industry reduces the impact on the environment during synthesis 4-Amino-2-methoxybenzonitrile. I believe this compound will play a more active role in future production and life.

Reference:
Patent; FORMA THERAPEUTICS, INC.; ASHWELL, Susan; CAMPBELL, Ann-Marie; CARAVELLA, Justin Andrew; DIEBOLD, R. Bruce; ERICSSON, Anna; GUSTAFSON, Gary; LANCIA, David R.; LIN, Jian; LU, Wei; WANG, Zhongguo; (141 pag.)WO2016/44782; (2016); A1;,
Nitrile – Wikipedia,
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Related Products of 123-06-8, The chemical industry reduces the impact on the environment during synthesis 123-06-8, name is Ethoxymethylenemalononitrile, I believe this compound will play a more active role in future production and life.

3.2 5-Amino-4-cyano-1-phenyl-1H-pyrazole (3a) A solution of phenylhydrazine (2d) (0.45 mL, 4.2 mmol) and ethoxymethylenemalononitrile (1b) (0.51 g, 4.2 mmol) in EtOH (4 mL) was irradiated at 120 C for 45 min in a sealed, pressure-rated Pyrex tube (10 mL) using a CEM Discover microwave synthesizer by moderating the initial power (100 W). After cooling in a flow of compressed air, the solvent was evaporated in vacuo. Purification by column chromatography on silica, eluting with light petroleum/EtOAc (5:1 v/v), gave the title compound (0.738 g, 95%) as a light brown solid, mp 137-139 C (lit. 29 mp 137 C) (found: 185.0827. C10H9N4 [MH] requires 185.0822); FTIR (KBr)/cm-1 numax 3302 (NH), 3240 (NH), 2230 (CN), 1577, 1530, 1368; 1H NMR (400 MHz; CDCl3) delta 7.58 (1H, s, H-3), 7.49-7.37 (5H, Ph), 4.52 (2H, br s, exch. D2O, NH2); 13C NMR (100 MHz, CDCl3) delta 141.9 (CH), 135 (C), 129.3 (C), 125.5 (CH), 124.1 (CH), 121.3 (CH), 115.6 (C), 86.2 (C); LRMS (APcI) m/z (rel intensity) 226 ([M+MeCNH]+, 100), 185 (MH+, 64).

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, Ethoxymethylenemalononitrile, other downstream synthetic routes, hurry up and to see.

Reference:
Article; Bagley, Mark C.; Baashen, Mohammed; Paddock, Victoria L.; Kipling, David; Davis, Terence; Tetrahedron; vol. 69; 39; (2013); p. 8429 – 8438;,
Nitrile – Wikipedia,
Nitriles – Chemistry LibreTexts