Category: nitriles-buliding-blocks

21524-39-0, 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.

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). Potassium permanganate (1.58 g, 10 mmmol) and montmorillonite K- 10 (3.16 g) are grounded together in a mortar until a fine homogeneous powder is obtained.KMn04-montmorillonite K-10 (3.2 g, 6.78 mmol) is added portionwise to a solution of ethyl l-[2-fluoro-6-(l-methyl-4,5-dihydroimidazol-2-yl)phenyl]-3-methyl-pyrazole-4- carboxylate (1.12 g, 3.39 mmol) (contaminated with the other pyrazole regioisomer in a ratio 75:25) in acetonitrile (84.76 mL, 1.62 moles). The mixture is stirred at room temperature for 6.5 hr. and more KMn04-montmorillonite K-10 (0.8 g, 1.69 mmol) is added portionwise and the mixture stirred at room temperature overnight. Ethanol is added and stirred for additional 20 min. Then the reaction mixture is filtered through a short pad of celite and the solid material is washed with acetonitrile. The solvent is evaporated under reduced pressure and the crude mixture is purified normal phase Isco chromatography using ethyl acetate as eluent to yield 518 mg of l-[2-fluoro-6-(l- methylimidazol-2-yl)phenyl]-3-methyl-pyrazole-4-carboxylate (contaminated with the other pyrazole regioisomer in a ratio 75:25). MS (m/z): 329 (M+1).

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 21524-39-0.

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

16532-79-9, 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. 16532-79-9, name is 4-Bromophenylacetonitrile, This compound has unique chemical properties. The synthetic route is as follows.

A solution of 4-Bromophenylacetonitrile (10.0 g, 51.0 mmol) in tetrahydrofuran (200 mL) was added slowly to a suspension of sodium hydride (60% in mineral oil, 6.0 g, 153 mmol) in tetrahydrofuran (400 mL) at room temperature over 30 minutes. After complete addition, methyl iodide (7.6 mL, 122 mmol) was added slowly over 30 minutes, maintaining the reaction temperature below 40 C. by occasional immersion into a water bath. The reaction was then stirred overnight at room temperature. The mixture was poured into water (500 mL) and extracted into ethyl acetate (2*300 mL). The combine organic layers were washed with brine (2*300 mL), dried over magnesium sulfate, filtered and concentrated. Crude purified on silica gel eluding with 2% ethyl acetate in hexanes) to give 2-(4-bromophenyl)-2-methylpropanenitrile (11 g, 96%) as a yellow oil. 1H NMR (300 MHz, CDCl3): delta ppm 1.70 (s, 6H), 7.35 (dd, 2H), 7.53 (dd, 2H).

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:
Patent; pfizer Inc; US2010/197591; (2010); A1;,
Nitrile – Wikipedia,
Nitriles – Chemistry LibreTexts

127946-77-4, Name is 1-Amino-1-cyclopropanecarbonitrile hydrochloride, 127946-77-4, 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.

A mixture of example 9a) (850 mg, 2.74 mmol, Eq: 1.00), 1-aminocyclopropane- carbonitrile hydrochloride (422 mg, 3.56 mmol, Eq: 1.30), sodium 2-ethylhexanoate (705 mg, 4.24 mmol, Eq: 1.55) in water (3 ml) and THF (2.00 ml) was stuffed at 55 C for 18 h. To the reaction mixture were added hydrochloric acid (189 mg, 157 tl, 1.91 mmol, Eq:0.70) and sodium chloride (1.36 g, 1.36 ml, 23.3 mmol, Eq: 8.50). The mixture was stuffed for 15 mm, then poured into AcOEt (25 ml) and extracted. The aqueous layer was back- extracted with AcOEt (3 x 20 ml). The organic layers were dried over Na2SO4 and concentrated in vacuo. The crude material was purified by flash chromatography (silica gel, 40 g, 0% to 90% EtOAc in heptane) to yield the title compound as white foam (560 mg;52 %). mlz = 393.0 [M+Hf?.

Statistics shows that 1-Amino-1-cyclopropanecarbonitrile hydrochloride is playing an increasingly important role. we look forward to future research findings about 127946-77-4.

Reference:
Patent; F. HOFFMANN-LA ROCHE AG; HOFFMANN-LA ROCHE INC.; ANSELM, Lilli; BANNER, David; HAAP, Wolfgang; KUHN, Bernd; LUEBBERS, Thomas; PETERS, Jens-Uwe; SPINNLER, Beat; WO2014/29722; (2014); A1;,
Nitrile – Wikipedia,
Nitriles – Chemistry LibreTexts

A common heterocyclic compound, 1897-41-2, name is 2,3,5,6-Tetrachloroterephthalonitrile, molecular formula is C8Cl4N2, 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. 1897-41-2.

0.60 g (0.015 mol) of sodium hydroxide was added to a solution of 1.22 g (0.0075 mol) of 3,5-dichloropyridin-4-amine in 40 mL of DMF, followed by addition of 2 g (0.0075 mol) of 2,3,5,6-tetrachloroterephthalonitrile under stirring, the mixture was stirred for 5 h after addition at room temperature. After the reaction was over by Thin-Layer Chromatography monitoring, the reaction mixture was poured into water and extracted with ethyl acetate, the organic phase was washed with water and saturated brine, dried over anhydrous magnesium sulfate, filtered and then concentrated under reduced pressure. The residue was purified through silica column (ethyl acetate/petroleum ether (boiling point range 60-90¡ã C.)=1:3, as an eluent) to give 2.16 g of compound C-124 as yellow solid, m.p. 202-204¡ã C. [0197] 1H-NMR (300 MHz, internal standard TMS, solvent CDCl3) delta (ppm): 7.28 (br, 1H, NH), 8.30 (s, 2H, Py-2,6-2H).

The synthetic route of 2,3,5,6-Tetrachloroterephthalonitrile has been constantly updated, and we look forward to future research findings.

Reference:
Patent; SHENYANG RESEARCH INSTITUTE OF CHEMICAL INDUSTRY CO., LTD.; SINOCHEM CORPORATION; Liu, Changling; Huang, Guang; Lan, Jie; Hao, Shulin; Li, Zhinian; Li, Huichao; Guan, Aiying; Jiang, Airu; Xu, Ying; US2014/213598; (2014); A1;,
Nitrile – Wikipedia,
Nitriles – Chemistry LibreTexts

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 939-80-0 as follows. 939-80-0

In a reactor, compound 2 (917 mg, 2.0 mmol), compound 4 (274 mg, 3.0 mmol) and Cs2CO3 (325 mg, 1.0 mmol) were added to dry THF (20 mL). Then the reactor was sealed under nitrogen, and the mixture was kept at 30 C., stirred for 12 hours. After the reaction, the mixture was diluted with dichloromethane (10 mL) and then filtered. The resulting filtrate was washed twice with water (2¡Á10 mL), and aqueous phases were combined, then the combined aqueous phases were extracted twice with dichloromethane (2¡Á10 mL). The organic layers were combined, dried over Na2SO4, and concentrated to obtain compound XVII as a light yellow powder (1004 mg, yield 90.2%), HPLC purity: 99.2%.

According to the analysis of related databases, 939-80-0, the application of this compound in the production field has become more and more popular.

Reference:
Patent; XU, YONG; (10 pag.)US2016/257667; (2016); A1;,
Nitrile – Wikipedia,
Nitriles – Chemistry LibreTexts

25808-30-4, 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. 25808-30-4 name is 2-(Methylamino)acetonitrile hydrochloride, 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.

[Example 50] Preparation of 3-methyl-1-(4-methylbenzyl)-4-(4-phenoxyphenyl)iminoimidazolidine-2-one (I-363) To a mixture of 4-methylbenzylamine hydrochloride (10 g, 83 mmol) and N,N-dimethylacetamide (50 mL) was added 1,1′-carbonyldiimidazole (14.05 g, 87 mmol) under ice-cooling. To the mixture was added DBU (18.66 mL, 124 mmol), and the resulting mixture was stirred at 0¡ãC for 30 minutes. To the reaction mixture was added 2-(methylamino)acetonitrile hydrochloride (10.55 g, 99 mmol) under ice-cooling. Further, to the mixture was added DBU (24.88 mL, 165 mmol) under ice-cooling, and the resulting mixture was stirred at room temperature for 45 minutes and stirred at 50¡ãC for additional 90 minutes. To the reaction mixture was added water (500 mL). The mixture was extracted with ethyl acetate (500 mL*2), washed by brine (500 mL), dried over anhydrous magnesium sulfate, and concentrated in vacuo. The resulting residue was purified by silica gel column chromatography (methanol/chloroform) to give 4-imino-3-methyl-1-(4-methylbenzyl)imidazolidine-2-one (9.43 g, Yield:52percent) as yellow solid. 1H-NMR (delta ppm TMS/CDCl3): 2.31 (3H, s), 2.94 (3H, s), 3.93 (2H, s), 4.66 (2H, s), 6.90 (1H, br.s), 7.11 (2H, d, J=8.2 Hz), 7.27 (2H, d, J=8.2 Hz).

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

Reference:
Patent; Shionogi & Co., Ltd.; KAI, Hiroyuki; ENDOH, Takeshi; JIKIHARA, Sae; ASAHI, Kentaro; HORIGUCHI, Tohru; EP2604260; (2013); 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

Take a two-necked round bottom flask, dissolve compound 8-1 in chloroform, and perform a Knoevenagel condensation reaction with malononitrile indanone ketone electronic unit under weakly basic conditions. After TLC monitors the reaction, directly use reaction oil The ether / dichloromethane eluent was passed through the column to obtain the final type of organic solar cell using diindenobisthiophene as the core; wherein, the compound 8-1, the electron-drawing unit, pyridine, and chloroform had a ratio of 0.2 to 2.2mmol: 0.3 3.0mmol: 0.01 0.5mmol: 10 50mL; yield is 84.7%;

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:
Patent; Xiamen University; Xie Suyuan; Zheng Shanyu; An Mingwei; Pei Yaqian; Deng Linlong; (31 pag.)CN110746440; (2020); A;,
Nitrile – Wikipedia,
Nitriles – Chemistry LibreTexts

78473-00-4, These common heterocyclic compound, 78473-00-4, name is 4-Amino-3,5-dichlorobenzonitrile, 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.

(i) Preparation of N-trifluoroacetyl-4-cyano-2,6-dichloroaniline Twenty-five grams (0.1337 mole) of 4-cyano-2,6-dichloroaniline was dissolved in 250 ml of methylene chloride, and 30.9 g (20.8 ml, 0.1471 mole) of trifluoroacetic anhydride was added slowly with stirring. The solution was allowed to stand overnight and then was neutralized by the addition of 5% aqueous sodium carbonate, precipitating a white crystalline solid which was filtered and dried to give 28.0 g (74% yield) of N-trifluoroacetyl-4-cyano-2,6-dichloroaniline, m.p.: 134-136 C.

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 78473-00-4.

Reference:
Patent; SmithKline Beckman Corporation; US4719223; (1988); A;,
Nitrile – Wikipedia,
Nitriles – Chemistry LibreTexts

939-79-7, These common heterocyclic compound, 939-79-7, name is 4-Methyl-3-nitrobenzonitrile, 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.

Synthesis of 3-(4-Methyl-3-nitro-phenyl)-4H-[1,2,4]triazole Hydrogen chloride was bubbled through a solution of 3-nitro-p-tolunitrile (0.49 g, 3 mmol) in 40 mL of ethanol at room temp for 10 min. The solution was continued stirring at room temp for 60 min and the solvent was then evaporated under vacuum to dryness to give a white solid. The intermediate so obtained was dissolved in 20 mL of ethanol, neutralized with sodium ethoxide solution and the resulting precipitate was removed by filtration. To the filtrate was added at room temp formic hydrazide (0.2 g, 3 mmol) and the solution was continued stirring at room temp for 2 h. After removal of volatiles in vacuo, the residue was dissolved in 30 mL of m-xylene and refluxed at 150 C. for 16 h. Removal of volatiles in vacuo and purification using flash chromatography afforded 0.26 g of the final productproduct. (Yield: 43%). MS (m/z) calcd for C9H8N4O2 (MH+) 205.2, found, 205.1.

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 939-79-7.

Reference:
Patent; Bristol-Myers Squibb Company; Pharmaceopeia, Inc.; US6906067; (2005); B2;,
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. 3939-09-1, name is 2,4-Difluorobenzonitrile, A new synthetic method of this compound is introduced below., 3939-09-1

Potassium nitrate (16.4 g, 147.4 mmol) was added to concentrated H2SO4 (85 ml, 1582 mmol) at 0 C, followed by slow addition of 2,4-difluorobenzonitrile (11.0 g, 79.1 mmol).The suspension was stirred at this temperature for an additional 4 hrs and quenched ice / water (800 ml). The resulting solid was collected by filtration and dried to give the title compound (13.8 g, 95%) as a white solid. NMR (400 MHz, CDCl3) 8.48 (m, IH), 7.24 (m, IH).

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; ASTRAZENECA AB; ASTRAZENECA UK LIMITED; WO2006/87530; (2006); A1;,
Nitrile – Wikipedia,
Nitriles – Chemistry LibreTexts