Month: August 2021

Electric Literature of 38487-86-4,Some common heterocyclic compound, 38487-86-4, name is 2-Amino-4-chlorobenzonitrile, molecular formula is C7H5ClN2, 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.

The commercially available 2-amino-4-chlorobenzonitrile (1 eq., 200 mg, 1.25 mmol) , NaN3 (1.37 eq., I l l mg, 0.06 mL, 1.71 mmol) and triethylamine hydrochloride (1.37 eq., 235 mg, 1.71 mmol) were dissolved in toluene (5 mL) and stirred at 80-100C overnight. The solution was allowed to cool to room temperature and water (5 mL) was then added (three times). The aqueous phases were reunified and acidified with concentrated HC1 to give a precipitate. The precipitate was filtered off and dried to give the 5-chloro-2-(lH- l,2,3,4-tetrazol-5-yl)aniline as a brown solid (195 mg, 80%). NMR (400MHz, d6-DMSO): 7.72 (d, 1H, J = 8.4 Hz), 6.96 (d, 1H, J = 2 Hz), 6.73 (dd, 1H, J = 8.4 -2 Hz) 13C NMR (100MHz, d6-DMSO): 148.52, 136.24, 129.73, 115.34, 115.09

The synthetic route of 38487-86-4 has been constantly updated, and we look forward to future research findings.

Reference:
Patent; INSERM (INSTITUT NATIONAL DE LA SANTE ET DE LA RECHERCHE MEDICALE); UNIVERSITE DE MONTPELLIER; CENTRE NATIONAL DE LA RECHERCHE SCIENTIFIQUE (CNRS); UNIVERSITE DE STRASBOURG; VALMIER, Jean; LEYRIS, Jean-Philippe; ROGNAN, Didier; SCHMITT, Martine; (80 pag.)WO2016/16370; (2016); A1;,
Nitrile – Wikipedia,
Nitriles – Chemistry LibreTexts

Reference of 869299-63-8,Some common heterocyclic compound, 869299-63-8, name is 3-Ethyl-4-fluorobenzonitrile, molecular formula is C9H8FN, 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.

Cesium carbonate (850 mg) was added to a solution of compound (5a) (200 mg) in DMSO (2.2 mL), and the mixture was heated to 130 C. The mixture was stirred for 10 minutes and 3-ethyl-4-fluorobenzonitrile (292 mg) was added thereto. The resulting mixture was stirred at the same temperature for 1.5 hours. After completion of the reaction, the reaction solution was allowed to standing still for cooling, and water was poured thereto. The reaction solution was partitioned between ethyl acetate and water. The organic layer was washed with saturated brine and dried by the addition of anhydrous sodium sulfate. After removal of the solvent by evaporation, the residue was purified by neutral silica gel column chromatography (chloroform/ethyl acetate/methanol) to obtain compound (6a) (151.8 mg, yield 54%) as a white foamy substance.

These compound has a wide range of applications. It is believed that with the continuous development of the source of the synthetic route 3-Ethyl-4-fluorobenzonitrile, its application will become more common.

Reference:
Patent; TAIHO PHARMACEUTICAL CO., LTD.; Kitade, Makoto; Ohkubo, Shuichi; Yoshimura, Chihoko; US2013/289072; (2013); A1;,
Nitrile – Wikipedia,
Nitriles – Chemistry LibreTexts

Adding a certain compound to certain chemical reactions, such as: 149793-69-1, name is 3-Fluoro-5-(trifluoromethyl)benzonitrile, 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 149793-69-1, category: nitriles-buliding-blocks

To an oven-dried round bottomed flask was added nBuLi (2.5 M in hexanes, 3.6 mL, 9.0 mmol, 1.1 eq) at -45 to -40 C. under N2. An Et2O solution (12 mL) of 2-bromo-6-methoxypyridine (1 mL, 8.14 mmol) was added dropwise at the above temperature. The resulting light brownish yellow solution was stirred at -40 to -35 C. for 20 min. The mixture was cooled to -78 C., an Et2O solution (3 ml) of 3-fluoro-5-trifluoromethyl-benzonitrile (1.50 g, 7.94 mmol) was added dropwise at -78 to -70 C. The resulting solution was stirred at this temperature for 1 h. Pretreated TMSCl (1.08 mL, 8.55 mmol, 1.05 eq) was added dropwise at -78 C. The mixture was allowed to warm to room temperature for 30 min, and then stirred at room temperature for 30 min. The reaction mixture was cooled back to -78 C., and benzyl magnesium chloride (4.1 ml, 8.2 mmol) was added dropwise. The resulting mixture was stirred at -78 C. for 0.8 h, and then warmed up to room temperature for 1 h. The reaction mixture was quenched by adding sat’d NH4Cl and 1N HCl, and stirred for 10 min. The resulting solution was extracted with EtOAc, washed with 1N NaOH, saturated NaHCO3, H2O, brine, dried over MgSO4, filtered, and concentrated to dryness. The residue was purified by flash chromatography (silica gel, hexanes/EtOAc) to give 1-(3-fluoro-5-(trifluoromethyl)phenyl)-1-(6-methoxypyridin-2-yl)-2-phenylethanamine as light brownish gum (1.42 g, yield: 44.7%). LC-MS ESI (10-90% MeOH in H2O with 0.1% TFA in a 4-min run), retention time=3.20 min, 391.12 (M+H); 1H NMR (400 MHz, CDCl3) delta ppm 7.73 (s, 1H), 7.47-7.57 (m, 2H), 7.11-7.21 (m, 4H), 6.99 (d, J=7.6 Hz, 1H), 6.80 (dd, J=7.6, 2.0 Hz, 2H), 6.61 (d, J=8.1 Hz, 1H), 3.93 (s, 3H), 3.92 (d, J=13 Hz, 1H) 3.40 (d, J=13 Hz, 1H).

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

Reference:
Patent; Bristol-Myers Squibb Company; US2007/161685; (2007); 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. 124289-21-0, name is 3-Bromo-5-methylbenzonitrile, A new synthetic method of this compound is introduced below., SDS of cas: 124289-21-0

3-Methyl-5-[(2-methyl-1,3-thiazol-4-yl)ethynyl]benzonitrile Tetrabutylammonium fluoride (3.2 mL, 1M in THF, 3.2 mmol) was added to a mixture of 3-bromo-5-methylbenzonitrile (394 mg, 2.01 mmol), 2-methyl-4-[(trimethylsilyl)ethynyl]-1,3-thiazole (605 mg, 3.10 mmol), triethylamine (0.60 mL, 4.3 mmol), copper (I) iodide (76 mg, 0.40 mmol), dichlorobis(triphenylphosphine)palladium(II) (138 mg, 0.20 mmol), and N,N-dimethylformamide (4 mL). Nitrogen was bubbled through the resulting mixture for 15 min, and the reaction was heated in a microwave reactor at 100 C. for 15 min. The solvent was removed in vacuo, and the resulting residue was chromatographed on silica gel with hexanes:EtOAc (9:1?1:1) to afford 3-methyl-5-[(2-methyl-1,3-thiazol-4-yl)ethynyl]benzonitrile as an off-white solid. 1H NMR (CDCl3, 500 MHz) delta 7.63 (s, 1H), 7.58 (s, 1H), 7.43 (s, 1H), 7.42 (s, 1H), 2.75 (s, 3H), 2.39 (s, 3H). MS (ESI) 239.5 (M++H).

The synthetic route of 124289-21-0 has been constantly updated, and we look forward to future research findings.

Reference:
Patent; MERCK & CO., INC.; US2007/60618; (2007); A1;,
Nitrile – Wikipedia,
Nitriles – Chemistry LibreTexts

Electric Literature of 19853-10-2, A common heterocyclic compound, 19853-10-2, name is 2-([1,1′-Biphenyl]-2-yl)acetonitrile, molecular formula is C14H11N, 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.

EXAMPLE 42 Preparation of 5-cyano-5-(1,1′-biphenyl-2-yl)pentyl chloride To a stirred solution of 4.3 g. of sodium amide in 300 ml. of toluene was added dropwise over thirty minutes a solution of 19.3 g. of (1,1′-biphenyl-2-yl)acetonitrile in 200 ml. of toluene. The reaction mixture was heated at reflux for three hours, and then cooled to room temperature and stirred while a solution of 18.1 g. of 4-bromobutyl chloride in 50 ml. of toluene was added dropwise over thirty minutes. Following complete addition, the reaction mixture was heated again to reflux and stirred for sixteen hours. The reaction mixture next was cooledto room temperature and added to 500 ml. of ice water. The product was extracted from the aqueous mixture into diethyl ether. The ethereal extracts were combined and the solvent was removed by evaporation to provide the product as an oil. The oil was distilled to give 16.5 g. of 5-cyano-5-(1,1′-biphenyl-2-yl)pentyl chloride. B.P. 141-165 C. at 0.06 torr.

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; Eli Lilly and Company; US4277471; (1981); A;,
Nitrile – Wikipedia,
Nitriles – Chemistry LibreTexts

These common heterocyclic compound, 103146-25-4, name is 4-(4-(Dimethylamino)-1-(4-fluorophenyl)-1-hydroxybutyl)-3-(hydroxymethyl)benzonitrile, 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. Application In Synthesis of 4-(4-(Dimethylamino)-1-(4-fluorophenyl)-1-hydroxybutyl)-3-(hydroxymethyl)benzonitrile

EXAMPLE 4 (+-)-Diol compound (VI) (7 g, 0.0205 mol) and oxalic acid dihydrate (2.96 g, 0.0235 mol) were added to n-butanol (77 ml) and the contents were heated to 80-85 C. to obtain a clear solution. Obtained solution was cooled slowly to 15-20 C. and stirred for 3 h to complete the crystallization. The product formed was filtered and washed with n-butanol (2*7 ml). Thereafter, product was dried at 50-60 C. under reduced pressure to give 8.5 g of diol oxalate salt (VIa), with HPLC purity of 99.93%.

The synthetic route of 4-(4-(Dimethylamino)-1-(4-fluorophenyl)-1-hydroxybutyl)-3-(hydroxymethyl)benzonitrile has been constantly updated, and we look forward to future research findings.

Reference:
Patent; Kaushik, Vipin Kumar; Mohammed, Umar Khan; Meenakshisunderam, Sivakumaran; US2009/99375; (2009); 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. 147754-12-9, name is 4-Fluoro-2-methylbenzonitrile, A new synthetic method of this compound is introduced below., SDS of cas: 147754-12-9

2-Bromomethyl-4-fluorobenzonitrile (32). A mixture of 4-fluoro-2-methylbenzonitrile (2 g, 14.8 mmol), NBS (2.64 g, 15 mmol) and AIBN (100 mg) in CCl4 was refluxed under nitrogen for 2 hours. The reaction was cooled to room temperature. The solid was removed by filtration. The organic solution was concentrated to give crude product as an oil, which was used in the next step without further purification. 1H-NMR (400 MHz, CDCl3): delta 7.68 (dd, J=5.2, 8.4 Hz, 1H), 7.28 (dd, J=2.4, 8.8 Hz, 1H), 7.12 (m, 1H), 4.6 (s, 2H).

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; Feng, Jun; Gwaltney, Stephen L.; Stafford, Jeffrey A.; Zhang, Zhiyuan; Brodluahrer, Paul R.; Elder, Bruce; Isbester, Paul; Fornicola, Richard S.; Kisanga, Philip B.; Mobele, Bingidimi I.; Palmer, Grant J.; Reeve, Maxwell M.; Salsbury, Jonathon S.; Ulysse, Luckner; Venkatraman, Sripathy; US2009/275750; (2009); A1;,
Nitrile – Wikipedia,
Nitriles – Chemistry LibreTexts

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. 77326-36-4, name is 2-Amino-6-fluorobenzonitrile, This compound has unique chemical properties. The synthetic route is as follows., Computed Properties of C7H5FN2

To a solution of 3-hydroxy-2,2-dimethyl-N-propy- lpropanamide (20.2 g, 0.127 mol) (Example 197d) in dry THF (500 mE) was carefully added NaH (60% in mineral oil, 7.64 g, 0.191 mol) in small portions at 0C. under nitrogen. The reaction mixture was then warmed to room temperature and stirred under nitrogen for 1 hr. To this solution was slowly added at room temperature 2-amino-6-fluorobenzo-nitrile (17.3 g, 0.127 mol) in THF (100 mE) and the reaction mixture refluxed overnight under nitrogen then cooled down to room temperature, quenched with brine, and extracted with EtOAc (3x). The combined organic layers were washed with brine, dried over Na2SO4, evaporated and the residue was crystallized from EtOAc/Hexane to give the compound as a white solid (16.5 g, 48%). MS 276 (MHj.

According to the analysis of related databases, 77326-36-4, the application of this compound in the production field has become more and more popular.

Reference:
Patent; SENOMYX, INC.; Tachdjian, Catherine; Karanewsky, Donald; Tang, Xiao Qing; Liu, Hanghui; US2015/245642; (2015); A1;,
Nitrile – Wikipedia,
Nitriles – Chemistry LibreTexts

Synthetic Route of 6136-68-1, 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 6136-68-1 as follows.

Part A. Sodium methoxide (25% in MeOH, 1.5 mL, 6.8 mmol) was added dropwise to a solution of 3-acetylbenzonitrile (0.987 gm, 6.8 mmol) and 4-cyanobenzaldehyde (0.891 gm, 6.8 mmol) in dry methanol. Within 5 minutes, a precipitate began to form. The mixture was stirred at room temperature for 4 hrs and diluted with methanol. The solids were filtered off, washed with cold methanol and dried to give 3-[3-(4-cyanophenyl)-1-oxo-2-propenyl]benzonitrile as a white solid 1.7 gm (97%). MS:(M+H)+ 259; 1H NMR (CDCl3): 7.55 (d, 1H), 7.65 (t, 1H), 7.75 (s, 4H), 7.85 (m, 2H), 8.25 (d, 1H), 8.30 (s, 1H).

According to the analysis of related databases, 6136-68-1, the application of this compound in the production field has become more and more popular.

Reference:
Patent; Bristol-Myers Squibb Pharma Company; EP892780; (2002); B1;,
Nitrile – Wikipedia,
Nitriles – Chemistry LibreTexts

Electric Literature of 2469-99-0, The chemical industry reduces the impact on the environment during synthesis 2469-99-0, name is 3-Oxobutanenitrile, I believe this compound will play a more active role in future production and life.

General procedure: In a 250 mL RBF, 3-aminobut-2-enenitrile (2.0 g, 0.24 mole) was added to a stirred solution of cyclohexyl hydrazine hydrochloride (4.0 g, 0.026 mole) and acetic acid (0.1 mL) in ethanol (60 mL). The reaction was refluxed for 6 h. Crude was evaporated and loaded on column to elute out product at 40% ethyl acetate in hexane. (1.74 g, 40%)

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, 3-Oxobutanenitrile, other downstream synthetic routes, hurry up and to see.

Reference:
Article; Sharma, Swagat; Kozek, Krystian A.; Abney, Kristopher K.; Kumar, Sushil; Gautam, Nagsen; Alnouti, Yazen; David Weaver; Hopkins, Corey R.; Bioorganic and Medicinal Chemistry Letters; vol. 29; 6; (2019); p. 791 – 796;,
Nitrile – Wikipedia,
Nitriles – Chemistry LibreTexts