Month: November 2020

These common heterocyclic compound, 6011-14-9, name is 2-Aminoacetonitrile hydrochloride, 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. 6011-14-9

General procedure: 2-Aminoacetonitrile hydrochloride 2 (7.0 mmol) and sodium acetate (8.0 mmol) were dissolved in 35 mL of methanol. Aldehyde 1 (7.0 mmol) was added to the grey solution, and the reaction mixture was stirred at room temperature. A solid suspension was formed after a few minutes (for compounds 3a, 3c, 3f and 3g). The suspension was stirred for 2 h and the solid filtered and washed with cold methanol, leading to the pure product 3. A second crop was isolated from the mother liquor after complete removal of methanol in the rotary evaporator, addition of dichloromethane (40 mL) and dry flash chromatography of the solution using dichloromethane (4¡Á10 mL) as eluent. The solution was concentrated in the rotary evaporator and the yellow oil was kept at 0 C leading to the product 3 that was filtered and washed with cold diethyl ether. For compounds 3b, 3d, 3e and 3h-k, the reaction mixture was stirred at room temperature for 2 h. The solvent was removed in the rotary evaporator and dichloromethane (40 mL) was added to the mixture. Dry flash chromatography of this mixture was performed using 20 mL of dichloromethane as eluent. The solvent was removed in the rotary evaporator leading to a solid product. Cold diethyl ether was added to the suspension, kept for a few minutes in an ice bath. The solid was filtered and washed with cold diethyl ether, leading to the pure (arylideneamino)acetonitrile 3.

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 6011-14-9.

Reference:
Article; Costa, Marta; Proena, Fernanda; Tetrahedron; vol. 67; 10; (2011); p. 1799 – 1804;,
Nitrile – Wikipedia,
Nitriles – Chemistry LibreTexts

The chemical industry reduces the impact on the environment during synthesis 1953-99-7, name is 3,4,5,6-Tetrachlorobenzene-1,2-dicarbonitrile, I believe this compound will play a more active role in future production and life. 1953-99-7

Synthesis Example 1: Synthesis of 4-(biphenyl-2-yloxy)-3,5,6-trichloro-phthalonitrile 5 g of 3,4,5,6-tetrachlorophthalonitrile, 3.21 g of 2-phenylphenol, 3.9 g of K2CO3, and 25 ml of acetone were put in a 100 ml flask, and then stirred while heated at 70¡ã C. When the reaction was complete, the resultant was filtered and washed with acetone, and a liquid therefrom was distillated to obtain a solid. Herein, the obtained solid was dissolved in a small amount of dichloromethane, and then several times washed with hexane, filtered, and vacuum-dried to obtain 4-(biphenyl-2-yloxy)-3,5,6-trichloro-phthalonitrile.

The chemical industry reduces the impact on the environment during synthesis 1953-99-7. I believe this compound will play a more active role in future production and life.

Reference:
Patent; SAMSUNG SDI CO., LTD.; JEONG, Euisoo; SEO, Hyewon; SHIN, Myoungyoup; SHIN, Sunwoong; JUNG, Juho; HAN, Gyuseok; (25 pag.)US2018/335547; (2018); A1;,
Nitrile – Wikipedia,
Nitriles – Chemistry LibreTexts

The chemical industry reduces the impact on the environment during synthesis 326-62-5, name is 2-(2-Fluorophenyl)acetonitrile, I believe this compound will play a more active role in future production and life. 326-62-5

To a soution of hydroxylamine hydrochloride (2.2 equiv.) and 2-(2-fluorophenyl)acetonitrile (1 equiv.) in methanol and water (5:1 ratio) was added sodium bicarbonate (2.4 equiv.). After stirring at 70 C for 20 h, the methanol was removed in vacuo and the resulting solution was diluted with water and dichloromethane (1:2 ratio). The layers were separated and the organic layer was washed with saturated aqueous sodium chloride. The organic layer was dried over magnesium sulfate, filtered, and the solvent was removed in vacuo to deliver the desired intermediate, 2-(2-fluorophenyl)-N-hydroxyacetimidamide (1 .13 g, 90% yield) as a white solid.

The chemical industry reduces the impact on the environment during synthesis 326-62-5. I believe this compound will play a more active role in future production and life.

Reference:
Patent; IRONWOOD PHARMACEUTICALS, INC.; PERL, Nicholas; NAKAI, Takashi; LEE, Thomas Wai-Ho; RENNIE, Glen Robert; RENHOWE, Paul Allan; IYENGAR, Rajesh R.; (251 pag.)WO2016/44441; (2016); A1;,
Nitrile – Wikipedia,
Nitriles – Chemistry LibreTexts

The chemical industry reduces the impact on the environment during synthesis 194853-86-6, name is 4-Fluoro-2-(trifluoromethyl)benzonitrile, I believe this compound will play a more active role in future production and life. 194853-86-6

Trans-cyclohexane-l,4-diol (4.30 mmol) and sodium hydride (60% suspension in oil, 2.15 mmol) are suspended in dry dimethylsulfoxide (4 mL) and a solution of 4-fluoro-2-trifluoromethyl-benzonitrile (2.15 mmol) in dry dimethylsulfoxide (4 mL) is added dropwise. The resulting mixture is stirred at room temperature. After 1 hour reaction time, the reaction is treated with water (10 mL), the precipitate formed is separated by filtration and the filtrate is extracted with dichloromethane (25 mL). The organic phase is washed with aqueous saturated ammonium chloride (5 mL), dried over magnesium sulfate, filtered and the filtrate is concentrated under reduced pressure. The precipitate is triturated with diethylether (15 mL), filtered and the filtrate concentrated under reduced pressure. Both fractions of crude product are combined, dissolved in dichloromethane and purified by chromatography through a short pad of silica gel (dichloromethane and then diethylether as eluents) to afford the desired product (60% yield).

The chemical industry reduces the impact on the environment during synthesis 194853-86-6. I believe this compound will play a more active role in future production and life.

Reference:
Patent; INTERVET INTERNATIONAL B.V.; CHASSAING, Christophe Pierre Alain; MEYER, Thorsten; WO2010/146083; (2010); A1;,
Nitrile – Wikipedia,
Nitriles – Chemistry LibreTexts

326-62-5, 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. 326-62-5 name is 2-(2-Fluorophenyl)acetonitrile, 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.

[0214] To a solution of (2-fluoro-phenyl)-acetonitrile (1.50 g, 11.1 mmol) and EtOAc (4.4 mL, 44.4 mmol) in THF (20 mL) was added NaH (0.90 g, 22.2 mmol). The mixture was stirred at room temperature overnight. Then the reaction mixture was acidified to pH = 6 with HC1 (1 mol/L) and extracted with EtOAc (10 mL x3). The combined organic layer was washed with brine (20 mL), dried with Na2S04 and concentrated to dryness in vacuum. The residue was purified by silica gel column chromatography (PE/EtOAc = 2/1) to afford 2-(2- fluoro-phenyl)-3-oxo-butyronitrile (1.48 g, yield: 76%) as a yellow solid.

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

Reference:
Patent; SANFORD BURNHAM PREBYS MEDICAL DISCOVERY INSTITUTE; SMITH, Layton H.; PINKERTON, Anthony B.; HERSHBERGER, Paul; MALONEY, Patrick; MCANALLY, Danielle; (167 pag.)WO2019/32720; (2019); A1;,
Nitrile – Wikipedia,
Nitriles – Chemistry LibreTexts

27126-93-8,Some common heterocyclic compound, 27126-93-8, name is 3,5-Bis(trifluoromethyl)benzonitrile, molecular formula is C9H3F6N, 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 15 Synthesis of 5-(3,5-bis(trifluoromethyl)phenyl)-1H-tetrazole (8) Anhydrous zinc bromide (93.5 g, 415 mmol, 0.99 equiv.), sodium azide (29.8 g, 458 mmol, 1.1 equiv.) and water (750 ml) were added to 3,5-bis(trifluoromethyl)benzonitrile (100.0 g, 418 mmol, 1.00 equiv.). The resulting suspension was stirred for 10 days at ambient temperature. The completion of the reaction was confirmed by reversed phase HPLC on a Waters Novapak C18 column (3.9*150 mm) eluding with a linear gradient from 40% to 100% acetonitrile in 250 mM triethylammonium acetate buffer pH 6.5 in 15.00 minutes with a flow rate of 1.0 mL/min, detection at lambda=270 nm, product retention time 2.0 min., educt retention time 6.5 min. Ethyl acetate (3.8 ltr.) and 10% citric acid in water were added and the resulting mixture was vigorously stirred for 15 minutes. The aqueous phase was separated and extracted with ethyl acetate (2*900 ml). The organic phases were combined and evaporated to dryness. The resulting solid was stirred in aqueous NaOH solution (0.25 M, 3.8 ltr.) for 30 minutes to give a suspension, which was filtered. The filtrate was acidified with aqueous HCl (375 ml conc. hydrochloric acid and 375 ml water) which caused the product to precipitate as a fine white powder. The product was collected by filtration after one hour, washed with cold hexanes (100 ml) and dried in a desiccator under vacuum, yield 72.7 g (62%) of compound (8) as white crystalline powder. The purified product had a purity of 100% by reversed phase HPLC as depicted in . 1H NMR (300 MHz, d6-DMSO) delta 8.26 (s, 1H), 8.59 (s, 1H), m.p. 179 C. The product can be recrystallized from toluene.

These compound has a wide range of applications. It is believed that with the continuous development of the source of the synthetic route 3,5-Bis(trifluoromethyl)benzonitrile, its application will become more common.

Reference:
Patent; Sigma-Aldrich Co.; US2006/247431; (2006); A1;,
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. 326-62-5 name is 2-(2-Fluorophenyl)acetonitrile, 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. 326-62-5

General procedure: A solution of aryl acetonitrile 2 (50 mg), and triethylamine (1.1 equiv.) in dimethylformamide dimethyl acetal (0.5 mL, 3.76 mmol) was heated in a microwave reactor at 120 C for 20 minutes. The mixture was cooled to RT, and solvents were then evaporated. To the resulting crude product 3 was added hydrazine mono-hydrobromide (3.0 equiv.), 200 proof EtOH (1.0 mL), and H2O (0.3 mL). The mixture was heated in a microwave reactor at 120 C for 20 minutes. The mixture was cooled to RT and concentrated in vacuo. The resulting residue was subjected to liquid-liquid extraction using saturated NaHCO3 (aq) and CH2Cl2. The organic layer was collected, dried over anhydrous MgSO4, filtered and removed under vacuum to afford 4.The resulting crude product 4 and 2-arylsubstitutedmalondialdehydes or 1,1,3,3tetramethoxypropane (1.0 equiv.) were dissolved in glacial AcOH (1.0 mL) and 200 proof EtOH (1.5 mL). The mixture was heated in a microwave reactor at 120 C for 20 minutes. After cooling on ice, the precipitate was collected on a fine scintered-glass frit and washed with icecold EtOH (2 x 1.0 mL). The resulting crystals 5-32 were dried and collected.

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

Reference:
Article; Singleton, Justin D.; Dass, Reuben; Neubert, Nathaniel R.; Smith, Rachel M.; Webber, Zak; Hansen, Marc D.H.; Peterson, Matt A.; Bioorganic and Medicinal Chemistry Letters; vol. 30; 2; (2020);,
Nitrile – Wikipedia,
Nitriles – Chemistry LibreTexts

26391-06-0, Adding some certain compound to certain chemical reactions, such as: 26391-06-0, name is 2-Cyano-N,N-diethylacetamide, 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 26391-06-0.

Example 1 Crystallographically pure (E)-N,N-Diethyl-2-cyano-3-(3,4-dihydroxy-5-nitrophenyl)acrylamide Form C 3,4-Dihydroxy-5-nitrobenzaldehyde (10.0 gm, 54.6 mmol), N,N-diethyl-cyanoacetamide (15.5 gm, 11.06 mmol) and piperidine (15.0 gm, 170.3 mmol) is charged to isopropanol (200 ml). The reaction mixture is heated at reflux for 12 to 15 hours until the starting material is disappeared. After the reaction is complete, the reaction mixture is cooled to room temperature and acetic acid glacial (15 ml) is added. The reaction mixture is concentrated, followed by dilution with ethyl alcohol (50 ml). The mixture is stirred overnight and filtered. The isolated product is dried under vacuum to provide crystallographically pure Form C of crystalline (E)-N, N-diethyl-2-cyano-3-(3,4-dihydroxy-5-nitrophenyl)acrylamide with melting point of 156-160 C. The title product is obtained as a crystalline solid in 75.5% yield. HPLC Purity=99.45% (Z-isomer 0.24%). Mass Spectra=m+1 306.1 (100%).

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 26391-06-0.

Reference:
Patent; Wockhardt Limited; US2008/4343; (2008); A1;,
Nitrile – Wikipedia,
Nitriles – Chemistry LibreTexts

Adding a certain compound to certain chemical reactions, such as: 1129-35-7, name is Methyl 4-cyanobenzoate, 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 1129-35-7, 1129-35-7

A mixture of methyl 4- cyanobenzoate (5.0 g, 31.0 mmol) and Omicron,Omicron-diethyl hydrogen dithiophosphate (10.41 g, 62 mmol) in water (100 mL) was stirred at 80 C for 16 h under N2. The mixture was cooled to 20 C and filtered. The precipitate was washed with water (50 mL) and dried under vacuum to give crude methyl 4-(aminocarbothioyl)benzoate (5.93 g, 98%) as a yellow powder: mp (water) 181-184 C; 1H NMR delta 10.04 (br s, 1 H, NH2), 9.65 (br s, 1 H, NH2), 7.83-8.00 (m, 4 H, H-2, H-3, H-5, H-6), 3.88 (s, 3 H, OCH3); MS m/z 196.5 (MH+, 100%).

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, Methyl 4-cyanobenzoate, other downstream synthetic routes, hurry up and to see.

Reference:
Patent; THE BOARD OF TRUSTEES OF THE LELAND STANFORD JUNIOR UNIVERSITY; AUCKLAND UNISERVICES LIMITED; RUGA CORPORATION; GIACCA, Amato; LAI, Edwin; RAZORENOVA, Olga; CHAN, Denise; HAY, Michael, Patrick; BONNET, Muriel; SUN, Connie; TABIBIAZAR, Ray; YUEN, Po-wai; WO2013/155338; (2013); A2;,
Nitrile – Wikipedia,
Nitriles – Chemistry LibreTexts

Some common heterocyclic compound, 2042-37-7, name is 2-Bromobenzonitrile, molecular formula is C7H4BrN, 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. 2042-37-7

EXAMPLE 1 3′-(Imidazo[1,2-alpha]-pyrazin-3-yl)biphenyl-2-carbonitrile A mixture of 2-bromobenzonitrile (9.1 g, 50 mmol), 3-aminobenzeneboronic acid monohydrate (11.6 g, 75 mmol) and tetrakis(triphenylphosphine)palladium(0) (1.73 g, 1.5 mmol) in dimethoxyethane (50 ml) and 2M sodium carbonate solution (25 ml) was heated at 80 C. for 20 h. After cooling to ambient temperature the reaction was partitioned between ethyl acetate (400 ml) and water (400 ml). The organics were washed with brine (400 ml), dried over anhydrous sodium sulfate, filtered and concentrated in vacuo. Purification of the residue by flash chromatography on silica gel, eluding with isohexane on a gradient of ethyl acetate (0-25%) gave 3′-aminobiphenyl-2-carbonitrile as a colourless oil that solidified on standing to afford a white solid (9.5 g, 98%): deltaH (400 MHz, CDCl3) 3.79 (2H, br), 6.75 (1H, ddd, J 8, 3 and 1), 6.84 (1H, dd, J 3 and 3), 6.92 (1H, dd, J 8 and 3), 7.25 (1H, dd, J 8 and 8), 7.40 (1H, ddd, J 8, 8 and 1), 7.50 (1H, dd, J 8 and 1), 7.62 (1H, ddd, J 8, 8 and 1), 7.73 (1H, dd, J 8 and 1).

These compound has a wide range of applications. It is believed that with the continuous development of the source of the synthetic route 2042-37-7, its application will become more common.

Reference:
Patent; Goodacre, Simon Charles; Hallett, David James; Street, Leslie Joseph; US2004/19057; (2004); A1;,
Nitrile – Wikipedia,
Nitriles – Chemistry LibreTexts