Month: June 2021

Application of 67515-59-7,Some common heterocyclic compound, 67515-59-7, name is 4-Fluoro-3-(trifluoromethyl)benzonitrile, molecular formula is C8H3F4N, 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.

14) l-[4-[(l-Methylpiperidin-4-yl)oxy]-3-(trifluoromethyl)phenyl]ethanamineA.4-[(l -Methylpiperidin-4-yl)oxy]-3-(trifluoromethyl)benzonitrile A mixture of 4-hydroxy-iV-methylpiperidine (133 mg, 1.15 mmol) and potassium tert-bu- toxide (150 mg, 1.27 mmol) in tetrahydrofuran (2.5 mL) was stirred under nitrogen for 10 min. 4-Fluoro-3-(trifluoromethyl)benzonitrile (218 mg, 1.15 mmol) was added, and the 5 reaction mixture was stirred at ambient temperature for 1 h. The solvent was removed in vacuo, and the residue was partitioned between a 1 M NaOH solution and ethyl acetate. The organic layer was dried (Na2SO4) and evaporated. The residue was purified by column chromatography on silica gel (eluent: CHCl3/MeOH/conc. NH3, 95:5:0.5) affording 0.18 g (54% yield) of the pure product as a colourless solid. MS (APCI) m/z 285 [M+H]. 1H NMR o (400 MHz, DMSO-D6) delta ppm 1.67-1.74 (m, 2 H), 1.89-1.95 (m, 2 H), 2.16 (s, 3 H), 2.26- 2.31 (m, 2 H), 2.44-2.48 (m, 2 H), 4.78-4.82 (m, 1 H), 7.51 (d, J = 8.8 Hz, 1 H), 8.08 (dd, J = 8.8, 2.0 Hz, 1 H), 8.14 (d, J = 2.0 Hz, 1 H).

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

Reference:
Patent; ASTRAZENECA AB; WO2007/73303; (2007); A2;,
Nitrile – Wikipedia,
Nitriles – Chemistry LibreTexts

Application of 874-97-5, These common heterocyclic compound, 874-97-5, name is 3-Cyanobenzyl alcohol, 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.

3-[(5-Amino-2H-pyrazol-3-yl)oxymethyl]benzonitrile, used as starting material, was prepared as follows: a) 3-Amino-5-hydroxypyrazole (2 g, 20.18 mmol, 1 eq) and triphenylphosphine (6.36 g, 24.22 mmol, 1.2 eq) were stirred in DCM (20 ml) for 30 mins. After this time, DIAD (4.77 ml, 24.22 mmol, 1.2 eq) was slowly added, keeping the temp below 20 C. with a water bath, and the resulting mixture stirred for a further 45 mins. A solution of 3-cyanobenzyl alcohol (3.23 g, 24.22 mmol, 1.2 eq) in DCM (10 ml) was added slowly and the reaction left to stir at RT for 24 hours. After this time the solid was filtered off and the solution extracted with 2M HCl solution (3×30 ml). The aqueous layer was back-washed with diethyl ether (2×30 ml), then basified to pH 9 using ammonium hydroxide, cooling the mixture to avoid a strong exotherm. The solution was extracted with DCM (3×30 ml) and the organic fractions combined, dried over magnesium sulphate and concentrated to give 3-[(5-amino-2H-pyrazol-3-yl)oxymethyl]benzonitrile as a colourless gum (321 mg, 7%). MS: m/z 215 (MH+)

Statistics shows that 3-Cyanobenzyl alcohol is playing an increasingly important role. we look forward to future research findings about 874-97-5.

Reference:
Patent; ASTRAZENECA AB; US2008/4302; (2008); A1;,
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Nitriles – Chemistry LibreTexts

Application of 6136-68-1, These common heterocyclic compound, 6136-68-1, name is 3-Acetylbenzonitrile, 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.

Part A. Preparation of ethyl 3-(3-cyanophenyl)-3-oxopropionate. To a suspension of sodium hydride (1.2 g of 60% suspension in mineral oil, hexane-washed, 30.3 mmol) in 40 mL of tetrahydrofuran was added diethyl carbonate (3.7 mL, 30.3 mmol) and 3-acetyl benzonitrile (2.2 g, 15.2 mmol). The resulting suspension was stirred at 65 C for 1 h and then was cooled to room temperature. There was added 40 mL of 10% aqueous HCl and the reaction mixture was diluted with ethyl acetate and the layers were separated. The organic layer was washed with brine, dried (MgSO4) and concentrated in vacuo to afford 3.2 g (96%) of the title compound, which was sufficiently pure to be used without purification. MS (NH3-CI) 218.3 (M+H)+.

The synthetic route of 6136-68-1 has been constantly updated, and we look forward to future research findings.

Reference:
Patent; Bristol-Myers Squibb Pharma Company; EP946528; (2003); B1;,
Nitrile – Wikipedia,
Nitriles – Chemistry LibreTexts

Adding a certain compound to certain chemical reactions, such as: 19924-43-7, name is 2-(3-Methoxyphenyl)acetonitrile, 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 19924-43-7, Formula: C9H9NO

To a solution of sodium hydride (1.79 g, 44.8 mmol) in dimethylsulfoxide (DMSO, 60 ml) is added a solution of (3-methoxyphenyl)acetonitrile (2.50 ml, 17.9 mmol) and 2-bromoethyl tert-butyldimethylsilyl ether (9.22 ml, 43.0 mmol) in ether (20 ml) at room temperature, and the mixture is stirred overnight. To the mixture is added water, and the mixture is extracted twice with ether. The organic layer is washed three times with water, dried over anhydrous magnesium sulfate, and the solvent is evaporated under reduced pressure. Then, the reaction mixture is dissolved in tetrahydrofuran (THF, 100 ml), and thereto is added tetrabutylammonium fluoride (TBAF, 12.2 g, 46.5 mmol), and the mixture is stirred at room temperature overnight. Water is added to the mixture, and the mixture is extracted twice with ethyl acetate. The organic layer is washed twice with water, dried over anhydrous magnesium sulfate, and the solvent is evaporated under reduced pressure. The residue is purified by silica gel chromatography to give the title compound (2.91 g) as colorless oil.1H-NMR delta (DMSO-d6): 1.97-2.02 (4H, m), 3.12-3.22 (2H, m), 3.32-3.45 (2H, m), 3.76 (3H, s), 4.59 (2H, t, J = 5.13), 6.87-7.03 (3H, m), 7.31-7.36 (1H, m).

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; Sumitomo Pharmaceuticals Company, Limited; EP1500648; (2005); A1;,
Nitrile – Wikipedia,
Nitriles – Chemistry LibreTexts

Related Products of 115661-37-5, A common heterocyclic compound, 115661-37-5, name is 2-Amino-3-fluorobenzonitrile, molecular formula is C7H5FN2, 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.

To a solution of 2-amino-3-fluorobenzonitrile (17.07 g, 0.125 mol) in 1,4-dioxane (20 ml) was added 48% aqueous hydrobromic acid (200 ml) and the solution was cooled to 0C before adding dropwise a solution of sodium nitrite (9.95 g, 0.144 mol) in water (22 ml) over 35 min so that the temperature did not rise above 3C. The resulting mixture was stirred at 2-3C for 2 h then poured onto a cooled (5C) solution of copper (I) bromide (26.98 g, 0.188 mol) in 48% hydrobromic acid (100 ml). The mixture was stirred for 10 min then heated to 50C over 1 h. The mixture was cooled to ambient temperature, diluted with water (11) and extracted with diethyl ether (2 x 500 ml). The combined organic extracts were washed with 1 M aqueous Na2SO3 (500 ml), then saturated aqueous NH4C1 (200 ml), dried (MgSO4), and evaporated to give a brown oil/solid. Purification by chromatography (silica gel, 10% EtOAc/isohexane) and trituration of a mixed fraction with isohexane afforded 13.22 g (53%) of 2-bromo-3- fluorobenzonitrile as a pale yellow solid : 1H NMR (360 MHz, CDCl3) 5 7.62-7. 68 (1H, m), 7.74-7. 85 (1H, ddd, J 9, 9,1), 7.74-7. 85 (1H, ddd, J 8, 1, 1).

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; MERCK SHARP & DOHME LIMITED; WO2003/93272; (2003); A1;,
Nitrile – Wikipedia,
Nitriles – Chemistry LibreTexts

17417-09-3, name is 2-Fluoro-5-nitrobenzonitrile, 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. category: nitriles-buliding-blocks

Part A: Preparation of 2-fluoro-5-aminobenzonitrile. To a solution of 2-fluoro-5-nitrobenzonitrile(2.0 g, 12 mmol) in ethyl acetate(50 mL) was added stannous chloride(27.0 g, 120 mmol). The reaction-mixture was stirred at reflux 1.5 h, then cooled to room temperature. Partitioned between ethyl acetate(150 mL) and saturated sodium bicarbonate(150 mL). Organic phase was separated and washed with water(5×75 mL), brine(75 mL); dried over sodium sulfate(anhy.); filtered and concentrated to give 2-fluoro-5-aminobenzonitrile (1.4 g) as pure compound.

The synthetic route of 17417-09-3 has been constantly updated, and we look forward to future research findings.

Reference:
Patent; Bristol-Myers Squibb Pharma Company; EP946508; (2009); B1;,
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. 623-00-7, name is 4-Bromobenzonitrile, A new synthetic method of this compound is introduced below., Product Details of 623-00-7

To a solution of 4-bromobenzonitrile (4.0 g, 22 mmol) in conc. H2SO4 (10 mL) was added dropwise at 0 C. nitric acid (6 mL). The reaction mixture was stirred at 0 C. for 30 min, and then at room temperature for 2.5 h. The resulting solution was poured into ice-water. The white precipitate was collected via filtration and washed with water until the washings were neutral. The solid was recrystallized from an ethanol/water mixture (1:1, 20 mL) twice to afford 4-bromo-3-nitrobenzonitrile as a white crystalline solid (2.8 g, 56%). 1H NMR (300 MHz, DMSO-d6) delta 8.54 (s, 1H), 8.06 (d, J=8.4 Hz, 1H), 7.99 (d, J=8.4 Hz, 1H); 13C NMR (75 MHz, DMSO-d6) delta 150.4, 137.4, 136.6, 129.6, 119.6, 117.0, 112.6; HPLC ret. time 1.96 min, 10-100% CH3CN, 5 min gradient; ESI-MS 227.1 Ink (MH+).

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; Vertex Pharmaceuticals Incorporated; Van Goor, Fredrick F.; Burton, William Lawrence; US2015/231142; (2015); 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. 25808-30-4, name is 2-(Methylamino)acetonitrile hydrochloride, A new synthetic method of this compound is introduced below., Recommanded Product: 2-(Methylamino)acetonitrile hydrochloride

REFERENCE SYNTHETIC EXAMPLE 41 2-(Methyl{[trans-4-(3-methyl-4-oxo-7-{[2-(trimethylsilyl)ethoxy]methyl}-2,3,4,7-tetrahvdro-1H-pyrrolo[3′,2′:5,6]pyrido[4,3-d]pyrimidin-1-yl)cyclohexyl]methyl}amino)acetonitrile To a solution of trans-4-(3-methyl-4-oxo-7-{[2-(trimethylsilyl)ethoxy]methyl}-2,3,4,7-tetrahydro-1H-pyrrolo[3′,2′:5,6]pyrido[4,3-d]pyrimidin-1-yl)cyclohexanecarbaldehyde (25 mg, 0.056 mmol) obtained in Reference Synthetic Example 29 in methanol (0.5 mL), methylaminoacetonitrile hydrochloride (7.8 mg, 0.073 mmol) and 2-picoline borane (8.1 mg, 0.073 mmol) were added, and the mixture was stirred at room temperature for 3 hours. The reaction mixture was mixed with 1 M aqueous sodium hydroxide and extracted with ethyl acetate. The organic layer was dried over anhydrous sodium sulfate and concentrated under reduced pressure. The residue was purified by silica gel thin-layer chromatography (ethyl acetate/2-propanol=9/1 (v/v)) to obtain the title compound as a colorless oil (27.5 mg, yield: 99percent).

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; Nissan Chemical Industries, Ltd.; TAKAHASHI, Keiji; WATANABE, Tsuneo; HAYASHI, Keishi; KURIHARA, Kazunori; NAKAMURA, Takanori; YAMAMOTO, Akio; NISHIMURA, Takuya; KAMIYAMA, Toshihiko; HIDAKA, Yuuki; EP2955181; (2015); A1;,
Nitrile – Wikipedia,
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Electric Literature of 64248-64-2, The chemical industry reduces the impact on the environment during synthesis 64248-64-2, name is 2,5-Difluorobenzonitrile, I believe this compound will play a more active role in future production and life.

Step A: 5-Fluoro-2-hydroxybenzonitrile (23t): 2,5-Difluorobenzonitrile (14.9 g, 107 mmol) and benzyl alcohol (11.1 mL, 11.6 g, 107 mmol) were dissolved in DMF (330 mL) and cooled to 0 C. Sodium hydride (60% in oil, 6.40 g, 161 mmol) was added to the solution at 0 C. and the reaction mixture was allowed to warm to room temperature. After stirring for 1 hour at room temperature, the reaction solution was cooled to 0 C. and water (330 mL) was gradually added to the solution. The mixture was transferred to a separatory funnel and extracted 3 times with 500 mL of Et2O. The combined organic layer was washed with 100 mL of water twice, brine once, then dried over MgSO4. After filtration, the solution was concentrated under reduced pressure to obtain a crude pale yellow solid. The crude solid was dissolved in MeOH (500 mL). To the solution was added 10% palladium on activated carbon under a nitrogen atmosphere. Replacing nitrogen gas with hydrogen gas, reaction mixture was stirred at room temperature (if the reaction did not proceed in 30 minutes, the palladium on carbon was filtered off and set up again). After 2 hours of stirring, the palladium on carbon was filtrated off and washed with MeOH. The solution was concentrated under reduced pressure to obtain a pale yellow solid. The solid was recrystallized from hot toluene (100 mL) by addition of hexane (10 mL) followed by cooling to 0 C. The obtained white needles were washed with 1:1 mixture of toluene and hexane (7.23 g, 49% yield). The mother liquor was concentrated and purified on silica gel with Et2O/hexane (2:3-1:1) to afford desired compound (23t) (6.94 g, 47% yield). Total 14.2 g (96% yield) over 2 steps. 1H-NMR (400 MHz, d6-DMSO) delta 11.09 (s, 1H), 7.58 (dd, J=8.4, 3.2 Hz, 1H), 7.40 (td, J=8.6, 3.2 Hz, 1H), 7.03 (dd, J=9.2, 4.4 Hz, 1H) ppm.

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, 2,5-Difluorobenzonitrile, other downstream synthetic routes, hurry up and to see.

Reference:
Patent; Munson, Mark; Kim, Youngboo; Groneberg, Robert D.; Rizzi, James; Rodriguez, Martha; Kim, Ganghyeok; Vigers, Guy; Rao, Chang; Balachari, Devan; US2004/180896; (2004); A1;; ; Patent; Munson, Mark; Mareska, David A.; Kim, Youngboo; Groneberg, Robert D.; Rizzi, James; Rodriguez, Martha; Kim, Ganghyeok; Vigers, Guy; Rao, Chang; Balachari, Devan; Harvey, Darren; US2004/192653; (2004); A1;,
Nitrile – Wikipedia,
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Some common heterocyclic compound, 1080-74-6, name is 2-(3-Oxo-2,3-dihydro-1H-inden-1-ylidene)malononitrile, molecular formula is C12H6N2O, 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. Recommanded Product: 2-(3-Oxo-2,3-dihydro-1H-inden-1-ylidene)malononitrile

To a three-necked round bottom flask were added 5,5′-(9,9′-spirobi[fluorene]-20,7-diyl)bis(4-(2-ethylhexyl)thiophene-2-carbaldehyde) (205 mg, 0.27 mmol), 1,1-dicyanomethylene-3-indanone (430 mg, 2.2 mmol), chloroform (50 mL), and 0.9 mLpyridine. The mixture was deoxygenated with nitrogen for 30 minand then refluxed for 12 h. After cooling down to room temperature,the mixture was poured into methanol (200 mL) and filtered.The residue was purified by column chromatography on silica gelusing petroleum ether/dichloromethane (1:1) as eluent yield anorange solid (207 mg, 69%). 1H NMR (400 MHz, CDCl3): delta 8.77 (s,2H), 8.68 (d, J 6.9 Hz, 2H), 7.96 (s, 1H), 7.93 (d, J 2.7 Hz, 2H), 7.89(d, J 4.8 Hz, 2H), 7.86 (d, J 1.8 Hz, 1H), 7.76 (m, 4H), 7.61 (d,J 5.4 Hz, 4H), 7.45 (t, J 7.5 Hz, 2H), 7.21 (t, J 7.5 Hz, 2H), 6.92 (s,2H), 6.82 (d, J 7.5 Hz, 2H), 2.39 (d, J 6.9 Hz, 4H),1.42 (m, 2H),1.09(m, 16H), 0.75 (m, 6H), 0.59 (t, J 6.9 Hz, 6H). 13C NMR (100 MHz,CDCl3): delta 188.63, 161.13, 157.22, 149.46, 149.27, 148.30, 143.36,141.49, 141.22, 140.47, 138.67, 137.35, 135.67, 135.47, 135.10, 133.58,130.17, 129.32, 128.84, 125.88, 125.17, 124.72, 124.37, 123.20, 121.23,121.15, 115.08, 114.99, 70.28, 66.57, 40.64, 32.95, 32.60, 28.90, 25.88,23.49, 14.65, 10.92. MS (MALDI): m/z calcd for C75H60N4O2S2 H:1114.4; found: 1114.1. Anal. Calcd for C75H60N4O2S2: C, 80.90; H,5.43; N, 5.03. Found: C, 80.77; H, 5.58; N, 5.33.

These compound has a wide range of applications. It is believed that with the continuous development of the source of the synthetic route 1080-74-6, its application will become more common.

Reference:
Article; Wang, Jiayu; Dai, Shuixing; Yao, Yuehan; Cheng, Pei; Lin, Yuze; Zhan, Xiaowei; Dyes and Pigments; vol. 123; (2015); p. 16 – 25;,
Nitrile – Wikipedia,
Nitriles – Chemistry LibreTexts