Month: September 2021

Synthetic Route of 796600-15-2, The chemical industry reduces the impact on the environment during synthesis 796600-15-2, name is 2-Chloro-4-fluoro-3-methylbenzonitrile, I believe this compound will play a more active role in future production and life.

Heat 2-chloro-4-fluoro-3-methyl-benzonitrile (144 mg, 0.85 mmol) and 2- . phenyl-pyrrolidine (0.15 g, 1.02 mmol, 1.20 equivalents) in N-methylmorpholine (0.11 ml, 1.02 mmol, 1.20 equivalents) at 150 0C overnight. Allow the reaction mixture to cool to room temperature, dilute with dichloromethane (1 ml), load on silica, and purify by chromatography (12 g silica gel, 0 to 100% ethyl acetate/hexanes over 20 minutes) to obtain 150 mg of an oily residue. Recrystallize from ethyl acetate/hexanes to obtain the title compound (92 mg, 37%). LCMS(APCI+): 297.0 (M+l)+; 1H NMR (400 MHz, CDCl3): delta 7.25 (s, 2H), 7.19 (m, 2H), EPO 6.65 (d, IH), 4.70 (m, IH), 4.06 (m, IH), 3.18 (m, IH), 2.44 (m, IH), 2.43 (s, 3H), 2.12 (m, IH), 1.94 (m, 2H).

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-Chloro-4-fluoro-3-methylbenzonitrile, other downstream synthetic routes, hurry up and to see.

Reference:
Patent; ELI LILLY AND COMPANY; WO2006/124447; (2006); A2;,
Nitrile – Wikipedia,
Nitriles – Chemistry LibreTexts

Electric Literature of 6621-59-6, These common heterocyclic compound, 6621-59-6, name is 6-Bromohexanenitrile, 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.

General procedure: A round bottom flask is charged with propargyl derivative of 2-hydroxy benzaldehyde (320 mg, 2 mmol), 4-acetylcoumarin (376.36 mg, 2 mmol), acetyl chloride (2 mL), 2-bromoacetonitrile (1 mL) and BF3.OEt2 (.5ml) and kept under stirring for 3h at room temperature. The progress of the reaction was monitored by TLC analysis at regular intervals. After 3h, the mixture was quenched with cold water. The solid residue separated was collected and purified by passing it through a silica gel column. Elution of the column with petroleum ether (60-80 C) / ethyl acetate (9: 1 v/v) afforded coumarin amidoalkyne 1a.

The synthetic route of 6621-59-6 has been constantly updated, and we look forward to future research findings.

Reference:
Article; Raj, P. Jithin; Bahulayan; Tetrahedron Letters; vol. 58; 22; (2017); p. 2122 – 2126;,
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. 64248-62-0, name is 3,4-Difluorobenzonitrile, A new synthetic method of this compound is introduced below., COA of Formula: C7H3F2N

A three-necked RB flask was charged with 3,4-difluorobenzonitrile (20 g, 144 mmol) and a mixture of EtOH (190 mL) and water (10 mL). To this homogenous solution were added hydroxylamine hydrochloride (22 g, 317 mg) and TEA (48 mL, 331 mmol). The reaction mixture was stirred at r.t. for 30 min followed by heating to 85 C. for 1 h. TLC indicated the reaction was complete. The mixture was transferred to a 500 mL RB flask, concentrated under reduced pressure to almost dryness, added water (50 mL) and stirred for 30 min. The white precipitates were collected and air dry 12 h before use. LRMS (M+H+) m/z 173.0.

The synthetic route of 64248-62-0 has been constantly updated, and we look forward to future research findings.

Reference:
Patent; LU, Pu-Ping; CHUANG, Chihyuan Grace; MORGAN, Bradley P.; MORGANS, JR., David J.; US2009/198057; (2009); A1;,
Nitrile – Wikipedia,
Nitriles – Chemistry LibreTexts

Some common heterocyclic compound, 38487-85-3, name is 2-Amino-4-methoxybenzonitrile, molecular formula is C8H8N2O, 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. category: nitriles-buliding-blocks

General procedure: In a 10-mL Schlenk tube, the mixture of 2-aminobenzonitriles 1 (1.0 mmol) and methyl 4,4-difluorobut-2-ynoate 2 (1.5 equiv.) was stirred in MeOH (2.0 mL) at 80 C for 12 h, then DBU (3.0 equiv.) was added and continued to be stirred at 80 C for another 1 h. The solvent was removed under reduced pressure. The residue was purified by flash column chromatography (petroleum ether / ethyl acetate or dichloromethane 10:1 to 1:1 as the eluent) on silica gel to give the desired 2-difluoromethylated quinolines 3.

These compound has a wide range of applications. It is believed that with the continuous development of the source of the synthetic route 38487-85-3, its application will become more common.

Reference:
Article; Fan, Zhenhua; Yang, Shanxue; Peng, Xin; Zhang, Cheng; Han, Jing; Chen, Jie; Deng, Hongmei; Shao, Min; Zhang, Hui; Cao, Weiguo; Tetrahedron; vol. 75; 7; (2019); p. 868 – 873;,
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. 96606-37-0, name is 2,4,6-Trifluorobenzonitrile, A new synthetic method of this compound is introduced below., name: 2,4,6-Trifluorobenzonitrile

NaH (60% in mineral oil, 1.21g, 30.3 mmol) was added in one portion to (E)-2-Buten-1-ol (1.62g, 20 mmol) in 20 ml THF with cooling from an ice water bath. The mixture was stirred for 10 min, then added dropwise to 2,4,6-trifluorobenzonitrile (3.2 g, 20 mmol) in 20ml THF, with cooling from an ice bath. The solution was stirred at room temperature for 4 hours, then quenched with acetic acid. This solution was dried onto silica gel and purified by normal phase chromatography using an ISCO Combiflash, eluted with ethyl acetate and hexane. Yield (3.2g, 80% yield). 1H NMR (300 MHz, CDCl3) delta 6.53(m, 2H) 5.93(m, 1H) 5.73(m, 1H) 4.60(m, 2H) 1.81(d, J=6Hz, 3H). LC/MS, 210.2 [M+H]+ calculated 210.2

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; CIDARA THERAPEUTICS, INC.; BALKOVEC, James, Michael; BENSEN, Daniel, C.; BORCHARDT, Allen; BRADY, Thomas, Patrick; CHEN, Zhi-yong; LAM, Thanh; TARI, Leslie, W.; (204 pag.)WO2016/201219; (2016); A1;,
Nitrile – Wikipedia,
Nitriles – Chemistry LibreTexts

Application of 53312-80-4, 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. 53312-80-4, name is 4-Amino-2-fluorobenzonitrile, This compound has unique chemical properties. The synthetic route is as follows.

A mixture of tert-butyl 2-oxo-6-azaspiro[3.4]octane-6-carboxylate (CAS: 203661-716) (675 mg, 3.0 mmol), 4-amino-2-fluorobenzonitrile (408 mg, 3.0 mmol) and decaborane (128 mg, 1.05 mmol) in MeOH (10 mL) was stirred at 50 C overnight. After the reaction was completed, the reaction mixture was concentrated under reduced pressure. The residue was purified by silica gel column chromatography (Petroleum ether/EtOAc = 3/1) to afford intermediate 47 (500 mg, 48% yield) as a white solid.

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

Reference:
Patent; JANSSEN PHARMACEUTICA NV; JOHNSON & JOHNSON (CHINA) INVESTMENT LTD.; DAI, Xuedong; QUEROLLE, Olivier Alexis Georges; KROSKY, Daniel Jason; CAI, Wei; FU, Liqiang; KONG, Linglong; LIU, Yingtao; WAN, Zhao-Kui; HERKERT, Barbara; PANDE, Vineet; EDWARDS, James Patrick; PATRICK, Aaron Nathaniel; ANGIBAUD, Patrick Rene; PONCELET, Virginie Sophie; (488 pag.)WO2019/120209; (2019); A1;,
Nitrile – Wikipedia,
Nitriles – Chemistry LibreTexts

Reference of 6011-14-9, 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 6011-14-9 as follows.

General procedure: For the aryl alpha-iminonitriles, a suspension of aminoacetonitrile hydrochloride (0.37 g, 4.0 mmol) and Et3N (1.0 mL, 7.2 mmol) in ethanol (10 mL) was stirred at room temperature for 0.5 h. To the resulting solution was added the corresponding aldehyde (2.0 mmol). After the reaction mixture was stirred for 1-2 h, the solvent was removed in vacuo. The residue was then diluted with EtOAc and washed with brine, dried over MgSO4, filtered and concentrated under in vacuo. The crude alpha-iminonitrile was used in next step without further purification.

According to the analysis of related databases, 6011-14-9, the application of this compound in the production field has become more and more popular.

Reference:
Article; Li, Jundong; Lin, Na; Yu, Lei; Zhang, Yandong; Tetrahedron Letters; vol. 57; 51; (2016); p. 5777 – 5780;,
Nitrile – Wikipedia,
Nitriles – Chemistry LibreTexts

These common heterocyclic compound, 64695-82-5, name is 2-Bromo-4,5-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. Safety of 2-Bromo-4,5-difluorobenzonitrile

2-Bromo-4,5-difluorobenzonitrile (1.0 g, 4.59 mmol), tert-butyl (2S)-2-methylpiperazine-1-carboxylate (0.96 g, 4.82 mmol), Pd2(dba)3 (0.21 g, 0.23 mmol), XantPhos (0.27 g, 0.46 mmol) and sodium tert-butoxide (1.32 g, 13.76 mmol) were suspended in 1,4-dioxane (20 ml) (degassed with nitrogen for 5 minutes) then the reaction was heated at 100 C. for 6 h. The reaction was cooled then filtered through Celite, using DCM. The filtrate was concentrated in vacuo then the residue was partitioned between DCM (50 ml) and water (30 ml) and the organics were separated, dried over Na2SO4, filtered and concentrated in vacuo. The residue was purified via flash column chromatography using gradients of 0% to 100% EtOAc in heptane followed by 0% to 100% MeOH in EtOAc, then the fractions containing product were concentrated in vacuo to yield the title compound as a pale yellow oil which crystallized on standing (548 mg, 35%). 1H NMR (500 MHz, DMSO-d6) 8.04 (dd, J=10.4, 8.8 Hz, 1H), 7.32 (dd, J=12.7, 7.2 Hz, 1H), 4.24 (s, 1H), 3.84 (d, J=13.2 Hz, 1H), 3.32 (d, J=2.1 Hz, 2H), 3.16 (t, J=11.4 Hz, 1H), 2.90 (dd, J=12.1, 3.7 Hz, 1H), 2.78 (td, J=11.9, 3.4 Hz, 1H), 1.42 (s, 9H), 1.27 (d, J=6.7 Hz, 3H). LCMS Method 2-Tr=1.28 min (ES+) (M+H+) 360.1

The synthetic route of 2-Bromo-4,5-difluorobenzonitrile has been constantly updated, and we look forward to future research findings.

Reference:
Patent; Navitor Pharmaceuticals, Inc.; O’Neill, David John; Saiah, Eddine; Kang, Seong Woo Anthony; Brearley, Andrew; Bentley, Jonathan; (519 pag.)US2018/127370; (2018); A1;,
Nitrile – Wikipedia,
Nitriles – Chemistry LibreTexts

Adding a certain compound to certain chemical reactions, such as: 115279-73-7, name is 1-(4-Aminophenyl)cyclopentanecarbonitrile, 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 115279-73-7, Product Details of 115279-73-7

A mixture of 2-chloronicotinoyl chloride (50 mg) and 1-(4-aminophenyl)-cyclopentanecarbonitrile (1 eq) and K2CO3 (80 mg) in dichloromethane (20 ml) was stirred at RT for 30 min. The reaction was filtered and the filtrate was evaporated. The residue was mixed with 6-aminoindazole (150 mg) neat and heated at 210 C. for 2 hour. The reaction was cooled and purified by column chromatography to give the title compound. Mass: (M+1), 423.

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; Chen, Guoqing P.; US2004/259916; (2004); A1;,
Nitrile – Wikipedia,
Nitriles – Chemistry LibreTexts

These common heterocyclic compound, 33143-29-2, name is 2,2-Dimethyl-2H-chromene-6-carbonitrile, 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. Recommanded Product: 33143-29-2

PREPARATION 8 2,2-Dimethyl-2H-1-benzopyran-6-carbonitrile (10 g) was dissolved in toluene (54 ml), and the solution was cooled to -78 C. under a nitrogen atmosphere, to this solution was added diisobutylaluminum hydride (1M solution in toluene, 81 ml) over 30 minutes, and the mixture was stirred at -78 C. for 10 minutes. The reaction mixture was quenched at -78 C. with ethyl acetate (54 ml) followed by 1M tartaric acid solution in water (100 ml). The cooling bath was removed and the mixture was vigorously stirred for 1 hour. The organic layer was separated and the aqueous layer was extracted with ethyl acetate. The combined organic layers were washed with brine, dried over anhydrous magnesium sulfate, and concentrated to give 2,2-dimethyl-2H-1-benzopyran-6-carbaldehyde (9.9 g) as a pale yellow oil, which was used without further purification. IR (Film): 1690, 1640 cm-1. NMR (CDCl3, delta): 1.47 (6H, s), 5.70 (1H, d, J=10Hz), 6.38 (1H, d, J=10Hz), 6.86 (1H, d, J=8Hz), 7.52 (1H, d, J=2Hz), 7.64 (1H, dd, J=2, 8Hz), 9.82 (1H, s).

The synthetic route of 2,2-Dimethyl-2H-chromene-6-carbonitrile has been constantly updated, and we look forward to future research findings.

Reference:
Patent; Fujisawa Pharmaceutical Company, Ltd.; US5104890; (1992); A;,
Nitrile – Wikipedia,
Nitriles – Chemistry LibreTexts