Month: November 2020

Some common heterocyclic compound, 3939-09-1, name is 2,4-Difluorobenzonitrile, molecular formula is C7H3F2N, 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. 3939-09-1

Potassium tert-butoxide (216 ml, 1M in tetrahydrofuran, 216 mmol) was added to ice-cooled methanol (8.7 ml, 216 mmol), and the solution stirred for 40 minutes. The resulting suspension was added dropwise to a solution of 2,4-difluorobenzonitrile (30 g, 216 mmol) in tetrahydrofuran at -78 C. Once addition was complete the reaction was allowed to warm to room temperature and stirred for 18 hours. The reaction was diluted with hexane (200 ml) and the mixture washed with water (200 ml), brine (2*200 ml), then dried (MgSO4) and evaporated under reduced pressure. The residual solid was recrystallized from ethyl acetate:hexane to give the title compound, 9.8 g. 1H-NMR (CDCl3, 300 MHz) delta: 3.90 (s, 3H), 6.70 (m, 2H), 7.55 (dd, 1H). LRMS: m/z ES+ 152 [MH+]

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

Reference:
Patent; Barber, Christopher Gordon; Bunnage, Mark Edward; Harvey, John Wilson; Mathias, John Paul; US2005/20611; (2005); A1;,
Nitrile – Wikipedia,
Nitriles – Chemistry LibreTexts

1735-53-1, In the next few decades, the world population will flourish. As the population grows rapidly and people all over the world use more and more resources, all industries must consider their environmental impact. 1735-53-1, name is 4-Bromo-3-(trifluoromethyl)benzonitrile belongs to nitriles-buliding-blocks compound, it is a common compound, a new synthetic route is introduced below.

Part C. tert-butyl (7bR,11aS)-6-[4-cyano-2-(trifluoromethyl)phenyl]-1,2,7b,10,11,11a-hexahydro-4H-pyrido[4,3-b][1,4]thiazepino[6,5,4-hi]indole-9(8H)-carboxylate. To a solution of tert-butyl (7bR,11aS)-6-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)-1,2,7b,10,11,11a-hexahydro-4H-pyrido[4,3-b][1,4]thiazepino[6,5,4-hi]indole-9(8H)-carboxylate (0.135 g, 0.28 mmol) in 15 mL of DMF and 2 mL of water was added 4-bromo-3-(trifluoromethyl)benzonitrile (0.143 g, 0.57 mmol) and sodium carbonate (0.15 g, 0.1.43 mmol). The mixture was degassed with a stream of nitrogen for 20 min and then there was added [1,1′-bis(diphenylphosphino)ferrocene]dichloropalladium (II) (20 mg, 0.028 mmol) and the mixture was stirred at 80 C. for 16 h. The reaction was allowed to cool to ambient temperature and was diluted with ethyl acetate, washed with sat’d aqueous sodium bicarbonate and brine, dried (MgSO4), filtered through Celite and concentrated in vacuo to afford 130 mg (88%) of the title compound, which was used without purification. LRMS (ES+): 516.1 (M+H)+.

The synthetic route of 4-Bromo-3-(trifluoromethyl)benzonitrile has been constantly updated, and we look forward to future research findings.

Reference:
Patent; Robichaud, Albert J.; Fevig, John M.; Mitchell, Ian S.; Lee, Taekyu; Chen, Wenting; Cacciola, Joseph; US2004/186094; (2004); A1;,
Nitrile – Wikipedia,
Nitriles – Chemistry LibreTexts

876-31-3, The chemical industry reduces the impact on the environment during synthesis 876-31-3, name is 4-(Cyanomethyl)benzonitrile, I believe this compound will play a more active role in future production and life.

General procedure: The general procedure for the synthesis and characterization of 1,1?-ferrocenyl-diacrylonitriles is displayed in Scheme 1 and has been previously reported [20]. In brief, 1,1?-ferrocenedicarboxaldehyde and substituted phenylacetonitriles (2.2 Eq.) were mixed in a Pyrex tube fitted with a ground glass joint. The compounds were thoroughly ground in the open air with a glass rod in the presence of 1-2 drops of piperidine to form a melt. The melt was first dried in open air, followed by drying under a vacuum line. The dry products were purified by means of silica gel chromatography. Formation of the products was determined by use of IR or NMR spectroscopy (1H- and 13C-NMR). In the solid-state IR spectra, the formation of the products was characterized by the disappearance of the sharp carbonyl absorption band at approximately 1650cm-1 and the appearance of a strong nitrile absorption band at approximately 2200cm-1. The 1H- and 13C-NMR spectra showed the disappearance of the carbonyl resonance (?10ppm) and the appearance of alkene resonance peaks (?7.4ppm). Pure compounds were further analyzed by melting point determination (DSC), mass spectrometry, microanalysis, and X-ray diffraction. 4.2.1 1,1?-Ferrocenyldi[-2(4-cyanophenyl)acrylonitrile] (para-CN catalyst) The general procedure for the synthesis of this catalyst is described in Section 4.2 and involves the use of 1,1?-ferrocenyldicarboxaldehyde (145.0 mg, 0.60 mmol) and 4-cyanophenylacetonitrile (188.0 mg, 1.32 mmol). Upon grinding, a deep maroon paste was formed which was dried to obtain a maroon solid. Reaction completion was monitored by use of preparative TLC plates with a solvent system of hexane/diethyl ether (1:1). The final product was then purified by means of column chromatography with a solvent system of hexane/diethyl ether (1:1) to obtain dark maroon crystals (219.0 mg, 74%) as the desired product and 37.0 mg of the recovered starting (1,1?-ferrocenedicarboxaldehyde). Product d.p. ca. 325 C; IR (cm-1) 3182, 2926, 2852, 2213, 1608, 1587, 1510, 1452, 1417, 1371, 1319, 1251, 1180, 1035, 996, 918, 830, 819, 542, 501, 486, 456, 425; 1H-NMR spectra (CDCl3) 7.55 (4H, d, J 8.4 Hz, ArH), 7.47 (4H, d, J 8.5 Hz, ArH), 7.34 (2H, s, CH), 5.08 (4H, s, C5H4), 4.65 (4H, s, C5H4); 13C-NMR spectra (CDCl3) 132.7, 125.3, 77.2, 73.7, 72.2; HR-MS (C30H18FeN4) ES: [M + H+] m/z calc. 491.0959, found 491.0969.

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

Reference:
Article; Ombaka; Ndungu; Omondi; McGettrick; Davies; Nyamori; Journal of Solid State Chemistry; vol. 235; (2016); p. 202 – 211;,
Nitrile – Wikipedia,
Nitriles – Chemistry LibreTexts

52133-67-2, The chemical industry reduces the impact on the environment during synthesis 52133-67-2, name is Ethyl 2-cyano-4,4-diethoxybutyrate, I believe this compound will play a more active role in future production and life.

The synthesis of target compound 3 (Scheme 1C), started with the synthesis of a reported method for compound i.?3 2-Bromo-i,i-diethoxyethane (compound 10) was reacted with ethyl2-cyanoacetate to obtain compound 1 lwhich was cyclized to compound 12 using acetamidine hydrochloride under basic conditions. Chlorination of compound 12 using POC13 provided compound 13 in 80% yield. Displacement of the chloride of compound 13 with 4-methoxy-N- methyl aniline (compound 14) and catalytic amounts of HC1 in isopropanol, provided compound1. Methylation of compound 1 with Mel under basic conditions afforded compound 3 in 85% yield. The synthesis of target compound 5 (Scheme 1C), involved N-formylation of 4-methoxy- 2-methylanline (compound 15) to afford compound 16 in 70% yield. LAH reduction of compound 16 provided substituted aniline compound 17. Displacement of the chloride of compound 13 with anilines (compounds 15 and 17) and catalytic amounts of HC1 in isopropanol provided compounds 4 and 5 (75% and 70% respectively).

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

Reference:
Patent; DUQUESNE UNIVERSITY OF THE HOLY SPIRIT; GANGJEE, Aleem; (91 pag.)WO2016/22890; (2016); A1;,
Nitrile – Wikipedia,
Nitriles – Chemistry LibreTexts

876-31-3, A common compound: 876-31-3, name is 4-(Cyanomethyl)benzonitrile, belongs to nitriles-buliding-blocks compound, it can change the direction of chemical reaction, and react with certain compounds to generate new functional products. A new synthetic method of this compound is introduced below.

General procedure: Benzonitrile 1a (103 mg, 1.0 mmol) and WEPPA (2.0 mL) were added into a 10-mL closed tubewith a stir bar. Then the reaction was stirred in a closed vessel synthesis reactor at 150 C for 0.5 h.After cooling to ambient temperature, the resulting precipitate was collected by filtration, washed withice water, and further dried in a vacuum drying oven. The filtrate was evaporated under reducedpressure. The resultant residue was purified by silica gel column chromatography (eluent: petroleumether (35-60 C)/EtOAc = 2:1 to 0:1, v/v). Finally, these two parts were combined to produce the desiredbenzamide 2a with a 94% yield.

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, 4-(Cyanomethyl)benzonitrile, other downstream synthetic routes, hurry up and to see.

Reference:
Article; Sun, Yajun; Jin, Weiwei; Liu, Chenjiang; Molecules; vol. 24; 21; (2019);,
Nitrile – Wikipedia,
Nitriles – Chemistry LibreTexts

78473-00-4, A common compound: 78473-00-4, name is 4-Amino-3,5-dichlorobenzonitrile, belongs to nitriles-buliding-blocks compound, it can change the direction of chemical reaction, and react with certain compounds to generate new functional products. A new synthetic method of this compound is introduced below.

3,5-Dichloro-4-isothiocyanatobenzonitrile To a cooled (0 C.) solution of 4-amino-3,5-dichlorobenzonitrile (1 equiv.) in anhydrous DCM (0.5 M) was added DIEA (3 equiv.) in one portion. SCCl2 (3 equiv.) was added dropwise over 20 min. After the addition, the reaction mixture was stirred for about 5 h at 0 C. The solvent was evaporated to give a brown solid, which was purified by column chromatography on silica gel (petroleum/ethyl acetate=25/1) to give 3,5-dichloro-4-isothiocyanatobenzonitrile as a light yellow solid (75%).

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, 4-Amino-3,5-dichlorobenzonitrile, other downstream synthetic routes, hurry up and to see.

Reference:
Patent; Signal Pharmaceuticals, LLC; Alexander, Matthew; Bahmanyar, Sogole; Hansen, Joshua; Huang, Dehua; Hubbard, Robert; Jeffy, Brandon; Leisten, Jim; Moghaddam, Mehran; Raheja, Raj K.; Raymon, Heather; Schwarz, Kimberly; Sloss, Marianne; Torres, Eduardo; Tran, Tam Minh; Xu, Shuichan; Zhao, JingJing; Boylan, John Frederick; (317 pag.)US2016/96841; (2016); 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. 326-62-5, name is 2-(2-Fluorophenyl)acetonitrile, This compound has unique chemical properties. The synthetic route is as follows., 326-62-5

General procedure: To a solution of 11a-c (10 mmol) in anhydrous DMF (15 mL) was added appropriate aryl acetonitriles (12 mmol). After stirring at -10C for about 15 min, 60% NaH (0.48 g, 12 mmol) was added portion wise under a nitrogen atmosphere and maintained at this condition for 1 h. Then, the resulting mixture was warmed slowly to room temperature and continued to react for 12-24 h. After that, additional NaH (0.48 g, 12 mmol) was added and the air was introduced, the mixture was stirred at room temperature for another 12-24 h to yield 13a-q. Without further purification, 13a-q were hydrolyzed with 30% aqueous sodium hydroxide at room temperature for 4 h, and afterwards, the mixture was poured into 300 ml H2O and neutralized with 3N HCl. The precipitate was collected and purified by column chromatography on silica gel (hexane: EtOAc=8:1-1:1) to afford the target compounds 7a-q.

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:
Article; Wu, Hai-Qiu; Yan, Zi-Hong; Chen, Wen-Xue; He, Qiu-Qin; Chen, Fen-Er; De Clercq, Erik; Balzarini, Jan; Daelemans, Dirk; Pannecouque, Christophe; Bioorganic and Medicinal Chemistry; vol. 21; 21; (2013); p. 6477 – 6483;,
Nitrile – Wikipedia,
Nitriles – Chemistry LibreTexts

The chemical industry reduces the impact on the environment during synthesis 151-18-8, name is 3-Aminopropanenitrile, I believe this compound will play a more active role in future production and life. 151-18-8

5.2.6 N-(2-Cyanoethyl)benzamide (85) 18 A solution of benzoyl chloride (11.98 g, 85.22 mmol) in THF (50 mL) was added dropwise to a solution of 3-aminopropionitrile (84, 5.98 g, 85.3 mmol) and triethylamine (15 mL, 107.6 mmol) in THF (50 mL) at -5 C (ice-salt bath). The reaction mixture was stirred overnight at room temperature before being poured into water and extracted into EtOAC (3*). The dried, evaporated extract was recrystallized from hexanes and the minimum volume of EtOAC to give white crystals (12.36 g, 83%): mp 94 C; 1H NMR (400 MHz, DMSO-d6) delta 8.83 (t, J = 5.7 Hz, 1H), 7.90-7.82 (m, 2H), 7.60-7.50 (m, 1H), 7.53-7.44 (m, 2H), 3.50 (td, J = 6.5, 5.7 Hz, 2H), 2.78 (t, J = 6.5 Hz, 2H); HPLC 100 area% (230 nm). Anal. Calcd for C10H10N2O: C, 68.95; H, 5.79; N, 16.08. Found: C, 68.86; H, 5.80; N, 16.22.

The chemical industry reduces the impact on the environment during synthesis 151-18-8. I believe this compound will play a more active role in future production and life.

Reference:
Article; Patrick, Donald A.; Wenzler, Tanja; Yang, Sihyung; Weiser, Patrick T.; Wang, Michael Zhuo; Brun, Reto; Tidwell, Richard R.; Bioorganic and Medicinal Chemistry; vol. 24; 11; (2016); p. 2451 – 2465;,
Nitrile – Wikipedia,
Nitriles – Chemistry LibreTexts

63069-50-1, 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. 63069-50-1, name is 4-Amino-3-fluorobenzonitrile, A new synthetic method of this compound is introduced below.

Example 57 (2519) 4-((7-Chloro-5-hvdroxy-1 ,1 -dioxido-2H-benzoreiri ,2,41thiadiazin-3-yl)amino)-3- fluorobenzonitrile (2520) To a solution of 3-bromo-7-chloro-5-hydroxy-4H-benzo[e][1 ,2,4]thiadiazine 1 ,1 -dioxide (lnt-3, 200 mg) in t-BuOH (5 ml_) were added 4-amino-3-fluorobenzonitrile (105 mg) and KH2PO4 (105 mg). The reaction mixture was stirred at 1 10 C for 16 hr under nitrogen. The reaction mixture was allowed to cool to RT and was diluted with cold water. The resulting precipitate was collected by filtration and dried under vacuum to afford the crude product (150 mg). The crude product was purified by preparative reversed phase HPLC (XBridge C18, 19×150 mm) using a gradient of 10-55% 0.1 % formic acid/water in acetonitrile. The appropriate fractions were pooled and evaporated under reduced pressure to afford the titled compound (12 mg). LCMS m/z 366.85 (M+H). 1H NMR after D20 exchange (400 MHz, DMSO-c/e) delta ppm 7.12 (d, J=2.19 Hz, 1 H) 7.24 (d, J=2.19 Hz, 1 H) 7.76 (d, J=8.55 Hz, 1 H) 7.92 (dd, J=1 1 .18, 1 .75 Hz, 1 H) 8.43 (t, J=8.33 Hz, 1 H).

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; GLAXOSMITHKLINE INTELLECTUAL PROPERTY DEVELOPMENT LIMITED; ADAMS, Jerry Leroy; ATOR, Laura E.; DUFFY, Kevin J.; GRAYBILL, Todd L.; KIESOW, Terence John; LIAN, Yiqian; MOORE, Michael Lee; RALPH, Jeffrey M.; RIDGERS, Lance Howard; (370 pag.)WO2017/98421; (2017); A1;,
Nitrile – Wikipedia,
Nitriles – Chemistry LibreTexts

133116-83-3, 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. 133116-83-3 name is 2-Fluoro-6-(trifluoromethyl)benzonitrile, 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.

To 2-fluoro-6- (trifluoromethyl) benzonitrile (45 g, 0.238 mmol) in 60 mL of THF was added 1 M BH3: THF slowly at 60 oC and the resulting solution was refluxed overnight. The reaction mixture was cooled to ambient temperature. Methanol (420 ML) was added slowly and stirred well. The solvents were then evaporated and the residue was partitioned between EtOAc and water. The organic layer was dried over Na2SO4. Evaporation gave 4a as a yellow oil (46 g, 0. 238 mmol). MS (CI) m/z 194. 0 (MH+).

At the same time, in my other blogs, there are other synthetic methods of this type of compound, 2-Fluoro-6-(trifluoromethyl)benzonitrile, and friends who are interested can also refer to it.

Reference:
Patent; NEUROCRINE BIOSCIENCES, INC.; WO2005/7633; (2005); A1;,
Nitrile – Wikipedia,
Nitriles – Chemistry LibreTexts