Month: April 2021

Synthetic Route of 654-70-6, A common heterocyclic compound, 654-70-6, name is 4-Cyano-3-trifluoromethylaniline, molecular formula is C8H5F3N2, 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.

4-Isothiocyanato-2-trifluoromethylbenzonitrile (96); 4-Amino-2-trifluoromethylbenzonitrile (2.23 g, 12 mmol) was added portionwise over 15 min into a well-stirred heterogeneous mixture of thiophosgene (1 mL, 13 mmol) in water (22 mL) at room temperature. Stirring was continued for an additional 1 h. The reaction medium was extracted with chloroform (3¡Á15 mL). The combined organic phase was dried over MgSO4 and evaporated to dryness under reduced pressure to yield desired product 4-Isothiocyanato-2-trifluoromethylbenzonitrile (96) (2.72 g, 11.9 mmol, 99%) as brownish solid and was used without further purification.

The synthetic route of 654-70-6 has been constantly updated, and we look forward to future research findings.

Reference:
Patent; The Regents of the University of California; US2009/111864; (2009); A1;,
Nitrile – Wikipedia,
Nitriles – Chemistry LibreTexts

Synthetic Route of 915394-28-4, A common heterocyclic compound, 915394-28-4, name is 2-Methyl-2-(3-nitrophenyl)propanenitrile, molecular formula is C10H10N2O2, 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.

2-Methyl-2-(3-nitrophenyl)propanenitrile (0.6 g, 3.15 mmol) obtained in Step (1) above was stirred in a solvent of methanol. The reaction solution was mixed with Pd/C (0.06 g, 0.56 mmol), followed by stirring under hydrogen conditions for about 2 hours at room temperature. The reaction mixture was filtered through a Celite pad under reduced pressure, and washed with methanol. The filtrate was concentrated under reduced pressure to obtain the title compound (0.48 g, 95 %). 1H-NMR Spectrum (300 MHz, DMSO-d6): delta 7.06 (t, 1H), 6.71 (s, 1H), 6.61 (d, 1H), 6.52 (d, 1H), 5.21 (s, 2H), 1.61 (s, 6H). MS (ESI+, m/z): 161 [M+H]+

The synthetic route of 915394-28-4 has been constantly updated, and we look forward to future research findings.

Reference:
Patent; Hanmi Pharm. Co., Ltd.; BAE, In Hwan; HAN, Sang Mi; KWAK, Eun Joo; AHN, Young Gil; SUH, Kwee Hyun; EP2876107; (2015); A1;,
Nitrile – Wikipedia,
Nitriles – Chemistry LibreTexts

Synthetic Route of 90381-43-4,Some common heterocyclic compound, 90381-43-4, name is 7-Methoxy-2-naphthonitrile, molecular formula is C12H9NO, 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.

A solution of 7-methoxy-2-naphthonitrile (501 mg, 2.74 mmol) and KOH (503 mg, 9.0 mmol) in 95% ethanol (5 mL) is heated to reflux for 24 hours. The reaction mixture is allowed to cool, diluted with water and then acidified to pH<2 with concentrated HCl. The resulting precipitate is collected by filtration, washed with water and dried by heating at 70 C. under vacuum to give 7-methoxy-2-naphthoic acid as a white solid (540 mg, 98%). HRMS (FAB) calculated for C12H10O3+H+: 203.0708, found 203.0701. These compound has a wide range of applications. It is believed that with the continuous development of the source of the synthetic route 7-Methoxy-2-naphthonitrile, its application will become more common. Reference:
Patent; Jacobsen, Eric Jon; Myers, Jason K.; Walker, Daniel Patrick; Wishka, Donn G.; Reitz, Steven Charles; Piotrowski, David W.; Acker, Brad A.; Groppi JR., Vincent E.; US2003/236270; (2003); A1;,
Nitrile – Wikipedia,
Nitriles – Chemistry LibreTexts

5414-21-1, name is 5-Bromovaleronitrile, 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. Formula: C5H8BrN

In a four-neck reactor equipped with a thermometer, in a nitrogen stream, 2-hydrazinobenzothiazole 10.0 g (60.5 mmol) of DMF were dissolved in 100 ml of DMF . To this solution, 41.8 g (304 mmol) of potassium carbonate, And 10.34 g of 5-bromovaleronitrile ( 60.6 mmol), and the whole was stirred at 60 C. for 8 hours. After completion of the reaction, The reaction solution was added to 20 C., and the mixture was poured into 1,000 ml of water, And extracted with 1000 ml of ethyl acetate. After drying the ethyl acetate layer with anhydrous sodium sulfate, Sodium sulfate was filtered off. Ethyl acetate was distilled off from the filtrate under reduced pressure by a rotary evaporator, A yellow solid was obtained. This yellow solid was dissolved in Siri Kagel column chromatography (N-hexane: ethyl acetate = 60: 40) To obtain 6.82 g of Intermediate T as a white solid (yield: 45.7%).

The synthetic route of 5414-21-1 has been constantly updated, and we look forward to future research findings.

Reference:
Patent; ZEON CORPORATION; SAKAMOTO, KEI; OKUYAMA, KUMI; SANUKI, KANAKO; (78 pag.)JP6090514; (2017); B1;,
Nitrile – Wikipedia,
Nitriles – Chemistry LibreTexts

Synthetic Route of 194853-86-6, 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. 194853-86-6 name is 4-Fluoro-2-(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.

COMPARATIVE EXAMPLE A This example illustrates the preparation of 4-[(1S, 4S)-4-Hydroxy-1- 0 methylpentyloxy]-2-trifluoromethylbenzonitrile, using a strong base under anhydrous conditions, as described in co-pending United States patent application serial number 11/053,010.A 10 L, jacketed ChemGlass reactor was fitted with a mechanical stirrer, nitrogen sweep line, and NesLab chiller. The vessel was purged with nitrogen for 5 15 minutes and then charged with 61 g (1.5 mol) of sodium hydride (60% in mineral oil) and 2.0 L of tetrahydrofuran (1THF”). The suspension was stirred and cooled to 6.5C and then a solution of 180.3 g (1.53 mol) of (2S,5S)-(+)-2,5- hexanediol in 1.0 L of THF was added, in 4 portions, over 35 minutes. The mixture became very thick and 1.0 L of THF was added about halfway through Q the addition in order to facilitate better stirring. The maximum internal temperature observed was 14.4C. The suspension was stirred for 30 minutes and then 288.1 g (1 .52 mol) of 4-fluoro-2-(trifluoromethyl)benzonitrile was added. The mixture was further diluted with another 1.0 L of THF and then warmed to room temperature and allowed to stir overnight (a clear solution was obtained after 30 minutes). HPLC analysis at the 21 hour point showed a 48:45 mixture of the expected product (3) to the bis-alkylated byproduct (4). Water (3.0 L) and ethyl acetate (4.0 L) were added and the layers separated. The organic layer was washed with 2 x 2.0 L of water and 1 x 2.0 L of brine. The aqueous layers were back-extracted with 2.0 L of ethyl acetate and then the organic layers were combined and evaporated at the Rotavap. The residue was twice dissolved in 1.0 L of 2-propanol and evaporated at the Rotavap (to remove water). The crude product was twice purified by flash chromatography on silica gel using dichloromethane/methanol. A third chromatography column (Biotage system) was carried out using ethyl acetate/hexanes. The purified target was isolated as 149.8 g (34%) of an oil. The material assayed at >99% purity (a/a, HPLC) and had a proton NMR spectrum consistent with structure.

At the same time, in my other blogs, there are other synthetic methods of this type of compound, 4-Fluoro-2-(trifluoromethyl)benzonitrile, and friends who are interested can also refer to it.

Reference:
Patent; WARNER-LAMBERT COMPANY LLC; WO2006/136910; (2006); 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. 3032-92-6, name is 4-Ethynylbenzonitrile, A new synthetic method of this compound is introduced below., Computed Properties of C9H5N

General procedure: An8 ml glass vial was charged with the alkyne (0.3 mmol), aryl iodide(0.25 mmol), K2CO3 (79 mg, 0.5 mmol), CuI (2.4 mg, 5 mol%), 3-Pphen(3.9 mg, 5 mol%), PEG-400 (20 mg, 20 mol%) and water (1 ml) under argon. The vial was closed with a Teflon cap and the heterogeneous reaction mixture was stirred at 100 C for 3 or 6 h (see Scheme 1). After cooling, the mixture was extracted with EtOAc, the extract was dried overMgSO4. After evaporation, the residue was purified by flash chromatography on silica gel with light petroleum as the eluent. 1H and 13C NMR spectroscopic data of products were consistent with those describedpreviously.13

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:
Article; Mitrofanov, Alexander Yu.; Beletskaya, Irina P.; Mendeleev Communications; vol. 29; 4; (2019); p. 378 – 379;,
Nitrile – Wikipedia,
Nitriles – Chemistry LibreTexts

Application of 5414-21-1, These common heterocyclic compound, 5414-21-1, name is 5-Bromovaleronitrile, 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-(2′-Aminopyrimidin-4′-yl)-1H-indole (80 mg, 0.38 mmol),KOH (30mg, 0.48mmol)With 5-bromopenteronitrile (0.23g, 1.43mmol)Miscible in DMF (6mL),And stirred at 40 C for 15 h,The resulting mixture was concentrated under reduced pressure to about 1/2 volume.Pour into H2O (20 mL),Extracted with EtOAc (15 mL¡Á3).The organic phase was combined and washed with saturated brine (20 mL).Anhydrous Mg2SO4 is dried,Silica gel layer filtration,The filtrate is evaporated to dryness.The resulting solid was dissolved in methanol (10 mL).Dry hydrogen chloride gas was passed at 0 C and stirred for 11 h, then evaporated to dryness.The resulting yellow solid was redissolved in methanol (10 mL).Slowly add 25% concentrated ammonia (1 mL) and stir for 3 h.The mixture is concentrated,Purified by column chromatography,Obtained a yellow solid (89 mg, yield 85%, a compound of formula I-26).

The synthetic route of 5414-21-1 has been constantly updated, and we look forward to future research findings.

Reference:
Patent; Tsingtao Ocean Bio-pharmaceutical Institute Co., Ltd.; Jiang Tao; Dong Xueyang; Zhang Lijuan; Tong Sheng; Yin Ruijuan; Zhang Hailin; (26 pag.)CN108218838; (2018); A;,
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., Recommanded Product: 77326-36-4

Example 24d 2-amino-6-(2-amino-2-methylpropoxy)benzonitrile To a solution of 2-amino-2-methylpropan-1-ol (14.4 g, 161 mmol) in anhydrous THF (150 mL) was added NaH (6.8 g, 161 mmol, 60% in mineral oil) in small portions at 0 C. under nitrogen. The mixture was stirred at 0 C. for 30 minutes and then stirred at room temperature for another 30 minutes. The solution was cooled down to 0 C. again, and to this solution was added dropwise a solution of 2-amino-6-fluorobenzonitrile (20.0 g, 147 mmol) in anhydrous THF (50 mL). The reaction mixture was then refluxed overnight under nitrogen. The reaction mixture was cooled down to room temperature and carefully quenched with aqueous NH4Cl solution and extracted with ethyl acetate (3*). The combined organic layers were washed with brine, dried over MgSO4, filtered and concentrated. The crude mixture was purified by chromatography on silica gel eluting with 10% MeOH in DCM to give the title compound as yellow solid (23.4 g 71%). 1H NMR (400 MHz, DMSO-d6) delta 1.08 (s, 6H), 3.15 (s, 2H), 3.64 (s, 2H), 5.98 (s, 2H), 6.13 (d, J=8.0 Hz, 1H), 6.31 (d, J=8.4 Hz, 1H), 7.15 (t, J=8.4 Hz, 1H). MS 236 (MH+).

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

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. 193290-27-6, name is 3-(2-Hydroxyethyl)benzonitrile, This compound has unique chemical properties. The synthetic route is as follows., name: 3-(2-Hydroxyethyl)benzonitrile

To a cooled (0 C) solution of S15 (150 mg, 1.019 mmol) (which was prepared as described in Lee, B. C; Choe, Y. S.; Lee, K. H.; Kim, B. T.; Chi, D. Y. J. Labelled Compd. Rad. 2001, 44, S404) in CH2C12(8 mL) were added MsCl (0.16 mL, 2.038 mmol) and Et3N (0.43 mL, 3.057 mmol). After stirring for 0.5 h at 0 C, brine was added. The layers were separated and the aqueous layer was extracted with CH2C12. The combined organic layers were dried over anhydrous Na2S04and concentrated in vacuo. To a cooled (0 C) solution of the crude mixture in THF/DMF (4/1, 15 mL) were added triphenylmethylsilane (TrtSH) (1.13 g, 4.076 mmol) and NaH (60% dispersion in mineral oil, 163 mg, 4.076 mmol). After stirring for 16 h at 25 C, the reaction mixture was quenched by the addition of saturated NH4C1 solution and diluted with EtOAc. The layers were separated and the aqueous layer was extracted with EtOAc. The combined organic layers were dried over anhydrous Na2S04and concentrated in vacuo. The residue was purified by column chromatography (silica gel, EtOAc/hexanes = 1/30) to afford S16 (1.8 g, 94% for two steps)

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 193290-27-6.

Reference:
Patent; HONG Jiyong; LUESCH Hendrik; WO2015/200699; A2; (2015);,
Nitrile – Wikipedia,
Nitriles – Chemistry LibreTexts

Adding a certain compound to certain chemical reactions, such as: 326-62-5, name is 2-(2-Fluorophenyl)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 326-62-5, Computed Properties of C8H6FN

General procedure: To a solution of 9 (20 mmol) in anhydrous DMF (100 mL) was added appropriate aryl acetonitriles (22 mmol) at room temperature. After the mixture was stirred for 0.5 h, 60% NaH (1.0 g, 24 mmol) was added portion wise at -10C under a nitrogen atmosphere. The whole mixture was stirred at the same temperature for 1 h, warmed to room temperature and then reacted for 48-72 h. The resulting mixture was acidified with acetic acid under ice cooling and concentrated under reduced pressure to afford the crude intermediate 10. Then, without further purification, EtOH (300 mL) was added at room temperature. After stirred for 0.5 h, 10% NaOH (100 mL) was added dropwise under ice cooling. The reaction mixture was then stirred at room temperature for 24-48 h and then acidified to pH 5-6 with acetic acid. After most of the solvent was removed under reduced pressure, the resulting residue was poured into water and extracted with CH2Cl2. The organic layer was dried over Na2SO4 and concentrated in vacuo to give the crude product, which was first purified by flash chromatography (eluent: CH2Cl2) and followed by recrystallization from MeOH or AcOEt, to afford target compounds 3a-h.

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-(2-Fluorophenyl)acetonitrile, other downstream synthetic routes, hurry up and to see.

Reference:
Article; Chen, Guo-Shen; Du, Fen; Zhao, Tian-Sheng; Xiong, Yuan-Zhen; Indian Journal of Heterocyclic Chemistry; vol. 28; 2; (2018); p. 255 – 260;,
Nitrile – Wikipedia,
Nitriles – Chemistry LibreTexts