Category: 654-70-6

These common heterocyclic compound, 654-70-6, name is 4-Cyano-3-trifluoromethylaniline, 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 4-Cyano-3-trifluoromethylaniline

4-cyano-3-trifluoromethyl-aniline is reacted with itaconic anhydride (66) to yield intermediate 67. Further epoxidation and opening of the epoxide ring with p-CN-phenol 50 yields compound XLVI as presented in Figure IG.

The synthetic route of 4-Cyano-3-trifluoromethylaniline has been constantly updated, and we look forward to future research findings.

Reference:
Patent; OSURF (OHIO STATE UNIVERSITY RESEARCH FOUNDATION); UNIVERSITY OF TENNESSEE RESEARCH FOUNDATION; WO2008/11072; (2008); A2;,
Nitrile – Wikipedia,
Nitriles – Chemistry LibreTexts

Electric Literature of 654-70-6,Some common heterocyclic compound, 654-70-6, name is 4-Cyano-3-trifluoromethylaniline, molecular formula is C8H5F3N2, 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.

The indicated aniline (0.52 g, 2.8 mmol) was added to a solution of the bromide (prepared according to the procedure of Example 5, 0.21 g, 0.56 mmol) in Toluene (3 mL), followed by Cs2CO3 (0.18 g, 0.56 mmol). The reaction mixture was heated at reflux overnight. The reaction mixture was cooled to room temperature and H2O was added. The resulting mixture was extracted with ethyl acetate (3×80 mL). The combined ethyl acetate extracts were washed with brine and dried over Na2SO4. Na2SO4 was then filtered off and solvent was evaporated in vac and the residue was chromatographed on silica gel using acetone:hexanes (20:80) 1% Et3N to give the titled compound. NaH (7.0 mg, 0.17 mmol) was added to the aniline (prepared according to the procedure of Example 19 Step 1, 41.0 mg, 0.09 mmol) in THF (1.5 mL) at -20 C. and stirred under N2 for 10 minutes. MeI (16.3 muL, 0.26 mmol) was added to the reaction mixture and the resulting mixture stirred at room temperature overnight. The residue was partitioned between ethyl acetate and H2O. The combined ethyl acetate extracts were dried over sodium sulfate and filtered. The solvent was evaporated in vac to give the titled compound. Aqueous NaOH (50, 2 mL) was added to the nitrile (prepared according to the procedure of Example 19 Step 2, 171.2 mg, 0.35 mmol) in MeOH (10 mL) and THF (4 mL). The reaction mixture was heated at reflux overnight. The reaction mixture was cooled to room temperature and neutralized with acetic acid, then extracted with ethyl acetate. The combined ethyl acetate extracts were washed with brine and dried over Na2SO4. Na2SO4 was then filtered off and solvent was evaporated in vac. The residue was chromatographed on silica gel using ethyl acetate:hexanes (20:80) 2.5% acetic acid to give the titled compound. 1H NMR (CDCl3) delta7.99 (d, 1H, J=9.0 Hz), 7.59 (d, 1H, J=9.0), 7.07 (m, 2H), 6.84 (m, 1H), 4.18 (t, 2H, J=5.5), 3.75 (t, 2H, J=7.5), 3.13 (s, 3H), 3.00 (t, 2H, J=7.5), 2.20 (m, 2H), 1.80 (m, 2H), 1.00 (t, 3H, J=7.5). MS: m/z=505 (M+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-Cyano-3-trifluoromethylaniline, its application will become more common.

Reference:
Patent; Adams, Alan D.; Huang, Shaei Y.; Szewczyk, Jason W.; US2006/178398; (2006); 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. 654-70-6, name is 4-Cyano-3-trifluoromethylaniline, This compound has unique chemical properties. The synthetic route is as follows., name: 4-Cyano-3-trifluoromethylaniline

Thionyl chloride (46.02 g, 0.39 mol) was added dropwise to a cooled solution (less than 4 C.) of (R)-3-bromo-2-hydroxy-2-methylpropanoic acid (51.13 g, 0.28 mol) in 300 mL of THF under an argon atmosphere. The resulting mixture was stirred for 3 h under the same condition. To this was added Et3N (39.14 g, 0.39 mol) and stirred for 20 min under the same condition. After 20 min, 5-amino-2-cyanobenzotrifluoride (40.0 g, 0.21 mol), 400 mL of THF were added and then the mixture was allowed to stir overnight at RT. The solvent was removed under reduced pressure to give a solid which was treated with 300 mL of H2O, extracted with EtOAc (2*400 mL). The combined organic extracts were washed with saturated NaHCO3 solution (2*300 mL) and brine (300 mL). The organic layer was dried over MgSO4 and concentrated under reduced pressure to give a solid which was purified from column chromatography using CH2Cl2/EtOAc (80:20) to give a solid. This solid was recrystallized fromCH2Cl2/hexane to give 55.8 g (73.9%) of (2R)-3-bromo-N-[4-cyano-3-(trifluoromethyl)phenyl]-2-hydroxy-2-methylpropanamide as a light-yellow solid.

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 654-70-6.

Electric Literature of 654-70-6, 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. 654-70-6 name is 4-Cyano-3-trifluoromethylaniline, 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.

1) Preparation of 4-(4,4-dimethyl-2,5-dioxoimidazolidin-1-yl)-2-trifluoromethyl-benzonitrile (1.1); Compound 1.1 can be prepared by method ?N-A?. To this end, 14.74 g (79.21 mmol) of 4-amino-2-trifluoromethylbenzonitrile were dissolved in 200 ml of dry acetonitrile. This solution was added dropwise with stirring to a 20% solution, heated to 70 C., of phosgene in toluene and then stirred for 1 h. The cooled reaction solution was concentrated under reduced pressure, the residue was taken up with toluene and concentrated again under reduced pressure. Finally, the residue was dissolved in 150 ml of dry acetonitrile and the solution was admixed with stirring with 15.5 g (79.21 mmol) of tert-butyl 2-amino-2-methylpropionate hydrochloride. 12.02 g (118.8 mmol) of triethylamine were slowly added dropwise to the reaction mixture which was then stirred at room temperature for 45 min. Thereafter, the mixture was admixed cautiously with 50 ml of concentrated hydrochloric acid and stirred at 70 C. for 1 h. The cooled reaction mixture was concentrated under reduced pressure and the residue was admixed with ethyl acetate and water. The organic phase was removed, washed with saturated sodium hydrogencarbonate solution and then with water, dried over sodium sulfate, filtered and concentrated under reduced pressure. The residue was purified chromatographically using silica gel with 2:1 heptane/ethyl acetate. This afforded 21.2 g (90% yield) of 4-(4,4-dimethyl-2,5-dioxoimidazolidin-1-yl)-2-trifluoromethylbenzonitrile 1.1 with melting point 208-211 C.

At the same time, in my other blogs, there are other synthetic methods of this type of compound, 4-Cyano-3-trifluoromethylaniline, and friends who are interested can also refer to it.

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

Application of 654-70-6, 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. 654-70-6, name is 4-Cyano-3-trifluoromethylaniline belongs to nitriles-buliding-blocks compound, it is a common compound, a new synthetic route is introduced below.

To a solution of the acetoxy derivative prepared in said example 2 (4.0 g, 0.0146 moles) in 20 mL of anhydrous toluene at room temperature is added 2.23 mL (0.016 moles) of triethylamine. After cooling to 0 C., 1.46 mL (0.0153 moles) of ethyl chloroformate is slowly added. After 1 hour the precipitated triethylamine hydrochloride formed is filtered off and 2.60 g (0.0140 moles) of 4-amino-2-trifluromethyl-benzonitrile dissolved in toluene is added to the filtrate and the resulting solution is heated at 75-80 C. until disappearance of the reagents is observed by HPLC.After cooling to room temperature the solution is washed with water, the phases are separated and dried with sodium sulphate and the solvent removed under reduced pressure. 5.85 g of crude intermediate is obtained which is used in the following reaction without further purification

The synthetic route of 4-Cyano-3-trifluoromethylaniline has been constantly updated, and we look forward to future research findings.

Reference:
Patent; Pizzatti, Enrica; Vigano, Enrico; Lussana, Massimiliano; Landonio, Ernesto; US2006/41161; (2006); A1;,
Nitrile – Wikipedia,
Nitriles – Chemistry LibreTexts

These common heterocyclic compound, 654-70-6, name is 4-Cyano-3-trifluoromethylaniline, 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: 4-Cyano-3-trifluoromethylaniline

To a solution of 4-amino-2- (trifluoromethyl) benzonitrile(XVII-I) (1.6 eq.) in THF (8.5 mL x mmol), cooled at -100C,LHMDS (4.5 eq.) was added drop wise. The reaction mixture was than stirred at this temperature for 40 min and HMPA(10% of the total THF) was added to the solution. After 5 min stirring, a solution of the ester XVIII-I (1 eq.) in THF (7 mL x mmol) was added to the reaction mixture. After 30 min at -100C, the solution was stirred 12h at room temperature. The reaction mixture was than quenched with 0. IN HCl and extracted with EtOAc. The crude material was purified by silica gel column chromatography. Yields range from 60 to 80%.(.R) -XXIV-3: 1H NMR (400 MHz, CDCl3) : 8.53 (broad s, IH) 7.63-7.72 (m, 2H), 7.50-7.55 (m, IH), 7.34-7.40 (m, 2H), 7.15-7.19 (m, 5H), 6.87 (dd, J= 8.8 Hz, IH) 3.87 (d, J= 14.4 Hz, IH), 3.45 (s, IH) . 3.22 (d, J= 13.6Hz, IH), 3.11 (d, J= 13.6Hz, IH), 2.95 (d, J= 14.4Hz, IH, CH2) . 13C NMR (100 MHz, CDCl3) Relevant: 172.1, 161.8 (d, J= 248Hz) 141.0,135.8, 134.5, 134.2 (d, J= 8.5Hz), 130.5, 128.8, 127.7, 122.6 (q) , 122.0, 117.6 (q, J= 5Hz) , 116.5 (d, J= 22.1Hz) 115.6, 105.0.

The synthetic route of 4-Cyano-3-trifluoromethylaniline has been constantly updated, and we look forward to future research findings.

Reference:
Patent; CONSIGLIO NAZIONALE DELLE RICERCHE; ISTITUTO SCIENTIFICO ROMAGNOLO PER LO STUDIO E LA CURA DEI TUMORI (I.R.S.T.) S.R.L.; VARCHI, Greta; TESEI, Anna; GUERRINI, Andrea; BRIGLIADORI, Giovanni; WO2010/116342; (2010); A2;,
Nitrile – Wikipedia,
Nitriles – Chemistry LibreTexts

Application of 654-70-6,Some common heterocyclic compound, 654-70-6, name is 4-Cyano-3-trifluoromethylaniline, molecular formula is C8H5F3N2, 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 reaction container was charged with 70 g of commercially available 4-cyano-3-trifluoromethylaniline (LC surface percentage: 99.39%) and 350 mL of ethanol, and the temperature was increased to 72C. After the mixture was stirred at 72 to 75C for 30 minutes, insoluble matters were removed by filtration at the same temperature and the mixture was further washed with 10 mL of ethanol. The filtrate thus obtained was cooled to 57C, and 360 mL of water was dropped at the same temperature over about 4 hours. 30 mg of 4-cyano-3-trifluoromethylaniline that had been previously purified was seeded thereto and the resultant mixture was cooled to 45C, and thereafter stirred at the same temperature for 30 minutes. Then, the mixture was cooled to 25C and stirred at the same temperature for 1 hour. Crystals were separated by filtration and washed with a mixed solvent of 56 mL of ethanol and 56 mL of water to give 83.81 g of wet crystals. The wet crystals were dried under reduced pressure to obtain 50.61 g of 4-cyano-3-trifluoromethylaniline. The LC surface percentage was 99.90%, and the yield was 72.3%. A reaction container was charged with 68 mL of N,N-dimethylacetamide, 22.1 g of methacrylic acid, and 38 mg of dibutylhydroxytoluene, and the temperature was reduced to -5C. Thionyl chloride in an amount of 30.6 g was dropped thereto at -3.8 to 0.3C over 50 minutes, and the mixture was kept at -4.0 to -0.8C for 30 minutes. A solution obtained by dissolving 36.0 g of 4-cyano-3-trifluoromethylaniline obtained as described above in 79 mL of N,N-dimethylacetamide was dropped into the reaction container at -5.3 to 0C over 65 minutes. The container for dropping was washed with 11 mL of N,N-dimethylacetamide, the washing liquid was added to the reaction solution, and the solution was kept at -5.3 to 0C for 1 hour. After completion of the reaction, the obtained reaction solution was dropped to a mixed solution of 306 mL of ethyl acetate and 252 mL of water at 20C or less. The solution was washed with 18 mL of N,N-dimethylacetamide and the washing solution and the mixed solution were combined, and 378.1 g of an aqueous 16% sodium carbonate solution was added to the solution to adjust the pH to 7.1. The resultant solution was stirred for 30 minutes and made to stand still for 30 minutes, followed by liquid separation. The liquid separation speed calculated in the same manner as in Example 1 was 1.7 m/hr. The organic layer was added with 571.8 g of 15% saline water to set the internal temperature to 60C. The resultant solution was stirred for 30 minutes and made to stand still for 30 minutes, followed by liquid separation. The liquid separation speed calculated in the same manner as in Example 1 was 3. 9 m/hr. The organic layer was added with 571.8 g of 15% saline water to set the internal temperature to 60C. The resultant solution was stirred for 30 minutes and made to stand still for 30 minutes, followed by liquid separation. The liquid separation speed calculated in the same manner as in Example 1 was 3. 6 m/hr. The organic layer was further added with 571. 8 g of 15% saline water to set the internal temperature to 60C. The resultant solution was stirred for 30 minutes and then made to stand still for 30 minutes, followed by liquid separation. The liquid separation speed calculated in the same manner as in Example 1 was 3. 0 m/hr. Then, the organic layer was charged with 180 mL of chlorobenzene, and ethyl acetate and chlorobenzene were distilled out in an amount of 222.3 g by vacuum concentration. Next, 504 mL of chlorobenzene, 1.8 g of activated carbon and 4.9 g of gamma-alumina were charged and the mixture was stirred at 75C for 30 minutes. The alumina and activated carbon were separated by filtration at the same temperature and washed with 36 mL of chlorobenzene. The filtrate and the washing solution were combined, and 545.5 g of chlorobenzene was distilled out by vacuum concentration, and then the mixture was cooled to 20C and stirred at 15 to 20C for 2 hours. Crystal were separated by filtration and washed with 108 mL of a chlorobenzene solution dissolved with 0.45 g of dibutylhydroxytoluene to give 48.94 g of wet crystals. After drying the crystal under reduced pressure, 45.27 g of crystals of N-methacryloyl-4-cyano-3-trifluoromethylaniline was obtained. The LC surface percentage was 99.92%, and the yield was 92.1%.

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

Reference:
Patent; Sumitomo Chemical Company, Limited; EP2204362; (2010); A1;,
Nitrile – Wikipedia,
Nitriles – Chemistry LibreTexts

Reference of 654-70-6,Some common heterocyclic compound, 654-70-6, name is 4-Cyano-3-trifluoromethylaniline, molecular formula is C8H5F3N2, 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.

Synthesis of 4-isothiocyanato-2-(trifluoromethyl)-benzyl cyanide (compound 2) Into an aqueous suspension (50 mL) of thiophosgene (30.2 g, 262.4 mmol) compound 1 (10.0 g, 53.7 mmol) was slowly added in portions. The reaction mixture was stirred at room temperature (20C) for one hour and then extracted with ethyl acetate for three times (3 * 50mL). The organic layer was combined, washed with saturated brine (100 mL), dried (Na2SO4), filtered and concentrated under reduced pressure to give a black solid. After purified by column chromatography, a white solid 2 (Compound 2, 11.24 g, yield 92%) was obtained. 1H NMR (CDCl3, 400MHz):delta(ppm)7.85(1H, d, J=8Hz), 7.59(1H, s), 7.48(1H, d, J=8.4Hz).MS: 229(M+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-Cyano-3-trifluoromethylaniline, its application will become more common.

Reference:
Patent; HC Pharmaceutical Co., Ltd.; CHEN, Yuanwei; EP2792674; (2014); A1;,
Nitrile – Wikipedia,
Nitriles – Chemistry LibreTexts

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. 654-70-6, name is 4-Cyano-3-trifluoromethylaniline belongs to nitriles-buliding-blocks compound, it is a common compound, a new synthetic route is introduced below. Formula: C8H5F3N2

Step 2: 4- [2, 5-Dioxo-3-methyl-4-phenylimidazolidin-l-yl]-2-trifluoromethyl-benzonitrile; [00272] To a solution of 1.26 g of triphosgene in 20 mL of anhydrous toluene is added slowly a solution of 1.18 g of 4-amino-2-trifluoromethylbenzonitrile in 16 mL of anhydrous dioxan. The mixture is refluxed for 1.5 hour. After cooling at rt the mixture is evaporated to dryness. To this crude product diluted with 50 mL of anhydrous THF is added 1.13 g of methyl 2-methylamino-2-phenylacetate in 10 mL of THF. The mixture is stirred at rt for 30 min. 1.96 mL of TEA is added, the mixture is refluxed for 1.5 hour and stirred at rt for 16 h then evaporated to dryness. The crude product is diluted with an aqueous solution of sodium bicarbonate and extracted with ethyl acetate. The organic phases are washed wiith water then brine, and dried over magnesium sulfate, filtered and evaporated. The crude product is crystallised in ethyl acetate, filtered and rinsed with ethyl ether to provide the desired product.TLC: Fr = 0.67 (dichloromethan/ethyl ether 90/10) delta 1H NMR (CDCl3): 3.06 (s, 3H); 5.06 (s, IH); 7.35-7.39 (m, 2H); 7.48-7.56 (m, 3H); 7.96 (d, IH); 8.03 (dd,IH); 8.18 (d, IH)LCMS : (rt = 2.91min, apolar method): not ionizable

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

Reference:
Patent; GALAPAGOS NV; NIQUE, Francois; JAGERSCHMIDT, Catherine; BLANQUE, Roland; LEFRANCOIS, Jean-Michel; PEIXOTO, Christophe; DEPREZ, Pierre; TRIBALLEAU, Nicolas; WIGERINCK, Piet, Tom, Bert, Paul; NAMOUR, Florence, Sylvie; WO2010/29119; (2010); A1;,
Nitrile – Wikipedia,
Nitriles – Chemistry LibreTexts