Category: nitriles-buliding-blocks

6136-68-1, 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. 6136-68-1 name is 3-Acetylbenzonitrile, 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.

A solution of n-BuLi (20.0 mL, 2.5 M, 50.0 mmol) was added to a solution of PPh3MeI (20.2 g, 50.0 mmol) in THF (200 mL) at -10 C. After the mixture was stirred at -10 C for 1 h, 3-acetylbenzonitrile (4.85 g, 33.4 mmol) was added. The mixture was allowed to warm up to r.t. and stirred at r.t. for 3 h. Water (400 mL) was added to the reaction mixture and it was extracted with CH2Cl2 (200 mL x 2). It was dried over anhydrous sodium sulfate, and purified by column chromatography (PE: EtOAc = 50: 1) to give the titled compound (3.4 g, 79%).

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

Reference:
Patent; F. HOFFMANN-LA ROCHE AG; BURCH, Jason; GOLDSMITH, Richard, A.; ORTWINE, Daniel, Fred; PASTOR, Richard; PEI, Zhonghua; WO2013/24011; (2013); A1;,
Nitrile – Wikipedia,
Nitriles – Chemistry LibreTexts

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 19179-31-8 as follows. 19179-31-8

Step 2: 3,5-dihydroxybenzonitrile To a solution of 3,5-dimethoxybenzonitrile (2 g, 2.2 mmol) in dichloromethane (20 mL) was added slowly BBr3 (15 mL, 1 M, 15 mmol) at -50 C. under N2. After addition, the mixture was stirred at -50 C. for 2 h and stirred at r.t for 20 hr. The mixture was slowly poured into ice-water with stirring and extracted with dichloromethane. The organic layer was washed with brine, dried over sodium sulfate, filtered and concentrated under reduced pressure. The residue was purified by column (petroleum ether/ethyl acetate (2:1) as eluent) to afford 3,5-dihydroxybenzonitrile (1.43 g). 1H NMR (DMSO-d6, 400 MHz): delta 10.02 (s, 2H), 6.56 (d, J=2.0 Hz, 2H), 6.51 (t, J=2.0 Hz, 1H).

According to the analysis of related databases, 19179-31-8, the application of this compound in the production field has become more and more popular.

Reference:
Patent; Arrington, Kenneth L.; Burgey, Christopher; Gilfillan, Robert; Han, Yongxin; Patel, Mehul; Li, Chun Sing; Li, Yaozong; Luo, Yunfu; Lei, Zhiyu; US2014/100231; (2014); A1;,
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A common heterocyclic compound, 1953-99-7, name is 3,4,5,6-Tetrachlorobenzene-1,2-dicarbonitrile, molecular formula is C8Cl4N2, 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. 1953-99-7.

[formula c] 0.0375 mol, [formula a]0.0125 mol, zinc bromide 0.015 mol and1,8- diazabicyclo [5.4.0] undec -7-ene 0.05 mol were added to amylalcohol 66 g and stirred. The reaction temperature was raised to 130 and the reaction was carried out for 8 hours. After thereaction was complete, the reaction solution was cooled down and concentratedunder reduced pressure to remove the solvent by 2/3. The addition of methanolwas followed by to crystalize the solution. The crystals were filtered underreduce pressure and was dispersedly filtered in the mixed solution of methanol50g for 1 hour. The crystals were suction filtered and vacuum dried at 60 to obtain phthalocyanine compound 7.9g.

The synthetic route of 3,4,5,6-Tetrachlorobenzene-1,2-dicarbonitrile has been constantly updated, and we look forward to future research findings.

Reference:
Patent; Kyung-In Synthetic Corporation; Park, Soon Hyeon; Kim, Jeong Ki; Kim, Jeong Rok; Lee, Yun Ah; Lee, Do kyeong; Lee, Min Jeong; Lee, Hui Jae; (16 pag.)KR2016/7024; (2016); A;,
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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 218632-01-0 as follows. 218632-01-0

Compound 161a: 3-Fluoro-4-nitro-benzamide: The urea/hydrogen peroxide complex (22.65 g, 240.8 mmol, 2.0 eq) was added to a solution of 3-fluoro-4-nitro-benzonitrile (20.0 g, 120.4 mmol, 1.0 eq) and potassium carbonate (33.28 g, 240.8 mmol, 2.0 eq) in 20% water/acetone (500 ml). The reaction was stirred at room temperature for 22 hours when urea/hydrogen peroxide complex (11.33 g, 120.4 mmol, 1.0 eq) and potassium carbonate (16.64 g, 120.4 mmol, 1.0 eq) were added. The reaction was stirred for a further 2 hours at room temperature then diluted with water (300 ml) and DCM (500 ml). The organic layer was removed and the aqueous extracted with DCM (2 x 500 ml). The organics were combined, washed with brine, dried over sodium sulphate, and the solvent removed in vacuo to give the title compound as an orange solid (14.065 g, 76.31 mmol, 63%). 1H NMR shows product in >95% purity.

According to the analysis of related databases, 218632-01-0, the application of this compound in the production field has become more and more popular.

Reference:
Patent; DEVELOGEN AKTIENGESELLSCHAFT; WO2006/136402; (2006); A1;,
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79463-77-7,Some common heterocyclic compound, 79463-77-7, name is Diphenyl N-cyanocarbonimidate, molecular formula is C14H10N2O2, 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 solution of (R)-3-tert-butoxycarbonylaminopipiridine (154.0 g, 0.769 mol) in iPrOH (3.0 L) was added diphenyl cyanocarbonimidate (183.2 g, 0.769 mol). The mixture was stirred at room temperature for 2.5 h. To the reaction mixture was added glycine ethyl ester¡¤hydrochloride (536.7 g, 3.85 mol) at 0 C, and the mixture was stirred at 80 C for 6 h. After cooling to room temperature, the reaction mixture was diluted with AcOEt (1.4 L) and the precipitate was removed by filtration through a Celite pad. The filtrate was concentrated in vacuo, and the residue was diluted with 5% sodium carbonate solution and extracted with CHCl3 three times. The combined organic layers were dried over Na2SO4, and concentrated in vacuo. The residue was purified by silica-gel column chromatography to give 7 (249.2 g, yield 92%) as a pale yellow oil. 1H NMR (300 MHz, CDCl3) delta 5.68 (br s, 1H), 4.66 (br s, 1H), 4.28-4.19 (m, 4H), 3.81-3.34 (m, 5H), 2.05-1.51 (m, 4H), 1.45 (s, 9H), 1.30 (t, J=7.2 Hz, 3H); 13C NMR (75 MHz, CDCl3) delta 169.6, 160.0, 155.5, 117.1, 80.1, 61.8, 51.2, 47.3, 45.4, 44.6, 29.8, 28.3, 22.8, 14.1; HRMS (ESI) [M+H]+ calcd for C16H28N5O4 354.2136, found 354.2128; IR (ATR): 1743, 1685, 1575, 1531, 1440, 1390, 1365, 1309, 1243, 1197, 1162, 1051, 1031, 1018 cm-1.

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

Reference:
Article; Ikuma, Yohei; Nakahira, Hiroyuki; Tetrahedron; vol. 67; 49; (2011); p. 9509 – 9517;,
Nitrile – Wikipedia,
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A common compound: 4640-67-9, name is 3-(4-Fluorophenyl)-3-oxopropanenitrile, 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. 4640-67-9

In a 25 mL reaction tube with a Teflon magnetic stir bar,Add 0.5 mmol of 4-fluorobenzoylacetonitrile, 0.5 mmol of 3-bromo-1,1,1-trifluoroacetone, 0.5 mmol of sodium acetate,Finally, 58 mmol of 1,4-dioxane was added, and the reaction was stirred at room temperature for 8 hours.Add 15 mL of water, extract three times with 10 mL of ether, and combine the organic phases.Washing with saturated sodium chloride solution, drying over anhydrous magnesium sulfate, and then removing the organic solvent by rotary evaporation;The obtained crude product was eluted with n-pentane and ethyl acetate (10:1, v/v).2-(4-Fluorophenyl)-5-hydroxy-5-(trifluoromethyl)-4,5-dihydrofuran-3-carbonitrile was isolated by silica gel column chromatography (yield: 76%).

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, 4640-67-9, other downstream synthetic routes, hurry up and to see.

Reference:
Patent; Fuzhou University; Weng Zhiqiang; Wang Junwen; (29 pag.)CN110272400; (2019); A;,
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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. 127946-77-4, name is 1-Amino-1-cyclopropanecarbonitrile hydrochloride, This compound has unique chemical properties. The synthetic route is as follows., 127946-77-4

b) (2S,4S)-4-Hydroxy-1-(1-trifluoromethyl-cyclopropanecarbonyl)-pyrrolidine-2 [0151] [0152] To the (2S,4R)-4-methanesulfonyloxy-1-(1-trifluoromethyl-cyclopropanecarbonyl)-pyrrolidine-2-carboxylic acid methyl ester (71.9 g, 200 mmol) were added under stirring and ice-cooling 2.0 M NaOH (120.0 mL, 240.0 mmol) all at once. The ice bath was removed and the white suspension was stirred at room temperature for 1 h. After neutralization by the addition of 2.0 M HCl (20.0 mL, 40.0 mmol; pH 7), 1-aminocyclopropanecarbonitrile hydrochloride (23.7 g 200 mmol) and sodium 2-ethylhexanoate (37.7 g, 220 mmol) were added all at once and the biphasic reaction mixture was stirred at 70 C. for 22 h and then cooled to 35 C. Dichloromethane (100 mL) and NaCl (16 g) were added and stirring was continued until the NaCl was dissolved (15 min). After acidification with 25% HCl (12 mL, pH 1), the reaction mixture was extracted with dichloromethane (3¡Á200 mL) and all three organic layers were washed separately with 5% NaHCO3 (40 mL pH 8). The combined organic layers were dried (Na2SO4), filtered, and evaporated (35-50 C./?5 mbar), affording beige, crystalline residue (88.5 g) which was dissolved in isobutyl acetate (500 mL) at -110 C. Crystallization, which started after seeding and cooling, was completed by stirring at room temperature for 1 h and at -20 C. for 4 h. Filtration and washing with cold isobutyl acetate gave after drying (10 mbar/55 C./4 h) the title product (47.7 g, 72.0%) as an off white, crystalline powder, mp. 156-157 C. [alpha]D20=-68.9 (c 1.0; CHCl3). 1H NMR (CDCl3, 400 MHz) delta 1.15-1.45 (m, 6H), 1.50-1.60 (m, 2H), 2.17-2.29 (m, 2H), 3.72 (dd, J1=11.8 Hz, J2=4.0 Hz, 1H), 3.98 (d, J=11.8 Hz, 1H), 4.40-4.52 (m, 2H), 4.95 (d, J=9.7 Hz, 1H), 7.93 (s, 1H). ESI-MS (m/z) [M+H]+332 (56).

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; Hoffmann-La Roche Inc.; Bartels, Bjoern; Bliss, Fritz; Cueni, Philipp; Pfleger, Christophe; Zutter, Ulrich; US2013/123512; (2013); A1;,
Nitrile – Wikipedia,
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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. 114897-91-5, name is 2-(4-Bromo-2-fluorophenyl)acetonitrile, This compound has unique chemical properties. The synthetic route is as follows., 114897-91-5

MeOH (16MMOL, 0.81 ml), TMSCI (20mmol, 2. 13g) and (4-bromo-2-fluorophenyl) acetonitrile (10MMOL, 2. 13g) were sequentially added to a dry flask under a nitrogen atmosphere at room temperature. The reaction mixture was heated at 50 C for 4 hours. After being cooled to room temperature, water (20MMOL, 0. 36MOI) was added to the mixture, followed by the addition of NA2CO3 (10mmol, 1. 06g) and CH2Cl2 (10ml). Drying over MGSO4 and concentrating at low pressure afforded product (0.85 g, 35% YIELD). H NMR (300 MHz, CDC13) No. : 3.57 (s, 2 H), 3.65 (s, 3H), 7.08 (t, J=8.3 Hz, 1H), 7.16-7. 21 (m, 2H).

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; PFIZER INC.; WO2004/74270; (2004); A2;,
Nitrile – Wikipedia,
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1813-33-8, The chemical industry reduces the impact on the environment during synthesis 1813-33-8, name is 2-Chloro-4-(trifluoromethyl)benzonitrile, I believe this compound will play a more active role in future production and life.

General procedure: A mixture of 2-chloro-4-(trifluoromethyl)-benzonitrile (1.00 mmol) and appropriate thiol (RSH, 3.00 mmol),18-crown-6-ether (cat.) and potassium carbonate (2.00 mmol)were dissolved in acetonitrile (3 ml). The mixture was refluxedfor 12 h and then cooled to ambient temperature. The mixturewas quenched by adding water and extracted with EtOAc.Extracted organic compound was dried over MgSO4, filtered, andconcentrated in vacuo. The residue was purified by flash columnchromatography on silica gel using EtOAc/hexane (1:4) eluantcondition. (RSH = CH3CO2(CH2)2SH for 42).

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

Reference:
Article; Ann, Jihyae; Jung, Aeran; Kim, Mi-Yeon; Kim, Hyuk-Min; Ryu, Hyungchul; Kim, Sunjoo; Kang, Dong Wook; Hong, Sunhye; Cui, Minghua; Choi, Sun; Blumberg, Peter M.; Frank-Foltyn, Robert; Bahrenberg, Gregor; Stockhausen, Hannelore; Christoph, Thomas; Lee, Jeewoo; Bioorganic and Medicinal Chemistry; vol. 23; 21; (2015); p. 6844 – 6854;,
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96606-37-0, A common heterocyclic compound, 96606-37-0, name is 2,4,6-Trifluorobenzonitrile, molecular formula is C7H2F3N, 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.

Example 3: Synthesis OF 3-AMINO-6- (4-AMINO-PIPERIDIN-1-YL)-4-FLUORO- BENZOLB] THIOPHENE-2-CARBOXYLIC acid amide H N i N O F NHZ NN O N i HN 0- HS-NH, N F N O F F THF, 50 C, 3h DMF, 15h F 0A0 F NH2 HCI NH2 na ff) / MeOH, 3 days 0 H2N~ 3 ‘3 To a solution of 1.0 g (6.4 mmol) of 2, 4,6-trifluorobenzonitrile in MEOH (25 mL) was added 1.3 g (6.5 mmol) OF 4-N-BOC-AMINO-PIPERIDINE along with 1.2 mL (6.7 mmol) of N, N-diisopropylethylamine. The mixture was stirred at room temperature for 3 days then concentrated under reduced pressure to provide a white, solid. The solid was washed with large amounts OF H20 and dried under vacuum. The solid was RECRYSTALLIZED from hexane /EtOAc to provide 1.23 g (56%) of [1- (4-CYANO-3, 5-difluoro-phenyl) -piperidin-4-yl]- carbamic acid tert-butyl ester as a white solid.

The synthetic route of 96606-37-0 has been constantly updated, and we look forward to future research findings.

Reference:
Patent; BOEHRINGER INGELHEIM PHARMACEUTICALS, INC.; WO2005/12283; (2005); A1;,
Nitrile – Wikipedia,
Nitriles – Chemistry LibreTexts