Category: nitriles-buliding-blocks

These common heterocyclic compound, 2571-52-0, name is 2,4,6-Trimethylbenzonitrile, 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. 2571-52-0

Example 32: Synthesis of 2- [4- (5-fluoro-2-methoxyphenyl)-2-hydroxy-4-methyl-2- trifluoromethylpentyl]-4, 6-dimethylbenzonitrile and 4- [4- (5-fluoro-2-methoxyphenyl)-2- hydroxy-4-methyl-2-trifluoromethylpentyl]-2, 6-dimethylbenzonitrile The title compounds were prepared as an inseparable mixture by methods analogous to those described in Example 5 as a result of performing a Grignard reaction with a 1: 1.4 mixture of 2- bromomethyl-4,6-dimethylbenzonitrile and 4-bromomethyl-2,6-dimethylbenzonitrile (prepared by N bromosuccinimide bromination of 2, 4, 6-trimethylbenzonitrile) The mixture was treated with boron tribromide according to methods analogous to those described in Example 7 followed by chromatography on a prep plate (silica gel, hexanes-isopropyl alcohol (97: 3,2X developed) ) to afford 2- [4- (5-fluoro-2-hydroxyphenyl)-2-hydroxy-4-methyl-2- trifluoromethylpentyl]-4, 6-dimethylbenzonitrile, m. p. 136C-138C, and 4- [4- (5-fluoro-2- hydroxyphenyl)-2-hydroxy-4-methyl-2-trifluoromethylpentyl]-2, 6-dimethylbenzonitrile, m. p. 152C-154C. Methylation of 2- [4- (5-fluoro-2-hydroxyphenyl)-2-hydroxy-4-methyl-2- trifluoromethylpentyl]-4, 6-dimethylbenzonitrile and 4- [4- (5-fluoro-2-hydroxyphenyl)-2- hydroxy-4-methyl-2-trifluoromethylpentyl] -2,6-dimethylbenzonitrile by analogous methods described in Example 8 gave the title compounds 2- [4- (5-fluoro-2-methoxyphenyl)-2-hydroxy- 4-methyl-2-trifluoromethylpentyl]-4, 6-dimethylbenzonitrile, m. p. 134C-136C, and 4- [4- (5- fluoro-2-methoxyphenyl)-2-hydroxy-4-methyl-2-trifluoromethylpentyl]-2, 6- dimethylbenzonitrile, m. p. 113C-115C.

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 2571-52-0.

Reference:
Patent; BOEHRINGER INGELHEIM PHARMACEUTICALS, INC.; WO2003/82787; (2003); A1;,
Nitrile – Wikipedia,
Nitriles – Chemistry LibreTexts

A common heterocyclic compound, 79463-77-7, name is Diphenyl N-cyanocarbonimidate, molecular formula is C14H10N2O2, 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. 79463-77-7.

To a solution of N-(2-dimethylaminoethyl)-2,5-dimethoxybenzene 1,4-diamine hydrochloride (0.05g, 0.143mmol) in distilled water (1mL) was added K2CO3 (0.065g, 0.47mmol). This was diluted with EtOAc (1mL) and diphenylcyano-carbonimidate (0.032g, 0.136mmol) was added. The reaction was stirred at RT for 18h. The precipitate was filtered and washed with minimal EtOAc to give the title compound as a light purple solid (0.015g, 29% yield). 1H-NMR (500 MHz, DMSO-d6) 10.11 (s, 1H), 7.51-7.33 (m, 2H), 7.31-6.98 (m, 3H), 6.81-6.64 (m, 1H), 6.28 (br s, 1H), 4.87 (br s, 1H), 3.85-3.62 (m, 5H), 3.12 (s, 3H), 2.17 (s, 6H) ppm; LC-MS 384.3 (M+H); HPLC 1.9 min(method A).

The synthetic route of Diphenyl N-cyanocarbonimidate has been constantly updated, and we look forward to future research findings.

Reference:
Patent; VERTEX PHARMACEUTICALS INCORPORATED; WO2004/46120; (2004); A2;,
Nitrile – Wikipedia,
Nitriles – Chemistry LibreTexts

67515-59-7, Adding some certain compound to certain chemical reactions, such as: 67515-59-7, name is 4-Fluoro-3-(trifluoromethyl)benzonitrile, 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 67515-59-7.

EXAMPLE 347A 4-(8-azabicyclo[3.2.1]oct-8-yl)-3-(trifluoromethyl)benzonitrile 4-Fluoro-3-(trifluoromethyl)benzonitrile (1.35 g, 7.14 mmol), 8-aza-bicyclo[3.2.1]octane hydrochloride (1.26 g, 8.57 mmol), and N,N-diisopropylethylamine (1.79 g, 13.8 mmol) were combined in DMSO (15 mL) and heated at 120 C. for 24 hours. The mixture was allowed to cool to ambient temperature and partitioned between diethyl ether and saturated NaHCO3 solution. The separated aqueous phase was extracted with diethyl ether and the combined organic layers were washed with water, brine, dried (Na2SO4), filtered, and the filtrate was concentrated under reduced pressure to provide the title compound which was used in the next step without further purification.

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 67515-59-7.

Reference:
Patent; Abbott Laboratories; US6933311; (2005); B2;,
Nitrile – Wikipedia,
Nitriles – Chemistry LibreTexts

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. 127946-77-4 name is 1-Amino-1-cyclopropanecarbonitrile hydrochloride, 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. 127946-77-4

Step 10: N2-[(1S)-1-(4-bromophenyl)-2,2,2-trifluoroethyl]-N1-(1-cyanocyclopropyl)-4-fluoro-L- leucinamide. Diisopropylethylamine (4.2 mL) was added to a 0 C suspension of the acid (1.5 g) from Step 9, 1-amino-1-cyclopropanecarbonitrile hydrochloride (1. 18 g), O-(7-azabenzotriazol-1-yl)-N, N, N’, N’-tetramethyluronium hexafluorophosphate (1.94 g) and DIMETHYLFORMAMIDE (5 mL) and the mixture was reacted at room temperature for 48 hrs. It was then poured on ice and dilute aqueous ammonium chloride. The mixture was extracted with ethyl acetate and ether (1: 1) and the combined organic layers were washed with pH 3 dilute NA2HP04 and brine. The solvents were evaporated to dryness and the residue was purified by chromatography on SI02 using ethyl acetate and hexanes (1: 2) to yield N2-[(1S)- 1- (4-BROMOPHENYL)-2, 2, 2-TRIFLUOROETHYL]-N -(L-CYANOCYCLOPROPYL)-4-FLUORO-L-LEUCINAMIDE in a sufficient purity state for the next step. 1H NMR (CD3 COCD3) No. 8.15 (1H, NH), 7.6 (2H, m), 7.45 (2H, m), 4.35-4. 45 (1H, m), 3.45-3. 55 (1H, M), 1.9-2. 1 (2H, m), 1.75-1. 85 (1H, NH), 1.35-1. 55 (8H, M), 1. 1-1. 15 (1H, M), 0.95-1. 05 (1H, M).

At the same time, in my other blogs, there are other synthetic methods of this type of compound, 1-Amino-1-cyclopropanecarbonitrile hydrochloride, and friends who are interested can also refer to it.

Reference:
Patent; MERCK FROSST CANADA & CO.; WO2005/21487; (2005); A1;,
Nitrile – Wikipedia,
Nitriles – Chemistry LibreTexts

Some common heterocyclic compound, 19472-74-3, name is 2-Bromophenylacetonitrile, molecular formula is C8H6BrN, 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. 19472-74-3

The appropriate amount of organic solvent (volume ratio of 1: 1,4-dioxane and a mixture of DMSO (dimethyl sulfoxide). 2), the compound on 100mmol formula (I), 200mmol formula (II) compound, 8mmol bicomponent catalyst (as 4mmol (a-taPhos)2PdCl2And 4 mmolCu (TFA)2The mixture), 5mmol phosphine ligand L1 and methanesulfonic acid 20mmol acidic compound; and then stirred warmed to 60 , and the reaction was stirred at this temperature for 12 hours.After completion of the reaction, filtered hot and the filtrate was cooled to room temperature, and the pH was adjusted to neutral, and then washed with deionized water sufficiently shaken, and then ethyl acetate was added and extracted 3 times, the combined organic phase was concentrated under reduced pressure, the concentrate was subjected to silica gel column chromatography, a volume ratio of 1: 2 acetone – chloroform mixture to wash, to afford the compound of formula (III), in a yield of 97.3%.

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

Reference:
Patent; Zhang, Yan; (9 pag.)CN105384674; (2016); A;,
Nitrile – Wikipedia,
Nitriles – Chemistry LibreTexts

Adding some certain compound to certain chemical reactions, such as: 194853-86-6, name is 4-Fluoro-2-(trifluoromethyl)benzonitrile, 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 194853-86-6. 194853-86-6

General procedure: A mixture of 9H,9’H-3,3′-bicarbazole (500 mg, 1.50 mmol), 4-fluoro-2-methylbenzonitrile (450 mg, 3.33 mmol) and K2CO3(0.99 g, 7.2 mmol) in dimethyl sulfoxide (DMSO) (6 mL) was stirredat 140 C for 12 h under nitrogen atmosphere. After cooling to roomtemperature, the mixture was poured into water, filtered and thenpurified by column chromatography over silica gel with CH2Cl2/petroleum ether (1: 1) as eluent to afford a white solid (760 mg,89%).

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 4-Fluoro-2-(trifluoromethyl)benzonitrile.

Reference:
Article; Cao, Xudong; Hu, Jia; Tao, Youtian; Yuan, Wenbo; Jin, Jie; Ma, Xiaoxuan; Zhang, Xinwen; Huang, Wei; Dyes and Pigments; vol. 136; (2017); p. 543 – 552;,
Nitrile – Wikipedia,
Nitriles – Chemistry LibreTexts

Adding a certain compound to certain chemical reactions, such as: 1813-33-8, name is 2-Chloro-4-(trifluoromethyl)benzonitrile, 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 1813-33-8, 1813-33-8

To commercially available 2-chloro-4-trifluoromethylbenzonitrile 13 (lml, 7.2 mmol) pyrrolidine (4equiv., 2.38 ml) was added and the solution was heated at 80C overnight. The reaction was evaporated and the residue was dissolved in AcOEt and washed with water and brine. The organic phase was evaporated obtaining 940mg of a yellow solid. Yield = 54% ‘HNMR (DMSO, 200 MHz) delta 1.95 (4H, m), 3.58 (4H, m), 6.94 (2H, m), 7.73 (1H, dd, J = 8 Hz, J’= 0.8 Hz).

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

Reference:
Patent; PHARMESTE S.R.L.; NAPOLETANO, Mauro; TREVISANI, Marcello; PAVANI, Maria Giovanna; FRUTTAROLO, Francesca; WO2011/120604; (2011); A1;,
Nitrile – Wikipedia,
Nitriles – Chemistry LibreTexts

52688-08-1, 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. 52688-08-1, name is Octan-2-yl 2-cyanoacetate belongs to nitriles-buliding-blocks compound, it is a common compound, a new synthetic route is introduced below.

General procedure: 1.40 moles of butyl cyanoacetate and 2.1 moles of methylene diacetate, obtained through the preparative example 1, were added to a 1 L reactor. Subsequently, the mixture was heated to a temperature comprised between 120 and 130 C. Then 5 mol% of piperazine and 15 mol% of p-toluenesulfonic acid monohydrate were added. The reaction was monitored by gas chromatography or nuclear magnetic resonance every 30 min. After 1 hour, the reaction was terminated, and the n-butyl cyanoacrylate was obtained with a selectivity of 94%, where the selectivity is understood as the amount of monomer produced with respect to the cyanoacetate that has reacted. Subsequently, acetic acid was removed under vacuum and stabilizers were added to the residue for the distillation of the monomer.

The synthetic route of Octan-2-yl 2-cyanoacetate has been constantly updated, and we look forward to future research findings.

Reference:
Patent; Afinitica Technologies, S. L.; Tchaplinski, Vladimir; Gherardi, Stefano; de la Fuente Molina, Veronica; EP2927209; (2015); A1;,
Nitrile – Wikipedia,
Nitriles – Chemistry LibreTexts

56043-01-7, The chemical industry reduces the impact on the environment during synthesis 56043-01-7, name is 2-Amino-6-methylbenzonitrile, I believe this compound will play a more active role in future production and life.

A solution of 2-amino-6-methylbenzonitrile (1.32 g, 10 mmol) and sulfamide (4.81 g, 50 mmol) in dry 1,4-dioxane (50 mL) was refluxed under nitrogen for 3 days. After the reaction mixture was cooled down to room temperature, the precipitate was filtered and washed with dioxane. The filtrate was concentrated under reduced pressure, and the residue was purified by chromatography on silica gel eluding with EtOAc/hexanes (3:7) to give the title compound as a pale-white solid. 1H NMR (400 MHz, DMSO-d6) delta 2.44 (s, 3H), 7.19-7.21 (m, 3H), 7.39-7.41 (d, J=8.4 Hz, 1H), 7.53 (t, J=8.0 Hz, 1H), 9.41 (s, 1H).

The chemical industry reduces the impact on the environment during synthesis 2-Amino-6-methylbenzonitrile. I believe this compound will play a more active role in future production and life.

Reference:
Patent; SENOMYX, INC.; US2008/306053; (2008); A1;,
Nitrile – Wikipedia,
Nitriles – Chemistry LibreTexts

These common heterocyclic compound, 147754-12-9, name is 4-Fluoro-2-methylbenzonitrile, 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. 147754-12-9

1.35 g 2-methyl-4-fluorobenzonitrile (10mmol) was dissolved in 20 mL of carbon tetrachloride, and 0.25g of p-toluene sulfonic acid (0.015 mmol) and 2.15g N-bromo succinimide (NBS) (12mmol) was added. The reaction was completed after heating for 4 hours, and then cooled to room temperature, filtered, and 20 mL saturated ammonium chloride solution was added and layers were obtained. The organic layer was washed with water and saturated sodium chloride aqueous solution (20 mL * 3) successively to clarification, dried over anhydrous sodium sulfate, filtered, and the solvent was distilled off under reduced pressure, and the obtained crude product was purified by column chromatography (petroleum ether: ethyl acetate = 3: 1) to obtain 2-bromomethyl-4-fluoro-benzonitrile (86percent yield). The 2-bromomethyl-4-fluorobenzonitrile (1.0 mmol) and p-toluidine (1.2mmol) was dissolved in 50 mL of tetrahydrofuran, stirred and heated to 60 ¡ã C under reflux, and was added 0.2g sodium ethoxide (3.0mmol) portionwise, and refluxed further 8 hours. After the reaction was confirmed complete by TLC monitoring, the reaction was cooled to room temperature, concentrated, and added 20 mL ethyl acetate, washed with water and saturated sodium chloride solution (20 mL * 3) successively to clarification, dried over anhydrous sodium sulfate, filtered, and evaporated under reduced pressure to remove the solvent. The resulting crude product was purified by column chromatography (petroleum ether: ethyl acetate = 10: 1) to give the intermediate compound (1.1) 2-(p-methylphenylamino) methyl-4-fluoro-benzonitrile (95percent yield), mass spectrum (ESI +): m/z = 241.4 (M + H) +.

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 147754-12-9.

Reference:
Patent; Institute of Medicinal Biotechnology, Chinese Academy of Medical Sciences; LI, Yanping; LI, Zhuorong; PENG, Zonggen; LI, Jianrui; JIANG, Xinbei; CHEN, Jinhua; JIANG, Jiandong; (30 pag.)EP3339287; (2018); A1;,
Nitrile – Wikipedia,
Nitriles – Chemistry LibreTexts