Tag: M.W=100-200

Adding a certain compound to certain chemical reactions, such as: 75279-55-9, name is 2-Chloro-6-fluorophenylacetonitrile, 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 75279-55-9, HPLC of Formula: C8H5ClFN

General procedure: A mixture of 15.3 g (100 mmol) of 2-(2,6difluorophenyl)acetonitrile, 152.5 g (70 mL, 812 mmol) of dibromoethane, and 32.7 g (144 mmol) of Et3BnN+Cl- was isolated from moisture and carbon dioxide and vigorously stirred at 60. A solution prepared from 95 g (1430 mmol, ?84.5%) of KOH and 95 mL of water was then added dropwise; the mixture was stirred during 6 h at 60-65C, and left overnight. On the next day, the reaction mixture was extracted with t-BuOMe (3×100 mL), the combined organic fractions were evaporated, and residual water was removed via azeotropic distillation with toluene. Then 60 mL of water and 40 mL of concentrated sulfuric acid were added to the obtained 1-(2,6-difluorophenyl)cyclopropanecarbonitrile, and the mixture was refluxed during 4 h. The reaction mass was cooled to ambient; the precipitate was filtered off and dried. Yield 17.82 g (90%), mp 156-157 (toluene).

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

Reference:
Article; Novakov; Yablokov; Navrotskii; Mkrtchyan; Vernigora; Babushkin; Kachala; Ruchko; Russian Journal of General Chemistry; vol. 87; 2; (2017); p. 224 – 230; Zh. Obshch. Khim.; vol. 87; 2; (2017); p. 247 – 254,8;,
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Electric Literature of 658-99-1,Some common heterocyclic compound, 658-99-1, name is 2-(3,4-Difluorophenyl)acetonitrile, molecular formula is C8H5F2N, 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.

Step 1: Methyl 4-cyano-4-(3,4-difluorophenyl)-3-(3-fluorophenyl)butanoate Under protective gas (Ar), 3.828 g (25.0 mmol) of (3,4-difluorophenyl)acetonitrile and 0.281 mg of potassium tert-butoxide were added to 4.099 g (22.7 mmol) of methyl 3-(3-fluorophenyl)acrylate in 25.0 ml of toluene, and the mixture was stirred in a closed vessel at 65 C. for 5 h. The solvent was removed under reduced pressure, the residue was taken up in ethyl acetate and the mixture was washed twice with in each case 25 ml of water. The combined organic phases were dried over sodium sulphate and the solvent was removed under reduced pressure. Chromatography of the residue on silica gel (ethyl acetate/heptane=20:80) gave 7.3 g (87% of theory) of the diastereomeric methyl 4-cyano-4-(3,4-difluorophenyl)-3-(3-fluorophenyl)butanoate (erythro:threo=65:35 according to integration of the methyl singlets in the 1H-NMR in CDCl3 at 3.68 and 3.59 ppm).

These compound has a wide range of applications. It is believed that with the continuous development of the source of the synthetic route 2-(3,4-Difluorophenyl)acetonitrile, its application will become more common.

Reference:
Patent; BAYER INTELLECTUAL PROPERTY GMBH; Mosrin, Marc; Jakobi, Harald; Angermann, Alfred; Gatzweiler, Elmar; Haeuser-Hahn, Isolde; Heinemann, Ines; Rosinger, Christopher Hugh; Lehr, Stefan; Schnatterer, Stefan; US2014/235446; (2014); A1;,
Nitrile – Wikipedia,
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Electric Literature of 17626-40-3, 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 17626-40-3 as follows.

Step 1 : 1 H-Benzo[dlimidazole-5-carbonitrile3,4-Diaminobenzonitrile (5.0 g; 37 mmol) was dissolved in 5 N HCI (200 ml). After addition of formic acid (20 ml) the mixture was heated to reflux for 3 h. After cooling to room temperature, the mixture was basified by means of aqueous NH3-solution and put into a fridge. The precipitated solid was collected by filtration, washed with water and used without further purification. Yield: 3.6 g (67.6%) MS m/z: 144.2 [M+H]+

According to the analysis of related databases, 17626-40-3, the application of this compound in the production field has become more and more popular.

Reference:
Patent; PROBIODRUG AG; HEISER, Ulrich; RAMSBECK, Daniel; HOFFMANN, Torsten; BOEHME, Livia; DEMUTH, Hans-Ulrich; WO2011/107530; (2011); A2;,
Nitrile – Wikipedia,
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These common heterocyclic compound, 77326-36-4, name is 2-Amino-6-fluorobenzonitrile, 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. Quality Control of 2-Amino-6-fluorobenzonitrile

[6-(4-Methyl-piperazin-1-yl)-1H-benzimidazol-2-yl]-acetic acid ethyl ester (250 g, 820 mmol) (dried with ethanol as described above) was dissolved in THF (3800 mL) in a 5000 mL flask fitted with a condenser, mechanical stirrer, temperature probe, and purged with argon. 2-Amino-6-fluoro-benzonitrile (95.3 g, 700 mmol) was added to the solution, and the internal temperature was raised to 40 C. When all the solids had dissolved and the solution temperature had reached 40 C., solid KHMDS (376.2 g, 1890 mmol) was added over a period of 5 minutes. When addition of the potassium base was complete, a heterogeneous yellow solution was obtained, and the internal temperature had risen to 62 C. After a period of 60 minutes, the internal temperature decreased back to 40 C., and the reaction was determined to be complete by HPLC (no starting material or uncyclized intermediate was present). The thick reaction mixture was then quenched by pouring i into H2O (6000 mL) and stirring the resulting mixture until it had reached room temperature. The mixture was then filtered, and the filter pad was washed with water (1000 mL 2×). The bright yellow solid was placed in a drying tray and dried in a vacuum oven at 50 C. overnight providing 155.3 g (47.9%) of the desired 4-amino-5-fluoro-3-[6-(4-methyl-piperazin-1-yl)-1H-benzimidazol-2-yl]-1H-quinolin-2-one.Procedure B A 5000 mL 4-neck jacketed flask was equipped with a distillation apparatus, a temperature probe, a N2 gas inlet, an addition funnel, and a mechanical stirrer. [6-(4-Methyl-piperazin-1-yl)-1H-benzimidazol-2-yl]-acetic acid ethyl ester (173.0 g, 570 mmol) was charged into the reactor, and the reactor was purged with N2 for 15 minutes. Dry THF (2600 mL) was then charged into the flask with stirring. After all the solid had dissolved, solvent was removed by distillation (vacuum or atmospheric (the higher temperature helps to remove the water) using heat as necessary. After 1000 mL of solvent had been removed, distillation was stopped and the reaction was purged with N2. 1000 mL of dry THF was then added to the reaction vessel, and when all solid was dissolved, distillation (vacuum or atmospheric) was again conducted until another 1000 mL of solvent had been removed. This process of adding dry THF and solvent removal was repeated at least 4 times (on the 4th distillation, 60% of the solvent is removed instead of just 40% as in the first 3 distillations) after which a 1 mL sample was removed for Karl Fischer analysis to determine water content. If the analysis showed that the sample contained less than 0.20% water, then reaction was continued as described in the next paragraph. However, if the analysis showed more than 0.20% water, then the drying process described above was continued until a water content of less than 0.20% was achieved. After a water content of less than or about 0.20% was achieved using the procedure described in the previous paragraph, the distillation apparatus was replaced with a reflux condenser, and the reaction was charged with 2-amino-6-fluoro-benzonitrile (66.2 g, 470 mmol)(in some procedures 0.95 equivalents is used). The reaction was then heated to an internal temperature of 38-42 C. When the internal temperature had reached 38-42 C., KHMDS solution (1313 g, 1.32 mol, 20% KHMDS in THF) was added to the reaction via the addition funnel over a period of 5 minutes maintaining the internal temperature at about 38-50 C. during the addition. When addition of the potassium base was complete, the reaction was stirred for 3.5 to 4.5 hours (in some examples it was stirred for 30 to 60 minutes and the reaction may be complete within that time) while maintaining the internal temperature at from 38-42 C. A sample of the reaction was then removed and analyzed by HPLC. If the reaction was not complete, additional KHMDS solution was added to the flask over a period of 5 minutes and the reaction was stirred at 38-42 C. for 45-60 minutes (the amount of KHMDS solution added was determined by the following: If the IPC ratio is <3.50, then 125 mL was added; if 10.0IPC ratio 3.50, then 56 mL was added; if 20.0IPC ratio 10, then 30 mL was added. The IPC ratio is equal to the area corresponding to 4-amino-5-fluoro-3-[6-(4-methyl-piperazin-1-yl)-1H-benzimidazol-2-yl]-1H-quinolin-2-one) divided by the area corresponding to the uncyclized intermediate). Once the reaction was complete (IPC ratio >20), the reactor was cooled to an internal temperature of 25-30 C., and water (350 mL) was charged into the reactor over a period of 15 minutes while maintaining the internal temperature at 25-35 C. (in one alternative, the reaction is conducted at 40 C. and water is added within 5 minutes. The quicker quench reduces the amount of impurity that forms over time). The reflux condenser was then replaced with a distillation apparatus and solvent was removed by distillation (vacuum or atmospheric) using heat as required. After 1500 mL of solvent had been removed, distillation was disc…

The synthetic route of 2-Amino-6-fluorobenzonitrile has been constantly updated, and we look forward to future research findings.

Reference:
Patent; Novartis AG; US2008/293738; (2008); A1;,
Nitrile – Wikipedia,
Nitriles – Chemistry LibreTexts

Electric Literature of 72291-30-6, The chemical industry reduces the impact on the environment during synthesis 72291-30-6, name is Methyl 2-cyano-2-methylpropanoate, I believe this compound will play a more active role in future production and life.

A mixture of cyano-dimethyl-acetic acid methyl ester (5 g, 39.4 mmol), Boc anhydride (17.2 g, 78.7 mmol), and NiCl2 (0.51 g, 3.94 mmol) in MeOH (200 mL) was cooled in an ice bath. NaBH4 (10.4 g, 276 mmol) was slowly added over 1 h at 0C, and the resulting mixture was stirred at r.t. for 16 h. Diethylenetriamine (4.3 mL, 39.4 mmol) was then added, and the mixture was stirred for 30 min. The solvent was evaporated, and the residue was partitioned between EtOAc (200 mL) and saturated NaHCC>3 (400 mL). The aqueous layer was extracted with additional EtOAc, and the organic layers were combined, dried over MgSO/t, and concentrated. The crude product was purified by column chromatography (0-40% EtOAc/hexanes) to give 2.5 g of the title compound as a clear oil. H NMR (CDCI3, 200 MHz): 8ppm= 4.95 (br s, 1H), 3.69 (s, 3H), 3.24 (d, 2H, J= 6.6 Hz), 1.44 (s, 9H), 1.20 (s, 6H).

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, Methyl 2-cyano-2-methylpropanoate, other downstream synthetic routes, hurry up and to see.

Reference:
Patent; FIBROGEN, INC.; HO, Wen-Bin; ZHAO, Hongda; DENG, Shaojiang; NG, Danny; WRIGHT, Lee R.; WU, Min; ZHOU, Xiaoti; AREND, Michael P.; FLIPPIN, Lee A.; WO2013/134660; (2013); A1;,
Nitrile – Wikipedia,
Nitriles – Chemistry LibreTexts

Related Products of 67515-59-7, A common heterocyclic compound, 67515-59-7, name is 4-Fluoro-3-(trifluoromethyl)benzonitrile, molecular formula is C8H3F4N, 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-fluoro-3-(trifluoromethyl)benzonitrile (1 g; 5.29 mmol; 1 eq.) and (S)-(+)-2-methylpiperidine (3.1 ml 26.4 mmol; 5 eq.) in DMSO (10 ml.) were heated at 10O0C under nitrogen for 12h. The reaction mixture was then diluted in EtOAc, washed with water, NaHCO3 sat and NH4CI sat. The organic phase was dried over MgSO4, filtered and evaporated under vacuum to give a yellow oil, that was submitted to the next step without further purification. LC/MS (Method B): 269.0 (M+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; MERCK SERONO S.A.; MUZERELLE, Mathilde; QUATTROPANI, Anna; MONTAGNE, Cyril; DORBAIS, Jerome; WO2010/69949; (2010); A1;,
Nitrile – Wikipedia,
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Related Products of 60899-34-5,Some common heterocyclic compound, 60899-34-5, name is 1-Oxo-2,3-dihydro-1H-indene-4-carbonitrile, molecular formula is C10H7NO, 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 stirred mixture of 1 -oxo-2,3 -dihydro- 1 H-indene-4-carbonitrile (mt 1) (20.Og, 98 wt%, 18.6 assay g, 124.8 mmol) in abs EtOH (20 mL), triethylorthoformate (80 mL, 481 mmol) and methanesulfonic acid (0.88 mL, 12.5 mmol) in toluene (80 mL)was heated at 43 -47C. After 1 h, GC analysis showed orthoformate consumed and 12.8 area% of mt 1 remaining. A further charge of triethylorthoformate (20 mL, 120.2 mmol) was made and after 45 mm GC analysis showed 1.5 area% mt 1. The batch was cooled to ambient temperature and then poured into 1 M aq. K2HPO4 (200 mL) with vigorous stirring while maintaining a quench temperature < 15 C. The two-phasemixture was vigorously stirred for 10 mm. The phases were separated and the aqueous phase (pH 11) was back extracted with toluene (100 mL). The organic phases were combined and distilled at atmospheric pressure to remove 340 mL distillate. Toluene was added (500 mL) and distilled at atmospheric pressure to remove 500 mL distillate. Total distillation time 3 h, temperature range 80-120 C. At this point the batch wasstored overnight at < 5 C. Excess orthoformate was removed by chasing with ethyl acetate (100 mL) under reduced pressure until distillation stopped. Another volume of ethyl acetate (100 mL) was added and then concentrated under reduced pressure until distillation stopped. A third volume of ethyl acetate (100 mL) was added and then concentrated under reduced pressure until distillation stopped, after which GC analysisconfirmed no orthoformate remaining. The crude was then stirred at 110 C for 1 h, to convert the intermediate ketal to 3-ethoxy-1H-indene-7-carbonitrile (mt 2). Upon cooling, the crude (mobile oil, 21.34 g) was assayed for mt 2 by ?H NIVIR employing mesitylene as an internal standard. The oil assayed at 78.1 wt% product = 16.73 assay g, 90.0 mmol = 72.1 % assay yield. The crude oil was then purified by filtration througha silica gel plug eluting with 15% EtOAc/hexane. The pure fractions were combined and utilized for the next step. ?H NIVIR (400 MHz, d6-DMSO) 7.78 (d, J = 8.4, 1H), 7.63 (m, 1H), 7.49 (m, 1H), 5.60 (m, 1H), 1.38 (t, J= 6.8 Hz, 1H), 1.19 (t, J= 6.8 Hz, 1H); LRMS: calcd for C,2H,2NO [M + H]: 186.2; Found: 186.2. These compound has a wide range of applications. It is believed that with the continuous development of the source of the synthetic route 1-Oxo-2,3-dihydro-1H-indene-4-carbonitrile, its application will become more common. Reference:
Patent; CELGENE INTERNATIONAL II SARL; MEADOWS, Kristen, R., Taylor; SKOLNICK, Brett; DALVIE, Deepak; (78 pag.)WO2018/208855; (2018); A1;,
Nitrile – Wikipedia,
Nitriles – Chemistry LibreTexts

Adding a certain compound to certain chemical reactions, such as: 29509-06-6, name is 4-Methyl-3-oxopentanenitrile, 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 29509-06-6, Quality Control of 4-Methyl-3-oxopentanenitrile

A mixture of a portion (0.6 g) of the material so obtained, hydrazine hydrate (0.288 ml) and ethanol (45 ml) was heated at 700C for 12 hours. The solvent was evaporated and the residue was purified by column chromatography on silica using a 19:1 mixture of methylene chloride and methanol as eluent. There was thus obtained the required starting material (0.574 g); 1H NMR: (DMSOd6) 1.13 (d, 6H), 2.76 (m, IH), 4.31 (br s, 2H), 5.17 (br s, IH), 11.05 (br s, IH); Mass Spectrum: M+H+ 126.

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; ASTRAZENECA AB; ASTRAZENECA UK LIMITED; WO2007/99317; (2007); A1;,
Nitrile – Wikipedia,
Nitriles – Chemistry LibreTexts

Related Products of 610-66-2,Some common heterocyclic compound, 610-66-2, name is 2-(2-Nitrophenyl)acetonitrile, molecular formula is C8H6N2O2, 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.

General procedure: To a solution of the correspongding catalyst 4k (5 mol%), K2CO3 (2 equiv) and 2-(2-nitrophenyl)acetonitrile (0.10 mmol) in CH2Cl2 (1.0 mL), and then was cooled to -20 C before the imines (0.12 mmol) was introduced. When the reaction was finished (determined by TLC analysis), the crude mixture was warmed to room temperature and purified by flash column chromatography (silica gel: petroleum ether/AcOEt = 5:1) to afford the products

These compound has a wide range of applications. It is believed that with the continuous development of the source of the synthetic route 2-(2-Nitrophenyl)acetonitrile, its application will become more common.

Reference:
Article; Pan, Renming; Zhang, Jiaxing; Zheng, Changwu; Wang, Hongyu; Cao, Dongdong; Cao, Weiguo; Zhao, Gang; Tetrahedron; vol. 73; 17; (2017); p. 2349 – 2358;,
Nitrile – Wikipedia,
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Electric Literature of 22364-68-7, 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. 22364-68-7 name is 2-(o-Tolyl)acetonitrile, 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.

EXAMPLE 5; Preparation of(Z)-2-(2-Methyl-phenyl)-3-(1H-pyrrol-2-yl)acryIonitrile Under High PressureA thick walled tube was charged with 1 H-pyrrole-2-carbaldehyde (2.0 g, 21.0 mmol), 2-methylphenyIacetonitrile (2.5 g, 18.9 mmol, 0.9 equivalents), ethanol (75 ml), and 40% aqueous Triton B (4.0 ml, 3.3 mmol). The tube was EPO sealed and heated to 90 0C for 4 days. Removal of the solvent, followed by chromatography on silica gel using dichloromethane/petroleum spirits (20:80) as eluant afforded a yellow solid (1.2 g). This is Compound 16 in Table 8.

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

Reference:
Patent; SCHERING-PLOUGH LTD.; WO2006/55565; (2006); A2;,
Nitrile – Wikipedia,
Nitriles – Chemistry LibreTexts