Month: April 2021

Synthetic Route of 630-18-2,Some common heterocyclic compound, 630-18-2, name is Pivalonitrile, molecular formula is C5H9N, 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 title compound is prepared from commercially available materials by those skilled in the art by adaptation of a patent reference (Neighbors et al, US 3,547,621).To a solution of hydroxylamine hydrochloride (6.80 g, 97.9 mmol) in water (15 mL) is added slowly a solution of potassium carbonate (6.15 g, 44.5 mmol) in water (10 mL) and 2,2- dimethyl propionitrile (6.25 g, 89.0 mmol) in ethanol (50 mL). The mixture is stirred at room temperature for 30 min then heated at reflux for 16 h. After this time, dichloromethane (75 mL) and water (50 mL) are added and the aqueous layer is extracted with dichloromethane (3 x 50 mL). The organic layers are combined, washed with brine (20 mL), dried (Na2SO4), filtered and concentrated under reduced pressure to afford the title compound as a white solid (6.15 g, 60%). 1H NMR (400 MHz, CHLOROFORM-d) delta ppm 1.21 (9 H, s), 4.57 (2 H, br. s.), 9.15 (1 H, br. s.).

The synthetic route of 630-18-2 has been constantly updated, and we look forward to future research findings.

Reference:
Patent; BOEHRINGER INGELHEIM INTERNATIONAL GMBH; BOEHRINGER INGELHEIM PHARMA GMBH & CO. KG; WO2009/140089; (2009); A2;,
Nitrile – Wikipedia,
Nitriles – Chemistry LibreTexts

Related Products of 29509-06-6, The chemical industry reduces the impact on the environment during synthesis 29509-06-6, name is 4-Methyl-3-oxopentanenitrile, I believe this compound will play a more active role in future production and life.

7-A. 5-Isopropyl-isoxazol-3-ylamine.; To a mixture of 4-methyl-3-oxopentanenitrile (11 g, 99 mmol) and water (200 mL) is added NaOH (4.95 g, 124 mmol). Once the NaOH pellets are completely dissolved, hydroxylamine sulfate (8.93 g, 109 mmol) is added and after 5 min the pH is measured (pH 7-8). The reaction is warmed to 40 0C and stirred for 72 h. At this point HCI (13.0 mL, 158 mmol, 37%) is added in one portion and the reaction warmed to 50 0C for 2.5 h. The reaction is removed from the oil bath and allowed to cool to rt. At this point a solution of NaOH (30% in H2O) is added to give a solution of pH 1 1. EtOAc is then added and the layers separated. The water layer is extracted with EtOAc (3 x) until no more product appears in the LCMS of the water layer. The combined organics are dried (Na2SO4) and evaporated to give 5-isopropyl- isoxazol-3-ylamine. MS (ESI) m/z 127.2 (M+1 ).

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, 4-Methyl-3-oxopentanenitrile, other downstream synthetic routes, hurry up and to see.

Reference:
Patent; NOVARTIS AG; ARTMAN III, Gerald David; ELLIOTT, Jason Matthew; JI, Nan; LIU, Donglei; MA, Fupeng; MAINOLFI, Nello; MEREDITH, Erik; MIRANDA, Karl; POWERS, James J.; RAO, Chang; WO2010/66684; (2010); A2;,
Nitrile – Wikipedia,
Nitriles – Chemistry LibreTexts

Electric Literature of 16932-49-3, 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. 16932-49-3, name is 2,6-Dimethoxybenzonitrile, This compound has unique chemical properties. The synthetic route is as follows.

General procedure: :2,6-dimethoxybenzonitrile (501 mg, 3.07 mmol) and4-amino-7-chloroquinoline (548 mg, 3.07 mmol) were dissolved together in 20 mLof anhydrous tetrahydrofuran. The vesselwas swept with nitrogen and chilled in an ice-water bath. Ethereal 3.0 M ethyl magnesium bromide (2.05 mL,6.14 mmol) was added dropwise over 3 min.After briefly forming an off-white solid suspended in a yellow solution,within minutes the mixture became a dark amber homogenous solution with someoff-white solid material remaining. Thevessel was placed in a 75 C oil bath for 21 h before diluting with 60 mL ofwater. The pH was decreased to ca. 14 byaddition of 4 pellets of NaOH. Themixture was then extracted with 60 mL of ethyl acetate, using solid NaCl tofacilitate partitioning. The organicswere dried over MgSO4 and concentrated to 1.27 g of a crude brownoily paste containing mostly unreacted starting materials. Flash chromatography (150 mL silica gel, 50%ethyl acetate / hexane, then neat ethyl acetate, then 10% methanol in ethylacetate) returned 100 mg (9.6%) ofN-(7-chloroquinolin-4-yl)-2,6-dimethoxybenzimidamide (G).

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

Reference:
Article; Hershberger, Paul M.; Hedrick, Michael P.; Peddibhotla, Satyamaheshwar; Mangravita-Novo, Arianna; Gosalia, Palak; Li, Yujie; Gray, Wilson; Vicchiarelli, Michael; Smith, Layton H.; Chung, Thomas D.Y.; Thomas, James B.; Caron, Marc G.; Pinkerton, Anthony B.; Barak, Lawrence S.; Roth, Gregory P.; Bioorganic and Medicinal Chemistry Letters; vol. 24; 1; (2014); p. 262 – 267;,
Nitrile – Wikipedia,
Nitriles – Chemistry LibreTexts

Reference of 1835-65-0, A common heterocyclic compound, 1835-65-0, name is 3,4,5,6-Tetrafluorophthalonitrile, molecular formula is C8F4N2, 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.

Synthesis of Exemplified Compounds (P-1-1), (P-2-1), and (P-3-1)Under nitrogen atmosphere, in 50 ml of 1-methyl-2-pyrrolidone, were dissolved 3.0 g (15 mmol) of tetrafluorophthalonitrile, 1.5 g (5.0 mmol) of synthesis intermediate (B), and 0.99 g (10 mmol) of copper chloride (I), and then stirred for 3 hours at 180¡ã C. After cooling the reaction mixture to room temperature, it was poured into 200 ml of a 5percent hydrochloric acid. Consequently, blue crystals were precipitated. These crystals were separated by a filtration under reduced pressure, followed by washing with water and then acetonitrile, and thereafter drying. Further, they were boiled with 50 ml of acetonitrile for 1 hour, and allowed to cool down to room temperature. The resultant precipitates were separated by a filtration under reduced pressure, and then dried. Thereby was obtained 2.2 g (Yield: 45percent) of a mixture (PP-1) (Melting point>200¡ã C.) containing the exemplified compounds (P-1-1), (P-2-1), and (P-3-1) of the present invention; and hexadecafluoro cupper phthalocyanine (F16CuPc).A mixing rate of phthalocyanine derivatives was measured by a liquid chromatography mass spectrometric analysis (LCMS). The result in terms of area ratio was as follows: (P-1-1):(P-2-1):(P-3-1):(F16CuPc)=54.0:26.4:4.1:15.5 (Since a molar absorption intensity of each of (P-1-1), (P-2-1), (P-3-1), and (F16CuPc) at a detecting wavelength of 254 nm is almost same, the ratio measured from the area results in equal to a molar ratio.).Measuring conditions: TSK gel ODS-80Ts (2 mm Phi.x.150 mm), elute: a mixed solution of A/B (volume ratio 3:7) from 0 minute to 15 minutes, and a mixed solution of A/B (volume ratio 15:85) from 15 minutes to 20 minutes) (elute A: water, elute B: a mixed solution of tetrahydrofuran/methanol (volume ratio 9:1)), flow rate: 0.2 ml/min, a detecting wavelength 254 nm, structural determination by atmospheric pressure chemical ionization (APCI)-mass spectrometry (MS) (It was confirmed using MS that a peak at the retention time=8.185 minutes was (F16CuPc), a peak at the retention time=11.676 minutes was (P-1-1), a peak at the retention time=13.905 minutes was (P-2-1), and a peak at the retention time=14.350 minutes was (P-3-1)). A peak was detected in the blank at the retention time of from 0 to 4 minutes, so that a measurement was started from 4 minutes.

The synthetic route of 1835-65-0 has been constantly updated, and we look forward to future research findings.

Reference:
Patent; FUJIFILM Corporation; US7947826; (2011); B2;,
Nitrile – Wikipedia,
Nitriles – Chemistry LibreTexts

Synthetic Route of 796600-15-2, A common heterocyclic compound, 796600-15-2, name is 2-Chloro-4-fluoro-3-methylbenzonitrile, molecular formula is C8H5ClFN, 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.

Examples 11 and 12Example 11 Example 12 11a to l ib(R)-2-(3 -chloro-4-cyano-2-methylphenylamino)-3 -hydroxypropanoic acidTo a stirred solution of 2-chloro-4-fluoro-3-methylbenzonitrile (1 la) (1.0 gm, 5.8 mmol) in DMSO (10 mL), D-Serine (1.4 gm, 13.3 mmol) was added followed by K2C03 (1.7 gm, 12.3 mmol) at room temperature. The resulting reaction mixture was heated to 90C for 12 h. After completion of reaction (by TLC), the reaction mixture was poured into ice-cold water (300 mL) and extracted with EtOAc (100 mL). The aqueous layer was acidified with citric acid (pH ~3) and extracted with EtOAc (2 x 100 mL). The combined organic extracts were dried over Na2S04, and concentrated under reduced pressure to afford the acid 1 lb (0.3 gm, crude) as off- white solid. The crude material was taken for the next step without purification.TLC: 10% MeOH/DCM (Rf: 0.2)1H NMR (500MHz, DMSO-c?, delta in ppm): 8.2-10.2 (br s, 1H), 7.54 (d, J= 8.5 Hz, 1H), 6.57 (d, J= 9.0 Hz, 1H), 5.79 (d, J= 7.5 Hz, 1H), 4.20 (t, J= 3.0 Hz, 1H), 3.86-3.79 (m, 2H), 3.22 (br s, 1H), 2.25 (s, 3H).

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; RADIUS HEALTH, INC.; MILLER, Chris, P.; WO2012/47617; (2012); A1;,
Nitrile – Wikipedia,
Nitriles – Chemistry LibreTexts

Reference of 2338-75-2,Some common heterocyclic compound, 2338-75-2, name is 4-(Trifluoromethyl)phenylacetonitrile, molecular formula is C9H6F3N, 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 50 mL of anhydrous ethnol was added NaOH (160 mg,4 mmol), 2-formyl pyrrole (380.4 mg, 4 mmol) and 4-trifluoromethyl benzyl cyanide (624 muL, 4 mmol). The reaction was heated to reflux with stirring for 3 h. After cooled to room temperature, the reaction solution was evaporated in vacuum. The residue was purified by silica gel column (hexane:ethyl actate = 40: 1) to give 10b as yellow solid ( 596 mg, 56.9%). 1H NMR (400MHz, CDCl3), delta 9.82 (s, 1H), 7.70-7.65 (m, 4H), 7.48 (s, 1H), 7.12-7.11 (dd, J = 4.0, 2.7Hz, 1H), 6.77-6.76 (m, 1H), 6.40-6.37 (dt, J = 3.7, 2.5 Hz, 1H).

The synthetic route of 2338-75-2 has been constantly updated, and we look forward to future research findings.

Reference:
Article; Chen, Ji-An; Zhang, Zhen-Yu; Gao, Jie; Tan, Jia-Hui; Gu, Xian-Feng; Tetrahedron Letters; (2019);,
Nitrile – Wikipedia,
Nitriles – Chemistry LibreTexts

Reference of 59997-51-2, 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. 59997-51-2, name is 4,4-Dimethyl-3-oxopentanenitrile belongs to nitriles-buliding-blocks compound, it is a common compound, a new synthetic route is introduced below.

Step j03:[0668]At room temperature 4,4-dimethyl-3-oxopentanenitrile (J-II) (1 equivalents, 5 g) was taken up in ethanol (100 mL), mixed with hydrazine hydrate (2 equivalents, 4.42 g) and refluxed for 3 h. The residue obtained after removal of the ethanol by distillation was taken up in water (100 mL) and extracted with ethyl acetate (300 mL). The combined organic phases were dried over sodium sulfate, the solvent was removed under vacuum and the product (JAI) (5 g, 89% yield) was obtained as a light red solid after recrystallisation from n-hexane (200 mL).

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

Reference:
Patent; Gruenenthal GmbH; FRANK, Robert; BAHRENBERG, Gregor; CHRISTOPH, Thomas; LESCH, Bernhard; LEE, Jeewoo; US2013/29962; (2013); A1;,
Nitrile – Wikipedia,
Nitriles – Chemistry LibreTexts

Adding a certain compound to certain chemical reactions, such as: 868-54-2, name is 2-Aminoprop-1-ene-1,1,3-tricarbonitrile, 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 868-54-2, name: 2-Aminoprop-1-ene-1,1,3-tricarbonitrile

General procedure: Et3N (0.3 mmol) was added to a stirred solution of salicylaldehyde (3 mmol), 2-aminoprop-1-ene-1,1,3-tricarbonitrile (3 mmol) and 3-trifluoromethyl-2-pyrazolin-5-one in 5 ml of n-PrOH at ambient temperature. Then mixture was refluxed for 4 h. After the reaction was finished and cooled the solid was filtered and dried to isolate pure substituted 2,4-diamino-5-(5-hydroxy-3-(trifluoromethyl)-1H-pyrazol-4-yl)-5H-chromeno[2,3-b]pyridine-3-carbonitrile. In some cases cristallisation from EtOH-DMSO is needed.

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:
Article; Elinson, Michail N.; Vereshchagin, Anatoly N.; Anisina, Yuliya E.; Fakhrutdinov, Artem N.; Goloveshkin, Alexander S.; Egorov, Mikhail P.; Journal of Fluorine Chemistry; vol. 213; (2018); p. 31 – 36;,
Nitrile – Wikipedia,
Nitriles – Chemistry LibreTexts

Reference of 63968-85-4,Some common heterocyclic compound, 63968-85-4, name is 2-(Trifluoromethoxy)benzonitrile, molecular formula is C8H4F3NO, 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 a mixture of2-(trifluoromethoxy)benzonitrile (0.342 mL, 1.999 mmol) and sodium borodeuteride (192mg, 4.60 mmol) in THF (10 mL) at 0 C was added over 45 mm, iodine (507 mg, 1.999mmol) as a solution in THF (4 ml). The reaction mixture was refluxed for 2 h. At thistime, it was cooled to 0 C and 6 N HC1 (2 ml) was carefully added. This mixture wasrefluxed for 30 mm. After cooling to rt, the mixture was partitioned between EtOAc (40ml) and iN NaOH (40 ml). The organic layer was washed with water (20 ml) and brine(20 ml). After drying (Na2504) and filtration, the organic layer was concentrated toafford 2-(trifluoromethoxy)dideuterobenzylammne (385 mg, 1.993 mmol, 100 % yield) asa light yellow oil. The material was impure and was used crude in the coupling step.

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

Reference:
Patent; BRISTOL-MYERS SQUIBB COMPANY; GUO, Junqing; HART, Amy, C.; MACOR, John, E.; MERTZMAN, Michael, E.; PITTS, William, J.; SPERGEL, Steven, H.; WATTERSON, Scott, Hunter; ANDAPPAN MURUGAIAH SUBBAIAH, Murugaiah; CHEN, Jie; DZIERBA, Carolyn, Diane; LUO, Guanglin; SHI, Jianliang; SIT, Sing-Yuen; (428 pag.)WO2018/148626; (2018); A1;,
Nitrile – Wikipedia,
Nitriles – Chemistry LibreTexts

Application of 60710-80-7, A common heterocyclic compound, 60710-80-7, name is 3-Amino-4-methylbenzonitrile, molecular formula is C8H8N2, 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.

To a suspension of imidazo[1 ,2-a]pyridine-3-carboxylic acid (1 ) (16.6 g, 102 mmol) in dichloromethane (300 mL) and DMF (0.5 mL) at 0 C was added oxalyl chloride (45 mL, 510 mmol) dropwise over 10 minutes. The reaction was slowly warmed to room temperature and stirred until complete conversion was detected by LCMS in MeOH. The reaction was subsequently reduced to dryness and suspended in dichloroethane (100 mL) and was added to a solution of 3-amino-4-methylbenzonitrile (7) (15 g, 1 13 mmol) in dichloroethane (200 ml_) and Pr2NEt (55 ml_) at 0 C. After the addition, the cold bath was removed and contents were stirred at room temperature for 1 hour and then heated to 50 C for another 2 hours. After the completion of the reaction, the mixture was cooled and a white precipitate formed. The mixture was filtered and the solid was washed with cold dichloromethane. About 10 g of the desired N-(5-cyano-2- methylphenyl)imidazo[1 ,2-a]pyridine-3-carboxamide (8) was obtained. The filtrate was washed with saturated NH4CI, saturated NaHC03, brine, dried over magnesium sulfate, filtered and reduced to dryness. The crude solid was triturated with diethyl ether to remove excess aniline and filtered to afford another crop of N-(5-cyano-2- methylphenyl)imidazo[1 ,2-a]pyridine-3-carboxamide (8) as a white solid. MS m/z 277.1 (M+1 ).

The synthetic route of 60710-80-7 has been constantly updated, and we look forward to future research findings.

Reference:
Patent; IRM LLC; LOREN, Jon; LI, Xiaolin; LIU, Xiaodong; MOLTENI, Valentina; NABAKKA, Juliet; NGUYEN, Bao; PETRASSI, Hank Michael James; YEH, Vince; RUCKER, Paul Vincent; WO2013/33203; (2013); A1;,
Nitrile – Wikipedia,
Nitriles – Chemistry LibreTexts