Month: June 2021

Reference of 1735-88-2, A common heterocyclic compound, 1735-88-2, name is 2-Cyano-N-(4-fluorophenyl)acetamide, molecular formula is C9H7FN2O, 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.

General procedure: By applying a two-steps Gewald synthesis, a mixture of the appropriate 2-cyano-N-(substituted)acetamide (1.0 equiv), cycloheptanone (4.0 equiv), ammonium acetate (1.3 equiv), and glacial acetic acid (3.5 equiv) in benzene (10mL/mmol) was heated at reflux for 16h in a Dean-Stark apparatus. After cooling, the mixture was diluted with CHCl3 and then washed with H2O, 10% NaCO3 solution, and finally H2O. The organic layer was concentrated to dryness to afford the crude Knoevenagel product, which was used directly in the successive step without further purification. Thus, to the crude Knoevenagel product (1.0 equiv) dissolved in EtOH, sulfur (4.0 equiv) and N,N-diethylamine (4.0 equiv) were added. The mixture was maintained at 40-50C for 2h and then concentrated to dryness to yield a residue, which was treated with a mixture of cyclohexane/Et2O and filtered.

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:
Article; Desantis, Jenny; Nannetti, Giulio; Massari, Serena; Barreca, Maria Letizia; Manfroni, Giuseppe; Cecchetti, Violetta; Palu, Giorgio; Goracci, Laura; Loregian, Arianna; Tabarrini, Oriana; European Journal of Medicinal Chemistry; vol. 138; (2017); p. 128 – 139;,
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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. 35202-54-1, name is 4,5-Dimethoxy-1-cyanobenzocyclobutane, This compound has unique chemical properties. The synthetic route is as follows., name: 4,5-Dimethoxy-1-cyanobenzocyclobutane

Plating on LB+agar+kanamycin, static incubation at 37° C. for 24 hours (strain 11216 of nitrilase of recombinant E. coli). (0112) Preculture in 5 ml of LB+kanamycin (50 mg/1), incubation at 37° C., 180 rpm overnight. Culture: transfer 50 ml of LB and 500 mul of preculture to non-baffled 250-ml Erlenmeyer flasks, incubation at 28° C., 160 rpm until the OD is equal to 0.6 (i.e. about 4 hours). (0113) Induction with IPTG (0.5 mM), incubation at 17° C., 160 rpm overnight (17 hours). (0114) Activity test: centrifuge the cultures at 4° C., 6000 rpm for 20 minutes, resuspend the slurry in 10 ml of 0.1M phosphate buffer pH 7. Add bicyclo[4.2.0]octa-1,3,5-triene-7-carbonitrile (10 mM)+2percent ethanol. Incubate at 220 rpm, 30° C. (0115) Note: If the culture is more than 50 ml when centrifuging, take off 50 ml and carry out the activity test using a slurry of 50 ml of culture. (0116) Hydrolysis monitoring by chiral chromatography: at 45 mins and 2 hours. Column: Phenomenex® LUNA HST 50*3 C18(2) 2.5 mum Eluant: A+B (from 0percent to 100percent B over 8 mins) A: 1000 water+25 ACN+1 TFA B: 1000 ACN+25 water+1 TFA 0.8 ml/min?40° C.?UV 210 nm Results: Monitoring by chiral chromatography shows that the reaction is not enantioselective.

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 35202-54-1.

Reference:
Patent; LES LABORATOIRES SERVIER; Pedragosa-Moreau, Sandrine; Lefoulon, Francois; (12 pag.)US9476071; (2016); B2;,
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Electric Literature of 198633-76-0,Some common heterocyclic compound, 198633-76-0, name is 2-Fluoro-6-methylbenzonitrile, molecular formula is C8H6FN, 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 A: 3-bromo-6-fluoro-2-methylbenzonitrile (Method A): Commercially available 2-fluoro-6-methylbenzonitrile (Apollo Scientific, 15.0 g, Ill mmol) was dissolved in triflic acid (75 mL)at 0 C then NBS (20.7 g, 117 mmol) was added. The reaction mixture was stirred at RT for 1 hthen poured into ice water and extracted twice with DCM. The organic layer was washed with brine, dried over Na2S04, then filtered and evaporated to dryness to yield 3-bromo-6-fluoro-2-methylbenzonitrile: LC-MS: M+ 1 = 214, 216.

These compound has a wide range of applications. It is believed that with the continuous development of the source of the synthetic route 2-Fluoro-6-methylbenzonitrile, its application will become more common.

Reference:
Patent; MERCK SHARP & DOHME CORP.; PASTERNAK, Alexander; BLIZZARD, Timothy; CHOBANIAN, Harry; DE JESUS, Reynalda; DING, Fa-Xiang; DONG, Shuzhi; GUDE, Candido; KIM, Dooseop; TANG, Haifeng; WALSH, Shawn; PIO, Barbara; JIANG, Jinlong; WO2013/28474; (2013); A1;,
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Synthetic Route of 874-89-5,Some common heterocyclic compound, 874-89-5, name is 4-(Hydroxymethyl)benzonitrile, molecular formula is C8H7NO, 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: Alcohol, phenol, and/or amine (1 mmol) were added to amixture of the ZnAl2O4SiO2 nanocomposite (100 mg) andacetic anhydride (1 mmol). The mixture was stirred at 75 C(for alcohols and phenols) or at room temperature (for amines)for a time. The progress of the reaction was monitored by TLCand/or GC-MS. When the reaction was completed, ethyl acetate(10 mL) was added and the mixture was filtered to separate offthe catalyst. The catalyst was washed twice with 7.5 mL ethylacetate. The combined organic phases were washed with a10% solution of NaHCO3 and then dried over MgSO4. The solventwas removed to yield the product. If further purificationwas needed, the product was passed through a short column ofsilica gel. All products were characterized on the basis ofGC-MS, FT-IR, and 1H-NMR spectral data by comparing thesespectra with those of standard samples or literature data.

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

Reference:
Article; Farhadi, Saeed; Jahanara, Kosar; Cuihua Xuebao/Chinese Journal of Catalysis; vol. 35; 3; (2014); p. 368 – 375;,
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Related Products of 22972-63-0, 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. 22972-63-0 name is 2-(3,5-Dimethoxyphenyl)-2-methylpropanenitrile, 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.

2-(3,5-dimethoxyphenyl)-2-methylpropanenitrile (10 g, 46.9 mmol, Eq: 1.00) was dissolved in MTBE (50 mL). The clear solution was cooled to 10C and 1 M DIBAL-H in heptane (56.3 mL, 56.3 mmol, Eq: 1.2) was added dropwise over 30 min. The reaction mixture was warmed to 20C over 30 min. After 2 h at 20C, the reaction mixture was added to a cold (0C) mixture of heptane (50 mL) and 2 M aqueous HC1 (100 mL). The water phase was separated and extracted with heptane (50 mL). The organic phases were washed twice sequentially with 2 M aqueous HC1 (2×50 mL), then half saturated aqueous NaHCC>3 (50 mL) and half saturated aqueous NaCl (50 mL). The organic phases were combined, dried over Na2S04, filtered and concentrated under reduced pressure to give 10.3 g of the crude title compound as an oil (97a% GC).

At the same time, in my other blogs, there are other synthetic methods of this type of compound, 2-(3,5-Dimethoxyphenyl)-2-methylpropanenitrile, and friends who are interested can also refer to it.

Reference:
Patent; YISSUM RESEARCH DEVELOPMENT COMPANY OF THE HEBREW UNIVERSITY OF JERUSALEM LTD.; ADAM, Jean-Michel; DOTT, Pascal; HOHLER, Marcus; BURGER, Tanja; TAGLIENTE, Orazio; MISCHLER, Ernst; (49 pag.)WO2018/87767; (2018); A1;,
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Adding a certain compound to certain chemical reactions, such as: 621-50-1, name is 2-(3-Nitrophenyl)acetonitrile, 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 621-50-1, Quality Control of 2-(3-Nitrophenyl)acetonitrile

(3-Nitro-phenyl)-acetonitrile (1.51 g, 9.31 mmol), dimethoxymethyl-dimethyl-andine (6.2 mL, 46.5 mmol) in xylene (30 mL) are stirred at reflux for 1 hour. After adding hexane (20 mL), the reaction mixture is cooled at 0C. Precipitating material is filtered-off to give compound of Stage 52.1 as brown solid (1.76 g, 8.19 mmol ; 88%); ES-MS: M+H = 218. 1; HPLC: tRet = 2.24 minutes. 1H-NMR (300 MHz, DMSO-d6) : 8.10-8. 05 (m, 1H), 7.90-7. 85 (m, 1H), 7.75-7. 72 (m, 1H), 7.70 (s, 1H), 7.65-7. 60 (m, 1H), 3.30 (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, 2-(3-Nitrophenyl)acetonitrile, other downstream synthetic routes, hurry up and to see.

Reference:
Patent; NOVARTIS AG; NOVARTIS PHARMA GMBH; WO2005/70431; (2005); A1;,
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Application of 21803-75-8, The chemical industry reduces the impact on the environment during synthesis 21803-75-8, name is 4-Amino-3-chlorobenzonitrile, I believe this compound will play a more active role in future production and life.

Thionylchloride (15 mL) was dropped into water (60 mL) with stirring and cooling sothat the temperature did not rise above -5C. Copper(I) chloride (19 mg) wasthen added. In parallel, 4-amino-3-chlorobenzonitrile (1.50g, 9.83 mmol) wasdissolved in cone. HCl (30 mL), cooled to -5C whereupon a solution of sodiumnitrite (746 mg, 10.8 mmol) in water (15 mL) was added . After completeaddition the solution of diazonium salt was added in over 2 mins to the firstsolution, both at -5 to OoC (gas evolution was observed) and a foam formed ontop of the solution. The temperature was allowed to come to room temperatureand the aqueous phase was then extracted with DCM (3 x 70 ml). The combinedorganic phase was washed with brine (5 mL), dried (Na2SC>4), themixture filtered and the filtrate evaporated to dryness to afford a yellowsolid containing the title compound (1.88 g, 88%); ‘H NMR (500 MHz, CDC13)delta 7.83 (dd, IH), 7.97 (d, IH), 8.31 (d, IH).

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-Amino-3-chlorobenzonitrile, other downstream synthetic routes, hurry up and to see.

Reference:
Patent; ACTIVE BIOTECH AB; FRITZSON, Ingela; LIBERG, David; EAST, Stephen; MACKINNON, Colin; PREVOST, Natacha; WO2014/184234; (2014); A1;,
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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 6574-97-6 as follows. Recommanded Product: 6574-97-6

EXAMPLE 56C 3-Amino-2-carbomethoxy-7-chloro-benzthiophene The product from Example 56B (1.7 g, 10 mmol) was treated with 1 eq of methyl thioglycolate and 1 eq sodium carbonate in methanol as described in Example 41A to give after chromatography (4:1 hexane/EtOAc) the title compound in 12percent yield. 1H NMR (300 MHz, CDCl3) d 3.81 (s, 3H), 5.90 (bs, 2H), 7.34 (t, J=8 Hz, 1H), 7.48 (dd, J=8.1 Hz, 1H), 7.56 (dd, J=8,1 Hz, 1H). MS (DCI/NH3) m/e 259 (M+NH4)+.

According to the analysis of related databases, 6574-97-6, the application of this compound in the production field has become more and more popular.

Reference:
Patent; Abbott Laboratories; US5597823; (1997); A;,
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Application of 103146-25-4, These common heterocyclic compound, 103146-25-4, name is 4-(4-(Dimethylamino)-1-(4-fluorophenyl)-1-hydroxybutyl)-3-(hydroxymethyl)benzonitrile, 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 solution of Racemic cyanodiol (300g, 0.88 moles) in isopropyl alcohol (1800 ml) at 25-35C (+)-Di-p-toluoyl-D-tartaric acid (169.2g, 0.44 mole) was added. The reaction mixture was then heated and maintained at 60-70 C for lhour. After maintaining was over the reaction mass was cooled and maintained at 28- 32 C for 2-4 hours. The precipitated solid was then filtered, washed with isopropyl alcohol (300 ml) and suck dried for 30minutes. The filtrate was preserved for the recovery of Racemic cyanodiol and (+)-Di-p-toluoyl-D-tartaric acid. The obtained wet cake of (S)-cyanodiol – (+)-DPTTA was suspended in isopropyl alcohol (1200 ml), heated and maintained at 55-65C for 60 minutes. After maintaining was over the reaction mass was cooled to 28-32C where it was maintained for 60 minutes. The precipitated solid was then filtered, washed with isopropyl alcohol (300 ml) and finally dried under vacuum at 60-70 C which provided the title compound (VI) as a white solid. The obtained filtrate was combined with the earlier obtained filtrate for the recovery of Racemic cyanodiol and (+)-Di-p-toluoyl-D-tartaric acid. Yield: 145g (61.96% by Theory) Purity by HPLC: 99.71% Chiral Purity: S-Isomer – 99.59% R-Isomer – 0.41%

Statistics shows that 4-(4-(Dimethylamino)-1-(4-fluorophenyl)-1-hydroxybutyl)-3-(hydroxymethyl)benzonitrile is playing an increasingly important role. we look forward to future research findings about 103146-25-4.

Reference:
Patent; IPCA LABORATORIES LIMITED; REGURI, Buchi Reddy; PRASAD, Ashok; RAWAT, Ajay Singh; RAJPUT, Sandip; SANTAN, Rohit B; (36 pag.)WO2017/9866; (2017); A1;,
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Some common heterocyclic compound, 10412-93-8, name is N-Benzyl-2-cyanoacetamide, molecular formula is C10H10N2O, 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. Product Details of 10412-93-8

General procedure: (E)–aryl–cyanoacrylamides 2 was prepared according to literature procedure.2 General procedure for 2a. To a solution of benzaldehyde (10 mmol 1.0 equiv), pyrrolidine (2 mmol, 20 mol %) in ethanol (20 mL) was added N-benzyl-2-cyanoacetamide (10 mmol, 1.0 equiv). The reaction mixture was stirred at room temperature until the reaction was complete (monitored by TLC), the solvent was removed under reduced pressure. The crude reaction mixture was purified through flash column chromatography on silica gel to afford 2a. 1H NMR (CDCl3, 400 MHz): delta (ppm) 8.68 (s, 1H), 7.78-7.74 (m, 1H), 7.70 (dd, J = 7.6, 1.4 Hz, 1H), 7.43 (t, J = 7.6 Hz, 1H), 7.30 (d, J = 8.0 Hz, 1H); 13C NMR (CDCl3, 100 MHz): delta (ppm) 167.9, 154.4, 137.8, 131.0, 126.4, 118.8, 115.6.

These compound has a wide range of applications. It is believed that with the continuous development of the source of the synthetic route 10412-93-8, its application will become more common.

Reference:
Article; Nie, Xufeng; Wang, Yachuan; Yang, Lijun; Yang, Zaijun; Kang, Tairan; Tetrahedron Letters; vol. 58; 31; (2017); p. 3003 – 3007;,
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