Category: nitriles-buliding-blocks

Researchers who often do experiments know that organic synthesis is a process of preparing more complex target molecules from simple raw materials through one or more chemical reactions. Generally, it requires fewer steps, and cheap raw materials. 90381-43-4, name is 7-Methoxy-2-naphthonitrile, A new synthetic method of this compound is introduced below., Quality Control of 7-Methoxy-2-naphthonitrile

EXAMPLE 185A 7-methoxy-2-cyanonaphthalene, (2.79 g, 5.23 mmol) and tetrabutylammonium iodide (17 mg, 0.157 mmol) were combined in a mixture of benzene (35 mL) and cyclohexanes (17.5 mL). The resulting solution was added to a rapidly stirring, cooled (ice/water) suspension of aluminum triiodide (6.21 g, 15.23 mmol) in a mixture of benzene (35 mL) and cyclohexanes (17.5 mL) under an inert atmosphere. After the addition, the resulting suspension was heated at reflux for 2.5 hours. The heating was removed and after cooling to near room temperature, the reaction mixture was cooled in an ice bath and quenched by the addition of water (100 mL). The resulting mixture was further diluted with 2 M aqueous sodium thiosulfate solution (50 mL) and extracted with ethyl acetate (3*80 mL). The combined organic layers were dried and evaporated. The resulting solid was dissolved in a minimum of hot ethyl acetate, diluted hot with hexanes to the cloud point and placed in a refrigerator for 2 hours. The desired compound was collected by filtration, (1.99 g, 77%). MS (DCI (NH3)) m/z 187 (M+NH4)+.

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; Abbott Laboratories; US6258822; (2001); B1;; ; Patent; Abbott Laboratories; US6284796; (2001); B1;,
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Electric Literature of 874-97-5, 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. 874-97-5 name is 3-Cyanobenzyl alcohol, 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.

Step e 3-(4-MethoxytrityloxymethvObenzonitrile (Ie”)3-(Hydroxymethyl)benzonitrile (2 g, 15 mmol) was dissolved in dry pyridine (120 ml). 4- methoxytrityl chloride (6 g, 19.5 mmol) was added and the mixture was stirred over night at room temperature (r.t.). The reaction was quenched with ethanol (EtOH), evaporated on rotavapor and the residue partitioned between dichloromethane (DCM) and saturated aqueous sodium bicarbonate. The organic phase was dried by sodium sulphate and evaporated. Silica gel column chromatography (gradient 30%DCM / hexane – DCM) gave the title compound (5.98 g,98%).1H-NMR (400MHz, CDCl3): delta 7.70-7.25 (m, 16H), 6.85 (d, 2H), 4.23 (s, 2H), 3.81 (s, 3H).

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

Reference:
Patent; MEDIVIR AB; WO2008/135488; (2008); A1;,
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Electric Literature of 4513-77-3, 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. 4513-77-3, name is 2-Oxocyclohexanecarbonitrile belongs to nitriles-buliding-blocks compound, it is a common compound, a new synthetic route is introduced below.

General procedure: A solution of 2-oxocyclohexanecarbonitrile (59, 2.57 g, 20.9 mmol) and ethyl hydrazineoxalate (60, 4.70 g, 31.3 mmol) in ethanol(40 mL) was stirred at reflux for 18 h, cooled to room temperature and thesolvent removed under reduced pressure.The residue was diluted with methylene chloride (150 mL) and saturatedaqueous sodium bicarbonate (100 mL) was added.The organic layer was separated and the aqueous layer was furtherextracted with methylene chloride (2 ×100 mL).The combined organic layers were washed with brine (50 mL), dried (MgSO4),filtered and concentrated under reduced pressure. The resulting residue was further purified byflash column chromatography on silica gel, eluting with methanol/methylenechloride (gradient of 2:98 to 4:96) to afford 2-ethyl-4,5,6,7-tetrahydro-2H-indazol-3-amine (61) as a while solid(2.73 g, 79%)

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

Reference:
Article; Rynearson, Kevin D.; Buckle, Ronald N.; Barnes, Keith D.; Herr, R. Jason; Mayhew, Nicholas J.; Paquette, William D.; Sakwa, Samuel A.; Nguyen, Phuong D.; Johnson, Graham; Tanzi, Rudolph E.; Wagner, Steven L.; Bioorganic and Medicinal Chemistry Letters; vol. 26; 16; (2016); p. 3928 – 3937;,
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Application of 21524-39-0, The chemical industry reduces the impact on the environment during synthesis 21524-39-0, name is 2,3-Difluorobenzonitrile, I believe this compound will play a more active role in future production and life.

A mixture of 3 -methyl- lH-pyrazole-4-carboxylic acid ethyl ester (1.25 g, 8.1 1 mmol), potassium carbonate (1.68 g, 12.16 mmol), 2,3-difluorobenzonitrile (1.08 mL, 9.73 mmol) in dimethylformamide (12 mL) is heated at 100C with the aid of a magnetic stirred. After 2.5 hr. the reaction mixture is treated with water and extracted with ethyl acetate. The organic layer is decanted, washed with brine, dried over magnesium sulfate and the solvent evaporated under reduced pressure to give 2.3 g of l-(2-cyano-6-fluoro- phenyl)-3 -methyl- lH-pyrazole-4-carboxylic acid ethyl ester (this compound is contaminated with the other pyrazole regioisomer in a ratio 75:25). MS (m/z): 274 (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, 2,3-Difluorobenzonitrile, other downstream synthetic routes, hurry up and to see.

Reference:
Patent; ELI LILLY AND COMPANY; BENITO COLLADO, Ana Belen; DIAZ BUEZO, Nuria; JIMENEZ-AGUADO, Alma Maria; LAFUENTE BLANCO, Celia; MARTINEZ-GRAU, Maria Angeles; PEDREGAL-TERCERO, Concepcion; TOLEDO ESCRIBANO, Miguel Angel; WO2011/60217; (2011); A1;,
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Reference of 179898-34-1, A common heterocyclic compound, 179898-34-1, name is 3-Bromo-5-fluorobenzonitrile, molecular formula is C7H3BrFN, 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 18 1,1-Dimethylethyl [(3-bromo-5-fluorophenyl)methyl]carbamate NaBH4 (1.99 g, 52.5 mmol) was cautiously added to a solution of NiCl2 (1.36 g, 10.5 mmol), Boc2O (4.58 g, 21.0 mmol) and 3-bromo-5-fluorobenzonitrile (2.10 g, 10.5 mmol) in absolute ethanol (30 mL) at 0 C. (vigorous reaction with the formation of a black precipitate). Once the reaction had subsided the mixture was left to stir at room temperature for 30 min. Ethanol was removed under reduced pressure and the precipitate was dissolved in EtOAc, filtered and repeatedly washed with EtOAc. The combined organic phase was washed with saturated NaHCO3, and dried over Na2SO4. After removing the solvent, the product was purified by flash column chromatography to yield 1,1-dimethylethyl [(3-bromo-5-fluorophenyl)methyl]carbamate (2.20 g, 69%). 1H NMR (400 MHz, CDCl3): delta 1.46 (S, 9H), 4.28-4.32 (m, 2H), 4.87 (br, 1H), 6.93-7.29 (m, 3H); 13C NMR (100 MHz, CDCl3): delta 20.3, 43.6, 44.1, 79.7, 80.0, 113.0, 114.0, 117.7, 122.5, 126.0, 123.0, 141.7, 155.9, 161.5, 164.0.

The synthetic route of 179898-34-1 has been constantly updated, and we look forward to future research findings.

Reference:
Patent; Glaxo Group Limited; US2009/197871; (2009); A1;,
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Reference of 403-54-3, These common heterocyclic compound, 403-54-3, name is 3-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.

General procedure: A mixture of nitrile (10 mmol), halohydrocarbons (11 mmol) and FeCl2·4H2O (2 mol %) was placed in a round bottom flask. Then the reaction mixture was heated at 80 C for the given time. After completion of the reaction monitored by thin layer chromatography (TLC), 5 ml water was added into reaction system and extracted with ethyl acetate (3 × 5 ml). The organic layers were collected, combined, washed with water (3 × 10 ml), dried over anhydrous Na2SO4, and concentrated under vacuum. The pure product was obtained by directly passing through a silica gel (200-300 mesh) column using petroleum ether/ethyl acetate and identified by 1HNMR and 13C NMR.

Statistics shows that 3-Fluorobenzonitrile is playing an increasingly important role. we look forward to future research findings about 403-54-3.

Reference:
Article; Feng, Cheng-Liang; Yin, Gui-Bo; Yan, Bin; Chen, Jun-Qing; Ji, Min; Chemical Papers; vol. 73; 2; (2019); p. 345 – 353;,
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These common heterocyclic compound, 51632-29-2, name is 2-(3-Phenoxyphenyl)acetonitrile, 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. Formula: C14H11NO

1.38 g (6.59 mmol) of 3-phenoxyphenylacetonitrile and 1.57 g (6.59 mmol) of cobalt(II) chloride hexahydrate are dissolved in 25 ml of methanol. The solution is cooled with an iced water bath and 1.74 g (46 mmol) of sodium borohydride are added in portions. The reaction mixture is stirred overnight at ambient temperature. It is filtered on paper and rinsed with twice 25 ml of methanol. The filtrate is concentrated under reduced pressure and the residue is taken up in 50 ml of aqueous hydrochloric acid (1N) and 25 ml of ether. After distinct phases have separated out they are separated. The aqueous phase is washed with three times 25 ml of ether. The aqueous phase is rendered alkaline with 10 ml of aqueous 36% sodium hydroxide and extracted with three times 50 ml of dichloromethane. The extracts are washed with saturated aqueous sodium chloride solution and dried over sodium sulphate and the filtrate is concentrated under reduced pressure. This gives 0.67 g of product in the form of a brown-orange oil, which is used as it is in the following step

The synthetic route of 2-(3-Phenoxyphenyl)acetonitrile has been constantly updated, and we look forward to future research findings.

Reference:
Nitrile – Wikipedia,
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Researchers who often do experiments know that organic synthesis is a process of preparing more complex target molecules from simple raw materials through one or more chemical reactions. Generally, it requires fewer steps, and cheap raw materials. 71825-51-9, name is 2-Methyl-2-(4-nitrophenyl)propanenitrile, A new synthetic method of this compound is introduced below., Recommanded Product: 2-Methyl-2-(4-nitrophenyl)propanenitrile

16 g (84.1 mmol) of 2-methyl-2-(4-nitro-phenyl)-propionitrile (Example Id) and 4.16 g of Raney-Ni are shacked in 160 ml of THF-MeOH (1: 1) under 1.1 bar of H2for 12 h. at RT. After completion of the reaction, the catalyst is filtered-off and the filtrate is evaporated to dryness. The residue is purified by flash chromatography on silica gel (hexane-EtOAc 3: 1 to 1:2) to provide the title compound as an oil. ES-MS: 161 (M + H)+; analytical HPLC: tret= 2.13 minutes (Grad 1).

The synthetic route of 71825-51-9 has been constantly updated, and we look forward to future research findings.

Reference:
Patent; NOVARTIS PHARMA AG; INCYTE CORPORATION; VANNUCCHI, Alessandro M.; BOGANI, Costanza; BARTALUCCI, Niccolo; WO2013/23119; (2013); A1;,
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Application of 10412-93-8, These common heterocyclic compound, 10412-93-8, name is N-Benzyl-2-cyanoacetamide, 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.

5.6. Synthesis Of (E)-2-(benzylaminocarbonyl)-3-(3-iodo-4,5-dihydroxyphenyl)acrylonitrile A preferred method of synthesis of (E)-2-(benzylaminocarbonyl)-3-(3-iodo-4,5-dihydroxyphenyl)acrylonitrile (Compound 6) is as follows: A mixture of 0.4 g of 2-cyano-3-(4-hydroxy-3-iodo-5-methoxy)phenylacrylonitrile (which was prepared by condensation of 4-hydroxy-3-iodo-5-methoxybenzaldehyde with N-benzylcyanoacetamide) and 0.5 ml of BBr3 in 20 ml dichloromethane was stirred for 2 hours at room temperature. Workup (H2 O, ethyl acetate) gave 0.16 g of a yellow solid (41 yield) having a melting point of 220 C. The product gave the following analytical data: NMR (acetone-d6) delta 8.05(1H,S,vinyl), 7.85(1H,d,J=2.1 Hz), 7.70(1H,d,J=2.1 Hz), 7.30(5H,in), 4.6(2H,S).

Statistics shows that N-Benzyl-2-cyanoacetamide is playing an increasingly important role. we look forward to future research findings about 10412-93-8.

Reference:
Patent; Sugen, Inc.; Yissum Research Development Co. of the Hebrew University of Jerusalem; US5792771; (1998); A;,
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Electric Literature of 3939-09-1,Some common heterocyclic compound, 3939-09-1, name is 2,4-Difluorobenzonitrile, molecular formula is C7H3F2N, 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: To a 0 C. solution of LiHMDS (360 mL, 359.5 mmol) in 148 THF (200 mL) was added drop wise, 439 2,4-difluorobenzonitrile (20 g, 143.8 mmol) in THF (100 mL). The reaction was warmed to rt and stirred for 4 hrs and c.HCl (100 mL) was added drop wise to keep the temperature below 30 C. 81 EtOAc was added and the aqueous layer was collected. The pH was adjusted to 10 by the careful addition of 6N 344 NaOH and the organic layer collected, dried and evaporated to dryness to give 440 2,4-difluoro benzimidamide (10 g, 44%) which was used without further purification in Step 2.

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

Reference:
Patent; CYSTIC FIBROSIS FOUNDATION THERAPEUTICS, INC.; Strohbach, Joseph Walter; Limburg, David Christopher; Mathias, John Paul; Thorarensen, Atli; Denny, Rajiah Aldrin; Zapf, Christoph Wolfgang; Elbaum, Daniel; Gavrin, Lori Krim; Efremov, Ivan Viktorovich; (159 pag.)US2018/141954; (2018); A1;,
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