Author: Jessica.F

Related Products of 1953-99-7,Some common heterocyclic compound, 1953-99-7, name is 3,4,5,6-Tetrachlorobenzene-1,2-dicarbonitrile, molecular formula is C8Cl4N2, 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 A 3,4,5,6-Tetrafluorophthalonitrile Anhydrous potassium fluoride (11.0 kg) is added to a 50 gallon stainless steel reactor. The salt is dried under 28 inches vacuum at 115°-138° C. for 48 hours. The salt is cooled to 100° C. and tetramethylenesulfone (19 liters) added followed by tetrachlorophthalonitrile (4.74 kg). The mixture is heated with stirring to 156° C. over a 30 minute period. Heating with vigorous agitation is continued for another 2.5 hours at 135°-162° C. The mixture was cooled to 31° C. (15 minutes) and ice (69 kg) and demineralized water (119 liters) were added. The resulting mixture was stirred 1.5 hours before centrifuging to collect crude product which was washed with demineralized water (120 liters). The crude product was transferred back into the 50 gallon stainless steel still and demineralized water (100 liters) added. The mixture was steam distilled until 80 liters of distillate were collected. The distillate was cooled to 0°-5° C. and the product collected on a centrifuge. The crystals were washed with demineralized water (2*90 liters) to give 2.82 kg wet product: LOD 6.4percent; calculated yield: 74percent. A small sample was dried under vacuum for two days at room temperature; mp 81°-83° C.

These compound has a wide range of applications. It is believed that with the continuous development of the source of the synthetic route 3,4,5,6-Tetrachlorobenzene-1,2-dicarbonitrile, its application will become more common.

Reference:
Patent; Warner-Lambert Company; US4782180; (1988); A;,
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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. 51762-67-5, name is 3-Nitrophthalonitrile, A new synthetic method of this compound is introduced below., Safety of 3-Nitrophthalonitrile

The K2CO3 (18.24 g) and NaNCh (8.27 g) were added to a stirring solution of 3-nitrophthalonitrile (1, 20.8 g, 120 mmol) in DMSO (90 mL) at ambient temperature. The resulting suspension was gently refluxed (oil bath) for 1.5 h. After the resulting hot black reaction mixture was poured into cold water (750 mL), pH was adjusted to 3 with concentrated HC1 (~25 mL) to give an orange suspension, which was kept in freezer for 30 min. The precipitate was collected by vacuum filtration, raised with H20/EtOH and kept under vacuum for overnight to give crude 3-hydroxylphthalonitrile. The product was used for next step without further purification.

The synthetic route of 51762-67-5 has been constantly updated, and we look forward to future research findings.

Reference:
Patent; CITY OF HOPE; KORTYLEWSKI, Marcin; SWIDERSKI, Piotr, Marek; ROSEN, Steven; (218 pag.)WO2019/241766; (2019); A1;,
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Some common heterocyclic compound, 6609-57-0, name is 2-Ethoxybenzonitrile, molecular formula is C9H9NO, 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. name: 2-Ethoxybenzonitrile

Add 97% in a 250mL four-necked bottleCompound IV 15.2g (0.1mol),9g (0.13mol) of hydroxylamine hydrochloride,17.9g (0.13mol) was added to 100mL of ethanol,The reaction was refluxed for 4 h.TLC traces the reaction to Compound IV completely, drops to room temperature, and removes the potassium salt in the reaction solution by filtration.The filtrate was evaporated to 80% ethanol, and a white solid precipitated upon cooling.Filter by suction and recover the filtrate.A white solid was obtained in an amount of 16.2 g, yield 90%.

These compound has a wide range of applications. It is believed that with the continuous development of the source of the synthetic route 6609-57-0, its application will become more common.

Reference:
Patent; Qingdao University of Science and Technology; Xu Liangzhong; Cui Jianqiang; Zhang Mingming; Liu Liancai; Hu Rao; Wang Minghui; (6 pag.)CN108341808; (2018); A;,
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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 1897-52-5 as follows. HPLC of Formula: C7H3F2N

20.0 g of 2,6-difluorobenzonitrile, anhydrous potassium carbonate 20.0 g and dimethyl sulfoxide 100 mL, add to the reaction flask, stir evenly, and warm to 90 C. Slowly drip morpholine 6.60g with stirring. Keep the temperature at 90 C for 3 hours. The reaction solution was naturally cooled to room temperature and poured into an appropriate amount of ice water. Precipitating a white solid powder, filtering, the filter cake was washed with water and dried to obtain 9.0 g of a product. That is, 2-fluoro-6-morpholinylbenzonitrile (1).

According to the analysis of related databases, 1897-52-5, the application of this compound in the production field has become more and more popular.

Reference:
Patent; Shanxi University Of Science And Technology; Lu Jiufu; Jin Lingxia; Yu Xiaohu; Zhao Caibin; Zhou Ke; Song Juan; (7 pag.)CN109879827; (2019); A;,
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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.

General procedure: To a solution of 4-bromobiphenyl 1a (3.0 mmol, 699.3 mg) in THF (3.0 mL) was added n-BuLi (4.5 mmol, 1.55 M in hexane, 2.87 mL) at 50 C. The obtained mixture was stirred for 30 min at 50 C under an argon atmosphere. Pivalonitrile (6.0 mmol, 498.8 mg) in THF (2.0 mL) was added to the mixture at 50 C and the obtained mixture was stirred for 30 min in the temperature range of 50 C to room temperature. MeOH (2.0 mL) was added to the mixture. Then, I2 (12.0 mmol, 3045.6 mg) and K2CO3 (12.0 mmol, 1658.4 mg) were added to the mixture at room temperature, and the obtained mixture was stirred for 6 h at 70 C. Sat. aq. Na2SO3 solution (20.0 mL) was added to the reaction mixture, and the product was extracted with AcOEt (10.0 mL x 3). The organic layer was dried over Na2SO4. After filtration and removal of the solvent, the residue was purified by silica-gel column chromatography (chloroform: n-hexane 1:1) to give 4-cyanobiphenyl 2a (451.6 mg, 84%).

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

Reference:
Article; Uchida, Ko; Togo, Hideo; Tetrahedron; vol. 75; 39; (2019);,
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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. 179898-34-1, name is 3-Bromo-5-fluorobenzonitrile, A new synthetic method of this compound is introduced below., Computed Properties of C7H3BrFN

To a solution of 3,5-dibromofluorobenzene in diethyl ether (100 cm3) at -78 C. was added n-butyl lithium (2.5 M, 8 cm3, 20 mmol) dropwise. After 30 min. the mixture was treated with DMF (20 cm3) in diethyl ether (10 cm3) and stirring was continued at -78 C. After 30 min. the mixture was quenched with dilute HCl aq., separated and the aqueous layer was extracted with EtOAc. The combined organic layers were combined, washed with water, brine, dried (MgSO4) and evaporated to give 3-fluoro-5-bromobenzaldehyde (4.0 g, 19.7 mmol, 100%) as an oil: 1H NMR (CDCl3) delta inter alia 7.50-7.53 (m, 2H), 7.82 (s, 1H) and 9.93 (m, 1H); MS (EI) m/z 202, 204 [M+]. To a solution of the last cited compound (4.0 g, 19.7 mmol) in ethanol:water (8:2, 50 cm3), was added sodium acetate (1.72 g, 21 mmol) and hydroxylamine hydrochloride (1.45 g, 21 mmol), and the mixture was heated under reflux. After 30 min., the mixture was cooled, evaporated and the residue partitioned between water and EtOAc. The aqueous layer was re-extracted with EtOAc and the combined organic layers were washed with water, saturated sodium hydrogen carbonate solution, brine, dried (MgSO4) and evaporated to give 3-fluoro-5-bromobenzaldehyde oxime (3.76 g, 17.24 mmol, 87%) which was used without further purification: 1H NMR (CDCl3) delta 7.24-7.27 (m, 2H), 7.50 (s, 1H), 7.68 (s, 1H) and 8.04 (s, 1H); MS (EI) m/z 217 [M+]. The above oxime (3.76 g, 17.24 mmol) and copper (II) acetate (370 mg) were dissolved in acetonitrile (100 cm3) under nitrogen and heated under reflux. After 5 h, the mixture was evaporated, the residue taken into EtOAc, washed with sulfuric acid (1N), water, brine, dried (MgSO4) and evaporated to give 3-fluoro-5-bromobenzonitrile (3.08 g, 15.39 mmol, 89%) which was used without further purification. The above bromide (3.0 g, 15 mmol) and tetrakis(triphenylphosphine)palladium (0) (0.86 g, 0.75 mmol) were dissolved in dimethoxyethane (130 cm3) under nitrogen. After 15 min. (2′-oxo-2,3-dihydrospiro[cyclohexane-1,3′-[3H]indol]-5′-yl) boronic acid (2.82 g, 11.5 mmol) and sodium carbonate (3.1 g, 29.3 mmol) dissolved in water (40 cm3) were added, and the mixture heated under reflux. After 8 h the mixture was cooled, poured into water and extracted with EtOAc (×3). The combined organic layers were then washed with water, dried (MgSO4) and evaporated. The residue was then purified by column chromatography (EtOAc:hexane, gradient elution), and the product recrystallized from methanol to give 3-(1,2-Dihydro-2-oxospiro[cyclohexane-1,3-[3H]indol]-5-yl)-5-fluorobenzonitrile (1.78 g, 5.55 mmol, 48%): mp 199-205 C.; 1H NMR (CDCl3) delta 1.64-2.03 (m, 10H), 7.03 (d, 1H, J=8 Hz), 7.31 (dt, 1H, J=7.7 and 1.6 Hz), 7.41 (dd, 1H, J=8, 1.7 Hz), 7.49 (dt, 1H, J=9.6, 2 Hz), 7.58 (d, 1H, J=2 Hz), 7.64 (s, 1H) and 8.37 (s, 1H): MS (EI) m/z 320 [M+].

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; American Home Products Corporation; Ligand Pharmaceuticals, Inc.; US6355648; (2002); B1;,
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2032-34-0, name is 3,3-Diethoxypropanenitrile, belongs to nitriles-buliding-blocks compound, is considered to be a conventional heterocyclic compound, which is widely used in drug synthesis. The chemical synthesis route is as follows. Recommanded Product: 3,3-Diethoxypropanenitrile

To a solution of ethyl 1 -amino- lH-pyrrole-2-carboxylate (15d) (3.0 g, 19.46 mmol) in EtOH (100 mL) was added 3,3-diethoxypropanenitrile (25 mL, 95%, 158.23 mmol), IN HCl (aq. 5 mL) and heated at reflux for 18 h. The reaction mixture was cooled to room temperature, treated with DBU (32.5 niL, 213.18 mmol), and stirred with heating at 80 0C for Ih. The reaction mixture was concentrated in vacuo to remove most of EtOH. The residue obtained was diluted with EtOAc (300 mL), washed with water (200 mL, 150 mL). The combined aqueous solution was acidified with 4N HCl to pH = 1 and extracted with chloroform (2 x 300 mL), chloroform/methanol (3:1, 200 mL). The combined extracts were dried over MgSO4, filtered and the filtrate was concentrated in vacuo. The residue obtained was purified by columnchromatography (silica gel 120 g, eluting with hexanes/ethyl acetate/MeOH, 1 :1 :0 to 2:2:1, product Rf = 0.35 with hexanes/ethyl acetate/MeOH 2:2:1) to give 4-hydroxypyrrolo[l,2- b]pyridazine-3-carbonitrile (15f) (1.44 g, 47%) as a brown solid. 1H NMR (300 MHz, DMSO- d6): delta 8.16 (s, IH), 7.90 (dd, J= 1.6, 2.6 Hz, IH), 7.08 (dd, J= 1.6, 4.5 Hz, IH), 6.80 (dd, J= 2.6, 4.5 Hz, IH); MS (ES”): 157.8 (M – H)1.

The synthetic route of 2032-34-0 has been constantly updated, and we look forward to future research findings.

Reference:
Patent; BIOCRYST PHARMACEUTICALS, INC.; BABU, Yarlagadda S.; KOTIAN, Pravin L.; KUMAR, V. Satish; WU, Minwan; LIN, Tsu-Hsing; WO2011/14817; (2011); A1;,
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Reference of 68385-95-5, These common heterocyclic compound, 68385-95-5, name is 2-Amino-3,5-dibromobenzonitrile, 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.

Bromine (110 mmol, 5.6 mL) was added dropwise to an acetic acid solution (150 mL) of 2-aminobenzonitrile (50 mmol, 5.9 g) in an argon atmosphere, and the mixture was stirred at room temperature for 5 hours. The reaction solution was poured into ice water (200 mL), and the resulting solid was collected by filtration and washed with water.The residue was recrystallized from ethyl acetate to obtain 2-amino-3,5-dibromobenzonitrile (6.9 g, yield 50%).The obtained 2-amino-3,5-dibromobenzonitrile (10.0 mmol, 2.75 g), tetrabutylammonium fluoride trihydrate (5.0 mmol, 1.58 g), trimethylsilyl azide (TMSN3) (15 0.0 mmol, 2.0 mL) was stirred at 85 C. for 2 hours under an argon atmosphere. Ethyl acetate was added to the reaction solution, and the mixture was extracted 3 times with 1M hydrochloric acid (5 mL), and then the organic layer was dried over magnesium sulfate and dried under reduced pressure.Ethyl acetate was distilled off. The residue was subjected to silica gel column chromatography (ethyl acetate: ethanol = 10: 1), and 2,4-dibromo-6- (1H-tetrazol-5-yl) aniline (1.40 g, yield 44%) was white. Obtained as a solid.

The synthetic route of 68385-95-5 has been constantly updated, and we look forward to future research findings.

Reference:
Patent; Tohoku University; Uozumi, Nobuyuki; Arisawa, Mieko; Suzuki, Futoshi; Endo, Akira; Hamamoto, Susumu; Ikenokami, Yoshiaki; (20 pag.)JP2019/137678; (2019); A;,
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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 6306-60-1 as follows. Formula: C8H5Cl2N

EXAMPLE IV A mixture of 18.5 parts of 2,4-dichlorobenzeneacetonitrile and 180 parts of N,N-dimethylformamide is stirred and cooled in an ice-bath while nitrogen gas is introduced. 3.2 Parts of a sodium hydroxide solution 78% are added portionwise and the whole is stirred for one hour. Then there are added dropwise, during a one hour-period, 17.8 parts of (bromomethyl)cyclohexane while still cooling and while nitrogen gas is still introduced. Upon completion, stirring is continued for 2 hours at room temperature. The reaction mixture is poured onto water. The precipitated product is filtered off and triturated in a mixture of methanol and water. The product is filtered off and dried, yielding 25.5 parts of 2,4-dichloro-alpha-(cyclohexylmethyl)benzeneacetonitrile; mp. 58.8 C.

According to the analysis of related databases, 6306-60-1, the application of this compound in the production field has become more and more popular.

Reference:
Patent; Janssen Pharmaceutica N.V.; US4598085; (1986); A;,
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Synthetic Route of 1885-38-7, 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. 1885-38-7, name is (E)-Cinnamonitrile belongs to nitriles-buliding-blocks compound, it is a common compound, a new synthetic route is introduced below.

To a stirred solution of cinnamonitrile (2.5 g, 19.38 mmol) in MeOH (50 mL) was added Br2 (6.2 g, 38.76 mmol) dropwise at 0oC. Then the reaction mixture was warmed to room temperature and stirred overnight. The resulting mixture was poured into water (50 mL) and basified with solid NaHCO3. The resulting mixture was extracted with EtOAc (3*50 mL). The combined organic layers were concentrated under reduced pressure. The residue was purified by CC on silica gel eluting with PE : EA =10:1 to PE : EA =4:1 to give 2,3-dibromo-3- phenylpropanenitrile (3.2 g) as a oil. (yield, 57.7 %). LC/MS (ESI, m/z): [M+1]+ = 290.1.

The synthetic route of (E)-Cinnamonitrile has been constantly updated, and we look forward to future research findings.

Reference:
Patent; KYMERA THERAPEUTICS, INC.; MAINOLFI, Nello; JI, Nan; KLUGE, Arthur F.; (282 pag.)WO2019/140387; (2019); A1;,
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