Author: Jessica.F

Application of 243128-37-2, A common heterocyclic compound, 243128-37-2, name is 4-Fluoro-3-methoxybenzonitrile, molecular formula is C8H6FNO, 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.

Step A. Under an argon atmosphere a mixture of commercially available 4-fluoro- 3-methoxybenzonitrile (5.O g), AlCl3 (8.8 g) and NaCl (1.94 g) was heated (melted) to 190C for 45 min, cooled, poured on ice (200 mL) and extracted with CHCI3 (3 x). The combined organic phases were washed with H2O, dried (MgSO4), filtered, concentrated and purified by chromatography (silica, cyclohexane/EtOAc 9:1 to 8:1) to afford the title compound as colorless needles (3.45 g, 76%). [MH]+ = 138.

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; ALANTOS PHARMACEUTICALS HOLDING, INC.; WO2008/63671; (2008); A2;,
Nitrile – Wikipedia,
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Application of 16532-79-9,Some common heterocyclic compound, 16532-79-9, name is 4-Bromophenylacetonitrile, molecular formula is C8H6BrN, 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) intermediate 20 Synthesis of 2-(4-bromophenyl)-2-methylpropanenitrile.The preparation of 2-(4-bromophenyl)-2-methylpropanenitrile is carried out as described in J. Med. Chem. (1995), no 38, page 1608-1628. Sodium Hydride (60% susp. in oil, 6.66 g, 166.3 mmol) is added in many portions over 1 hour to 2-(4-bromophenyl)-acetonitrile (1Og, 51.0 mmol), dissolved in anhydrous DMF and methyl iodide (14.838g, 102.0 mmol) at 0 0C. This solution turns to a thick and brown orange paste. It is left stirring to slowly warm up to room temperature (18h). The organic solution is partitioned between water and ethyl acetate, separated, dried over anhydrous sodium sulfate and filtered. The solution is concentrated under reduced pressure and the resulting crude is purified on silicagel using a 0 to 20 % ethyl acetate in hexane gradient to yield the desired compound (4.9 g, 42%) as a clear oil. IH NMR (400 MHz, CHLOROFORM-D) delta ppm 1.71 (s, 6 H) 7.35 (d, /=8.79 Hz, 2 H) 7.52 (d, /=8.79 Hz, 2 H)

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

Reference:
Patent; ASTRAZENECA AB; WO2008/18827; (2008); A1;,
Nitrile – Wikipedia,
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Application of 77326-36-4, 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. 77326-36-4, name is 2-Amino-6-fluorobenzonitrile belongs to nitriles-buliding-blocks compound, it is a common compound, a new synthetic route is introduced below.

Example 2: Methyl- (2-cyano-3-methoxy-phenyl) sulfonamide; 2.1 : 2-Amino-6-methoxy-benzonitrile A solution of 70 g (0.5 mol) of 2-amino-6-fluoro-benzonitrile (prepared, e. g. according to US 4,504, 660) in 250 ml of N, N-dimethylformamide was initially charged and a solu- tion of 30.6 g (0.55 mol) sodium methoxide in 70 ml of methanol was added dropwise at room temperature while stirring. The mixture was then refluxed for 5 hours under stirring. The completion of the reaction was monitored by TLC. Additional 25 g of so- dium methoxide in 35 ml methanol were added and the reaction mixture was refluxed for additional 4 hours while stirring. The reaction mixture was concentrated under re- duced pressure, the resulting residue was triturated with water, sucked off and the ob- tained solids were dissolved in ethyl acetate. The resulting solution was concentrated in vacuo. The obtained residue was triturated with petroleum ether and sucked off to afford 48 g (63% of theory) of a brownish solid having a melting point of 143-146C.

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

Reference:
Patent; BASF AKTIENGESELLSCHAFT; WO2005/35486; (2005); A1;,
Nitrile – Wikipedia,
Nitriles – Chemistry LibreTexts

Electric Literature of 145689-34-5, 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. 145689-34-5 name is 2-(2,3-Difluorophenyl)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 65; 2-[1-(2,3-Difluoro-phenyl)-ethyl]-4,5-dihydro-1H-imidazole; a) rac-2-(2,3-Difluoro-phenyl)-propionitrile; A solution of 1.586 g (16 mmol) diisopropylamine in 25 ml tetrahydrofuran was cooled with sodium chloride/ice to -10 C. A solution of 9 ml (14 mmol) 1.6 M butyl lithium in hexanes was added drop-wise. After stirring for 10 min the resulting LDA solution was cooled to -78 C. and a solution of 2.00 g (13 mmol) 2,3-difluorophenyl-acetonitrile in 5 ml tetrahydrofuran slowly added. The reaction mixture was stirred at -78 C. for 40 min, then 2.22 g (16 mmol) methyl iodide were added and the cooling bath was removed after 5 min. The mixture was stirred for 2.5 h at room temperature, and then aqueous ammonium chloride solution was added. The mixture was extracted twice with ethyl acetate. The combined organic layers were dried over MgSO4, filtered and evaporated. The residue was purified using column chromatography (SiO2, heptanes/ethyl acetate 9:1) to yield 1.12 g of rac-2-(2,3-difluoro-phenyl)-propionitrile as a light yellow liquid; MS (EI): 167.1 (M+·), 152.1 (((M-CH3)+·), 100%).

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

Reference:
Patent; Galley, Guido; Zbinden, Katrin Groebke; Hoener, Marius; Kolczewski, Sabine; Norcross, Roger; Stalder, Henri; US2007/197621; (2007); A1;,
Nitrile – Wikipedia,
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These common heterocyclic compound, 874-97-5, name is 3-Cyanobenzyl alcohol, 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. Recommanded Product: 3-Cyanobenzyl alcohol

After 3-(hydroxymethyl)benzonitrile (1.33 g, 10 mmol) was dissolved in dimethylformamide (18 mL), triphenylphosphine (3.14 g, 12 mmol) and imidazole (0.82 g, 12 mmol) were added thereto, and the mixture was cooled to -20C. Iodine (2.79 g, 11 mmol) was added dividing in 5 portions thereto, and the result was stirred for 2 hours at -10C. A 5% aqueous ammonium chloride solution (60 mL) was added to the reaction solution, and the result was extracted with a diethyl ether/ethyl acetate=1/1 solution (60 mLx2). The organic layers were combined, washed with a 1% aqueous sodium thiosulfate solution to remove excess iodine, washed with salted water, dried with anhydrous magnesium sulfate, and then concentrated under reduced pressure. The residue was separated and purified using silica gel column chromatography (ethyl acetate/normal-hexane=1/9) to give a target compound (1.9 g, 78%) in a white powder state. 1H-NMR (300 MHz, CDCl3) delta 4.41 (s, 2H), 7.2-7.66 (m, 4H); MS (EI, m/e)=243 (M+).

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

Reference:
Patent; Korea Research Institute of Chemical Technology; SON, Jong Chan; KIM, Bong Jin; KIM, Jae Hak; LEE, Ill Young; YUN, Chang Soo; LEE, Sang Ho; LEE, Chong Kgo; (98 pag.)EP2781519; (2014); A1;,
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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. 78473-00-4, name is 4-Amino-3,5-dichlorobenzonitrile, This compound has unique chemical properties. The synthetic route is as follows., Computed Properties of C7H4Cl2N2

3,5-Dichloro-4-aminobenzylamine To lithium aluminum hydride (0.57 g, 15 mmol) in dry THF (20 mL) was added dropwise 3,5-dichloro-4-aminobenzonitrile (1.87 g, 10 mmol) in THF (30 mL). The mixture was stirred at rt for 2 h. Then, sodium sulfate decahydrate (4.83 g, 15 mmol) was added and the mixture was stirred for 30 min. The solid was filtered off and washed with THF three times. The solvent was removed under vacuum and the residue was purified by chromatography with Methanol/DCM (3:7) as the eluant. 3,5-Dichloro-4-aminobenzylamine was obtained as an off-white solid (1.5 g, 80%). 1H NMR (300 MHz, CD3OD): delta3.65 (s, 2H), 7.2 (s, 2H).

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 78473-00-4.

Reference:
Patent; Bristol-Myers Squibb Company; US2007/232581; (2007); A1;,
Nitrile – Wikipedia,
Nitriles – Chemistry LibreTexts

Reference of 19924-43-7,Some common heterocyclic compound, 19924-43-7, name is 2-(3-Methoxyphenyl)acetonitrile, 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.

General procedure: Amidoxime Formation To a solution of nitrile (1 eq.) in EtOH (12 mL mmol-1) was added hydroxylamine (50% v/v in H20, 4 mL mmol-1) and the reaction mixture heated under reflux for 5 hours. After removal of all volatiles under reduced pressure the crude produce was used without further purification.

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-Methoxyphenyl)acetonitrile, its application will become more common.

Reference:
Patent; IMPERIAL INNOVATIONS LIMITED; LEATHERBARROW, Robin; TATE, Edward; YU, Zhiyong; RACKHAM, Mark; WO2013/83991; (2013); A1;,
Nitrile – Wikipedia,
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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. 41963-20-6, name is 4-Bromo-3-methylbenzonitrile belongs to nitriles-buliding-blocks compound, it is a common compound, a new synthetic route is introduced below. name: 4-Bromo-3-methylbenzonitrile

Preparations 27-31 are prepared essentially as described for Preparation 26 using the appropriate boronic acid and l-(3-bromo-pyridin-2-yl)-piperazine.Preparation 32: 3-Methyl-4-(4,4,5,5-tetramethyl-[l,3,2]dioxaborolan-2-yl)-benzonitrile Stir together 4-bromo-3-methylbenzonitrile (5.20 mmol, 1.02 g), bis(pinacolato) diboron (5.62 mmol, 1.43 g), potassium acetate (15.6 mmol, 1.53 g), and palladium acetate (0.16 mmol, 40 mg) in dry N,N-dimethylformamide (20 mL). Purge the reaction for 30 min. then heat to 85 0C overnight. Partition between water (100 mL) and ethyl acetate (100 mL), wash aqueous layer with ethyl acetate (100 mL). Combine ethyl –50-acetate washings and dry over magnesium sulfate, filter and concentrate in vacuo. Purify (silica gel chromatography, eluting with 0: 100 to 20:80 ethyl acetate:isohexane) to give the title preparation as a white powder (560 mg, 44% yield). MS (ES): m/z = 244 [M+H]+.

The synthetic route of 41963-20-6 has been constantly updated, and we look forward to future research findings.

Reference:
Patent; ELI LILLY AND COMPANY; WO2008/141020; (2008); A1;,
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Reference of 876-31-3, 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. 876-31-3, name is 4-(Cyanomethyl)benzonitrile belongs to nitriles-buliding-blocks compound, it is a common compound, a new synthetic route is introduced below.

4-(1-Cyanocyclopentyl)benzonitrile [S11]. In a flamed dried 50 mL flask, 710.8 mg (5.0 mmol) of 2-(4-cyanophenyl)acetonitrile was dissolved in 7.5 mL anhydrous DMF. 316.0 mg (95% purity, 12.5 mmol, 2.5 equiv.) of NaH was added in portions at 0 C. and the reaction was allowed to stir for 1 hour at 0 C. 1.0797 g (0.59 mL, 5.0 mmol, 1.0 equiv.) of 1,4-dibromobutane was added dropwise at 0 C. and the reaction was allowed to stir overnight at room temperature. The reaction was quenched carefully with -10 mL water and extracted with 30 mL EtOAc three times. The combined organic layer was washed with 50 mL brine, dried with MgSO4, filtered, and concentrated. Flash column chromatography on silica (50 mm fritted glass column, 300 mL SiO2) using 5% EtOAc/hexanes?10% EtOAc/hexanes as eluent gave 880.1 mg (4.48 mmol) of pure product as a colorless oil (90% yield). 1H-NMR (500 MHz, CDCl3) delta 7.69-7.67 (m, 2H), 7.59-7.57 (m, 2H), 2.52-2.48 (m, 2H), 2.09-1.94 (m, 6H). 13C-NMR (126 MHz, CDCl3) delta 145.2, 132.8, 127.0, 123.3, 118.3, 112.0, 48.0, 40.7, 24.5. HRMS (EI+) m/z calculated for C13H12N2 [M]+: 196.1000, found 196.1004.

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-(Cyanomethyl)benzonitrile, other downstream synthetic routes, hurry up and to see.

Reference:
Patent; The Board of Trustees of the University of Illinois; WHITE, M. Christina; ZHAO, Jinpeng; (94 pag.)US2020/87331; (2020); A1;,
Nitrile – Wikipedia,
Nitriles – Chemistry LibreTexts

Adding a certain compound to certain chemical reactions, such as: 654-70-6, name is 4-Cyano-3-trifluoromethylaniline, 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 654-70-6, Application In Synthesis of 4-Cyano-3-trifluoromethylaniline

[003 19j Thionyl chloride (46.02 g, 0.39 mol) was added dropwise to a cooled solution (less than 4C) of (R)-3-bromo-2-hydroxy-2-methylpropanoic acid (51.13 g, 0.28 mol) in 300 mL of THF under an argon atmosphere. The resulting mixture was stirred for 3 h under the same condition. To this was added Et3N (39.14 g, 0.39 mol) and stirred for 20 mm under the same condition. After 20mm, 5-amino-2-cyanobenzotrifluoride (40.0 g, 0.21 mol), 400 mL of THF were added and then the mixture was allowed to stir overnight at RT. The solvent was removed under reduced pressure to give a solid which was treated with 300 mL of H20, extracted with EtOAc (2 x400 mL). The combined organic extracts were washed with saturated NaHCO3 solution (2 x 300 mL) and brine (300 mL). The organic layer was dried over MgSO4 and concentrated under reduced pressure togive a solid which was purified from column chromatography using CH2CWEtOAc (80:20) to give a solid. This solid was recrystallized from CH2CWhexane to give 55.8 g (73.9%) of (2R)-3-bromo- N-[4-cyano-3 -(trifluoromethyl)phenylj -2-hydroxy-2-methylpropanamide as a light-yellow solid. Mp 134.0-136.5C;[00320j ?H NMR (CDC13fFMS) oe 1.66 (s, 3H, CH3), 3.11 (s, 1H, OH), 3.63 (d, J= 10.8 Hz, 1H,CH2), 4.05 (d, J= 10.8 Hz, 1H, CH2), 7.85 (d, J= 8.4 Hz, 1H, Ar]), 7.99 (dd, J=2.1, 8.4 Hz, 1H,ArH), 8.12 (d, J = 2.1 Hz, 1H, ArH), 9.04 (bs, 1H, NH). MS (ESI) 349.0 [M – Hj M.p.: 124- 126C.

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-Cyano-3-trifluoromethylaniline, other downstream synthetic routes, hurry up and to see.

Reference:
Patent; GTX, INC.; UNIVERSITY OF TENNESSEE RESEARCH FOUNDATION; NARAYANAN, Ramesh; MILLER, Duane D.; PONNUSAMY, Thamarai; HWANG, Dong-Jin; DUKE, Charles B.; COSS, Christopher C.; JONES, Amanda; DALTON, James T.; (159 pag.)WO2016/172330; (2016); A1;,
Nitrile – Wikipedia,
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