Category: nitriles-buliding-blocks

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. 123-06-8 name is Ethoxymethylenemalononitrile, 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. 123-06-8

To a mixture of commercially available cyclopentylhydrazine hydrochloride(R-i4b) (1.82 g, 18.18 mmol) and commercially available compound 4:(ethoxymethylene)malononitrile (1.34 g, 10.97 mmol) in EtOH (20 mL), was added Et3N (3.03 g, 29.93 mmol) in one portion at r.t. under N2. The mixture was stirred at r.t. for 10 mm. Then heated to 50C and stirred for 2 hrs. The mixture was cooled to r.t. and concentrated in reduced pressure. The residuewas poured into water and the aqueous phase was extracted with EA (50 mL). The combined organic phase was washed with saturated brine (20 mL), dried with anhydrous Na2SO4, filtered and concentrated in vacuum. The residue was purified by silica gel chromatography to afford intermediate I-44b (1 .22 g, 69% yield) as yellow solid. ESI-MS (Mi-i): 177.1 calc. for C9H12N4: 176.1.

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

Reference:
Patent; FUNDACION PARA LA INVESTIGACION MEDICA APLICADA; CUADRADO TEJEDOR, Maria Del Mar; FRANCO FERNANDEZ, Rafael; GARCIA OSTA, Ana Maria; OYARZABAL SANTAMARINA, Julen; RABAL GRACIA, Maria Obdulia; WO2014/131855; (2014); A1;,
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179898-34-1, 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. 179898-34-1, name is 3-Bromo-5-fluorobenzonitrile belongs to nitriles-buliding-blocks compound, it is a common compound, a new synthetic route is introduced below.

824 mg (0.900 mmol) of tris(dibenzylideneacetone)dipalladium and 1.23 g (1.98 mmol) of rac-1,1′-binaphthalene-2,2′-diylbis(diphenylphosphane) are added to 9.00 g (45.0 mmol) of 3-bromo-5-fluorobenzenecarbonitrile in toluene (300 ml) under an argon atmosphere. After the addition of 19.5 g (54.0 mmol) of (1-ethoxyvinyl)tributylstannane, the mixture is stirred under reflux overnight. The reaction mixture is subsequently concentrated and the residue is taken up in 300 ml of THF. After the addition of 100 ml of an aqueous 2N hydrogen chloride solution the mixture is stirred at room temperature for 2 h. The reaction mixture is subsequently neutralized with a saturated aqueous sodium bicarbonate solution and extracted with ethyl acetate. The combined organic phases are dried over magnesium sulfate, filtered and concentrated in vacuo. The crude product is purified by flash chromatography (mobile phase: cyclohexane/ethyl acetate 9:1). 7.11 g (97% of theory) of the title compound are obtained.1H-NMR (400 MHz, DMSO-d6): delta=8.28 (t, 1H), 8.18-8.14 (m, 1H), 8.08-8.04 (m, 1H), 2.65 (s, 3H).GC-MS (Method 11): Rt=3.97 min; MS (EIpos): m/z=163 [M]+.

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

Reference:
Patent; AiCuris GmbH & Co. KG; US2011/124618; (2011); A1;,
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79463-77-7, name is Diphenyl N-cyanocarbonimidate, 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. 79463-77-7

To a solution of heptadecan-9-yl 8-((3-aminopropyl)(8-(nonyloxy)-8- oxooctyl)amino)octanoate (220 mg, 0.3 mmol) in 5 mL 2-propanol was added triethylamine (0.04 mL, 0.3 mmol) followed by diphenyl cyanocarbonimidate (72 mg, 0.3 mmol) and the mixture stirred at rt for two hours. To the reaction mixture was added a 2M dimethylamine solution in THF (0.75 mL, 1.5 mmol) and the resulting solution heated to 75 C for 18 hours. Additional 2M dimethylamine/THF solution (0.75 mL, 1.5 mmol) was added and the temperature increased to 85 C. After six hours the reaction was complete by LC/MS so the solution was reduced under vacuum, diluted with DCM and washed once with a saturated aqueous sodium bicarbonate solution. The organic phase was dried (MgSC^), filtered and the filtrate evaporated in vacuo. The residue was purified by silica gel chromatography (0-50% (mixture of 1 % NH4OH, 20% MeOH in dichloromethane) in dichloromethane) to give heptadecan-9-yl (Z)-8-((3-(2-cyano-3,3-dimethylguanidino)propyl)(8-(nonyloxy)-8- oxooctyl)amino)octanoate (119.2 mg, 0.14 mmol, 49%) as a colorless syrup. UPLC/ELSD: RT = 3.52 min. MS (ES): m/z (MH+) 819.0 for C49H95N5O4. XH NMR (300 MHz, CDC13) delta: ppm 7.62 (br. s., 1H); 4.86 (quint, 1H, J = 6 Hz); 4.05 (t, 2H, J = 7.5 Hz); 3.68 (d, 2H, J= 3 Hz); 2.99 (s, 6H); 2.59 (br. s, 2H); 2.43 (br. s, 3H); 2.28 (m, 4H); 1.71 (br. s, 2H); 1.62 (m, 8H); 1.49 (m, 5H); 1.26 (br. m, 50H); 0.88 (t, 9H, J = 7.5 Hz).

Statistics shows that 79463-77-7 is playing an increasingly important role. we look forward to future research findings about Diphenyl N-cyanocarbonimidate.

Reference:
Patent; MODERNATX, INC.; BENENATO, Kerry, E.; KUMARASINGHE, Ellalahewage, Sathyajith; CORNEBISE, Mark; (305 pag.)WO2017/49245; (2017); A2;,
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103146-25-4, A common heterocyclic compound, 103146-25-4, name is 4-(4-(Dimethylamino)-1-(4-fluorophenyl)-1-hydroxybutyl)-3-(hydroxymethyl)benzonitrile, molecular formula is C20H23FN2O2, 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.

19.5 g (115.7 mmol) of 48% hydrobromic acid was added dropwise to the solution at 30 C. or lower over 30 minutes. At about 25 C., 60.0 mg (0.18 mmol) of hydrobromide of diol compound (4) was added as a seed crystal and stirred for 30 minutes to confirm crystallization of hydrobromide of diol compound (4). did. Then, it was cooled to around 5 C., and 48.6 g (288.5 mmol) of 48% hydrobromic acid was added dropwise at around 5 C. over 30 minutes. After stirring for 1 hour at around 5 C., the precipitated crystals were separated by centrifugation and washed with 100 mL of water. Further, the crystals were washed with 100 mL of ethyl acetate. The obtained wet body is dried at 40 C. for 15 hours and then dried.118.4 g (279.8 mmol) of hydrobromide of the compound (4) was obtained. The isolated yield of the hydrobromide salt of the diol compound (4) was 97.0% based on the number of moles of the diol compound (4). Moreover, as a result of measuring the obtained hydrobromide salt of the diol compound (4) by HPLC, the purity of the hydrobromide salt of the diol compound (4) was 99.54%. Further, during crystallization of the hydrobromide salt of the diol compound (4), no crystal adhesion (scaling) was observed on the container wall surface.

The synthetic route of 103146-25-4 has been constantly updated, and we look forward to future research findings.

Reference:
Patent; Tokuyama Corporation; Miyanoku, Takayuki; Yokoo, Yoshihiro; (12 pag.)JP2019/119710; (2019); A;,
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623-26-7, 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. 623-26-7 name is Terephthalonitrile, 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 3; Hydrogenation; Into a 1-L autoclave equipped with an electromagnetic stirrer, 4 g of Raney nickel catalyst (“NDHT” manufactured by Kawaken Fine Chemicals Co., Ltd.) was charged. Then, 60 g of terephthalonitrile, 60 g of MX and 120 g of methanol were charged into the autoclave and the inner atmosphere thereof was replaced with nitrogen. After introducing 120 g of NH3, the autoclave was heated to 80C. Then, hydrogen gas was introduced into the autoclave to perform the hydrogenation under 8 MPaG at 80C. After initiating the hydrogenation, the reaction liquids were sampled at regular time intervals and analyzed by gas chromatography. After three hours from the initiation, the nitrile conversion reached 97.9 mol%. At this time, the residue of terephthalonitrile was 0.0 mol%, the yield of p-xylylenediamine was 79.0 mol%, and the yield of 4-cyanobenzylamine was 4.3 mol%. After three hours from the initiation, the reaction temperature was raised to 120C to continue the hydrogenation for 1.5 h (overall reaction time = 4.5 h). The results of gas chromatographic analysis showed that the nitrile conversion was 99.99 mol%, the residue of terephthalonitrile was 0.0 mol%, the yield of p-xylylenediamine was 83.9 mol%, and the yield of 4-cyanobenzylamine was 0.015 mol%. Purification of Xylylenediamine After releasing the pressure, MX and methanol were removed from the recovered reaction liquid in a rotary evaporator. By distilling the resultant solution under 0.5 kPa, p-xylylenediamine was obtained as the major distillate. The purity was 99.9% by weight or more and the content of 4-cyanobenzylamine was 0.016% by weight. COMPARATIVE EXAMPLE 3; Hydrogenation; The procedure of Example 3 was repeated except for performing the hydrogenation for 6 h at a constant reaction temperature of 80C. After 6 h of the initiation of hydrogenation, the reaction liquid was analyzed by gas chromatography. The residue of terephthalonitrile was 0.0 mol%, the yield of p-xylylenediamine was 82.2 mol%, and the yield of 4-cyanobenzylamine was 0.4 mol%. Although the hydrogenation was continued longer than in Example 3, a larger amount of the intermediate 4-cyanobenzylamine remained.Purification of Xylylenediamine After releasing the pressure, MX and methanol were removed from the recovered reaction liquid in a rotary evaporator. By distilling the resultant solution under 0.5 kPa, p-xylylenediamine was obtained as the major distillate. The obtained p-xylylenediamine contained 0.4% by weight of 4-cyanobenzylamine. COMPARATIVE EXAMPLE 4; The procedure of Example 3 was repeated except for performing the hydrogenation for 4.5 h at a constant reaction temperature of 120C. The results of gas chromatographic analysis showed that the residue of terephthalonitrile was 0.0 mol%, the yield of p-xylylenediamine was 74.2 mol%, and the yield of 4-cyanobenzylamine was 0.01 mol%.

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

Reference:
Patent; MITSUBISHI GAS CHEMICAL COMPANY, INC.; EP1454895; (2004); A1;,
Nitrile – Wikipedia,
Nitriles – Chemistry LibreTexts

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. 78473-00-4 name is 4-Amino-3,5-dichlorobenzonitrile, 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. 78473-00-4

Step 1 : Synthesis of 4-amino-3,5-diisobutylbenzonitrile Into a 1000 mL three-neck flask were put 9.4 g (50 mmol) of 4-amino-3,5-dichlorobenzonitrile, 26 g (253 mmol) of isobutylboronic acid, 54 g (253 mmol) of tripotassium phosphate, 2.0 g (4.8 mmol) of 2-dicyclohexylphosphino-2′,6′-dimethoxybiphenyl (S-phos), and 500 mL of toluene. The atmosphere in the flask was replaced with nitrogen, and this mixture was degassed while being stirred under reduced pressure. After the degassing, 0.88 g (0.96 mmol) of tris(dibenzylideneacetone)palladium(0) was added, and the mixture was stirred under a nitrogen stream at 130 C for 8 hours to be reacted. Toluene was added to the reacted solution, and the solution was filtered through a filter aid in which Celite, aluminum oxide, and Celite were stacked in this order. The obtained filtrate was concentrated to give an oily substance. The obtained oily substance was purified by silica column chromatography. Toluene was used as a developing solvent. The resulting fraction was concentrated to give 10 g of a yellow oily substance in a yield of 87 %. The obtained yellow oily substance was identified as 4-amino-3,5-diisobutylbenzonitrile by nuclear magnetic resonance (NMR) spectroscopy. The synthesis scheme of Step 1 is shown in (a-1) below.

At the same time, in my other blogs, there are other synthetic methods of this type of compound, 4-Amino-3,5-dichlorobenzonitrile, and friends who are interested can also refer to it.

Reference:
Patent; SEMICONDUCTOR ENERGY LABORATORY CO., LTD.; SEO, Satoshi; WATABE, Takeyoshi; INOUE, Hideko; YAMADA, Yui; MITSUMORI, Satomi; TAKAHASHI, Tatsuyoshi; HARA, Tomoka; (444 pag.)WO2016/203350; (2016); 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. 21524-39-0, name is 2,3-Difluorobenzonitrile, This compound has unique chemical properties. The synthetic route is as follows., 21524-39-0

A mixture of 2,3-difluorobenzonitrile (0.04 g), potassium carbonate (0.06 g), 7,8-dimethyl-6-(4-(1H-pyrazol-1-yl)benzyl)quinazolin-4(3H)-one (0.05 g) and DMF (1 mL) was stirred under an argon atmosphere at 150 C. overnight. To the reaction mixture was added water, and the mixture was extracted with ethyl acetate. The organic layer was washed with saturated brine, and dried over anhydrous sodium sulfate. The solvent was evaporated under reduced pressure. The residue was purified by silica gel column chromatography (ethyl acetate/hexane) and further purified by preparative HPLC (C18, water/acetonitrile, containing 0.1% trifluoroacetic acid), and the object fraction was neutralized with saturated aqueous sodium hydrogen carbonate solution, and the mixture was extracted with ethyl acetate. The organic layer was dried over anhydrous sodium sulfate and the solvent was evaporated under reduced pressure to give the title compound (0.01 g). 1H NMR (300 MHz, CDCl3) delta2.32 (3H, s), 2.63 (3H, s), 4.20 (2H, s), 6.44 (1H, s), 7.21 (2H, d, J=8.5 Hz), 7.52-7.73 (6H, m), 7.88 (1H, d, J=2.5 Hz), 7.95 (1H, d, J=0.9 Hz), 8.09 (1H, s).

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:
Patent; Takeda Pharmaceutical Company Limited; Sugimoto, Takahiro; Suzuki, Shinkichi; Sakamoto, Hiroki; Yamada, Masami; Nakamura, Minoru; Kamata, Makoto; Shimokawa, Kenichiro; Ogino, Masaki; Kimura, Eiji; Murakami, Masataka; Kojima, Takuto; Yonemori, Jinichi; (63 pag.)US10548899; (2020); B2;,
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A common compound: 17626-40-3, name is 3,4-Diaminobenzonitrile, belongs to nitriles-buliding-blocks compound, it can change the direction of chemical reaction, and react with certain compounds to generate new functional products. A new synthetic method of this compound is introduced below. 17626-40-3

5.0 g (37.56 mmol) of 3,4-diaminobenzonitrile was dissolved in 20 ml of trifluoroacetic acid, the reaction was refluxed under nitrogen atmosphere for 10 hours, then sinking into water, the filtrate was collected by filtration, washed three times with water, and dried to give 4.91 g (62.0% yield)

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, 17626-40-3, other downstream synthetic routes, hurry up and to see.

Reference:
Patent; Chen Yaoteng; Huang Bingzhao; Zheng Zhilong; Chen Siyuan; Wei Anxing; (19 pag.)CN103896849; (2017); B;,
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194853-86-6, name is 4-Fluoro-2-(trifluoromethyl)benzonitrile, 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. 194853-86-6

To a solution of 4-fluoro-2-(trifluoromethyl)benzonitrile (2.0 g) in ethanol (10.0 mL) was added Raney Ni (catalytic amount). The reaction mixture was subjected for hydrogenation in Parr apparatus under 50 psi for 2-3 h. The reaction mass was filtered through celite and the filtrate was concentrated to afford 0.400 g of desired product. 1HNMR (CDCl3): delta 3.98 (s, 2H), 7.24 (t, J – 9.0 Hz, 1H), 7.34 (d, – 8.7 Hz, 1H), 7.54 (t, J = 7.8 Hz, 1H); MS [M+H]+ : 194.03.

Statistics shows that 194853-86-6 is playing an increasingly important role. we look forward to future research findings about 4-Fluoro-2-(trifluoromethyl)benzonitrile.

Reference:
Patent; GLENMARK PHARMACEUTICALS S.A.; GHARAT, Laxmikant Atmaram; MUTHUKAMAN, Nagarajan; KHAIRATKAR-JOSHI, Neelima; KATTIGE, Vidya Ganapati; WO2013/186692; (2013); A1;,
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Adding a certain compound to certain chemical reactions, such as: 3598-14-9, name is Phenoxyacetonitrile, 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 3598-14-9, 3598-14-9

Diisobutylaluminum hydride (DIBAL-H, 1. OM in toluene, 20.0 mL) is added dropwise to a stirred solution OF PHENOXYACETONITRILE (2.22 g, 16.7 mmol) in anhydrous CH2CL2 (18 mL) at-78 C under nitrogen. The resultant solution is allowed to stir at 0 C for 1 hour. Methanol (2 mL) is added dropwise to quench excess of DIBAL-H, followed by the successive addition of Et2O (40 mL) and 2N HCl (60 mL) in small portions to the cold mixture. The resultant two-layered solution is allowed to stir vigorously at ambient temperature for 1 hour. Ethyl ether (30 mL) and saturated aqueous NACL solution (30 ML) are added to the mixture. The organic layer is separated, dried over MGS04, filtered and concentrated at ambient temperature to give 2.27 g of the crude phenoxyacetaldehyde as oil. The oil is diluted in Et2O to form a stock solution (60 mg/mL), which is used for the subsequent REACTION. 1H NMR (CDC13) : W4. 57 (s, 2H), 9.87 (s, 1H). A 6.06 mL of the above stock solution (No.1.1 mmol) is added to a stirred mixture of 4A molecular sieve (600 mg) and isoquinoline-5-solfonic acid (2-amino-ethyl)-amide (244 mg, 0.971 mmol) in anhydrous CH30H (5 ML), and the resultant mixture is stirred at ambient temperature for 16 hours. The mixture is cooled to 0 C before it is treated with powdered sodium borohydride (81 mg, 2.1 mmol). The mixture is stirred at 0 C for 1 hour then at ambient temperature for another 1 hour. After filtration and subsequent concentration in vacuo, the crude product is chromatographed on silica (gradient 5-30% CH30H in EtOAc) to give 156 mg (0.420 mmol, 43% yield) of the free amine product as oil. The free amine (154 mg, 0.415 mmol) is dissolved in EtOAc (15 mL) and treated dropwise with 1N HCI/ETZO solution (1.24 mL) with stirring under nitrogen. The white suspension is stirred for 15 minutes, filtered and dried under vacuum at 60 C to give 177 mg (0.398 mmol, 96% yield) of the title compound as a hygroscopic white powder. ESIMS: m/z 372 (M+H) +.

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, Phenoxyacetonitrile, other downstream synthetic routes, hurry up and to see.

Reference:
Patent; ELI LILLY AND COMPANY; WO2004/94386; (2004); A1;,
Nitrile – Wikipedia,
Nitriles – Chemistry LibreTexts