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. 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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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;,
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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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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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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;,
Nitrile – Wikipedia,
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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;,
Nitrile – Wikipedia,
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654-01-3, Name is 2-(2,6-Difluorophenyl)acetonitrile, 654-01-3, 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.

A mixture of 15.3 g (100 mmol) of 2-(2,6difluorophenyl)acetonitrile, 152.5 g (70 mL, 812 mmol) of dibromoethane, and 32.7 g (144 mmol) of Et3BnN+Cl- was isolated from moisture and carbon dioxide and vigorously stirred at 60. A solution prepared from 95 g (1430 mmol, ?84.5%) of KOH and 95 mL of water was then added dropwise; the mixture was stirred during 6 h at 60-65C, and left overnight. On the next day, the reaction mixture was extracted with t-BuOMe (3¡Á100 mL), the combined organic fractions were evaporated, and residual water was removed via azeotropic distillation with toluene. Then 60 mL of water and 40 mL of concentrated sulfuric acid were added to the obtained 1-(2,6-difluorophenyl)cyclopropanecarbonitrile, and the mixture was refluxed during 4 h. The reaction mass was cooled to ambient; the precipitate was filtered off and dried. Yield 17.82 g (90%), mp 156-157 (toluene). IR spectrum, nu, cm-1: 412 s, 772 m, 946 m, 994 m, 1048 s, 1246 m, 1270 m, 1306 m, 1324 m, 1414 m, 1468 m, 1474 m, 1504 s, 1624 m, 1666 m, 1726 s. 1 NMR spectrum (400.16 MHz, DMSO-d6), delta, ppm: 1.18 m (2H, 2eq, c-Pr), 1.58 m (2H, 2ax, c-Pr), 7.03 m (2H, 3,5H), 7.36 m (1H, C4H), 12.54 br.s (1H, OH). Mass spectrum (EI), m/z (Irel, %): 197.9 (100) [M]+, 153.0 (37) [M – COOH)]+, 133.0 (35) [M – COOH – HF]+, 127.2 (32) [2,6-F2C6H3CH2]+. Found, %: C 60.50; H 4.08. C10H8F2O2. Calculated, %: C 60.61; H 4.07.

Statistics shows that 2-(2,6-Difluorophenyl)acetonitrile is playing an increasingly important role. we look forward to future research findings about 654-01-3.

Reference:
Article; Novakov; Yablokov; Navrotskii; Mkrtchyan; Vernigora; Babushkin; Kachala; Ruchko; Russian Journal of General Chemistry; vol. 87; 2; (2017); p. 224 – 230; Zh. Obshch. Khim.; vol. 87; 2; (2017); p. 247 – 254,8;,
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31643-49-9,Some common heterocyclic compound, 31643-49-9, name is 4-Nitrophthalonitrile, molecular formula is C8H3N3O2, 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.

4-nitrophthalonitrile (1.00 g, 5.78 mmol) and 4-hydroxybenzaldehyde (0.71 g, 5.78 mmol) were dissolved inN,N-dimethylformamide (15 mL) and degassed with argon ina dual-bank vacuum-gas manifold system. After stirring for15 min, finely ground anhydrous potassium carbonate (2 g,14.45 mmol) was added portion-wise within 2 h period withthe efficient stirring. The progress of the reaction was monitoredby TLC using DCM / hexane (3/1) solvent system. Thestirring of the suspension was maintained at room temperaturefor further 24 h. The resulting mixture was poured into aniced-water/acetone mixture (5/1: v/v). The occured precipitatewas collected by filtration, washed several times with ethanoland dried in vacuo. The desired pure compound (1) was obtainedas a yellowish powder in sufficient purity. Yield 1.30 g,90 %. m.p. 154 C. FT-IR (PIKE MIRacleTM ATR) nu max/cm-1: 3105-3041(Ar, C-H), 2805-2764 (OC-H), 2237 (C?N),1691 (C=O), 1587-1506 (Ar, C=C), 1489-1309 (C-C), 1255(Ar-O-Ar), 1209, 1155, 1111, 1087, 950, 858, 839, 821. 1HNMR(CDCl3) delta (ppm) : 10.03 (s, 1H, OCH)), 8.01 (d, 2H,ArH), 7.81 (d, 1H, ArH), 7.41-7.34(m, 2H, ArH), 7.23 (d, 2H,ArH). 13C-NMR (CDCl3) delta (ppm): 190.7, 160.3, 159.1,135.9, 134.1, 132.6, 123.0, 122.9, 120.59, 118.2, 115.3,114.9, 110.6.

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

Reference:
Article; Sen, Pinar; Atmaca, Goeknur Ya?a; Erdo?mu?, Ali; Dege, Necmi; Genc, Hasan; Atalay, Yusuf; Yildiz, S. Zeki; Journal of Fluorescence; vol. 25; 5; (2015); p. 1225 – 1234;,
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6330-25-2,Some common heterocyclic compound, 6330-25-2, name is 2-Cyano-N-methyl-acetamide, molecular formula is C4H6N2O, 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 0.87 g t-BuOK (7.8 mmol) in 10 cm3 drymethanol, 2-cyanoacetamide 2a-2g (2.9 mmol) was added.The reaction mixture was stirred for 10-15 min, followed by cooling to 0 C and adding a solution of o-(azidomethyl)benzoate 1a-1c (2.6 mmol) in 5 cm3 drymethanol. After heating the reaction mixture back to room temperature, it was stirred under TLC monitoring for36-48 h and evaporated. Water (15 cm3) was added to the residue and it was acidified with HCl to pH 4-5. The resulting precipitate was filtered off and recrystallized from acetic acid.

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

Reference:
Article; Yakovenko, Georgiy G.; Yagodkina, Marta S.; Bol?but, Andriy V.; Shishkina, Svitlana V.; Vovk, Mykhailo V.; Monatshefte fur Chemie; vol. 148; 6; (2017); p. 1035 – 1041;,
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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. 939-80-0, name is 4-Chloro-3-nitrobenzonitrile belongs to nitriles-buliding-blocks compound, it is a common compound, a new synthetic route is introduced below. 939-80-0

In a flask equipped with a reflux condenser, frans-4-aminocyclohexanol hydrochloride(2.70g, 17.80mmoles) was suspended in iso-propanol (15m1). To this stirred suspension,triethylamine (4,40m1, 31 .49mmoles) was slowly added, followed by 4-chloro-3- nitrobenzonitrile (2.50g, 13.69mmoles). The resulting yellow suspension was heated at 65C for 36h, allowed to cool down to room temperature before water (lOml) was added to the reaction mixture. The resulting precipitate was collected by filtration andsuccessively washed with water and iso-propanol, to yield 4-(((1R,4R)-4- hydroxycyclohexyl)amino)-3-nitrobenzonitrile as a yellow crystalline solid (3 .28g, 12.55mmoles, 92%). The resulting solid was further purified by recrystallization from hot ethanol.mlz 262.2 [MJ-1]+?H NMR (500 MHz, DMSO-d6) oe 8.49 (s, 1H), 8.18 (d, J = 7.8 Hz, 1H), 7.79 (d, J = 9.0 Hz, 1H), 7.26 (d, J = 9.1 Hz, 1H), 4.63 (s, 1H), 3.67 (dtd, J = 14.9, 10.4, 4.0 Hz, 1H), 3.57-3.41 (m, 1H), 2.05-1.88 (m, 2H), 1.89-1.75 (m,2H), 1.53-1.19 (m, 4H).

The synthetic route of 939-80-0 has been constantly updated, and we look forward to future research findings.

Reference:
Patent; RE:VIRAL LTD; COCKERILL, Stuart; MATHEWS, Neil; WARD, Simon; LUNN, Graham; PARADOWSKI, Michael; GASCON SIMORTE, Jose Miguel; (72 pag.)WO2016/55780; (2016); A1;,
Nitrile – Wikipedia,
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