Month: July 2021

Synthetic Route of 492-98-8,Some common heterocyclic compound, 492-98-8, name is 1H,1’H-2,2′-Biimidazole, molecular formula is C6H6N4, 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.

2,2′-Biimidazole (0.27 g, 2 mmol) and NaOH (0.32 g, 8 mmol) were placed in a 100 mL round bottomed flask with 20 mL of acetonitrile. The mixture was stirred at room temperature for two hours. 2-Picolyl chloride hydrochloride (0.65 g, 4 mmol) in acetonitrile (20 mL) was added to the mixture and refluxed for 24 h at 50-60 C. The reaction was monitored with TLC and upon completion the solvent was removed by rotary evaporation. The residue was dissolved in water (50 mL) and extracted with methylene chloride (30 mL * 3). Organic layers were combined, dried over anhydrous MgSO4 and rotary evaporated to obtain the pale brown color powder as the product. Yield: 0.25 g (40%); mp 180-183 C; 1H NMR (deltaH; CDCl3, 400 MHz): 8.53 (d, 2H), 7.53 (t, 2H), 7.15 (t, 2H), 7.12 (s, 2H), 7.07 (s, 2H), 7.05 (d, 2H), 5.87 (s, 4H).

These compound has a wide range of applications. It is believed that with the continuous development of the source of the synthetic route 1H,1’H-2,2′-Biimidazole, its application will become more common.

Reference:
Article; Aakeroey, Christer B.; Wijethunga, Tharanga K.; Desper, John; Journal of Molecular Structure; vol. 1072; 1; (2014); p. 20 – 27;,
Imidazole – Wikipedia,
Imidazole | C3H4N2 – PubChem

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 26832-08-6 as follows. Recommanded Product: 26832-08-6

In a dried 125 mL, three-neck flask fitted with a magnetic stirrer, temperature probe, a reflux condenser, and a positive nitrogen atmosphere set-up was charged with 4-imidazole carboxamide 2.0 gm (18 mmol), acetonitrile 25 ml, and POCl3 6.6 gm (43.2 mmol). The brown slurry was agitated and heated to reflux. The reaction mixture was maintained at reflux for at least 15 hrs. Then the excess POCl3 was distilled under reduced pressure. After aqueous work up, the reaction mixture was adjusted to a pH of 9-11 using 25% sodium hydroxide, and extracted with 4×70 ml ethyl acetate. The combine ethyl acetate extracts were treated with 20 gm silica gel, distilled under pressure to remove ethyl acetate and to afford 4-cyanoimidazole as a white solid. After drying the 4-cyanoimidazole weighed 1.1 gm (65.9% yield): HPLC purity, >99.0 area %; 1H NMR (300 MHz, DMSO-D6) delta 7.89 (s, 1H), 8.08 (s, 1H); 13C NMR (300 MHz, DMSO-D6) delta 111.8, 116.0, 127, 138.1.

According to the analysis of related databases, 26832-08-6, the application of this compound in the production field has become more and more popular.

Reference:
Patent; Ampac Fine Chemicals LLC; US2009/292122; (2009); A1;,
Imidazole – Wikipedia,
Imidazole | C3H4N2 – PubChem

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. 1003-91-4, name is 2,4,5-Tribromo-1-methylimidazole, This compound has unique chemical properties. The synthetic route is as follows., SDS of cas: 1003-91-4

To a solution of Example 69b (84 g, 263.3 mmol) in dry THF (2L) was added EtMgBr (88 mL, 263.3 mmol, 3.0M in ether) slowly under N2.The reaction was stirred at r.t. for 2 hours. Then about 2.0L water was added and filtered concentrated and the residue was extracted with EtOAc (50 mL * 2). The combined organic phase was washed with brine, dried over Na2S04, filtrated and concentrated under reduced pressure to give the crude product which was further purified by silica gel chromatography to give the pure product Example 69d (14.0 g) as white solid ‘HNMR (400 MHz, Chloroform- ) delta 7.48 (s, 1H), 3.63 (s, 3H). Example 69c (14.0g) as white solid. NMR (400 MHz, Chloroform- ) delta 6.94 (s, 1H), 3.60 (s, 3H). A solution of Example 69c&d (2.4 g, 10.0 mol) in ether (100 mL) was cooled to -78 C. under nitrogen atmosphere and then a 2.5 M n-BuLi solution in hexane (4.0 mL, 10.0 mol) added dropwise over 15 mins. The mixture was stirred at -78 C. for 30min and then DMF (2.0 mL) was added dropwise over 15 min. The mixture was stirred at -78 C. for 30min and quenched with saturated IN HQ (50 mL) at -78 C. The residue was extracted with EtOAc (50 mL * 2). The combined organic phase was washed with brine, dried over Na2S04, filtrated and concentrated under reduced pressure to give the crude product which was further purified by silica gel chromatography to give the pure product Example 69e (1.8 g, yield 95%) as yellow solid. NMR (400 MHz, Chloroform-d) delta 9.77 (d, J = 0.9 Hz, 1H), 7.51 (s, 1H), 3.93 (s, 3H).

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 1003-91-4.

Reference:
Patent; FRONTHERA U.S. PHARMACEUTICALS LLC; JIN, Bohan; DONG, Qing; HUNG, Gene; (212 pag.)WO2017/218960; (2017); A1;,
Imidazole – Wikipedia,
Imidazole | C3H4N2 – PubChem

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. 3314-30-5, name is 1H-Benzo[d]imidazole-2-carbaldehyde, This compound has unique chemical properties. The synthetic route is as follows., category: imidazoles-derivatives

Example 4 3-(1H-benzimidazol-2-methylene)-5-(cyclohexylaminosulfo)-2-indolone (Indo 4) 0.15 g (0.5 mmol) 5-(cyclohexylaminosulfo)-2-indolone and 0.10 g (0.685 mmol) 1H-benzimidazol-2-formaldehyde were suspended in 6 mL anhydrous ethanol, followed by addition of 2 drops of piperidine. The mixture was heated and refluxed in an oil bath for 30 min. A large quantity of yellow solid was precipitated, filtered, and washed with anhydrous ethanol, to obtain 0.17 g pale yellow solid, with a yield of 80.6percent. Analytical result by NMR spectroscopy: 1H-NMR (DMSO-d6) delta (ppm): delta13.86 (s, 1H), 11.68 (s, 1H), 8.35 (s, 1H), 8.08 (s, 1H), 7.76-7.84 (m, 3H), 7.48 (d, 1H, J=7.2 Hz), 7.66 (d, 1H, J=6.4 Hz), 7.38 (t, 1H), 7.31 (t, 1H), 7.10 (d, 1H, J=8.0 Hz), 3.02 (b, 1H), 1.60 (b, 5H), 1.50 (b, 5H). ESI-MS m/z: 421 [M-H]+ (100). Analysis showed that, the pale yellow solid is 3-(1H-benzimidazol-2-methylene)-5-(cyclohexylaminosulfo)-2-indolone, the structural formula of which is shown in Formula I, wherein R1 is cyclohexylaminosulfo, and R2 is hydrogen.

According to the analysis of related databases, 3314-30-5, the application of this compound in the production field has become more and more popular.

Reference:
Patent; INSTITUTE OF RADIATION MEDICINE, CHINA ACADEMY OF MILITARY MEDICAL SCIENCES PLA; Yang, Xiaoming; Wang, Lin; Li, Changyan; Zhan, Yiqun; Liu, Jing; Luo, Teng; Yan, Haiyan; Zhang, Shouguo; Li, Wei; Wen, Xiaoxue; Peng, Tao; Li, Lu; (18 pag.)US2016/151334; (2016); A1;,
Imidazole – Wikipedia,
Imidazole | C3H4N2 – PubChem

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. 17325-26-7, name is Methyl 1H-imidazole-5-carboxylate, A new synthetic method of this compound is introduced below., Formula: C5H6N2O2

General procedure: Method B: Compounds 22 or 23 (1.2 mmol) and cesium carbonate (390 mg, 1.2 mmol) were dissolved in dry DMF (3 mL) under argon. After stirring of the mixture for 30 min at 50 C, a solution of the tosyl ester 12c or 12d (1 mmol) dissolved in dry DMF (3 mL) was added and the stirring was continued overnight at 50 C under argon. After evaporation of DMF in high vacuo, the residue was dissolved in EtOAc and the organic phase was washed with brine to neutral pH, dried over Na2SO4 and evaporated under reduced pressure. The residual product was purified by column chromatography (silica gel) using the appropriate solvent systems as it will be defined, in each case, below.

The synthetic route of 17325-26-7 has been constantly updated, and we look forward to future research findings.

Reference:
Article; Moutevelis-Minakakis, Panagiota; Papavassilopoulou, Eleni; Michas, George; Georgikopoulou, Kalliopi; Ragoussi, Maria-Eleni; Neophytou, Niki; Zoumpoulakis, Panagiotis; Mavromoustakos, Thomas; Hadjipavlou-Litina, Dimitra; Bioorganic and Medicinal Chemistry; vol. 19; 9; (2011); p. 2888 – 2902;,
Imidazole – Wikipedia,
Imidazole | C3H4N2 – PubChem

Application of 17289-19-9, These common heterocyclic compound, 17289-19-9, name is Methyl 1-methyl-1H-imidazole-4-carboxylate, 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.

To a solution of Example 63a (1.40 g, 10.0 mmol) in CHC13 (30.0 mL) was added NBS (2.13g, 12.0 mmol). The reaction mixture was then stirred 18hrs at 50C and then cooled to room temperature. The residue was extracted with EtOAc (200 mL * 2). The combined organic phase was washed with brine, dried over Na2S04, filtrated and concentrated under reduced pressure to give the crude product which was further purified by silica gel chromatography to give the pure product Example 63b (500 mg, yield 22.8%). NMR (400 MHz, Chloroform- ) delta 7.60 (s, 1H), 3.91 (s, 3H), 3.67 (s, 3H).

The synthetic route of 17289-19-9 has been constantly updated, and we look forward to future research findings.

Reference:
Patent; FRONTHERA U.S. PHARMACEUTICALS LLC; JIN, Bohan; DONG, Qing; HUNG, Gene; (212 pag.)WO2017/218960; (2017); A1;,
Imidazole – Wikipedia,
Imidazole | C3H4N2 – PubChem

Electric Literature of 52099-72-6, A common heterocyclic compound, 52099-72-6, name is 1-(Prop-1-en-2-yl)-1H-benzo[d]imidazol-2(3H)-one, molecular formula is C10H10N2O, 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 IX To a stirred solution of 8.5 parts of 1,3-dihydro-1-(1-methylethenyl)-2H-benzimidazol-2-one in 45 parts of N,N-dimethylformamide are added portionwise 1.7 parts of a sodium hydride dispersion 78%. After stirring for 1 hour at room temperature, the whole is cooled to 0-5 C and 8.65 parts of 1-bromo-3-chloropropane are added dropwise (slowly). Upon completion, stirring is continued for 3 hours at room temperature. The reaction mixture is poured into crushed ice and the product is extracted with methylbenzene. The extract is washed with water, dried, filtered and evaporated. The residue is crystallized from 2-propanol, yielding 5.5 parts (44%) of 1-(3-chloropropyl)-1,3-dihydro-3-(1-methylethenyl)2H-benzimidazol-2-one; mp. 115 C.

The synthetic route of 52099-72-6 has been constantly updated, and we look forward to future research findings.

Reference:
Patent; Janssen Pharmaceutica N.V.; US4066772; (1978); A;,
Imidazole – Wikipedia,
Imidazole | C3H4N2 – PubChem

Some common heterocyclic compound, 57090-88-7, name is 1H-Imidazole-4-carbonitrile, molecular formula is C4H3N3, 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. Computed Properties of C4H3N3

lH-imidazole-4-carbonitrile (1 g, 10.74 mmol) and potassium carbonate (2.97 g, 21.49 mmol) were added to a round bottomed flask and placed under an atmosphere of nitrogen by evacuation-refill. Acetone (10 mL) was added, evacuation-refill of the vessel repeated, and the mixture stirred prior to addition of (2- (chloromethoxy)ethyl)trimethylsilane (2.091 mL, 11.82 mmol). The reaction vessel was placed under an atmosphere of nitrogen and stirred at RT for 48 h. The solvent was removed under reduced pressure, and the residue redissolved in 30 mL EtOAc and washed sequentially with 20 mL water and 20 mL brine. The combined aqueous layers were extracted with further EtOAc (2 x 30 mL). The organic layers were combined and passed through a hydrophobic frit, and the solvent was removed under reduced pressure. The sample was dissolved in DCM and purified by column chromatography using a silica cartridge (120 g) with an ethyl acetate-cyclohexane solvent system [3CV, 10-20percent; 3CV, 20percent; 5CV, 20-50percent; 9CV, 50percent]. The appropriate fractions were combined and the solvent removed in vacuo to afford the title compound in a 2: 1 ratio of the l-((2-(trimethylsilyl)ethoxy)methyl)-lH-imidazole-4-carbonitrile and l-((2- (trimethylsilyl)ethoxy)methyl)-lH-imidazole-5-carbonitrile regioisomers, as a pale yellow oil (1.71 g, 7.66 mmol, 71percent). LCMS (System B): tRET = 1.08 min; MH+ 224 (both regioisomers). l-((2-(Trimethylsilyl)ethoxy)methyl)-lH-imidazole-4-carbonitrile (for an example preparation, see Intermediate 15, 1.68 g, 7.52 mmol (2: 1 ratio of l-((2- (trimethylsilyl)ethoxy)methyl)-lH-imidazole-4-carbonitrile and H(2- (trimethylsilyl)ethoxy)methyl)-lH-imidazole-5-carbonitrile)) was added to a round bottomed flask containing THF (40 mL). Once dissolved, /V-bromosuccinimide (1.473 g, 8.27 mmol) was added, and the flask placed under an atmosphere of nitrogen. The reaction mixture was stirred at 60 °C overnight. Further 0.2 equivalents of /V-bromosuccinimide (0.268 g, 1.504 mmol) was added to the reaction mixture and the reaction left stirring at 60 °C for a further 8h. The reaction mixture was quenched with saturated sodium hydrogencarbonate solution (40 mL) and brine (40 mL) and extracted with EtOAc (3 x 40 mL). The combined organic layers were passed through a hydrophobic frit and the solvent removed under reduced pressure. The sample was loaded as a neat liquid and purified by column chromatography using a silica cartridge (80 g) with an ethyl acetate-cyclohexane solvent system [3CV, 0percent; 7CV, 0-10percent; 3CV, 10percent]. The appropriate fractions were combined and the solvent removed in vacuo to give the crude product. The crude product was dissolved in diethyl ether and filtered through Celite®, the solvent was removed from the filtrate under reduced pressure to afford the title compound as a pale yellow oil, (1.24 g, 4.10 mmol, 55percent). LCMS (System A): tRET = 1.23 min; MH+ 302, 304.

These compound has a wide range of applications. It is believed that with the continuous development of the source of the synthetic route 57090-88-7, its application will become more common.

Reference:
Patent; GLAXOSMITHKLINE INTELLECTUAL PROPERTY (NO.2) LIMITED; BAXTER, Andrew; BIT, Rino, Antonio; BROWN, John, Alexander; HIRST, David; HUMPHREYS, Philip; JONES, Katherine, Louise; PATEL, Vipulkumar, Kantibhai; (124 pag.)WO2018/41964; (2018); A1;,
Imidazole – Wikipedia,
Imidazole | C3H4N2 – PubChem

Electric Literature of 570-22-9, 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. 570-22-9 name is 1H-Imidazole-4,5-dicarboxylic acid, 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.

A mixture of CuCl2 (0.2 mmol, 26.9 mg), 4,5-H3imdc(0.1 mmol, 15.8 mg), and phen (0.1 mmol, 19.8 mg) in themolar ratio of 2:1:1 was dissolved in 4 mL distilled water and4 mL DMF (DMFDN,N0-dimethylformamide) and stirred30 min. Then, the mixture was transferred and sealed in10 mL glassflask heated at 85C for 96 h. After the samplewas cooled to room temperature, the crystals were washedwith distilled water and blue strip crystals werefiltered offand dried at room temperature. The yield of the blue crystalline product was 54% (based on Cu). Anal. Calcd forC17H10N4O4Cu: C, 51.28; H, 2.51; N, 14.08%. Found: C,51.13; H, 2.49; N, 14.02%. IR (KBr, cm1): 3687(w), 3045(m), 1683(m), 1572(s), 1474(s), 1428(s), 1238(m), 1107(m),995(w), 851(m), 779(w), 720(m), 675(w), 511(w).

At the same time, in my other blogs, there are other synthetic methods of this type of compound, 1H-Imidazole-4,5-dicarboxylic acid, and friends who are interested can also refer to it.

Reference:
Article; Zhang, Huijie; Zhou, Guangpeng; Fan, Ruiqing; Wang, Xinming; Yang, Yulin; Synthesis and Reactivity in Inorganic, Metal-Organic, and Nano-Metal Chemistry; vol. 46; 8; (2016); p. 1224 – 1235;,
Imidazole – Wikipedia,
Imidazole | C3H4N2 – PubChem

Adding a certain compound to certain chemical reactions, such as: 2301-25-9, name is 1-(4-Nitrophenyl)-1H-imidazole, belongs to imidazoles-derivatives 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 2301-25-9, name: 1-(4-Nitrophenyl)-1H-imidazole

Part B. Preparation of 1-(3-cyanophenyl)-3-methyl-5-[(4′-(N-imidazolyl)phenyl)aminocarbonyl]pyrazole The product from part A was then coupled to 1-(3-cyanophenyl)-3-methylpyrazole-5-carboxylic acid via the acid chloride methodology described previously to afford the desired amide which was then purified via standard reverse phase HPLC techniques to afford the desired material. 1 H-NMR (DMSO-d6, 300 MHz) delta: 10.73 (s,1H) 9.35 (bs,1H) 8.13 (s,1H) 7.95 (s,1H) 7.90-7.60 (complex,8H) 7.0 (s,1H) 2.30 (s,3H) ppm; ESI mass spectrum analysis m/z (rel. intensity) 369 (m+H, 100); HRMS calc. mass 369.146384; found 369.145884.

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; DuPont Pharmaceuticals Company; US6020357; (2000); A;,
Imidazole – Wikipedia,
Imidazole | C3H4N2 – PubChem