Month: June 2021

Some common heterocyclic compound, 10111-08-7, name is Imidazole-2-carboxaldehyde, molecular formula is C4H4N2O, 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. COA of Formula: C4H4N2O

Example 1: Ethyl (2-formyl-1H-imidazol-1-yl)acetate To an N-methylpyrrolidone (25 mL) solution of 1H-imidazole-2-carbaldehyde (2.0 g), potassium carbonate (2.9 g) and ethyl chloroacetate (6.7 mL) were added. The resultant solution was stirred at room temperature for 6 hours. To the reaction solution, water (50 mL) was added. The aqueous layer was extracted twice with ethyl acetate. The organic layers were combined, washed with saturated brine and then dried over anhydrous sodium sulfate. The anhydrous sodium sulfate was removed by filtration and then the organic solvent was conentrated under reduced pressure. The residue was purified by silica gel chromatography (n-hexane : ethyl acetate = 60 : 40 ? 0 : 100) to obtain the title compound having the following physical properties (2.9 g). TLC: Rf 0.54 (dichloromethane: methanol : 28% ammonia water = 90 : 10 : 1); NMR(CDCl3): delta 1.30(t, J = 7.2 Hz, 3H), 4.25(q, J = 7.2 Hz, 2H), 5.14(s, 2H), 7.15(d, J = 0.9 Hz, 1H), 7.33(d, J = 0.9 Hz, 1H), 9.79(s, 1H).

These compound has a wide range of applications. It is believed that with the continuous development of the source of the synthetic route 10111-08-7, its application will become more common.

Reference:
Patent; Ono Pharmaceutical Co., Ltd.; EP2055705; (2009); A1;,
Imidazole – Wikipedia,
Imidazole | C3H4N2 – PubChem

Adding a certain compound to certain chemical reactions, such as: 939-70-8, name is 1-(1H-Benzo[d]imidazol-2-yl)ethanone, 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 939-70-8, name: 1-(1H-Benzo[d]imidazol-2-yl)ethanone

Synthesis of target compound Y-0: 2-acetylbenzimidazole (1 mmol) at 0 CTo a solution of ethanol (10 mL) was added 60% aqueous potassium hydroxide solution (3 mL) and benzaldehyde (1 mmol),Stir at room temperature until the reaction is complete. TLC monitors the progress of the reaction.After the reaction is complete, add crushed ice and dilute hydrochloric acid solution, adjust the pH to form a precipitate,The crude extract was dried by filtration and purified by column chromatography to obtain the target compound Y-0.(Synthesis method see literature: European Journal of Medicinal Chemistry 143 (2018) 66-84) Yield: 62.6%;

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; Lanzhou University; Liu Yingqian; Wang Renxuan; Li Juncai; Yang Chengjie; Chen Yongjia; Peng Jingwen; Yin Xiaodan; Yan Yinfang; (10 pag.)CN110839636; (2020); A;,
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. 3034-38-6, name is 5-Nitro-1H-imidazole, A new synthetic method of this compound is introduced below., HPLC of Formula: C3H3N3O2

EXAMPLE 2 202 parts of 5-nitroimidazole is dissolved in 600 parts of formic acid (90% by weight), 250 parts of dimethyl sulfate is added and the whole is heated for 6 hours. The formic acid is distilled off in vacuo. 420 parts of water is added to the residue, the whole cooled to from 0 to 5 C. and the unreacted 5-nitroimidazole (60 parts) is centrifuged off. The mixture is adjusted to pH 10 with aqueous ammonia solution (25% by weight) and the precipitate is separated at 0 to 5 C. 130 parts of 1-methyl-5-nitroimidazole having a melting point of 58 to 60 C. is obtained; this is equivalent to a yield of 82% of theory based on reacted 4(5)-nitroimidazole.

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; BASF Aktiengesellschaft; US4021442; (1977); A;,
Imidazole – Wikipedia,
Imidazole | C3H4N2 – PubChem

144689-93-0, name is Ethyl 4-(1-hydroxy-1-methylethyl)-2-propylimidazole-5-carboxylate, belongs to imidazoles-derivatives compound, is considered to be a conventional heterocyclic compound, which is widely used in drug synthesis. The chemical synthesis route is as follows. Product Details of 144689-93-0

Example 3; Preparation of olmesartan medoxomilTo dimethyl acetamide (800 ml) was added 4-(1-hydroxy-1-methylethyl)-2-propyl imidazol- 5-carboxylic acid ethyl ester (100 gms) and powdered potassium carbonate (200 gms). To this was charged 4-[2-(trityltetrazol-5-yl)phenyl]benzyl bromide (300 gms) at 45-50C. The contents were stirred for 8-10 hours at 45-50C. The insolubles were filtered. The contents were cooled to 5-100C. Potassium tertiary butoxide (100 gms) was charged at a temperature below 45C. The reaction was maintained at 40-450C for 3 hrs. To this was slowly added 5-methyl-2-oxo-1 ,3-dioxane-4-yl) methyl chloride at 40-450C over a period of 1 hour. The contents were heated to 60-650C and maintained for 4 hours. The reaction mass was then cooled to 30-350C and was neutralized with concentrated hydrochloride acid. The reaction mass was filtered to remove inorganics. The reaction mass was charcoalized using charcoal (10 gms) and was stirred for 30 minutes at 40-450C. The reaction mass was filtered over hyflo. The clear filtrate was acidified with hydrochloric acid (100 ml) slowly at 25-30C. The contents were stirred at 60C for 1 hour. The reaction mass was chilled to 0-5C and was filtered to remove tritanol. The reaction mass was concentrated under reduced pressure. The residue was quenched with water (500 ml), neutralized with base and extracted in dichloromethane (500 ml).The clear dichloromethane extract was then concentrated under reduced pressure, stripped off with acetone. The residue thus obtained was isolated from the acetone (250 ml) to give 55 gms of the title compound. Chromatogrphic purity- > 99%

The synthetic route of 144689-93-0 has been constantly updated, and we look forward to future research findings.

Reference:
Patent; CIPLA LIMITED; CURTIS, Philip, Anthony; WO2008/43996; (2008); A2;,
Imidazole – Wikipedia,
Imidazole | C3H4N2 – PubChem

Application of 15108-18-6,Some common heterocyclic compound, 15108-18-6, name is 2-Hydrazinyl-1H-benzo[d]imidazole, molecular formula is C7H8N4, 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 2-hydrazino-1 H-benzimidazole (5.0 g, 33.7 mmol) in ethanol (30 ml) is added sequentially triethylamine (5 ml, 33.7 mmol) and N-cyanoformimidic acid ethyl ester (3.3 g, 33.7 mmol) with cooling. After stirring for 2 hours at 0C the resulting precipitate is filtered with suction and dried to give 3-, amino-2-(1 H-benzimidazol-2-yl)-1, 2, 4-triazole. 1H- NMR (400 MHz, d6-DMSO) : 13.0 (s, 1 H) ; 7.77 (s, 1 H) ; 7.70 (m, 2H); 7.50 (m, 2H); 7.20 (s, 2H).

The synthetic route of 15108-18-6 has been constantly updated, and we look forward to future research findings.

Reference:
Patent; BASILEA PHARMACEUTICA AG; WO2005/77939; (2005); A1;,
Imidazole – Wikipedia,
Imidazole | C3H4N2 – PubChem

These common heterocyclic compound, 3314-30-5, name is 1H-Benzo[d]imidazole-2-carbaldehyde, 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. Safety of 1H-Benzo[d]imidazole-2-carbaldehyde

General procedure: A suspension of methyl 2-(2-aminoethyl)-1 ,3-thiazole-4-carboxylate (5) (1.96 g, 10.52 mmol), 1 H- benzimidazole-2-carbaldehyde (2.31 g, 15.79 mmol) and DIPEA (1.83 ml, 10.52 mmol) in MeOH (100 ml) was stirred at room temperature for 12 h. The reaction mixture was cooled to 0°C, NaBH4 (0.597 g, 15.79 mmol) was added and the mixture stirred at room temperature for 2 h. The reaction mixture was concentrated in vacuo and the residue dissolved in EtOAc (100 ml) and washed with saturated NC03 (2 x 50 ml). The combined aqueous layers were extracted with EtOAc (3 x 50 ml) and the combined organic layers dried (MgS04), filtered and evaporated in vacuo. Purification by flash column chromatography (KP- NH, eluting with a gradient of 0-10percent MeOH / DCM) afforded the title compound (1.4 g, 38percent, 90percent purity) as a tan solid. 1 H-NMR (Methanol-d4, 250 MHz): d[ppm]= 8.27 (s, 1 H), 7.60 – 7.49 (m, 2H), 7.29 – 7.17 (m, 2H), 4.09 (s, 2H), 3.92 (s, 3H), 3.26 (t, J = 6.3 Hz, 2H), 3.10 (t, J = 6.8 Hz, 2H) HPLCMS (Method A): [m/z]: 317 [M+H]+In a similar fashion using general procedure 3, 2-(2-aminoethyl)-N-[(3-fluoropyridin-2-yl)methyl]-5-methyl- 1 ,3-thiazole-4-carboxamide dihydrochloride (113) (274 mg, 0.75 mmol), 1 H-1 ,3-benzodiazole-2- carbaldehyde (109 mg, 0.75 mmol), DIPEA (0.45 ml, 2.61 mmol) and anhydrous MgSQ (200 mg) in MeOH (10 ml) and DCM (10 ml) at room temperature for 20 h, followed by addition of NaB4 (60 mg, 1.48 mmol) afforded the title compound (140 mg, 44percent) as a pale yellow solid after purificatbn by prep-HPLC. 1 H-NMR (DMSO-d6, 500 MHz): d[ppm]= 12.17 (s, 1 H), 8.59 (t, J = 5.6 Hz, 1 H), 8.36 (dt, J = 4.7, 1.4 Hz,1 H), 7.70 (ddd, J = 9.9, 8.4, 1 .1 Hz, 1 H), 7.53 (d, J = 7.5 Hz, 1 H), 7.44 (d, J = 7.5 Hz, 1 H), 7.40 (dt, J = 8.5, 4.4 Hz, 1 H), 7.13 (p, J = 6.6 Hz, 2H), 4.65 – 4.59 (m, 2H), 3.96 (s, 2H), 3.10 (t, J = 6.8 Hz, 2H), 2.94 (t, J = 6.8 Hz, 2H), 2.68 (s, 3H) HPLCMS (Method C): [m/z]: 425.2 [M+H]+

The synthetic route of 1H-Benzo[d]imidazole-2-carbaldehyde has been constantly updated, and we look forward to future research findings.

Reference:
Patent; VIFOR (INTERNATIONAL) AG; DUeRRENBERGER, Franz; BUHR, Wilm; BURCKHARDT, Susanna; BURGERT, Michael; KALOGERAKIS, Aris; REIM, Stefan; MANOLOVA, Vania; BOYCE, Susan; YARNOLD, Christopher John; PENA, Paula; SHEPHERD, Jon; LECCI, Cristina; JARJES-PIKE, Richard; SCOTT, John; (416 pag.)WO2017/68089; (2017); A2;,
Imidazole – Wikipedia,
Imidazole | C3H4N2 – PubChem

Electric Literature of 137049-00-4, A common heterocyclic compound, 137049-00-4, name is 1-Methyl-1H-imidazole-4-sulfonyl chloride, molecular formula is C4H5ClN2O2S, 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 Example 242 B (12.74 g, 57.1 mmol) in 15 mL of dichloromethane were added triethylamine (12.13 g, 120 mmol) and 4-dimethylaminopyridine (0.35 g, 2.85 mmol). The reactionmixture was cooled to 0 C. 1 -methyl- lH-imidazole-4-sulfonyl chloride (10.82 g, 59.9 mmol) was added portion wise at 0 C. The reaction mixture was slowly warmed up to room temperature and stirred for 1 hour. The reaction mixture was partitioned with dichloromethane, and water. The organic fraction was collected, washed with water, concentrated, and purified by flash- chromatography on silica gel (100% ethyl acetate) to afford the title compound. MS (ESI) m/z 368.0 (M+H)+.

The synthetic route of 137049-00-4 has been constantly updated, and we look forward to future research findings.

Reference:
Patent; ABBVIE DEUTSCHLAND GMBH & CO. KG; ABBVIE INC.; AMBERG, Wilhelm; POHLKI, Frauke; LANGE, Udo; WANG, Ying X.; ZHAO, Hongyu H.; LI, Huan-Qiu; BREWER, Jason T.; ZANZE, Irini; DIETRICH, Justin; VASUDEVAN, Anil; DJURIC, Stevan, W.; LAO, Yanbin; HUTCHINS, Charles W.; WO2014/140310; (2014); A1;,
Imidazole – Wikipedia,
Imidazole | C3H4N2 – PubChem

Electric Literature of 641571-11-1, 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. 641571-11-1 name is 3-(4-Methyl-1H-imidazol-1-yl)-5-(trifluoromethyl)aniline, 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.

General procedure: To a solution of chloroanhydride in dry CHCl3 was addedamine R2NH2 (one equivalent) and Et3N (1.5 equivalents). The reaction mixture was stirred atroom temperature. The reaction progress was monitored by TLC. Cold water was added to thereaction mixture. The organic layer was separated from the water. The combined organic layers weredried over Na2SO4, filtered, and concentrated under vacuum. The product was purified by columnchromatography on silica gel.

At the same time, in my other blogs, there are other synthetic methods of this type of compound, 3-(4-Methyl-1H-imidazol-1-yl)-5-(trifluoromethyl)aniline, and friends who are interested can also refer to it.

Reference:
Article; Kalinichenko, Elena; Faryna, Aliaksandr; Kondrateva, Viktoria; Vlasova, Alena; Shevchenko, Valentina; Melnik, Alla; Avdoshko, Olga; Belko, Alla; Molecules; vol. 24; 19; (2019);,
Imidazole – Wikipedia,
Imidazole | C3H4N2 – PubChem

Some common heterocyclic compound, 68282-53-1, name is 5-Methyl-1H-imidazole-4-carbaldehyde, molecular formula is C5H6N2O, 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. category: imidazoles-derivatives

Triphenylphosphine (47.64 g, 181.64 mmol) and diisopropyl azodicarboxylate (36.73 g, 181.64 mmol) were dissolved in tetrahydrofuran (120.00 mL) at 0 C under a nitrogen atmosphere, followed by sequential addition of compound 1 (10.00 g, 90.82 mmol) and n-propanol (10.91 g, 181.64 mmol). The mixture was warmed to 25 C and stirred for 12 hours under a nitrogen atmosphere. After completion of the reaction, dilute hydrochloric acid (1 M) was added to the mixture to adjust to pH = 1 and extracted with ethyl acetate (50 mL × 3). The aqueous phase was adjusted to pH = 13 with sodium hydroxide (1M) and extracted with ethyl acetate (50 mL × 4). The organic phases were combined, washed with saturated brine (50 mL 2), dried over anhydrous sodium sulfate, filtered and concentrated under reduced pressure. The obtained residue was purified by column chromatography (petroleum ether: ethyl acetate = 20:1-5:1) to obtain the title compound BB-3H-2 ((12.00 g, pale-yellow oily liquid, yield: 27.60%). 1H NMR (400MHz,CDCl3) delta: 9.81 (s, 1H), 7.50 (s, 1H), 4.19 (t, J = 7.1 Hz, 2H), 2.49 (s, 3H), 1.98- 1.74 (m, 2H), 0.89 (t, J = 7.5 Hz, 3H).

These compound has a wide range of applications. It is believed that with the continuous development of the source of the synthetic route 68282-53-1, its application will become more common.

Reference:
Patent; Medshine Discovery Inc.; LUO, Yunfu; BA, Yuyong; CHEN, Shuhui; (135 pag.)EP3567028; (2019); A1;,
Imidazole – Wikipedia,
Imidazole | C3H4N2 – PubChem

Synthetic Route of 930-62-1, 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. 930-62-1, name is 2,4-Dimethylimidazole belongs to imidazoles-derivatives compound, it is a common compound, a new synthetic route is introduced below.

General procedure: The ILs as illustrated in Scheme 1, including [Ch][Im], [Ch]-[2-MIm], [Ch][4-MIm], [Ch][2,4-DMIm], [Ch][PhO] and[Ch][2-OP], were synthesized by neutralization of cholinehydroxide ([Ch][OH]) with the corresponding proton donors(i.e., imidazole, 2-methyl imidazole, 4-methyl imidazole,2,4-dimethyl imidazole, phenol, and 2-methyl phenol), respectively.In a typical experiment to synthesize [Ch][Im], anethanol solution of [Ch][OH] was mixed with equimolarimidazole, and was then stirred at room temperature for 24 h.Subsequently, ethanol and water were distilled off at 70 C under reduced pressure. The obtained [Ch][Im] was dried inhigh vacuum for 24 h at 70 C to remove possible trace ofwater. The water content of these ILs was determined by using a Karl Fisher titration and found to be less than0.1 wt%. The as-synthesized ILs were characterized byNMR spectroscopy to verify their chemical structures.

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, 2,4-Dimethylimidazole, other downstream synthetic routes, hurry up and to see.

Reference:
Article; Li, Ruipeng; Zhao, Yanfei; Li, Zhiyong; Wu, Yunyan; Wang, Jianji; Liu, Zhimin; Science China Chemistry; vol. 62; 2; (2019); p. 256 – 261;,
Imidazole – Wikipedia,
Imidazole | C3H4N2 – PubChem