Category: imidazoles-derivatives

Electric Literature of 152628-02-9, 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. 152628-02-9 name is 1,7′-Dimethyl-2′-propyl-1H,1’H-2,5′-bibenzo[d]imidazole, 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.

90 gm of BIM in 500 ml DMF was added at about 150C followed by addition of 41.4 gm potassium tertiary butoxide and stirred for about 15-20 minutes at 15-200C. 138.7 gm of Ethyl-4-(bromomethyl) biphenyl-2-carboxylate in 250 ml DMF was added slowly over 45 to 60 minutes maintaining temperature 15-200C. The reaction mixture was stirred for about 30 minutes. 1500 ml of Ethyl acetate and 2000 ml water were added to the reaction mixture at 20-300C and the layer was allowed to separate. Aqueous layer was extracted with 1000 ml of ethyl acetate. The combined organic layer was washed with water [3 X 1000 ml]. The organic layer was dried over anhydrous sodium sulfate and dried ethyl acetate solution was filtered. The ethyl acetate was removed by distillation under vacuum at 50-550C. 500 ml of fresh ethyl acetate was added to the residue to make a solution at 60-650C. The reaction mixture was cooled to 50-550C. 200 ml of hexane was added and stirred for 30 minutes. The reaction mixture was cooled to 100C and further stirred for about 1 hour at 5-10 C.The material was filtered and washed with a mixture of ethyl acetate and 200 ml hexane (7:3 v/vl) at 8-120C. The wet cake was dissolved in 600 ml ethyl acetate at 60-650C and cooled to ~50 0C. 240 ml of hexane was added and mixture was cooled with stirring to 100C and then stirred for about one hour. The material was filtered and washed with a mixture of 120 ml Ethyl acetate and hexane (7:3 v/v) at 8-12 C. The material was suction dried and used as such. 108.2 gm of product is obtained with 99.6 % purity (By HPLC).

At the same time, in my other blogs, there are other synthetic methods of this type of compound, 1,7′-Dimethyl-2′-propyl-1H,1’H-2,5′-bibenzo[d]imidazole, and friends who are interested can also refer to it.

Reference:
Patent; CADILA PHARMACEUTICALS LTD.; KHAMAR, Bakulesh, Mafatlal; SIDDIQUI, Ishrat, Husain; PONNAIAH, Ravi; MODI, Indravadan, Ambalal; WO2010/18441; (2010); A2;,
Imidazole – Wikipedia,
Imidazole | C3H4N2 – PubChem

Adding a certain compound to certain chemical reactions, such as: 822-36-6, name is 4-Methyl-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 822-36-6, Recommanded Product: 822-36-6

Example 18: Preparation of 3-(4-methyl-imidazol-1-yl)-5-trifluoromethyl benzoic acid : In 3 lit four necked round bottom flask equipped with mechanical stirrer, thermometer, reflux condenser and an addition funnel, 3-fluoro-5-(trifluoromethyl)benzoic acid (80 g), 4-methylimidazole (47.2 g) and dimethylacetamide (400 ml) was added, heated to 80-85C and stirred for 12 hrs at the same temperature. The reaction mass was cooled to room temperature, diluted with water (500 ml) and extracted with ethyl acetate (1000 ml). The solvent from organic layer was distilled off under vacuum and th obtained residue was titrated with water to get the title compound. Yield: 63 g.

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

Reference:
Patent; LAURUS LABS LTD; BOLLU, Ravindra Babu; BANDLAMUDI, Veera Narayana; KUDIRILLA, Vivek Kumar; VEMULA, Rambabu; VASIREDDI, Uma Maheswer Rao; (36 pag.)WO2019/130254; (2019); A1;,
Imidazole – Wikipedia,
Imidazole | C3H4N2 – PubChem

Application of 1402838-08-7, 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. 1402838-08-7, name is 2-(1-Trityl-4-imidazolyl)benzaldehyde, This compound has unique chemical properties. The synthetic route is as follows.

The compound 5-e (540 mg, 1.30 mmol), compound 29-e (see Patent: WO2012142237)(400 mg, 1.37 mmol), potassium carbonate (360 mg, 2.60 mmol) and ethanol (20 mL) was refluxed for 1 hour. Will reverseThe mixture was concentrated under reduced pressure, dichloromethane (50 mL) was added, washed successively with water (20 mL x 3) and saturated brine (50 mL).The organic phase was dried over anhydrous sodium sulfate, filtered and concentrated under reduced pressure. The residue was recrystallized from petroleum ether and ethyl acetate to giveCompound 29-d (590 mg, 78%) as a white solid.

The chemical industry reduces the impact on the environment during synthesis 2-(1-Trityl-4-imidazolyl)benzaldehyde. I believe this compound will play a more active role in future production and life.

Reference:
Patent; Shanghai Yingli Pharmaceutical Co., Ltd.; Xu Zusheng; Lou Yangtong; Wu Tianzhi; (87 pag.)CN106478634; (2017); A;,
Imidazole – Wikipedia,
Imidazole | C3H4N2 – PubChem

Related Products of 14741-71-0,Some common heterocyclic compound, 14741-71-0, name is Ethyl 2-(1H-benzo[d]imidazol-2-yl)acetate, molecular formula is C11H12N2O2, 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: Et3N(4 mmol) was added dropwise to a stirred solution of the benzimidazole (1.5 mmol) and the dichloride compound 1(2 mmol) in CH2Cl2 (3 mL) at 0 C. The resulting mixture was stirred at room temperature overnight and worked up as for Method A.

These compound has a wide range of applications. It is believed that with the continuous development of the source of the synthetic route Ethyl 2-(1H-benzo[d]imidazol-2-yl)acetate, its application will become more common.

Reference:
Article; Innes, Dylan; Perkins, Michael V.; Liepa, Andris J.; Francis, Craig L.; Australian Journal of Chemistry; vol. 71; 1; (2018); p. 58 – 69;,
Imidazole – Wikipedia,
Imidazole | C3H4N2 – PubChem

Related Products of 53484-15-4,Some common heterocyclic compound, 53484-15-4, name is 5-Bromo-1-methyl-1H-benzo[d]Imidazole, molecular formula is C8H7BrN2, 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.

Into a 100-mL round-bottom flask purged and maintained with an inert atmosphere of nitrogen, was placed a solution of (S)-(4-(4-(tert-butoxycarbonyl)-3-methylpiperazine-l- carbonyl)-3-fluorophenyl)boronic acid (837 mg, 2.29 mmol, 1.00 equiv) in toluene (20 mL), 5-bromo-l-methyl- lH-l,3-benzodiazole (400 mg, 1.90 mmol, 0.83 equiv), Pd(PPh3)4 (264 mg, 0.23 mmol, 0.10 equiv), sodium carbonate(2M, 10 mL), ethanol (2.8 mL). The resulting mixture was stirred overnight at 95C. After cooled to room temperature, the resulting solution was diluted with 20 mL of H20, extracted with 3×30 mL of ethyl acetate. The organic layers were combined, dried over anhydrous sodium sulfate and concentrated under vacuum. The residue was applied onto a silica gel column with dichloromethane/methanol (90: 10). The collected fractions were combined and concentrated under vacuum. This resulted in 800 mg (77%) of the title compound as a brown solid. LC-MS (ES, m/z) 453 [M+H]+

These compound has a wide range of applications. It is believed that with the continuous development of the source of the synthetic route 5-Bromo-1-methyl-1H-benzo[d]Imidazole, its application will become more common.

Reference:
Patent; FORMA THERAPEUTICS, INC.; BAIR, Kenneth, W.; LANCIA, David, R.; LI, Hongbin; LOCH, James; LU, Wei; MARTIN, Matthew, W.; MILLAN, David, S.; SCHILLER, Shawn, E.r.; TEBBE, Mark, J.; WO2014/164749; (2014); A1;,
Imidazole – Wikipedia,
Imidazole | C3H4N2 – PubChem

Adding a certain compound to certain chemical reactions, such as: 7189-69-7, name is 1,1′-Sulfonyldiimidazole, 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 7189-69-7, Product Details of 7189-69-7

To a pre-washed (hexane) suspension of NaH (60% in mineraloil, 284 mg, 7.11 mmol) in dry DMF (10 mL), a soln of 7 (1.06 g,1.42 mmol) in dry DMF (15 mL) was slowly added under argonatmosphere at 0 C. The mixture was stirred at 0 C for 30 min,cooled to 30 C, treated with Im2SO2 (411.5 mg, 2.08 mmol) andfurther stirred at 30 C. After 1 h, TLC analysis (4:6 hexane-EtOAc) revealed the complete disappearance of the starting material.The reaction mixture was then cooled to 40 C, the excess ofNaH was destroyed by addition of MeOH (0.5 mL). After 10 min,Et2O (20 mL) and crushed iced-water were added. The organicphase was separated and the aqueous layer was extracted withEt2O (3 50 mL). The collected organic phases were dried, filtered,and concentrated under diminished pressure. Flash chromatographicpurification over silica gel of the reaction product (6:4 hexane-EtOAc) gave pure 8 (1.02 g, 83% yield) as a clear syrup; Rf 0.37(6:4 hexane-EtOAc), [a]D 13.6 (c 1.16, CHCl3); 1H NMR (CD3CN): d8.01 (dd, 1H, J2,4 1.3 Hz, Im-H2), 7.46 (dd, 1H, J2,5 0.9 Hz, J4,5 1.6 Hz,Im-H4), 7.40-7.24 (m, 15H, Ar-H), 7.01 (dd, 1H, Im-H5), 5.25 (dd,1H, J10,20 0.6 Hz, J20,30 2.3 Hz, H-20), 4.94 (d, 1H, H-10), 4.68, 4.48(AB system, 2H, JA,B 10.8 Hz, CH2Ph), 4.64, 4.49 (AB system, 2H,JA,B 11.8 Hz, CH2Ph), 4.56, 4.47 (AB system, 2H, JA,B 11.9 Hz, CH2Ph),4.35 (m, 2H, H-1, H-2), 4.20 (dt, 1H, J4,5 4.9 Hz, J5,6a = J5,6b 6.4 Hz,H-5), 4.03 (dd, 1H, J2,3 7.3 Hz, J3,4 1.9 Hz, H-3), 3.94 (m, 2H, H-6a,H-6b), 3.89 (dd, 1H, H-4), 3.70 (dd, 1H, J30,40 10.5 Hz, H-30), 3.68(m, 3H, H-40 , H-60a, H60b), 3.39 (m, 1H, H-50), 3.38, 3.35 (2s, each3H, 2 OMe-1), 1.35, 1.34, 1.32, 1.29 (4s, each 3H, 2 CMe2);13C NMR (CD3CN): d 139.3, 139.1, 138.4 (3 Ar-C), 138.1 (Im-C2),131.2 (Im-C4), 129.3-128.6 (Ar-CH), 119.7 (Im-C5), 110.5, 109.0(2 CMe2), 106.3 (C-1), 99.0 (C-10), 84.6 (C-20), 78.7 (C-4), 78.0

At the same time, in my other blogs, there are other synthetic methods of this type of compound, 1,1′-Sulfonyldiimidazole, and friends who are interested can also refer to it.

Reference:
Article; Guazzelli, Lorenzo; Catelani, Giorgio; D’Andrea, Felicia; Gragnani, Tiziana; Carbohydrate Research; vol. 388; 1; (2014); p. 44 – 49;,
Imidazole – Wikipedia,
Imidazole | C3H4N2 – PubChem

Some common heterocyclic compound, 288-32-4, name is 1H-Imidazole, molecular formula is C3H4N2, 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. name: 1H-Imidazole

General procedure: NH-containing heterocycle (1.4 mmol) and DMF (2.0 mL) were added to a mixture of CuCl (15.0 mol%) and ligand 1 (20.0 mol%) in DMF (2.0 mL), aryl iodide (1.0 mmol), NaOH (2.0 mmol). The mixture was vigorously stirred at 120 C for 14 h under a dry nitrogen atmosphere. After completion of the reaction (as monitored by TLC), H2O was added and the organic layer was extracted with EtOAc, washed with brine and dried over MgSO4. The solution was filtered and the solvent was evaporated under reduced pressure. The residue was purified by column chromatography. The purity of the compounds was checked by 1H NMR and yields are based on aryl iodide. All the products are known and the spectroscopic data (FT-IR and NMR) and melting points were consistent with those reported in the literature.

These compound has a wide range of applications. It is believed that with the continuous development of the source of the synthetic route 288-32-4, its application will become more common.

Reference:
Article; Sajadi, S. Mohammad; Maham, Mehdi; Journal of Chemical Research; vol. 38; 2; (2014); p. 128 – 129;,
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 17228-38-5 as follows. Safety of N-Methyl-1H-benzo[d]imidazol-2-amine

Example 2.03 can also be prepared as follows:(3R)-4-(2-Chloro-6-(1-((R)-S-methylsulfonimidoyl)cyclopropyl)pyrimidin-4-yl)-3-methylmorpholine (179 mg, 0.54 mmol), N-methyl-1H-benzo[d]imidazol-2-amine (159 mg, 1.08 mmol) and cesium carbonate (529 mg, 1.62 mmol) were suspended in DMA (2 ml) and sealed into a microwave tube. The reaction mixture was heated to 80 C. for 90 minutes in a microwave reactor and then cooled to RT. The reaction mixture was filtered and then purified by preparative HPLC, using decreasingly polar mixtures of water (containing 1% NH3) and MeCN as eluents. Fractions containing the desired compound were evaporated to afford a solid (55.0 mg). In an additional procedure: (R)-4-(2-Chloro-6-(1-((R)-S-methylsulfonimidoyl)cyclopropyl)pyrimidin-4-yl)-3-methylmorpholine (89 mg, 0.27 mmol), N-methyl-1H-benzo[d]imidazol-2-amine (79 mg, 0.54 mmol) and cesium carbonate (263 mg, 0.81 mmol) were suspended in DMA (2 ml) and sealed into a microwave tube. The reaction mixture was heated to 80 C. for 5 hours in a microwave reactor and then cooled to RT. The reaction mixture was filtered, and combined with the solid from the previous procedure and then purified by preparative HPLC using decreasingly polar mixtures of water (containing 1% NH3) and MeCN as eluents. Fractions containing the desired compound were evaporated and the residue was purified by preparative HPLC using decreasingly polar mixtures of water (containing 0.1% formic acid) and MeCN as eluents. Fractions containing the desired compound were evaporated and the residue purified again by preparative HPLC using decreasingly polar mixtures of water (containing 1% NH3) and MeCN as eluents. Fractions containing the desired compound were evaporated to afford the title compound (38.4 mg, 32%); 1H NMR (400 MHz, DMSO-d6) 1.29 (3H, d), 1.52 (3H, m), 1.72-1.86 (1H, m), 3.02 (3H, s), 3.03 (3H, d), 3.26-3.33 (1H, m), 3.52 (1H, t), 3.66 (1H, d), 3.80 (1H, d), 4.01 (2H, m), 4.12 (1H, s, obscured by methanol peak), 4.51 (1H, s), 6.77 (1H, s), 6.98 (1H, t), 7.09 (1H, t), 7.25 (1H, d), 8.08 (1H, d), 8.71 (1H, d); m/z: (ES+) MH+, 442.16. Chiral HPLC: (HP1100 System 4, 20 mum Chiralpak AS (250 mm×4.6 mm) column eluting with iso-Hexane/IPA/TEA 70/30/0.1) Rf, 11.984 97.9%.

According to the analysis of related databases, 17228-38-5, the application of this compound in the production field has become more and more popular.

Reference:
Patent; ASTRAZENECA AB; US2011/306613; (2011); 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. 50995-95-4, name is 2-Propylimidazole, A new synthetic method of this compound is introduced below., Safety of 2-Propylimidazole

Add 2,4-dichloropyrimidine (3.000 g, 20.2 mmol), 2-propylimidazole (2.662 g, 24.2 mmol) and potassium carbonate (4.168 g, 30.3 mmol)Add it to a round bottom flask (100 mL), using acetonitrile (40 mL) as a solvent,The reaction was carried out at 50 C for 11 hours. TLC was followed until the reaction was complete,Cooled to room temperature, distilled under reduced pressure,Purification by column chromatography to obtain white solid intermediate III-7(1.453 g), yield: 32.4%.

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; Southwest University; Zhou Chenghe; Wang Ya; Li Ruixue; Wang Jie; Geng Rongxia; (21 pag.)CN110452224; (2019); 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. 288-32-4, name is 1H-Imidazole, A new synthetic method of this compound is introduced below., Recommanded Product: 1H-Imidazole

Take 7kg sodium hydride DMF solution with 20% concentration, add 7kg 20% imidazole DMF solution under ice-cooling at a speed of 2ml/s with stirring, stir at 60C for 60min; use ice salt After the bath is cooled, 5 kg of 1-chloro-4-(4-chlorophenyl)-2-butanol is slowly added, and the reaction is stirred at 60 C. for 120 min. After cooling with an ice bath, the reaction solution is obtained; in the reaction 25% by weight of n-hexane was added to the solution, stirred for 15 minutes at 3 revolutions per second, and then added to the solution.35 wt% of ice water was stirred at 3 rev/s until the precipitation stopped. After filtration, the cake was washed once with water 1/3 times the weight of the cake, and dried at 2825 r/min. After 60 minutes, ethyl acetate and activated charcoal were used 2.5 times and 0.05 times the weight of the centrifugally dried product, respectively, and allowed to stand at -5 C. for 13 hours to recrystallize, and the recrystallized product was dried at 50 C., ie, 1-(2-Hydroxy-4-(4-chlorophenyl)butyl)-1H-imidazole, purity99.31%.

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; Zhuzhou Qianjin Pharmaceutical Co., Ltd.; Li Sanxin; Peng Kaifeng; Ling Yonggen; Wen Fengqiu; Gong Yun; Li Fujun; (13 pag.)CN105198818; (2018); B;,
Imidazole – Wikipedia,
Imidazole | C3H4N2 – PubChem