Category: imidazoles-derivatives

Some common heterocyclic compound, 22884-10-2, name is 2-(1H-Imidazol-1-yl)acetic acid, molecular formula is C5H6N2O2, 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. 22884-10-2

Example 1; [0022] An oven-dried 250 ml_ 4-neck RB flask was fitted with a mechanic stirrer, K-thermocouple, condenser, nitrogen inlet and outlet and two 1/8 inch polytetrafluoroethylene (PTFE) feeding lines. The system was flushed with nitrogen for 30 minutes. Under nitrogen protection, imidazoIe-1-ylacetic acid (15.97 g, 0.13 mole), sulfolane (70 ml_) and phosphorous acid (2.67 g, 0.033 mol) were charged to the RB flask. The reaction mixture was mixed at 210 RPM and heated to 600C. PCI3 (9.18 g, 0.067mol) was added slowly (1.3 mL/mn) via a masterflex tubing pump. Five minutes were allowed for mixing. Alternately fed were 26 wt% phosphorous acid sulfolane solution (30.7 g, 10.23 g each addition at 1.6 mL/min) and PCI3 (27.5 g, 9.18 g each portion at 1.3 mL/min). Three to five minutes of mixing were allowed between additions. The addition took 1 hr 3 min and temperature was maintained between 600C and 670C. After addition was complete, the temperature of the reaction mixture was raised to 800C and was held at this temperature for 4 hours. Then the temperature of the reaction mixture was raised to 880C and held for 30 minutes. Ambient temperature water (50 g) was added in to quench the reaction. The solution was refluxed for 3 hrs . temperature, the product was vacuum-filtered and rinsed with 38 g of acetone. Zoledronic acid was obtained as a white crystalline solid (24.1 g, 95.3wt% purity by quantitative NMR, 65% yield). Example 2; [0023] An oven-dried 250 mL 4-neck RB flask was fitted with a mechanic stirrer, K-thermocouple, condenser, nitrogen inlet and outlet and two 1/8 inch PTFE feeding lines. The system was flushed with nitrogen for 30 minutes. Under nitrogen protection, imidazole-1-ylacetic acid (15.97 g, 0.13 mole), sulfolane (70 mL) and phosphorous acid (2.67 g, 0.033 mol) were charged to the RB flask. The reaction mixture was mixed at 300 RPM and heated to 600C. PCI3 (9.18 g, 0.067mol) was added in slowly (1.3 mL/min) via a masterflex tubing pump. Five minutes were allowed for mixing. Alternately fed were 26 wt% phosphorous acid sulfolane solution (30.7 g, 10.23 g each addition at 1.6 mL/min) and PCI3 (27.5 g, 9.18 g each portion at 1.3 mL/min. Three to five minutes of mixing were allowed between additions. The addition took 1 hr 6 min and temperature was maintained between 54 and 64C. After addition was complete, the temperature of the reaction mixture was raised to 800C and held for 4 hours. Then the temperature of the reaction mixture was raised to 880C and held for 30 minutes. This slurry was transferred via 3/8″ PTFE tubing using nitrogen pressure into 100 mL of pre-heated (80C) water under mixing. The resultant water solution was heated to refluxing and held at that temperature for 4 hr. It was then slowly cooled to room temperature then to 1-2C and held for 1.5 hr at this temperature. The product was collected via vacuum filtration. The cake was rinsed with acetone (20 g) and zoledronic acid was obtained as a white crystalline solid (19.1 g, 98.3 wt% purity by quantitative NMR, 53% yield). Example 3; [0024] An oven-dried 250 mL 4-neck RB flask was fitted with a mechanic stirrer, K-thermocouple, condenser, nitrogen inlet and outlet and two 1/8 inch PTFE feeding lines. The system was flushed with nitrogen for 30 minutes. Under nitrogen protection, imidazole-1-ylacetic acid (15.9 g, 0.13 mole), sulfolane (70 mL) and phosphorous acid (2.67 g, 0.033 mol) were charged to the RB flask. The reaction mixture was mixed and heated to 6O0C. PCI3 (36.7 g, 0.267 mol) and phosphorous acid (8.0 g, 0.098 mol) in – . mL/min respectively. Reaction temperature remained between 6O0C and 67C during feeding, After addition of PCI3 and phosphorous acid, the reaction slurry was heated to 800C and held at that temperature for 4 hours. This slurry was then transferred via 3/8″ PTFE tubing using nitrogen pressure into 50 m._ of pre-heated (8O0C) water under mixing. The resultant water solution was heated to refluxing and held at that temperature for 4 hr. It was then slowly cooled to 48-500C. Acetone (200 ml_) was added in slowly and then it was cooled to 1-2C and held for 2 hr at this temperature. The product was collected via vacuum filtration. The cake was rinsed with acetone (35 g) and zoledronic acid was obtained as a white crystalline solid (22.1 g, 98.6 wt% purity by quantitative NMR, 61 % yield). Example 4; [0025] A 2.5 L resin-kettle was fitted with a mechanic stirrer, K-thermocouple, condenser, nitrogen inlet and outlet, two 1/8 inch PTFE tubing as PCI3 and phosphorous acid sulfolane solution feeding lines. The system was dried under a stream of nitrogen. Under nitrogen, imidazoleacetic acid (79.92 g, 0.63 mol), phosphorous acid (13.90 g, 0.17 mol) and sulfolane (350 ml_) were added to the resin-kettle and mixed at 200 RPM. The mixture was heated to 62C then PCI3 (36.7 g, 0.267 mol) was added in slowly (1.3 mL/min) using a masterflex tubing pump. The slurry was mixed for 5 minutes. Phosphoro…

These compound has a wide range of applications. It is believed that with the continuous development of the source of the synthetic route 22884-10-2, its application will become more common.

Reference:
Patent; ALBEMARLE CORPORATION; WO2008/157050; (2008); A1;,
Imidazole – Wikipedia,
Imidazole | C3H4N2 – PubChem

3543-74-6, Adding some certain compound to certain chemical reactions, such as: 3543-74-6, name is Ethyl 4-(5-(bis(2-hydroxyethyl)amino)-1-methyl-1H-benzo[d]imidazol-2-yl)butanoate, 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 3543-74-6.

Example 12 Synthesis of 4-[5-[bis(2-chloroethyl)amino]-1-methyl-1H-benzimidazol-2-yl]butanoic acid (9, Bendamustine) To a solution of compound (7) (5.00 g, 14 mmol) in 40 ml methylene chloride thionyl chloride (4.26 g, 36 mmol) is added at 5 C. Afterwards, the solution is stirred at ambient temperature for 16 h. The solvent is removed by distillation under vacuum. To the thereby produced brown oil 45 ml of 37% hydrochloric acid and 30 ml water is added and heated to 95 C. for 30 min. Subsequently 0.9 g activated carbon is added and stirred for 10 minutes at 95 C. The product is filtered and concentrated under vacuum until a dried product is formed. Afterwards a crystallisation of compound (9) is carried out in 20 ml water. The product was filtered, washed with water and acetone and dried under vacuum for 2 h at 50 C. The yield of compound (9) amounts to 4.3 g (11 mmol) with a content >99% (73% of theory).

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 3543-74-6.

Reference:
Patent; Heyl Chemisch-pharmazeutische Fabrik GmbH & Co. KG; Frey, Michael; Walther, Dirk-Detlef; US2014/31560; (2014); A1;,
Imidazole – Wikipedia,
Imidazole | C3H4N2 – PubChem

52099-72-6, 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. 52099-72-6 name is 1-(Prop-1-en-2-yl)-1H-benzo[d]imidazol-2(3H)-one, 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 V 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 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 onto 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.

At the same time, in my other blogs, there are other synthetic methods of this type of compound, 1-(Prop-1-en-2-yl)-1H-benzo[d]imidazol-2(3H)-one, and friends who are interested can also refer to it.

Reference:
Patent; Janssen Pharmaceutica N.V.; US4035369; (1977); A;,
Imidazole – Wikipedia,
Imidazole | C3H4N2 – PubChem

2301-25-9,Some common heterocyclic compound, 2301-25-9, name is 1-(4-Nitrophenyl)-1H-imidazole, molecular formula is C9H7N3O2, 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 1-(substituted) 4-nitrobenzene IVa,b,e,f(0.01 mol) in NH4OH (20 mL, 30%), a solution of sodium dithionite(7 g, 0.04 mol) in water (30 mL) was quickly added, the reactionmixture was refluxed for 15 min. After cooling, the crude productwas filtered, washed and crystallized from methylene chloride toyield target compounds Va,b,e,f. 4-(1H-imidazol-1-yl) aniline Va Yield 70% as gray solid, mp 147 C, (as reported) [64,65].

These compound has a wide range of applications. It is believed that with the continuous development of the source of the synthetic route 2301-25-9, its application will become more common.

Reference:
Article; Abdel-Atty, Mona M.; Farag, Nahla A.; Kassab, Shaymaa E.; Serya, Rabah A.T.; Abouzid, Khaled A.M.; Bioorganic Chemistry; vol. 57; (2014); p. 65 – 82;,
Imidazole – Wikipedia,
Imidazole | C3H4N2 – PubChem

3752-24-7, 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. 3752-24-7, name is 4,5,6,7-Tetrahydro-1H-benzo[d]imidazole, This compound has unique chemical properties. The synthetic route is as follows.

General procedure: To a solution of Intermediate VI (50 mg, 0.12 mmol) in N,N-dimethylformamide (2 mL) were added phenol (17 mg, 0.18 mmol) and cesium carbonate (76 mg, 0.23 mmol). The resulting mixture was stirred for 12 h at 100C. The reaction mixture was then cooled and quenched with water (50 mL), after which the reaction mixture was extracted with dichloromethane (3 x 25 mL). The organic extracts were combined, dried over anhydrous magnesium sulfate, and filtered. The filtrate was concentrated under vacuum to give a residue, which was purified by reverse phase preparative HPLC [Column: Xbridge Prep C18 5 m OBD, 19 x 150 mm; Mobile phase: A: Water (10 mM NH4HCO3), B: acetonitrile (22% – 40%); Flow rate: 20 mL/min; UV detection: 220/254 nm] to afford compound 8-5. Compound 8-8 was prepared in an analogous fashion to Example 19C, using 4,5,6,7-tetrahydro- 1 H-benzo[d]imidazole instead of phenol.

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; MERCK SHARP & DOHME CORP.; ACHAB, Abdelghani Abe; ALTMAN, Michael D.; DENG, Yongqi; KATTAR, Solomon; KATZ, Jason D.; METHOT, Joey L.; ZHOU, Hua; MCGOWAN, Meredeth; CHRISTOPHER, Matthew P.; GARCIA, Yudith; ANTHONY, Neville John; FRADERA LLINAS, Francesc Xavier; YANG, Liping; MU, Changwei; WANG, Xiaona; SHI, Feng; YE, Baijun; ZHANG, Sixing; ZHAO, Xiaoli; ZHANG, Rong; FONG, Kin Chiu; LENG, Xiansheng; WO2014/75393; (2014); A1;,
Imidazole – Wikipedia,
Imidazole | C3H4N2 – PubChem

3314-30-5, Adding some certain compound to certain chemical reactions, such as: 3314-30-5, name is 1H-Benzo[d]imidazole-2-carbaldehyde, 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 3314-30-5.

General procedure: The equimolar aldehyde 3a?3d (1 mmol) and substituted phenylhydrazine 5a?5s (1 mmol) weremixed in CH3OH (10 mL) and stirred at room temperature [18]. After about 2 h, the reaction wascompleted (monitored by TLC). The residual crude was purified via silica gel column chromatogramusing a gradient mixture of petroleum ether and ethyl acetate to obtain the pure target compounds6a?6ai (in 45?80percent yield).

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 3314-30-5.

Reference:
Article; Wang, Xing; Chen, Yong-Fei; Yan, Wei; Cao, Ling-Ling; Ye, Yong-Hao; Molecules; vol. 21; 11; (2016);,
Imidazole – Wikipedia,
Imidazole | C3H4N2 – PubChem

7098-07-9, name is 1-Ethyl-1H-imidazole, 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. 7098-07-9

General procedure: B(OH)3 (7.43 g, 121.80 mmol) was dissolved in a warm MeOH/H2O (100 ml, 1:1) 100 ml. 1-Methylimidazole (2.00 g, 24.36 mmol) was added to the solution which was warmed for 1 h. The solvent was removed by rotary evaporation and the resulting solid was dried at 110 ¡ãC for 24 h to yield product as a white solid (7.03 g, 96percent).

Statistics shows that 7098-07-9 is playing an increasingly important role. we look forward to future research findings about 1-Ethyl-1H-imidazole.

Reference:
Article; Beckett, Michael A.; Horton, Peter N.; Hursthouse, Michael B.; Timmis, James L.; Polyhedron; vol. 77; (2014); p. 96 – 102;,
Imidazole – Wikipedia,
Imidazole | C3H4N2 – PubChem

641571-11-1, Name is 3-(4-Methyl-1H-imidazol-1-yl)-5-(trifluoromethyl)aniline, 641571-11-1, 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.

A mixture of 3 (100 mg, 0.41 mmol), p-toluic acid (42) (56 mg, 0.41 mmol), HATU (312 mg, 0.82 mmol) and DIEA (207 mg, 1 .6 mmol) in DMF (2 mL) was heated at 60 C overnight. After cooling, the reaction was directly purified by reverse prep-HPLC andthen silica gel prep-TLC to give 4-methyl-N-(3-(4-methyl-1H-imidazol-1-yl)-5- (trifluoromethyl)phenyl)benzamide (21 mg, 14%) as an off-white solid.

Statistics shows that 3-(4-Methyl-1H-imidazol-1-yl)-5-(trifluoromethyl)aniline is playing an increasingly important role. we look forward to future research findings about 641571-11-1.

Reference:
Patent; CARDIO THERAPEUTICS PTY LTD; TREUTLEIN, Herbert; ZENG, Jun; DIXON, Ian; JAMES, Ian; PALMER, James T; (169 pag.)WO2018/165718; (2018); A1;,
Imidazole – Wikipedia,
Imidazole | C3H4N2 – PubChem

872-82-2, 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. 872-82-2, name is 2-(1H-Imidazol-5-yl)ethanol, This compound has unique chemical properties. The synthetic route is as follows.

General procedure: 0.291 g (1 mmol) of cobalt(II) nitrate hexahydrate was dissolvedin 5 mL of methanol. In a separate flask 0.224 g (2 mmol) 4(5)-(bhydroxyethyl)imidazole was dissolved in 5 mL of methanol. Bothsolutions were mixed and refluxed for 60 min. The resulting solutionwas left to evaporate in room temperature. After severalmonths reddish crystals of 1 were formed in the initially obtainedpink oil.

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:
Article; Ciborska, Anna; Do??ga, Anna; Kentner, Weronika; Ma?lewski, Piotr; Wyrzykowski, Dariusz; Polyhedron; vol. 178; (2020);,
Imidazole – Wikipedia,
Imidazole | C3H4N2 – PubChem

3314-30-5, 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. 3314-30-5, name is 1H-Benzo[d]imidazole-2-carbaldehyde, A new synthetic method of this compound is introduced below.

A mixture of (S)-(+)-2-(diphenylphosphine oxide)-1,1′-binaphthyl-2′-amine 6 (200 mg, 0.426 mmol) and 2-formyl-1H-benzoimidazole (187 mg, 1.278 mmol) in the presence of 4 A MS (0.85 g) in dry toluene (8 mL) was stirred at 110 ¡ãC for 14 h in a pressure tube.

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:
Article; Eliseenko, Sviatoslav S.; Liu, Fei; Tetrahedron; vol. 75; 4; (2019); p. 518 – 526;,
Imidazole – Wikipedia,
Imidazole | C3H4N2 – PubChem