Author: Jessica.F

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. 71759-89-2 name is 5-Iodo-1H-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. 71759-89-2

After dissolving 4-iodo -1Himidazole(compound 1) (1.9g, 10mmol) in dichloromethane (40mL), under ice-cooling,triethylamine (2.1mL, 15mmol), trityl chloride (3.4g, 12mmol) It was added, under argon, andstirred for 17 hours at room temperature (25 C). After completion of the reaction, water wasadded, and the mixture was extracted twice with dichloromethane. The combineddichloromethane layers were dried anhydrous sodium sulfate and concentrated under reducedpressure, silica and the resulting crude product was gel column chromatography (eluent:chloroform / n-hexane = 1/1 ? chloroform) at Purification, Compound 2 It was obtained (4.1g,9.3mmol, 93% yield).

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

Reference:
Patent; Japan Medi-Physics Co., Ltd.; Kyoto University; Okumura, Yuki; Izawa, Akihiro; Akama, Kei; Kobashi, Shinya; Abe, Tsutomu; Saji, Hideo; Kimura, Hiroyuki; (20 pag.)JP2015/93833; (2015); A;,
Imidazole – Wikipedia,
Imidazole | C3H4N2 – PubChem

33468-69-8, The chemical industry reduces the impact on the environment during synthesis 33468-69-8, name is 4-(Trifluoromethyl)-1H-imidazole, I believe this compound will play a more active role in future production and life.

a) To a vial was added 4-trifluoromethyl-1H-imidazole (953 mg, 7 mmol), 7 mL of ethanol, and sodium ethoxide (524 mg, 7.7 mmol). To this mixture was slowly added ethyl bromoacetate (1.29 g, 7.7 mmol). After 18 hours, an additional 100 muL of ethyl bromoacetate and approximately 100-200 mg of NaOEt were added. After 90 minutes, the reaction was quenched with NaHCO3 and extracted with 3¡ÁEtOAc. The organic layer was concentrated and the residue was purified by flash chromatography (SiO2, 80 g column, eluting with 15-90% EtOAc in hexanes) to provide 746 mg (48%) of the title compound as a crystalline solid. MS: (ES) m/z calculated for C8H10F3N2O2 [M+H]+ 223.1, found 223.1.

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

Reference:
Patent; ChemoCentryx, Inc.; Chen, Xi; Dragoli, Dean R.; Fan, Pingchen; Li, Yandong; Powers, Jay P.; Punna, Sreenivas; Tanaka, Hiroko; Zhang, Penglie; US2014/57937; (2014); A1;,
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 2302-25-2 as follows. 2302-25-2

Step 1: To a stirred mixture of DMF (15 mL) and NaH (60% dispersion in mineral oil, 539 mg, 21 mmol) at 0C under argon was added 4-bromo-1H-imidazole (3 g, 20 mmol) in one portion. The mixture was stirred for 5 min at 0C. A solution of 2-(trimethylsilyl)ethoxymethyl chloride (4.3 mL, 24 mmol) in DMF (3 mL) was added dropwise. Afterstirring at 0 C for 1 h, the mixture was warmed slowly to rt and stirred for 6 h. The mixture was then partitioned betweenEtOAc (100 mL) and water (50 mL). The EtOAc layer was separated and washed with brine, dried over Na2SO4, filtered,and the filtrate was concentrated under reduced pressure. The residue was purified via silica gel flash chromatography(eluting with a gradient of 100% hexanes to 100% EtOAc) to afford a regioisomeric mixture of 4-bromo-1-((2-(trimethylsilyl)ethoxy)methyl)-1H-imidazole and 5-bromo-1-((2-(trimethylsilyl)ethoxy)methyl)-1H-imidazole as an oil (2.9 g, 53%). Step 2: To a mixture of 4-bromo-1-((2-(trimethylsilyl)ethoxy)methyl)-1H-imidazole and 5-bromo-1-((2-(trimethylsilyl)ethoxy)methyl)-1H-imidazole (345 mg, 1.3 mmol) from Step 1 of this Example, and 1-methylpyrazole-4-boronicacid pinacol ester (390 mg, 1.9 mmol) in DME (3 mL) was added K2CO3 (691, 5 mmol). Argon was bubbled into themixture for 5 min followed by the addition of Pd(PPh3)2Cl2 (44 mg, 0.06 mmol). Argon was bubbled into the mixture foran additional 5 min. Then the reaction vessel was sealed and the mixture was heated at 100 C for 15 h. The mixturewas cooled to rt, then partitioned between EtOAc (100 mL) and water (50 mL). The EtOAc layer was separated andwashed with brine, dried over Na2SO4, filtered, and concentrated under reduced pressure. The residue was purified viasilica gel flash chromatography eluting with a gradient of 100% CH2Cl2 to 10% MeOH in CH2Cl2 to afford a regioisomericmixture of 1-methyl-4-(1-((2-(trimethylsilyl)ethoxy)methyl)-1H-imidazol-4-yl)-1H-pyrazole and 1-methyl-4-(1-((2-(trimethylsilyl)ethoxy)methyl)-1H-imidazol-5-yl)-1H-pyrazole as an oil (280 mg, 82%). LCMS (ESI) m/z 280 (M+H)+. Step 3: A mixture of 1-methyl-4-(1-((2-(trimethylsilyl)ethoxy)methyl)-1H-imidazol-4-yl)-1-pyrazole and 1-methyl-4-(1-((2-(trimethylsilyl)ethoxy)methyl)-1H-imidazol-5-yl)-1H-pyrazole (170 mg, 0.7 mmol) from Step 2 of this Examplewere stirred in a 1:1 mixture of TFA and CH2Cl2 (5 mL) for 15 h. The mixture was then concentrated under reducedpressure to afford 4-(1H-imidazol-4-yl)-1-methyl-1H-pyrazole (248 mg) as an oil and was used in the next step withoutfurther purification. LCMS (ESI) m/z 149 (M+H)+.

According to the analysis of related databases, 2302-25-2, the application of this compound in the production field has become more and more popular.

Reference:
Patent; Ambit Biosciences Corporation; HADD, Michael J.; HOCKER, Michael D.; HOLLADAY, Mark W.; LIU, Gang; ROWBOTTOM, Martin W.; XU, Shimin; (299 pag.)EP2766359; (2016); B1;,
Imidazole – Wikipedia,
Imidazole | C3H4N2 – PubChem

1003-21-0, A common heterocyclic compound, 1003-21-0, name is 5-Bromo-1-methyl-1H-imidazole, molecular formula is C4H5BrN2, 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 5-Bromo-1-methyl-imidazole (18.8 g, 117 mmol) in dichloromethane (50 mL) was added dropwise ethylmagnesium bromide (3 M in Et2O, 38.9 mL, 117 mmol). After stirring at room temperature for 30 min, the reaction mixture was cooled down to 0C with an ice-brine bath and N-methoxy-N-methylthiophene-3-carboxamide (20.0 g, 117 mmol) was added dropwise. The mixture was stirred for 3.5h at room temperature. The mixture was worked-up by addition of water (400 ml_), then acidified with aq. HCI (1 M) until pH = 7. After extraction with dichloromethane (3 x 100 ml_), the organic layers were washed with water (100 ml_) then dried over MgSO4 and concentrated in vacuo. Purification of the residue on silica gel afforded (1- methyl-1H-imidazol-5-yl)(3-thienyl)methanone [11.6 g, yield 41% ; HPLC/MS : m/z = 193 (M+H) ; logP(HcooH) = 0.43].

The synthetic route of 1003-21-0 has been constantly updated, and we look forward to future research findings.

Reference:
Patent; BAYER CROPSCIENCE SA; WO2009/130193; (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. 934-22-5, name is 6-Aminobenzimidazole, This compound has unique chemical properties. The synthetic route is as follows., 934-22-5

1 equivalent of the aldehyde was dissolved in AcOH (5 mL in case of 4 mmol starting material) and 1.1 equivalents of the amine were added. 1 equivalent of TMSCN was then added to the mixture. The mixture was stirred for 1.5 h at r.t.The mixture was then poured on ice/ammonia (containing 12 mL of a 25% NH3 solution in case of 4 mmol starting material). The aqueous layer was extracted 3 times by means of CH2Cl2 the organic phases were combined, dried, filtrated and the solvent was removed. The remains were re-dissolved in concentrated HCl and kept at 40 C. overnight. Water was added and the solution was neutralized by adding NaOH. The aqueous phase was extracted three times by means of CH2Cl2, thereafter the organic phases were combined and dried. The solvent was removed and the remains were taken up in triethyl-ortho formate. The mixture was kept under reflux for 1 h. The orthoester was removed and the remaining oil was dissolved in MeOH and NaBH4 (1.5 equivalents) were added. The mixture was kept at ambient temperature for 1 h, followed by 60 C. for 1 h and the reaction was quenched by addition of an aqueous solution of ammonia (12%). The aqueous layer was extracted three times by means of CH2Cl2, thereafter the organic phases were combined and dried. The solvent was removed and the remaining mixture was subjected to preparative HPLC. Example 631-(1H-benzo[d]imidazol-5-yl)-5-phenylimidazolidin-4-oneThe compound was synthesized starting from 5-aminobenzimidazole (0.75 g, 5.61 mmol), benzaldehyde (0.52 mL, 5.1 mmol), TMSCN (0.64 mL, 5.1 mmol), conc. aqueous HCl (10 mL), triethyl orthoformate (13 mL, excess), NaBH4 (0.227 g, 6 mmol) as described in method 4. Yield: 0.088 g (6.2%); MS m/z 279.3 (M+H)+; 1H NMR (400 MHz, DMSO-D6): delta 4.78-4.80 (m, H); 5.04-5.05 (m, H); 5.17-5.19 (m, H); 6.23 (d, H, J=2.1 Hz); 6.79 (dd, H, 3J=9.1 Hz, 4J=2.1 Hz); 7.24-7.27 (m, H); 7.30-7.36 (m, 4H); 7.59 (d, H, J=9.1 Hz); 8.89 (s, H); 9.16 (s, H), HPLC (lambda=214 nm), [B]: rt 6.43 min (97.8%).

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; PROBIODRUG AG; US2011/92501; (2011); A1;,
Imidazole – Wikipedia,
Imidazole | C3H4N2 – PubChem

6160-65-2, 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. 6160-65-2, name is 1,1′-Thiocarbonyldiimidazole belongs to imidazoles-derivatives compound, it is a common compound, a new synthetic route is introduced below.

4-Aminobenzoic acid (5.00 g, 36.5 mmol) was added to a methylene chloride solution (51 mL) of thiocarbonyldiimidazole (8.45 g, 47.4 mmol) and triethylamine (5.6 mL, 40.2 mmol) at an internal temperature of at most 5 C., followed by stirring under cooling with ice for one hour. The mixture was dropped to a separately prepared mixed solution of concentrated hydrochloric acid (12.2 mL, 140.5 mmol) and n-heptane (51 mL) so that the internal temperature became from 25 C. to 30 C., whereupon a pale yellow suspension was obtained. This was stirred under cooling with ice for 3 hours, and the solid was collected by filtration and washed with water (50 mL) to obtain a pale yellow crude product. The obtained crude product was subjected to an operation of washing with water (50 mL) with stirring and collection by filtration twice, followed by drying under reduced pressure to obtain 4-isothiocyanatobenzoic acid as a pale yellow solid (6.23 g, yield: 95%, HPLC purity: 100.0%).1H-NMR (DMSO-d6) delta: 7.52 (d, J=8.7 Hz, 2H), 7.97 (d, J=8.7 Hz, 2H), 13.20 (brs, 1H).

The synthetic route of 6160-65-2 has been constantly updated, and we look forward to future research findings.

Reference:
Patent; NISSAN CHEMICAL INDUSTRIES, LTD.; Takada, Junko; Iwamoto, Shunsuke; Nakano, Satoshi; US2013/245305; (2013); A1;,
Imidazole – Wikipedia,
Imidazole | C3H4N2 – PubChem

152628-03-0, 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. 152628-03-0, name is 4-Methyl-2-propyl-1H-benzo[d]imidazole-6-carboxylic acid belongs to imidazoles-derivatives compound, it is a common compound, a new synthetic route is introduced below.

Preparation 1 7-Methyl-2-propyl-3H-benzoimidazole-5-carboxylic acid ((R)-1-benzyl-2-benzyloxycarbamoylethyl)amide To a solution of 7-methyl-2-propyl-3H-benzoimidazole-5-carboxylic acid (164 mg, 752 mumol) and (R)-3-amino-N-benzyloxy-4-phenylbutyramide (TFA salt: 300 mg, 754 mumol) in DMF (10 mL) containing triethylamine (210 muL), was added HOBt (151 mug, 755 mumol) and EDC (151 mg, 788 mumol). The mixture was stirred at room temperature overnight and concentrated in vacuo, yielding a pale brown residue. The residue was dissolved in DCM (100 mL) and washed sequentially with 1M H3PO4, a saturated NaHCO3 solution, and saturated aqueous NaCl. The organic layer was collected, dried over MgSO4, and concentrated to afford the title compound as a pale yellow oil (150 mg; 41% yield), which was used without further treatment. ESMS [M+H]+ calcd for C29H32N4O3, 485.26; found 485.5.

The synthetic route of 4-Methyl-2-propyl-1H-benzo[d]imidazole-6-carboxylic acid has been constantly updated, and we look forward to future research findings.

Reference:
Patent; Choi, Seok-Ki; Fatheree, Paul R.; McKinnell, Robert Murray; Olson, Brooke; US2009/149521; (2009); A1;,
Imidazole – Wikipedia,
Imidazole | C3H4N2 – PubChem

22884-10-2, These common heterocyclic compound, 22884-10-2, name is 2-(1H-Imidazol-1-yl)acetic acid, 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.

A mixture of 1-imidazolylacetic acid (25g; 0.1538mol) and H3PO3 (18.9g; 0.2306mol) in N,N’-dimethylethyleneurea (DMEU) (150ml) is heated to a temperature of from 4O0C to 500C. PCl3 (26ml; 0.3076mol) is slowly added to the resulting suspension. The resulting mixture is heated to a temperature of from 500C to 6O0C and stirred until reaction is complete by HPLC. Water is slowly added to the reaction mixture and the resulting solution is heated, with stirring, to a temperature of from 800C to 1000C until the reaction is complete. The reaction mixture is cooled to ambient temperature and the pH is adjusted to pH 8.0 to 9.0 with aqueous sodium hydroxide solution. The resulting solution is filtered and the pH of the solution is adjusted to pH 1.5 to 2.0. Ethanol is added and precipitation of solids occurs. The solid is filtered, washed and dried under vacuum at a temperature of from 45C to 550C to a constant weight. 25.7g of zoledronic acid is obtained (molar yield: 85.6%) with a HPLC purity higher than 99.5% in area. [The yield was calculated on dry basis]The product was characterized as follows:1H NMR (D2O) delta=4.71 (t, 2H, CH2); 7.28 (dd., IH3CH); 7.44 (dd., IH, CH); 8.62 (s., IH, CH)31P NMR (D2O) delta= 16.03

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 22884-10-2.

Reference:
Patent; HOVIONE INTER LIMITED; TURNER, Craig, Robert; WO2008/56129; (2008); A1;,
Imidazole – Wikipedia,
Imidazole | C3H4N2 – PubChem

1003-21-0, A common heterocyclic compound, 1003-21-0, name is 5-Bromo-1-methyl-1H-imidazole, molecular formula is C4H5BrN2, 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.

General procedure: To a solution 5-bromo-1-methyl-(1H)-imidazole (180mg, 1.13 mmol) in THF (10 mL) HMPA (Hexamethylphosphoramide)was added (130 mg, 0.75 mmol) followed by t-BuLi (170 mg, 2.6 mmol) at -78oC, the resulted mixture wasallowed to stir at rt for 1 h. Then it was cooled back to -78oCand amidosulphone 4a-4j (0.75 mmol) was added in THF (5mL) slowly. The reaction mixture was slowly allowed to stirat rt for 2 h. Then, the reaction mixture was quenched withNH4Cl and extracted into EtOAc. The combined organiclayers were dried over Na2SO4 and distilled in vacuum to getcrude compounds 5a-5j and were purified by column chromatography using 5 % MeOH in DCM to get the final compounds5a-5j with 59-65 % yield.

The synthetic route of 1003-21-0 has been constantly updated, and we look forward to future research findings.

Reference:
Article; Thripuram, Vijaya Durga; Bollikolla, Hari Babu; Mule, Siva Nagi Reddy; Battula, Sailaja Kumari; Ala, Vasu Babu; Letters in Organic Chemistry; vol. 15; 7; (2018); p. 569 – 574;,
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 3543-73-5 as follows. 3543-73-5

[0079] To a solution of 81.3 g (650.6 mmol) 2-bromoethanol, 1 g potassium iodide and 100 g water was added 17.0g (65 mmol) compound (6). The reaction mixture was heated to 65-70 C and held at this temperature for 8 h to 12 h.The pH value of the solution was held between 4.2-5.5 during this period by dropwise addition of a solution of 20.0 g(151.4 mmol) diammonium hydrogen phosphate in 35 g water. The control of pH over the duration of the reaction waseffected through use of a pH electrode. The conversion was followed by HPLC. The reaction was continued until thefraction of compound (7A) was ? 1.5 %. Thereby ca. 8% of compound (7B) had formed and the proportion of compound(7) was ca. 87%. The reaction mixture was subsequently concentrated to dryness at ca. 55-60 C under vacuum. Tothe residue was added 150 g water and, preferably with an alkali metal carbonate, the pH value adjusted to ca. 8.5. Thedesired product (7) was extracted with 200 g methylene chloride or 225 g chloroform, and the organic phase subsequentlywashed with 60 – 80 g water. The organic phase was then concentrated to dryness and the remaining oil or alreadycrystalline residue dissolved in 200 g ethyl acetate or alternatively in 60 g actetonitrile. Compound (7) crystallised at ca.5 C and was filtered under suction, washed with 20 g cold ethyl acetate or alternatively with 15 g cold acetonitrile anddried at 60 -70 C. The yield of compound (7) was 18.3 g (52.4 mmol) with a content of ? 98.2% (80.5 % of theory). Thecrude product contained ?0.6% compound (7A) and compound (7B) respectively as well as 99.2%, wherein compound (7A)was removed below a content of 0.2 % and compound (7B) below 0.3 %. Through the course of the reaction, the contentof compound (7C) was kept below 0.15 %, as this compound can only poorly be removed by recrystallization from theabove described solvents. The overall yield of this step was 76.5% of theory and was thus ca. 12.5% higher than thatdescribed in the procedure using ethylene oxide as according to DD34727 and ca. 31% higher in comparison to thefavoured procedure of W02011079193 involving addition of Huenig?s base.Example 5: Synthesis of ethyl 4-[5-[bis(2-hydroxyethyl)amino]-1-methyl-1H-benzimidazol-

According to the analysis of related databases, 3543-73-5, the application of this compound in the production field has become more and more popular.

Reference:
Patent; HEYL Chemisch-Pharmazeutische Fabrik GmbH und Co. KG; Frey, Michael; Walther, Dirk-Detlef; EP2690096; (2014); A1;,
Imidazole – Wikipedia,
Imidazole | C3H4N2 – PubChem