Month: August 2021

Electric Literature of 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.

Ethyl magnesium bromide (3.0 M in diethyl ether, 21.5 mL, 64.4 mmol) was added via syringe over a few minutes to a clear colorless solution of 5-bromo-1-methyl-1H-imidazole (10.4 g, 64.4 mmol) in THF (100 mL) under a nitrogen atmosphere in an ice bath. A white precipitate formed during the addition. The mixture was removed from the ice bath and was stirred for 20 minutes, then was again cooled in an ice bath before addition of 4-chloro-N-methoxy-N-methylbenzamide (10.7 g, 53.6 mmol, Intermediate 1: step a). The resulting white suspension was stirred overnight at room temperature. The reaction was quenched by addition of saturated aqueous NH4Cl and diluted with water. The mixture was partially concentrated to remove THF and was diluted with DCM. The mixture was acidified to pH 1 with 1 N aqueous HCl, then neutralized with saturated aqueous NaHCO3. The phases were separated and the aqueous phase was further extracted with DCM. The organic extracts were washed with water, then were dried (Na2SO4), filtered, and concentrated, affording a white solid. The crude product was triturated with a mixture of EtOAc:heptanes (1:1, 150 mL). The precipitated solid was collected by vacuum filtration, washing with heptanes, to afford the title compound.

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; Janssen Pharmaceutica NV; Leonard, Kristi A.; Barbay, Kent; Edwards, James P.; Kreutter, Kevin D.; Kummer, David A.; Maharoof, Umar; Nishimura, Rachel; Urbanski, Maud; Venkatesan, Hariharan; Wang, Aihua; Wolin, Ronald L.; Woods, Craig R.; Pierce, Joan; Goldberg, Steven; Fourie, Anne; Xue, Xiaohua; US2014/107094; (2014); A1;,
Imidazole – Wikipedia,
Imidazole | C3H4N2 – PubChem

20034-00-8, name is (5-Nitro-1H-benzo[d]imidazol-2-yl)methanol, 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. COA of Formula: C8H7N3O3

General procedure: One of compounds 4a-4f (5 mmol) was dissolved in THF (25 mL) and DCC (1.24 g, 6 mmol), and DMAP (0.12 g, 1 mmol) was slowly added and the mixture was stirred for 30 min. Compounds 2a-2c (5 mmol) was added and the mixture was stirred for 7-9 h. The by-product, N,N’-dicyclohexylurea, was removed by filtration. The filtrate was concentrated in vacuum to give a solid which was dissolved in CH2Cl2 and the product 5a-5n was filtered off.

The synthetic route of 20034-00-8 has been constantly updated, and we look forward to future research findings.

Reference:
Letter; Zhang; Xu; Wang; Kang; Russian Journal of General Chemistry; vol. 87; 12; (2017); p. 3006 – 3016;,
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. 10364-94-0, name is (1H-Imidazol-1-yl)(phenyl)methanone, A new synthetic method of this compound is introduced below., Formula: C10H8N2O

General procedure: To a solution of substrate (100 mg) in 2.5 mL MeCN (dry) was added DBU (0.2 equiv.), and themixture was allowed to stir at 50 C for 10 min. 1-Benzoylimidazole (1.1 equiv.) in MeCN (dry, 0.5 mL)was added to the reaction mixture in two portions and it was allowed to stir at 50 C for 8 h. MeCNwas removed under reduced pressure and the resulting mixture was purified by flash columnchromatography (ethyl acetate/petroleum ether = 1:6 to 2:1) to afford benzoylated products.

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; Lu, Yuchao; Hou, Chenxi; Ren, Jingli; Xin, Xiaoting; Xu, Hengfu; Pei, Yuxin; Dong, Hai; Pei, Zhichao; Molecules; vol. 21; 5; (2016);,
Imidazole – Wikipedia,
Imidazole | C3H4N2 – PubChem

Related Products of 3287-79-4,Some common heterocyclic compound, 3287-79-4, name is 5,6-Dimethyl-1H-benzo[d]imidazole-2(3H)-thione, molecular formula is C9H10N2S, 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-Ethylthio-5,6-dimethylbenzimidazole (I). 0,65 g (6 mmol) Ethylbromide was added to a solution 0,89 g (0,005 mol) 2-mercapto-5,6-dimethylbenzimidazole and 0,24 g (0,006 mol) sodium hydroxide in 1 ml of water and 10 ml of ethanol. The reaction mixture was refluxed for 1.5 hr before disappearing starting thione (control by using TLS), cooled and added water. The precipitated product was filtered off, washed with water and dried under atmospheric conditions. The yield was 0,91 g (88%) of compound I, m.p. 123-124 C. (from water-ethanol).1H NMR (CDCl3), delta: 1.37 (3H, t, CH2CH3); 2,32 (6H, s, 2CH3); 3,27 (2H, q, CH2CH3); 7,31 (2H, s, ArH).

These compound has a wide range of applications. It is believed that with the continuous development of the source of the synthetic route 5,6-Dimethyl-1H-benzo[d]imidazole-2(3H)-thione, its application will become more common.

Reference:
Patent; Nauchno-Issledovatelsky Institut Farmakologii Rossiiskoi Akademii Meditsinskikh Nauk; US6376666; (2002); B1;,
Imidazole – Wikipedia,
Imidazole | C3H4N2 – PubChem

Synthetic Route of 2034-22-2, 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 2034-22-2 as follows.

Preparation 15-Bromo-2-ethoxy-3H-imidazole-4-carbaldehyde 2,4,5-Tribromo-1H-imidazole (1a) (98.7 g, 324 mmol, 1.0 eq) was dissolved into 1.20 L of DCM and cooled to 0 C. To this was added DIPEA (62 mL, 360 mmol, 1.1 eq) followed by the slow addition of [beta-(trimethylsilyl)ethoxy]methyl chloride (60.2 mL, 340 mmol, 1.05 eq). The solution was slowly warmed to room temperature. After 2 hours the mixture was washed with 1M H3PO4/saturated aqueous NaCl (1:10; 2×600 mL). The organic layer was dried over MgSO4, and evaporated to dryness, yielding intermediate (1b) as faint yellow liquid that solidified on standing (137 g).Intermediate (1b) (130 g, 290 mmol, 1.0 eq) was dissolved into anhydrous EtOH (650 mL). To this was slowly added potassium t-butoxide (98.6 g, 879 mmol, 3.0 eq) and the mixture was heated to reflux for 16 hours. The mixture was then cooled to room temperature, filtered and concentrated. The resulting oil was dissolved in EtOAc (800 mL) and washed with saturated NaHCO3 (400 mL). The layers were separated and the organic was washed with saturated aqueous NaCl, dried over MgSO4, filtered and concentrated, yielding intermediate (1c) as a brown oil (115.3 g). MS m/z: [M+H+] calcd for C11H20Br2N2O2Si, 401.9 found 401.2.Intermediate (1c) (69.5 g, 174 mmol, 1.0 eq) was dissolved in anhydrous THF (600 mL) and cooled to -78 C. under nitrogen. A 2.5M solution of n-butyllithium in hexanes (72.9 mL, 180 mmol, 1.05 eq) was added dropwise and the mixture was stirred at -78 C. for 10 minutes. DMF (40 mL, 520 mmol, 3.0 eq) was then added and the mixture was stirred at -78 C. for 15 minutes and was then warmed to room temperature. The reaction was quenched with water (10 mL), diluted with EtOAc (600 mL) and was washed with water (100 mL), saturated aqueous NaCl, dried over MgSO4 and concentrated under reduced pressure. The recovered material was purified by silica gel chromatography (15-30% EtOAc:hexanes) to produce intermediate (1d) as a pale yellow oil (45 g).Intermediate (1d) (105.8 g, 303 mmol, 1.0 eq) was cooled at 0 C. in ice. TFA (300 mL) was added and the mixture was stirred at 0 C. for 15 minutes, then warmed to room temperature. After 90 minutes the mixture was concentrated under reduced pressure and redissolved in EtOAc (700 mL). The organic was washed with saturated bicarbonate (2×600 mL), saturated aqueous NaCl, dried over MgSO4, and concentrated under reduced pressure to produce a yellow solid. The material was suspended in hexanes (300 mL) and stirred at 0 C. for 30 minutes. The material was filtered and the solid was washed with cold hexanes (150 mL) to yield the title compound as a pale white solid (61.2 g). 1H-NMR (CDCl3) delta (ppm): 1.4 (m, 3H), 4.5 (m, 2H), 5.2 (s, 1H), 9.2 (d, 1H).

According to the analysis of related databases, 2034-22-2, the application of this compound in the production field has become more and more popular.

Reference:
Patent; Chao, Robert S.; Zhang, Weijiang; US2010/81697; (2010); A1;,
Imidazole – Wikipedia,
Imidazole | C3H4N2 – PubChem

Adding a certain compound to certain chemical reactions, such as: 6160-65-2, name is 1,1′-Thiocarbonyldiimidazole, 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 6160-65-2, Computed Properties of C7H6N4S

To a solution of TCDI (3.87 g, 19.55 mmol, 2.0 equiv) and DMAP (0.60 g, 4.88 mmol, 0.5 equiv) in DCM (110 mL) was added a solution of 12 (2.06 g, 9.77 mmol, 1.0 equiv) in DCM (38 mL) at 0 C. After being stirred for 10 h at rt, the resulting mixture was quenched with saturated NH4Cl solution (50 mL). The layers were separated and the aqueous layer was extracted with DCM (3×50 mL). The organic layers were combined, dried over Na2SO4, filtered, and concentrated under reduced pressure. The residue was purified by flash column chromatography on silica gel (petroleum ether/EtOAc 2:1) to furnish 11 (2.06 g, 84%) as a white powder. Colorless block-shaped crystals of 11 were obtained by slow evaporation of a petroleum ether/DCM solution after several days. Mp 185-186 C; IR (thin film): numax 2966, 2924, 1707, 1565 cm-1; 1H NMR (400 MHz, CDCl3): delta 4.48 (d, J=8.8 Hz, A of AB, 1H), 4.35 (d, J=8.8 Hz, B of AB, 1H), 2.95 (dd, J=13.2, 3.2 Hz, 1H), 2.60 (d, J=14.4 Hz, A? of A?B?, 1H), 2.55 (d, J=14.4 Hz, B? of A?B?, 1H), 2.51 (dd, J=16.2, 5.0 Hz, 1H), 2.28 (ddd, J=16.5, 11.6, 8.0 Hz, 1H), 2.16-2.11 (m, 1H), 1.87-1.81 (m, 1H), 1.69 (ddd, J=8.0, 8.0, 3.6 Hz, 1H), 1.54 (dddd, J=12.6, 12.6, 12.6, 5.4 Hz, 1H), 1.02-0.95 (m, 1H), 0.76 (ddd, J=7.2, 3.6, 3.6 Hz, 1H), 0.61 (s, 3H); 13C NMR (100 MHz, CDCl3): delta 208.8, 190.7, 94.3, 72.6, 63.1, 56.3, 39.9, 39.3, 28.2, 27.9, 19.2, 18.3, 12.5; HRMS (ESI): m/z calcd for C13H16O3SNa [M+Na]+ 275.0718, found 275.0710.

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

Reference:
Article; Yue, Guizhou; Yang, Li; Yuan, Changchun; Du, Biao; Liu, Bo; Tetrahedron; vol. 68; 47; (2012); p. 9624 – 9637,14;,
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 934-32-7 as follows. COA of Formula: C7H7N3

General procedure: A mixture of 2-aminobenzimidazole (1, 1 mmol), 4-bromobenzaldehyde (2a, 1 mmol), malononitrile (3,1 mmol) and p-TSA (10 mol%) was stirred at 80 8C undersolvent-free conditions for 30 min (Table 3, entry 1). Theprogress of the reaction was monitored by TLC. Aftercompletion of the reaction, the reaction mixture waswashed with water and ethanol, and the residue recrystallizedfrom ethanol to afford the pure product 4a (92%).

According to the analysis of related databases, 934-32-7, the application of this compound in the production field has become more and more popular.

Reference:
Article; Reddy, Mudumala Veeranarayana; Oh, Jeongsu; Jeong, Yeon Tae; Comptes Rendus Chimie; vol. 17; 5; (2014); p. 484 – 489;,
Imidazole – Wikipedia,
Imidazole | C3H4N2 – PubChem

Reference of 7189-69-7, 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. 7189-69-7, name is 1,1′-Sulfonyldiimidazole, This compound has unique chemical properties. The synthetic route is as follows.

A 20-mL vial was charged with N-(4-methoxybenzyl)-2-methylpyrimidin-4-amine (prepared analogous to Intermediate A, pages 43-44 of WO2013122897, wherein l,2,4-thiadiazol-5-amine was replaced with 2-methylpyrimidin-4-amine and 2,4-dimethoxybenzaldehyde was replaced with 4-methoxybenzaldehyde) (864 mg, 4.36 mmol) then purged with nitrogen. 2-Methyltetrahydrofuran (10.0 mL) and a solution of lithium hexamethyldisilazide in THF (1.0 M, 4.27 mL, 4.27 mmol) were added via syringe to the stirred reaction mixture. The vial was sealed with a Teflon coated cap and the reaction was warmed to 90 C and stirred vigorously. After 2 h, the red reaction mixture was allowed to cool to ambient temperature. The reaction mixture was diluted with water (25 mL) and EtOAc (25 mL). The layers were separated and the aqueous layer extracted with additional EtOAc (2 x 25 mL). The combined organic layers were washed with brine (50 mL), dried over anhydrous magnesium sulfate, filtered, concentrated under reduced pressure and purified by flash column chromatography (100-g silica gel Biotage column, eluent: gradient, 20 to 80% 3:1 EtOAc/EtOH in heptane with DCM as a 10% additive) to afford N-(4-methoxybenzyl)-N-(2-methylpyrimidin-4-y 1)-1 H-imidazole-1 -sulfonamide (450 mg, 1.25 mmol, 57.4 % yield) asa light-yellow solid, m/z (ESI) 360.2 (M+H)+

The chemical industry reduces the impact on the environment during synthesis 1,1′-Sulfonyldiimidazole. I believe this compound will play a more active role in future production and life.

Reference:
Patent; USA Anjin Corporation; M .weisi; B .C.miergelamu; T .dining; J .siteerwogen; A .gusiman-peileisi; A .beiqiao; I .E.makesi; (177 pag.)CN107531705; (2018); 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. 1003-21-0, name is 5-Bromo-1-methyl-1H-imidazole, A new synthetic method of this compound is introduced below., SDS of cas: 1003-21-0

Isopropylmagnesium chloride lithium chloride complex (1.3 M in tetrahydrofuran, 2.0 mL, 2.60 mmol) was added to an ice-water cooled solution of 5-bromo-1-methyl-1H-imidazole (444 mg, 2.76 mmol) in tetrahydrofuran (12 mL). The resulting white suspension was stirred for 5 minutes then the cooling bath was removed. After 10 minutes, the suspension was added dropwise by syringe to an ice-water cooled mixture of (3-(4-(1H-1,2,4-triazol-1-yl)benzyl)-4-chloro-2-methoxyquinolin-6-yl)(4-chlorophenyl)methanone (772 mg, 1.59 mmol, Intermediate 45, step e) and lanthanum(III) chloride bis(lithium chloride) complex solution (0.6 M in tetrahydrofuran, 5.25 mL, 3.16 mmol) in tetrahydrofuran (15 mL). After 20 minutes, saturated aqueous ammonium chloride solution was added (2 mL) then the cooling bath was removed. The mixture was diluted with water (25 mL) and ethyl acetate (50 mL). The layers were separated. The aqueous layer was extracted with ethyl acetate (25 mL). The organic layers were combined and the combined solution was dried with sodium sulfate. The dried solution was filtered and the filtrate was absorbed onto 6 g of silica gel for dry-load flash-column chromatography on silica gel eluting with 100% dichloromethane initially for 5 minutes, grading to 7% methanol-dichloromethane over 30 minutes to afford the titled compound as a white solid. 1H NMR (400 MHz, CDCl3) delta ppm 8.43 (s, 1H), 8.12 (d, J=2.1 Hz, 1H), 8.06 (s, 1H), 7.79 (d, J=8.8 Hz, 1H), 7.58-7.50 (m, 3H), 7.41 (d, J=8.5 Hz, 2H), 7.36 (d, J=1.1 Hz, 1H), 7.31 (s, 4H), 6.38 (d, J=1.1 Hz, 1H), 4.33 (s, 2H), 4.12 (s, 1H), 4.08 (s, 3H), 3.38 (s, 3H); MS m/e 571.1 [M+H]+. (3-(4-(iH-i,2,4-triazol-i-yl)ben- zyl)-4-chloro-2-methoxyquinolin-6-yl)(4-chlorophenyl)(i – methyl-iH-imidazol-5-yl)methanol was purified by HPEC (Chiralpak IA column, 50 mmx2SO mm, ethanol with 0.2% triethylamine as eluent, 30 mE/minute, 254 nm wavelength) to give two enantiomers. The first eluting enantiomer was Example 648: ?H NMR (400 MHz, CDC13) oe ppm 8.43 (s, iH), 8.12 (d, J=2.i Hz, iH), 8.06 (s, iH), 7.78 (d, J=8.7 Hz, iH), 7.56-7.50 (m, 3H), 7.41 (d, J=8.5 Hz, 2H), 7.36 (d, J=i .1 Hz, iH), 7.31 (s, 4H), 6.38 (d, J=i.i Hz, iH), 4.33 (s, 2H), 4.08 (s, 3H), 3.38 (s, 3H); MS mle 571.1 [M+H]+ and the second eluting enantiomer was Example 64C: ?H NMR (400 MHz, CDC13) oeppm8.43 (s, iH), 8.12 (d, J=2.i Hz, iH), 8.06 (s, iH), 7.78 (d, J=8.7 Hz, iH), 7.58-7.49 (m, 3H), 7.41 (d, J=8.6 Hz, 2H), 7.35 (s, iH), 7.31 (s, 4H), 6.38 (s, iH), 4.33 (s, 2H), 4.21 (s, iH), 4.08 (s, 3H), 3.38 (s, 3H); MS mle 571.1 [M+H] +.

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; Janssen Pharmaceutica NV; Leonard, Kristi A.; Barbay, Kent; Edwards, James P.; Kreutter, Kevin D.; Kummer, David A.; Maharoof, Umar; Nishimura, Rachel; Urbanski, Maud; Venkatesan, Hariharan; Wang, Aihua; Wolin, Ronald L.; Woods, Craig R.; Pierce, Joan; Goldberg, Steven; Fourie, Anne; Xue, Xiaohua; US2014/107094; (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 2963-77-1 as follows. Formula: C13H11N3

General procedure: A suspension of amine A1-A3 (1 mmol) in water is takenin a round bottomed flask; to this sulphonyl chloride(1 mmol) was added. This was stirred at room temperature while monitoring the reaction. The product was filtered,recrystallised using methanol-water and column purified.The structures were confirmed by 1H NMR, 13C NMR, IRand mass spectral analysis.

According to the analysis of related databases, 2963-77-1, the application of this compound in the production field has become more and more popular.

Reference:
Article; Vangala, Radhika; Sivan, Sree Kanth; Peddi, Saikiran Reddy; Manga, Vijjulatha; Journal of Computer-Aided Molecular Design; vol. 34; 1; (2020); p. 39 – 54;,
Imidazole – Wikipedia,
Imidazole | C3H4N2 – PubChem