Author: Jessica.F

Some common heterocyclic compound, 705-09-9, name is 2-(Difluoromethyl)-1H-benzo[d]imidazole, molecular formula is C8H6F2N2, 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: C8H6F2N2

A mixture of 2-difluoromethyl-lH-benzimidazole (2.22 g), 2,4-dichloro- 6-morpholinopyrimidine (2.81 g), potassium carbonate (6.63 g) and DMF (50 ml) was stirred under nitrogen and heated to 90C for 16 hours. The resultant mixture was cooled, filtered and the filtrate was evaporated. The resultant product was purified by column chromatography on silica using increasingly polar mixtures of ethyl acetate in methylene chloride as eluent. The solid so obtained was washed with a 1 : 1 mixture of isohexane and diethyl ether. There was thus obtained 4-chloro-2-(2-difiuoromethylbenzimidazol- 1 -yl)-6-morpholinopyrimidine (3.17 g); NMR Spectrum: (DMSOd6) 3.75 (s, 8eta), 7.09 (s, IH), 7.45-7.47 (m, IH), 7.50-7.54 (m, IH), 7.57-7.83 (t, IH), 7.87 (d, IH), 8.31 (d, IH); Mass Spectrum: M+H+ 366.

These compound has a wide range of applications. It is believed that with the continuous development of the source of the synthetic route 705-09-9, its application will become more common.

Reference:
Patent; ASTRAZENECA AB; ASTRAZENECA UK LIMITED; BUTTERWORTH, Sam; GRIFFEN, Edward, Jolyon; PASS, Martin; WO2008/32072; (2008); A1;,
Imidazole – Wikipedia,
Imidazole | C3H4N2 – PubChem

Reference of 3314-30-5, 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. 3314-30-5, name is 1H-Benzo[d]imidazole-2-carbaldehyde belongs to imidazoles-derivatives compound, it is a common compound, a new synthetic route is introduced below.

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).

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

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

Synthetic Route of 1632-83-3, The chemical industry reduces the impact on the environment during synthesis 1632-83-3, name is 1-Methylbenzimidazole, I believe this compound will play a more active role in future production and life.

General procedure: A solution of copper(II) acetate (7.3 mg, 0.04 mmol), triphenylphosphine (21 mg, 0.08 mmol), benzothiazole (1, 22 muL, 0.2 mmol), N-methylaniline 2a (0.088 mL, 0.8 mmol) and NaOAc (66 mg, 0.8 mmol) in 1.0 mL of xylene was stirred at 140 C for 20 h under O2. After cooling to room temperature, the mixture was passed through a Celite pad, which was washed with chloroform repeatedly. The filtrate was washed with water three times. The organic layer was concentrated under reduced pressure to leave a crude oil, which was purified by column chromatography on silica gel to afford 39 mg of 3a as a colourless oil (75%).

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, 1-Methylbenzimidazole, other downstream synthetic routes, hurry up and to see.

Reference:
Article; Mitsuda, Shinobu; Fujiwara, Taiki; Kimigafukuro, Katsuyoshi; Monguchi, Daiki; Mori, Atsunori; Tetrahedron; vol. 68; 18; (2012); p. 3585 – 3590;,
Imidazole – Wikipedia,
Imidazole | C3H4N2 – PubChem

68282-53-1, name is 5-Methyl-1H-imidazole-4-carbaldehyde, 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. Quality Control of 5-Methyl-1H-imidazole-4-carbaldehyde

43[0095] To a solution of O-adamantylhydroxylamine (0.17g, lmmol) and 4-methyl-lH- imidazole-5-carbaldehyde (0.1 Ig, lmmol) in 5ml anhydrous DMSO was added 3mul CH3COOH. The resulting mixture was stirred at ambient temperature overnight. H2O (40ml) was added and the mixture was lyophilized to give white solid. (0.25g, Yield: 96%). 1H-NMR (360 MHz, CDCl3) delta 8.08 (s, IH), 7.55 (s, IH), 2.31 (s, 3H), 2.18 (br s, 3H), 1.88 (br s, 6H), 1.63 (br s, 6H); 13C-NMR (90 MHz, CDCl3) delta 138.5, 138.3, 135.22, 78.16, 41.79, 36.65, 30.84, 12.10; ESI-MS: Calculated for C15H2iN3O (M + H)+ 260.4, Found: 260.2.

The synthetic route of 68282-53-1 has been constantly updated, and we look forward to future research findings.

Reference:
Patent; THE TRUSTEES OF THE UNIVERSITY OF PENNSYLVANIA; DeGRADO, William, F.; WANG, Jun; WO2011/22191; (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. 1072-63-5, name is 1-Vinyl-1H-imidazole, A new synthetic method of this compound is introduced below., name: 1-Vinyl-1H-imidazole

(1) Add an appropriate amount of acetonitrile as a solvent to dissolve N-vinylimidazole in a three-necked flask for later use, weigh and configure it as Br (CH2) 6Br:N-vinylimidazole = 1: 2 (molar ratio) mixed product is ready for use; N-vinylimidazole acetonitrile solution is circulated at 82 C under reflux conditions.The above mixture was added dropwise to a three-necked flask and continuously stirred for 24 h.After the reaction, a pale yellow liquid was obtained, and the residual solvent was evaporated under reduced pressure.It was washed several times with ethyl acetate and acetone successively; the product was dried under vacuum to obtain (ViIm) 2C6 (Br) 2.

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; Chengdu Mingdian Shijia Biological Technology Co., Ltd.; Song Hang; (15 pag.)CN110590675; (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., Quality Control of 1H-Imidazole

(a) N-Benzylimidazole To a solution of 24 g (1 mol) of sodium hydride in 500 ml of N,N-dimethylformamide, there was added, drop-by-drop, a solution of 68 g (1 mol) of imidazole in 150 ml of N,N-dimethylformamide. The medium was stirred for 2 hours and then 126.6 g (1 mol) of benzyl chloride were added. The solvent was eliminated and the residue was taken up with ethyl acetate and washed with water. The organic phase was dried and concentrated to provide an oil which crystallized when cold. In this manner, N-benzylimidazole was obtained in a yield of 70%.

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; Sanofi; US5017579; (1991); A;,
Imidazole – Wikipedia,
Imidazole | C3H4N2 – PubChem

Synthetic Route of 405173-97-9, 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. 405173-97-9 name is 2-(2-Chloroethyl)-1H-benzo[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.

EXAMPLE 230 N-[2-(2-(2-Benzimidazolyl)ethyl)thioethyl]-N’-cyano-N”-methylguanidine Using 2-(2-chloroethyl)benzimidazole, prepared by treating 2-(2-hydroxyethyl)benzimidazole with thionyl chloride, as the starting material in the procedure of Example 17 gives the title compound.

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

Reference:
Patent; Smith Kline & French Laboratories Limited; US3950333; (1976); A;,
Imidazole – Wikipedia,
Imidazole | C3H4N2 – PubChem

Synthetic Route of 39021-62-0,Some common heterocyclic compound, 39021-62-0, name is 1-Methyl-1H-imidazole-5-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.

To a flask containing 6-bromo-4-chloro-2-methoxy-3-(4-(trifluoromethyl)benzyl)quinoline (3.0 g, 6.97 mmol, Intermediate 10: step d) was added THF (40 ml) and the solution was cooled to -70 C. n-BuLi (2.5 M in hexanes, 2.8 mL, 7 mmol) was added dropwise. After 2 minutes, 1-methyl-1H-imidazole-5-carbaldehyde (1.2 g, 9 mmol, in 10 mL THF) was introduced. After 15 minutes, the dry-ice bath was replaced with a 0 C. bath. After 35 minutes the reaction mixture was quenched with aqueous NH4Cl solution and the aqueous portion was extracted with EtOAc:THF (10:2) 5*50 mL. The combined organics were washed with brine, dried over Na2SO4, filtered and concentrated. Chromatography on silica gel (30% acetone-DCM increasing to 5% MeOH) provided the title compound. 1H NMR (500 MHz, CDCl3) delta ppm 8.21 (s, 1H), 7.82 (d, J=8.6 Hz, 1H), 7.60 (dd, J=8.6, 1.9 Hz, 1H), 7.50 (d, J=8.2 Hz, 2H), 7.39 (d, J=8.1 Hz, 2H), 7.33 (s, 1H), 6.65 (s, 1H), 6.04 (s, 1H), 4.34 (s, 2H), 4.07 (s, 3H), 3.55 (s, 3H). MS (ESI): mass calcd. for C23H19ClF3N3O2, 461.1, m/z found 462.1 [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 1-Methyl-1H-imidazole-5-carbaldehyde, its application will become more common.

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.; FOURIE, ANNE; XUE, XIAOHUA; CUMMINGS, MAXWELL D.; US2015/105372; (2015); 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 152628-02-9 as follows. HPLC of Formula: C19H20N4

4-Methyl-6-(l -methyl benzimidazol-2-yl)-2-n-propyl lH-benzimidazole (50gms) is suspended in acetone (500 ml), aqueous potassium hydroxide solution (13.8 gms in 31.4 ml of water) is added and mixed for 30 min at temperature of 25 – 3O0C. The mass is cooled, t-Butyl 4″-(bromomethyl)-2-biphenyl-2-carboxylate (50 gms) slowly added over 30 min and maintained the reaction mass at temperature of 0 – 50C for 6 hrs. The solvent is distilled off from the reaction mass at temperature below 5O0C under vacuum. Water (500 ml), Methylene chloride (300 ml) is added to the residue and mixed for about 15 min. pH of the reaction mass is adjusted with hydrochloric acid to 1.8 at temperature of 20 – 250C. Reaction mass is allowed to settle, layers are separated, aqueous layer is extracted with methylene chloride (100 ml). Combined organic layer is washed water (100 ml), treated with charcoal (5 gms) and dried the organic layer over anhydrous sodium sulphate (10 gms). Solvent is distilled off from the dried organic layer at EPO temperature below 50upsilonC finally under vacuum. Acetone (100 ml) is added to the residue,* mixed for about 10 min and solvent is distilled off under vacuum at temperature below5O0C. Acetone (300 ml) is added to the residue, cooled the mass to 3O0C and pH of the mass is adjusted to 2.8 with IPA HCl (about 2 ml). Temperature of reaction mass is raised, maintained for 1 lir at reflux temperature, cooled and maintained for 30 min at 25- 3O0C. Product is filtered, wet cake is washed with acetone (50 ml) and dried the wet cake at temperature of 60 – 7O0C till becomes constant weight.The Dry weight of tert Butyl 4Lambda-[4-Methyl-6-(l-methyl-lH-benzimidazol-2-yl)-2-n- propyl- lH-benzimidazol-l-yl-methyl]biphenyl-2-carboxylate hydrochloride is 73 gms (Yield: 73%). HCl content: 5.85 % w/w

According to the analysis of related databases, 152628-02-9, the application of this compound in the production field has become more and more popular.

Reference:
Patent; MATRIX LABORATORIES LIMITED; WO2007/10558; (2007); 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. 17289-25-7, name is (1-Methyl-1H-imidazol-4-yl)methanol, This compound has unique chemical properties. The synthetic route is as follows., Quality Control of (1-Methyl-1H-imidazol-4-yl)methanol

Step 4: Diisopropylazodicarboxylate 40percent solution in toluene (0.27 mL, 0.51 mmol) was added under stirring to a solution of 5-(4-(trifluoromethoxy)phenyl)benzo[d]isoxazol-3-ol (100 mg, 0.34 mmol), triphenylphosphine on resin (3 mmol/g) (330 mg, 1 mmol), and 1-methylimidazol-4-yl methanol (60 mg, 0.51 mmol) in THF. The reaction mixture was stirred at ambient temperature overnight. Volatiles were evaporated under vacuum and the residue was purified on 12 g silica gel with 0-20percent methanol in dichloromethane and gave the title compound (40 mg, 0.103 mmol) as yellowish oil. 1H NMR (400 MHz, DMSO-d6) delta 8.07-7.97 (m, 2H), 7.89-7.81 (m, 2H), 7.54 (d, J=8.7 Hz, 1H), 7.50-7.41 (m, 3H), 7.12 (d, J=1.3 Hz, 1H), 5.03 (s, 2H), 3.59 (s, 3H). MS: 390 (MH+).

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 17289-25-7.

Reference:
Patent; Graupe, Michael; Lu, Yafan; Zablocki, Jeff A.; US2015/175560; (2015); A1;,
Imidazole – Wikipedia,
Imidazole | C3H4N2 – PubChem