CN104910076A - Preparation for bis-benzimidazolium salts and applications in intramolecular coupling reaction - Google Patents

Abstract

The invention discloses the preparation of bisbenzimidazolium salt and its application in intramolecular coupling reaction. It is the preparation method of bis-benzimidazolium salt bridged by biphenol and its palladium-catalyzed C-C coupling reaction. In the present invention, benzimidazole, 2,2'-biphenol, chloroethanol, thionyl chloride, etc. are used as raw materials to synthesize bisbenzimidazole ligands, and metal salts of palladium are used to catalyze the ligands to obtain intramolecular C-C couples. In order to study the intramolecular coupling reaction of such bisbenzimidazolium salts under metal palladium catalysis. It has the advantages of simple preparation and obvious catalytic effect, can be used to synthesize benzimidazole-containing biaryl units, and is expected to be applied in the field of catalytic intramolecular coupling.

Description

Preparation of Bisbenzimidazolium Salt and Its Application in Intramolecular Coupling Reaction

Statement Regarding Funding Research or Development

This invention is supported by the National Natural Science Foundation of China (fund No. 21172172), Tianjin Natural Science Foundation (fund No. 11JCZDJC22000), Tianjin University Innovation Team Training Program (fund No. TD12-5038) and Tianjin Normal University Application Development Research Funded by the Fund (fund number: 52XK1202).

technical field

The invention belongs to the technical field of organic synthesis and intramolecular catalysis, and relates to the synthesis of biphenol bridged bisbenzimidazolium salt and its intramolecular C-C coupling reaction under the catalysis of palladium salt. More specifically, the research on the preparation method of bisbenzimidazoles with biphenol bridges as precursors and their intramolecular C-C coupling reactions.

Background technique

A coupling reaction is the process of reacting two molecules to form a new molecule. The formation of new carbon-carbon bonds is extremely important in organic chemistry. When synthesizing organic substances such as drugs and plastics, it is necessary to use small organic molecules to connect carbon atoms together to build new complex macromolecules. Therefore, the efficient method of connecting carbon-carbon bonds in organic synthesis is an important tool in organic synthetic chemistry. . Because the chemical properties of carbon atoms are inactive, carbon atoms are not easy to combine with each other, so the chemical reaction between two carbon atoms requires more stringent conditions. With the deepening of the research on organic synthesis, in the late 20th century, scientists discovered a large number of reactions to create new organic molecules catalyzed by transition metals, which promoted the rapid development of organic synthesis chemistry.

It is well known that transition metal-catalyzed C–C coupling reactions are widely used in organic synthesis and industry. Among numerous catalysts, palladium-based catalysts play an important role in the formation of C–C bonds, C–N bonds, and other C-heteroatom bonds. Palladium-catalyzed cross-coupling reactions are one of the most efficient methods and are widely used in the synthesis of biaryl units. Palladium-catalyzed coupling reactions are widely used in the synthesis of natural products, the pharmaceutical industry and the synthesis of new materials. At present, a large number of literatures have reported the use of palladium-catalyzed coupling reactions to synthesize high-molecular polymers and functional complex molecules. Benzimidazolium salts have attracted much attention due to their applications in organic light-emitting diodes, ionic liquids, fluorescent recognition, batteries, and cells.

Contents of the invention

The object of the present invention is to provide an intramolecular coupling compound with bisbenzimidazole bridged by biphenol as a precursor.

The invention also relates to methods of preparing precursors of such intramolecularly coupled compounds.

The present invention also relates to a method for preparing such intramolecular coupling compounds, and carries out crystallographic characterization thereof.

The present invention relates to methods for growing crystals of such intramolecularly coupled compounds, measurement data and data research.

The intramolecular coupling compounds involved in the present invention are all cultivated by means of diffusion or volatilization.

The intramolecular coupling compounds in the present invention are all measured and characterized by X-ray diffractometer.

The invention further discloses the application of biphenol-bridged bisbenzimidazolium salt ligands in the preparation of intramolecular coupling compounds.

For accomplishing above-mentioned each invention object, technical scheme of the present invention is as follows:

The invention discloses a bisbenzimidazolium salt ligand with a biphenol bridge, which has the following structure:

The present invention further discloses a preparation method of the intramolecular coupling compound, which is characterized in that:

(1) Stir 2,2'-biphenol and potassium carbonate in an organic solvent at 50°C under nitrogen protection for 0.5 h, then slowly add chloroethanol dropwise; the mixed solution reacts at 110°C for 24 h, and post-treatment 2,2'-bis(2-hydroxyethyl)biphenyl was obtained as a white solid;

(2) Stir and mix 2,2'-bis(2-hydroxyethyl)biphenyl and pyridine in an organic solvent, then slowly add thionyl chloride dropwise; the mixed solution reacts at 70˚C for 6 h, Post-treatment gave 2,2'-bis(2-chloroethoxy)biphenyl as a light yellow solid;

(3) Stir the tetrahydrofuran solution of 2,2'-bis(2-chloroethoxy)biphenyl at room temperature for 10-20 min, add NaI and the tetrahydrofuran solution containing N-ethylbenzimidazole, and the mixed solution Stirred at 60-70˚C for 5 days, a white precipitate formed, and after work-up, a white solid of 2,2'-bis[2-(N-ethylbenzimidazolyl)ethoxy]biphenyliodonium salt was obtained ; Add the methanol solution of ammonium hexafluorophosphate to the methanol solution of 2,2'-bis[2-(N-ethyl benzimidazolyl) ethoxy] biphenyl iodide salt, white precipitate is separated out, after post-treatment Obtain 2,2'-bis[2-(N-ethylbenzimidazolyl)ethoxy]biphenyl hexafluorophosphate ( 1 );

The molar ratio of 2,2'biphenol:potassium carbonate:chloroethanol in step (1) is 1:4:4.

The molar ratio of 2,2'-bis(2-hydroxyethyl)biphenyl:pyridine:thionyl chloride in step (2) is 1:5:5.

In step (3), the molar ratio of 2,2'-bis(2-hydroxyethyl)biphenyl:N-ethylbenzimidazole:NaI:ammonium hexafluorophosphate is 1:1.3:1.6:1.6.

The organic solvent is selected from one or a mixture of tetrahydrofuran, dichloromethane, chloroform, anhydrous ether, acetonitrile, anhydrous methanol, and N,N-dimethylformamide.

The present invention further discloses the application of bis-benzimidazolium salt ligands bridged by biphenols in the preparation of intramolecular coupling compounds. The experiment proves that the bisbenzimidazolium salt ligand bridged by biphenol can undergo intramolecular C-C coupling reaction under the catalysis of palladium metal salt.

Crystal data and structure refinement parameters are included in the supporting information in the present invention. Conducted on a Bruker SMART 1000 CCD diffractometer at 113(2)K at 50kV and 20mA, operated with Mo-Kα radiation (0.71073Å), using SMART and SAINT software for data collection and reduction, the range of θ is 1.8 < θ < 25º. Apply the SADABS procedure for empirical absorption correction. The crystal structure was solved by the direct method, and the thermal anisotropy parameters of all non-hydrogen atomic coordinates were corrected by the full matrix least squares method using the SHELXTL package.

The crystal structure diagram of the coupling compound obtained in Application Example 1 is shown in the accompanying drawing 1 of the specification.

Description of drawings:

Fig. 1 is the crystal structure diagram of the intramolecular coupling compound prepared in application example 1.

Detailed ways

For the purpose of simplicity and clarity, descriptions of known technologies are appropriately omitted below, so as not to affect the description of the technical solution with unnecessary details. Below in conjunction with preferred embodiment, the present invention will be further described, especially, the starting material N-ethylbenzimidazole of preparation compound of the present invention, 2,2' biphenol, chloroethanol, sulfur oxychloride etc. are commercially available or readily prepared by known methods.

The reagents used in the preparation of the compounds of the present invention are all from Tianjin Yuanlihe Kewei Chemical Co., Ltd., and the grades are analytically pure.

In addition, it should be noted that the solvents used in all experimental operations were purified by standard procedures. All reagents used in the synthesis and analysis were of analytical grade and were not further processed. Melting points were determined by Boetius intercept. ¹ H NMR spectra were recorded by a mercury variable Vx400 spectrophotometer, and the measurement intervals were 400 MHz and 100 MHz, respectively. Chemical shift, δ, was determined with reference to the international standard TMS. Elemental analysis was determined by a Perkin-Elmer 2400C elemental analyzer.

Example 1 ( 1 )

Add 2,2'-biphenol (1.000 g, 5.4 mmol) to a suspension of potassium carbonate (2.980 g, 21.6 mmol) in N,N-dimethylformamide (150ml) and store at 50˚C under nitrogen protection After stirring for 0.5 h, chloroethanol (1.740 g, 21.6 mmol) was added dropwise, and stirred at 110°C for 24 h after the addition was complete. A dark yellow solution was obtained after filtration. Add 400 ml of water to the filtrate and extract with dichloromethane (30 mL × 3). The extract was dried over anhydrous magnesium sulfate. Removal of dichloromethane gave 2,2'-bis(2-hydroxyethyl)biphenyl as a white solid. Yield: 1.296 g (87%). Melting point: 42-44 °C.

¹ H NMR (400 MHz, CDCl ₃ ): δ 7.36 (t, J = 7.8 Hz, 2H, PhH), 7.26 (q, J = 2.9 Hz, 2H, PhH), 7.10 (t, J = 7.4 Hz, 2H , PhH), 7.02 (d, J = 8.0 Hz, 2H, PhH), 4.05 (t, J = 4.2 Hz, 4H, CH ₂ ), 3.72 (t, J = 4.4 Hz, 4H, CH ₂ ), 2.80 ( s, 2H, OH). ¹³ C NMR (100 MHz, CDCl ₃ ): δ 155.8, 131.3, 129.0, 122.1 and 114.1 (PhC), 71.5 (OCH ₂ CH ₂ ), 61.1 (OCH ₂ CH ₂ ).

Thionyl chloride (2.170 g, 18.2 mmol) was added dropwise to a solution of 2,2'-bis(2-hydroxyethyl)biphenyl (1.000 g, 3.65 mmol) and pyridine (1.440 g, 18.2 mmol) in chloroform ). The mixed solution was stirred at 70°C for 6 h. After the reaction was completed, 300 ml of water was added thereto, and the layers were separated to obtain a chloroform layer, which was dried with anhydrous magnesium sulfate. Removal of chloroform gave 2,2'-bis(2-chloroethoxy)biphenyl as a pale yellow solid. Yield: 0.738 g (65%). Melting point: 52-54 °C.

¹ H NMR (400 MHz, CDCl ₃ ): δ 7.31 (m, 2H, PhH), 7.28 (m, 2H, PhH), 7.06 (t, J = 7.4 Hz, 2H, PhH), 6.96 (d, J = 8.0 Hz, 2H, PhH), 4.18 (t, J = 6.2 Hz, 4H, CH ₂ ), 3.65 (t, J = 6.2 Hz, 4H, CH ₂ ). ¹³ C NMR (100 MHz, CDCl ₃ ): δ 155.6, 131.8, 128.2, 121.2 and 112.7 (PhC), 68.7 (OCH ₂ CH ₂ ), 41.8 (OCH ₂ CH ₂ ).

Add N-ethylbenzimidazole (1.690 g, 11.6 mmol), 2,2'-bis(2-chloroethoxy) biphenyl (1.500 g, 8.9 mmol) and sodium iodide (2.170 g, 14.5 mmol) was refluxed and stirred for 5 days. A white precipitate precipitated out. After suction filtration, rinse with a small amount of tetrahydrofuran to obtain bis-benzimidazolium salt 2,2'-bis[2-(N-ethylbenzimidazolyl)ethoxy]biphenyl iodide salt as a white solid. Ammonium hexafluorophosphate (2.360 g, 14.5 mmol) was added to 100 ml of methanol solution of 2,2'-bis[2-(N-ethylbenzimidazolyl)ethoxy]biphenyl iodide salt, and white Precipitate out. After suction filtration, rinse with a small amount of methanol to obtain 2,2'-bis[2-(N-ethylbenzimidazolyl)ethoxy]biphenyl hexafluorophosphate. Yield: 2.417 g (61%). Melting point: 104-106 °C.

Anal. Calc. For C ₃₄ H ₃₆ N ₄ O ₂ P ₂ F ₁₂ : C, 49.64; H, 4.41; N, 6.81. Found: C, 49.53; H, 4.25; N, 6.62. ¹ H NMR (400 MHz , DMSO-d ₆ ): δ 9.33 (s, 2H, 2-bimiH), δ 8.02 (d, J = 7.6 Hz, 2H, PhH), 7.64 (t, J = 6.8 Hz, 2H, PhH), 7.55 ( d, J = 8.0 Hz, 2H, PhH), 7.45 (d, J = 6.8 Hz, 2H, PhH), 7.32 (d, J = 1.6 Hz, 2H, PhH), 6.98 (d, J = 8.0 Hz, 2H , PhH), 6.86 (s, 4H, PhH), 4.68 (s, 4H, CH ₂ ), 4.41 (d, J = 6.4 Hz, 4H, CH ₂ ). 4.26 (s, 4H, CH ₂ ), 1.45 ( s, 6H, CH ₃ ). ¹³ C NMR (100 MHz, DMSO-d ₆ ): δ 154.6 (PhC), 141.7 (bimi-NCN), 131.1, 130.7, 130.5, 128.7, 126.4, 126.2, 120.9, 113.5, 113.4 and 112.5 (PhC), 65.7 (OCH ₂ CH ₂ ), 48.5 (OCH ₂ CH ₂ ), 42.1 (CH ₂ CH ₃ ), 13.9 (CH ₃ ) (bimi = benzimidazole).

The experimental procedure is as follows:

Application example 1

Sodium acetate (0.199 g, 2.4 mmol), palladium acetate (0.080 g, 0.36 mmol) and ligand ( 1 ) (0.200 g, 0.2 mmol) were added to 10 ml of acetonitrile and 10 ml of dichloromethane, 50˚ under nitrogen protection C stirred for 24 h. The filtrate was obtained by filtration, and the filtrate was slowly diffused in ether. After two weeks, a yellow transparent block crystal suitable for X-ray single crystal diffraction test grew on the wall of the test tube ( 2 ). Yield: 0.083 g (38%), melting point: 192-194 °C. Anal. Calc. for C ₃₈ H ₃₈ F ₁₂ N ₆ O ₂ P ₂ : C, 50.67; H, 4.25; N, 9.33. Found: C, 49.95; H, 3.87; N, 6.96. ¹ H NMR (400 MHz , DMSO-d ₆ ): δ 8.26 (m, 4H, PhH), 8.02 (t, J = 7.6 Hz, 4H, PhH), 7.80 (m, 4H, PhH), 7.75 (t, J = 7.8 Hz, 2H , PhH), 4.80 (t, J = 5.4 Hz, 4H, CH ₂ ) 4.72 (q, J = 7.2 Hz, 4H, CH ₂ ), 4.64 (t, J = 5.6 Hz, 4H, CH ₂ ), 1.60 ( t, J = 7.2 Hz, 6H, CH ₃ ). ¹³ C NMR (100 MHz, DMSO-d ₆ ): δ 151.0 (bimi-NCN), 146.0, 135.3, 130.8, 129.6, 128.9, 125.2, 123.5, 116.4, 115.1, 112.2 and 111.4 (PhC), 74.6 (OCH ₂ CH ₂ ), 41.0 (OCH ₂ CH ₂ ), 40.0 (CH ₂ CH ₃ ), 12.8 (CH ₃ ).

The experimental procedure is as follows:

The crystal structure is shown in Figure 1 of the specification.

Intramolecular coupling compound crystal structure parameters prepared by application example 1

In summary, the content of the present invention is not limited to examples, and people of insight in the same field can easily propose other examples within the technical guidance of the present invention, but this example is all included in the present invention. within the range.

Claims (4)

1. have the bis-benzimidazole salt part by xenol bridging, its structure is as follows:

。

2. the preparation method of the bis-benzimidazole salt part of xenol bridging described in claim 1, is characterized in that:

(1) in organic solvent 2,2 '-xenol, salt of wormwood are stirred 0.5 h under nitrogen protection 50 C, then slowly drip chloroethanol; Mixing solutions to react 24 h at 110 C, and aftertreatment obtains 2, the white solid of 2 '-bis-(2-hydroxyethyl) biphenyl;

(2) in organic solvent 2,2 '-bis-(2-hydroxyethyl) biphenyl and pyridine are uniformly mixed, then slowly drip thionyl chloride; Mixing solutions to react 6 h at 70 C, and aftertreatment obtains 2, the light yellow solid of 2 '-bis-(2-chloroethoxy) biphenyl;

(3) by 2, the tetrahydrofuran solution of 2 '-bis-(2-chloroethoxy) biphenyl at room temperature stirs 10-20 min, add NaI and the tetrahydrofuran solution containing N-ethyl benzo imidazole, this mixing solutions stirs 5 days adularescent throw outs and generates under 60-70 C, 2 are obtained, the white solid of 2 '-bis-[2-(N-ethyl benzo imidazole base) oxyethyl group] biphenyl salt compounded of iodine after aftertreatment; To 2, the methanol solution of ammonium hexafluorophosphate is added in the methanol solution of 2 '-bis-[2-(N-ethyl benzo imidazole base) oxyethyl group] biphenyl salt compounded of iodine, adularescent Precipitation, 2 are obtained after aftertreatment, 2 '-bis-[2-(N-ethyl benzo imidazole base) oxyethyl group] biphenyl hexafluorophosphate ( 1);

Wherein 2,2 ' xenol in step (1): salt of wormwood: the mol ratio of chloroethanol is 1:4:4;

2,2 '-bis-(2-hydroxyethyl) biphenyl in step (2): pyridine: the mol ratio of thionyl chloride is 1:5:5;

2,2 '-bis-(2-hydroxyethyl) biphenyl in step (3): N-ethyl benzo imidazole: NaI: the mol ratio of ammonium hexafluorophosphate is 1:1.3:1.6:1.6.

3. preparation method as claimed in claim 2, wherein said organic solvent is selected from the mixture of one or more in tetrahydrofuran (THF), methylene dichloride, trichloromethane, anhydrous diethyl ether, acetonitrile, anhydrous methanol, DMF.

4. the bis-benzimidazole salt part of xenol bridging described in claim 1 is in the application of intramolecular coupling compound in preparation in coupling compound, and the single crystal data of the intramolecular coupling compound prepared by it is:

。