CN108947910B

CN108947910B - Bis-benzimidazole hexafluorophosphate compound and preparation method and application thereof

Info

Publication number: CN108947910B
Application number: CN201810851475.XA
Authority: CN
Inventors: 柳清湘; 胡则亮; 赵志翔; 于少聪
Original assignee: Tianjin Normal University
Current assignee: Tianjin Normal University
Priority date: 2018-07-30
Filing date: 2018-07-30
Publication date: 2021-07-02
Anticipated expiration: 2038-07-30
Also published as: CN108947910A

Abstract

The invention discloses a preparation method and application of a novel bis-benzimidazole salt. The method comprises the steps of taking 1, 8-dihydroxy-9, 10-anthraquinone as a raw material in an organic solvent, reacting the raw material with 1, 2-dibromoethane to obtain 1- (2-bromoethoxy) -8-hydroxy-9, 10-anthraquinone (I) and 1, 8-bis (2-bromoethoxy) -9, 10-anthraquinone (II), reacting the (II) with benzimidazole to obtain 1, 8-bis [2- (benzimidazole-1-yl) ethoxy ] -9, 10-anthraquinone (III), reacting the obtained 1, 8-bis [2- (benzimidazole-1-yl) ethoxy ] -9, 10-anthraquinone (III) with bromide obtained by the reaction of the (I), reacting the bromide with hexafluorophosphate to obtain 1, 8-bis {2- { N- [2 '- (8' -hydroxy-9, 10-anthraquinone-1 '-yloxy) ethyl ] benzimidazolemethyl } -9', 10' -anthraquinone hexafluorophosphate (IV). The bis-benzimidazole salt compound (IV) has the advantages of simple preparation, adjustable structure and obvious fluorescence sensitization effect, can be used for manufacturing a fluorescence molecule recognition system, and is mainly applied to the technical field of fluorescence recognition.

Description

Bis-benzimidazole hexafluorophosphate compound and preparation method and application thereof

Statement regarding sponsoring research or development

The invention is carried out under the subsidy of national science fund (fund number: 21572159).

Technical Field

The invention belongs to the technical field of organic chemistry, and relates to a bis-benzimidazole hexafluorophosphate compound (IV) prepared from 1, 8-dihydroxy-9, 10-anthraquinone, 1, 2-dibromoethane and benzimidazole as raw materials, in particular to a preparation method of the bis-benzimidazole hexafluorophosphate compound (IV) and research on fluorescence recognition performance of the bis-benzimidazole hexafluorophosphate compound (IV).

Background

Benzimidazole and its derivatives have been studied for over a century. Since the discovery that 5, 6-dimethylbenzimidazole is a component of vitamin B12 in 1955, benzimidazole compounds have been increasingly used because they are known to be less toxic and capable of inhibiting fungal growth. The benzimidazole derivatives have good biological activity and corrosion resistance, such as anticancer, antifungal, anti-inflammatory, hypoglycemia treatment and physiological disorder treatment, have very important significance in medicinal chemistry, and can be used for simulating the active site of natural superoxide dismutase (SOD) to research the biological activity so as to obtain the benzimidazole derivatives with good biological activity and corrosion resistanceAnd epoxy resin curing agent, catalyst and some metal surface treating agent, and may be also used as the intermediate for organic synthesis reaction. The benzimidazole compound has been a focus of attention, and the benzimidazole compound has a flexible structure, namely, an imidazole ring structure of benzimidazole has two sp²One nitrogen atom can be used as an ion coordination site, and the other nitrogen atom can be used as a reactive site to enable probe molecules to be easily and covalently modified on the surface of a material. In general, in the course of carrying out a preliminary experimental design route, it is most common to change the inherent characteristics of the original bridge chain by introducing different bridges so as to exert more advantages of the bridge chain. In recent years, a fluorescence analysis method has been studied in the field of fluorescent probes because of its high sensitivity and selectivity and the good fluorescence characteristics of benzimidazole compounds. With the development of research and the expansion of research range, benzimidazole salt compounds are bound to be applied in the fields of chemical disciplines, life disciplines, environmental analysis, clinical medicine and the like as subject compounds of fluorescent switches.

Disclosure of Invention

The invention aims to provide a novel bis-benzimidazole hexafluorophosphate compound and a preparation method thereof.

The invention further relates to application of the bis-benzimidazole hexafluorophosphate compound in the field of fluorescence recognition.

In order to accomplish the above objects, the technical solution of the present invention is as follows:

a bis-benzimidazole salt compound having the structure:

IV

the invention further discloses a preparation method of the benzimidazole hexafluorophosphate compound (IV), which is characterized by comprising the following steps:

(1) 1, 8-dihydroxy-9, 10-anthraquinone is used as a raw material in an organic solvent and reacts with 1, 2-dibromoethane to obtain 1- (2-bromoethoxy) -8-hydroxy-9, 10-anthraquinone (I) and 1, 8-di (2-bromoethoxy) -9, 10-anthraquinone (II); wherein the molar ratio of the 1, 8-dihydroxy-9, 10-anthraquinone to the 1, 2-dibromoethane is 1:1 and 1: 2;

(2) reacting the obtained 1, 8-bis (2-bromoethoxy) -9, 10-anthraquinone (II) with benzimidazole in an organic solvent under an alkaline condition to obtain 1, 8-bis [2- (benzimidazole-1-yl) ethoxy ] -9, 10-anthraquinone (III), wherein the molar ratio of the (II) to the benzimidazole is 1: 2;

(3) 1, 8-di [2- (benzimidazole-1-yl) ethoxy]Reacting-9, 10-anthraquinone (III) with 1- (2-bromoethoxy) -8-hydroxy-9, 10-anthraquinone (I) to obtain bromide, and reacting with NH₄PF₆In a molar ratio of 1:1.5, dissolving in organic solvent, reacting at room temperature for 1 day, filtering, and washing to obtain 1, 8-bis {2- { N- [2 ' - (8 ' -hydroxy-9, 10-anthraquinone-1 ' -yloxy) ethyl]Benzimidazolemethyl } -9 ', 10' -anthraquinone hexafluorophosphate (IV). Wherein the raw materials are 1, 8-dihydroxy-9, 10-anthraquinone, 1, 2-dibromoethane, potassium carbonate, benzimidazole, ammonium hexafluorophosphate and tetrabutylammonium bromide.

The organic solvent is one or a mixture of more of dichloromethane, acetone, methanol, diethyl ether, acetonitrile and ethyl acetate.

A typical benzimidazole compound:

a typical bis-benzimidazole salt compound (IV) has the molecular formula C₆₄H₄₆F₁₂N₄O₁₂P₂。

Specifically illustrated is the following single crystal data for bis-benzimidazole salt compound (IV) (measured using Bruker APEX II CCD diffractometer):

the preparation method of the bis-benzimidazole salt compound (IV) crystal is characterized in that the bis-benzimidazole salt compound (IV) is dissolved in acetonitrile and then is put into a test tube, and the solution is diffused in a non-benign solvent to slowly crystallize to obtain a light yellow crystal. The non-benign solvent is diethyl ether.

The invention further discloses application of the bis-benzimidazole hexafluorophosphate compound (IV) and the crystal thereof in the field of fluorescence identification; the fluorescence recognition refers to the fact that the subject (IV) is coupled with Co²⁺Having selective recognition capability; adding different kinds of nitrates into acetonitrile solvent of the host (IV) at 25 ℃ respectively as guest (different kinds of nitrates, such as Li⁺, Na⁺, K⁺, NH₄ ⁺, Ca²⁺, Co²⁺, Ni²⁺, Cu²⁺, Zn²⁺, Cd²⁺, Cr³⁺, Al³⁺, Pb²⁺ and Hg²⁺) Dissolving a host and an object in an organic solvent at 25 ℃, mixing the host solution with different object solutions respectively at a certain concentration, and measuring the fluorescence spectrum of the mixture to find out the object which can be identified by the host. For the guest that the host can recognize, the host was titrated with different concentrations of guest (5.0 × 10)^-6 mol L^-1) The fluorescence spectrum was measured. Adding nitrate solution (0-20 × 10) with gradually increasing concentration by microsyringe^-6 mol L^-1). The excitation wavelength of the host solution is 410 nm, and the emission spectrum has an emission peak at 488-710 nm. After each addition, reaction equilibrium was reached for 8-10 minutes to determine the corresponding fluorescence intensity. The bis-benzimidazole hexafluorophosphate compound (especially crystal) serving as the main body has obvious fluorescent sensitization effect on nitrate compounds, has obvious fluorescent emission at 488-710 nm in a fluorescent spectrum, and can be used for manufacturing a fluorescent probe (figure 2) and is expected to be applied to the field of fluorescence chemistry.

The bis-benzimidazole hexafluorophosphate compound (IV) provided by the invention is a high-grade fluorescent material which can stably exist in a standard state, has the advantages of simple preparation, adjustable structure and obvious fluorescent photosensitive effect, can be used for preparing fluorescent materials and fluorescent molecule recognition systems, and is expected to be applied in the field of fluorescence chemistry.

Description of the drawings:

FIG. 1 is a crystal structure diagram of a bis-benzimidazole salt-containing compound (IV) (example 1);

FIG. 2 shows bis-benzimidazole hexafluorophosphate compound (IV) (example 1) as a guest (different nitrate species, e.g.: Li) in acetonitrile as a solvent at 25 ℃ with addition of different nitrate species⁺, Na⁺, K⁺, NH₄ ⁺, Ca²⁺, Co² ⁺, Ni²⁺, Cu²⁺, Zn²⁺, Cd²⁺, Cr³⁺, Al³⁺, Pb²⁺ and Hg²⁺) The subsequent fluorescence spectrogram; the results show that the host (IV) is against Co²⁺Having selective recognition capability;

FIG. 3 is a plot of the fluorescence titration spectra of bis-benzimidazole hexafluorophosphate compound (IV) (example 1) at 25 ℃ after addition of cobalt nitrate solutions at different concentrations in acetonitrile as a solvent; the results show that with Co²⁺The fluorescence of the host gradually decreases as the concentration increases, when Co²⁺After the concentration reaches a certain value, the fluorescence is not obviously reduced.

Detailed Description

The invention is described below by means of specific embodiments. Unless otherwise specified, the technical means used in the present invention are well known to those skilled in the art. In addition, the embodiments should be considered illustrative, and not restrictive, of the scope of the invention, which is defined solely by the claims. It will be apparent to those skilled in the art that various changes or modifications in the components and amounts of the materials used in these embodiments can be made without departing from the spirit and scope of the invention. The raw materials and reagents used in the invention are commercially available; wherein

1, 8-dihydroxy-9, 10-anthraquinone, 1, 2-dibromoethane, potassium carbonate, benzimidazole, ammonium hexafluorophosphate, tetrabutylammonium bromide, etc. are commercially available or can be easily prepared by known methods.

The reagents used for preparing the compound are all from Keruisi chemical Co., Ltd, Tianjin, and the grade is analytical purity.

It should be further noted that: all experimental procedures were performed using Schlenk techniques and the solvents were purified by standard procedures. All reagents used for synthesis and analysis were analytically pure and were not further processed. Melting points were determined by a Boetius zone cutter.¹H and¹³C{¹h } NRM spectra were recorded by mercury variable Vx400 spectrophotometer, measurement interval: 400 MHz and 100 MHz. The chemical shift is carried out by the chemical shift,

reference is made to the international standard TMS assay. Fluorescence spectra were determined by Cary Eclipse fluorescence spectrophotometer.

Example 1

Preparation of 1- (2-bromoethoxy) -8-hydroxy-9, 10-anthraquinone (I):

1, 8-dihydroxy-9, 10-anthraquinone (0.500 g, 2.0 mmol), anhydrous K₂CO₃A solution of (0.150 g, 1.0 mmol) and dry TBAB (0.100 g, 0.3 mmol) in acetone (150 mL) was stirred under half reflux for one hour. After cooling, 1, 2-dibromoethane (0.400 g, 2.0 mmol) was slowly added to the mixture and stirred continuously for 48 hours at 40 ℃. The resulting solution was filtered and concentrated to 5mL, which was purified by silica gel flash chromatography using a mixture solvent of petroleum ether and ethyl acetate (petroleum ether/ethyl acetate = 99: 1) as an eluent. 1- (2-Bromoethoxy) -8-hydroxy-9, 10-anthraquinone (I) is obtained as a yellow powder. Yield: 0.190 g (51%), melting point: 161 + 163C. Calcd for C₁₆H₁₁O₄Br: C, 55.35; H, 3.19%. Found: C, 54.98; H, 3.14%。¹H NMR (CDCl₃, 400 MHz): δ3.80 (t, J = 6.8 Hz, 2H, CH ₂), 4.50 (t, J = 3.4 Hz, 2H, CH ₂), 7.26 (s, 1H, ArH), 7.31 (q, J = 3.0 Hz, 1H, ArH), 7.36 (d, J = 8.4 Hz, 1H, ArH), 7.62 (t, J = 8.4 Hz, 1H, ArH), 7.79 (m, 2H, ArH), 8.03 (d, J = 2.9 Hz, 1H, ArH), 12.93 (s, 1H, ArOH)。¹³C NMR (CDCl₃, 100 MHz): δ188.0 (CO), 182.1 (CO), 162.1 (ArC), 158.9 (ArC), 135.5 (ArC), 135.4 (ArC), 135.2 (ArC), 132.3 (ArC), 124.3 (ArC), 121.4 (ArC), 120.8 (ArC), 120.3 (ArC), 118.4 (ArC), 116.6 (ArC), 69.6 (CH₂), 27.9 (CH₂)。

Preparation of 1, 8-bis (2-bromoethoxy) -9, 10-anthraquinone (II):

50 mL of 1, 8-dihydroxyanthraquinone (5.000 g, 20.8 mmol) and anhydrous K₂CO₃(14.384 g, 109.0 mmol) and tetrabutylammonium bromide (0.162 g, 2.1 mmol) in treated CH₃The CN suspension was stirred at room temperature for 30 minutes. 1, 2-dibromoethane (20.300 g, 100.5 mmol) was placed in a constant pressure funnel, added dropwise, and reacted for 3 days under reflux. After the reaction was complete, the system was cooled to room temperature, filtered and the excess solvent was spun off to give a yellow material which appeared oily. By CH₂Cl₂(20 mL) this oily substance was dissolved, and the solution was thoroughly washed with water, followed by separating the aqueous layer from the mixed solution of methylene chloride and adding anhydrous Mg₂SO₄Excess water was removed from the organic phase and kept dry. The solvent was spin dried and recrystallized from ethyl acetate to give the 1, 8-bis (2-bromopropoxy) anthraquinone product as a pale yellow solid with a yield of 4.813 g, yield: 4.813 g (75%), melting point: 122 + 124 ℃. Anal, Calcd for C₁₈H₁₄Br₂O₄: C, 47.61; H, 3.11%. Found: C, 47.84; H, 3.44%. ¹H NMR (400 MHz, DMSO-d ₆): δ 3.86 (t, J = 5.6 Hz, 4H, CH ₂), 4.50 (t, J = 5.6 Hz, 4H, CH ₂), 7.58 (q, J = 3.4 Hz, 2H, ArH), 7.76 (t, J = 2.6 Hz, 4H, ArH)。

Preparation of 1, 8-bis [2- (benzimidazol-1-yl) ethoxy ] -9, 10-anthraquinone (III):

after stirring a suspension of benzimidazole (2.600 g, 22.0 mmol), KOH (1.802 g, 32.0 mmol), TBAB (0.305 g, 0.9 mmol) and 1, 8-bis (2-bromoethoxy) -9, 10-anthraquinone (1.001 g, 2.2 mmol) in THF (120 mL) at 40 ℃ for 24 hours. Filtration and removal of the solvent under vacuum. Then recrystallizing with THF to obtain 1, 8-di [2- (benzimidazole-1-yl) ethoxy]9, 10-anthraquinone, as yellow needle crystals. Yield: 0.922 g (77.6%), melting point: 205 + 207C. Anal, Calcd for C₃₂H₂₈O₄N₄: C, 72.16; H, 5.29; N, 10.51%. Found: C, 72.06; H, 5.55; N, 10.82%.¹H NMR (400 MHz, DMSO-d ₆): δ 4.52 (t, J = 4.8 Hz, 4H, CH ₂), 4.91 (t , J = 5.0 Hz, 4H, CH ₂), 7.20 (m,2H, ArH), 7.27 (m,2H, ArH), 7.71 (m, 6H, ArH), 7.80 (d, J = 8.0 Hz, 2H, ArH), 8.67 (s, 2H, 2-bimH) (bimi = benzimidazole)。

Preparation of 1, 8-bis {2- { N- [2 '- (8' -hydroxy-9, 10-anthraquinon-1-yloxy) ethyl ] benzimidazolemethyl } -9 ', 10' -anthraquinone hexafluorophosphate (IV):

1- (2-Bromoethoxy) -8-hydroxy-9, 10-anthraquinone (I) (0.305 g, 1.0 mmol) and 1, 8-bis [2- (benzimidazol-1-yl) ethoxy]-CH of 9, 10-anthraquinone (III)₃CN (100 mL) solution of Ethoxy]9, 10-anthraquinone (0.101 g, 0.5 mmol) was stirred at reflux for 4 days, forming a yellow precipitate. After filtration, the precipitate (0.302 g, 0.3 mmol) was dissolved in methanol (40 mL) and NH was added₄PF₆(0.133 g, 0.8 mmol) in methanol (20 mL). The mixed solution was stirred at room temperature for 2 days to precipitate a yellow solid. The solid was collected by filtration and washed with diethyl ether (5 mL) to give 1, 8-bis {2- { N- [2 '- (8' -hydroxy-9, 10-anthraquinon-1-yloxy) ethyl ] ethyl as a yellow powder]Benzimidazolemethyl } -9 ', 10' -anthraquinone hexafluorophosphate (IV). Yield: 0.240 g (80%), melting point: 283 Buchner 285C. Anal, Calcd for C₆₄H₄₆N₄O₁₂F₁₂P₂: C, 56.81; H, 3.42; N, 4.14%. Found: C, 56.69; H, 3.55; N, 4.02%. ¹H NMR (400 MHz, DMSO-d ₆): δ 4.47 (t, J = 4.4 Hz, 4H, CH ₂), 4.63 (t, J = 4.4 Hz, 4H, CH ₂), 4.99 (t, J = 1.6 Hz, 4H, CH ₂), 5.08 (t, J = 2.0 Hz, 4H, CH ₂), 6.85 (m, 4H, ArH), 6.90 (t, J = 4.0 Hz, 2H, ArH), 7.01 (d, J = 8.0 Hz, 2H, ArH), 7.07 (d, J = 7.2 Hz, 4H, ArH), 7.17 (d, J = 8.0 Hz, 2H, ArH), 7.44 (t, J = 3.6 Hz, 2H, ArH), 7.52 (t, J = 4.0 Hz, 2H, ArH), 7.68(m, 4H, ArH), 8.23 (d, J = 8.4 Hz, 2H, ArH), 8.35 (d, J = 8.8 Hz, 2H, ArH), 9.72 (s, 2H, 2-bimiH), 11.86 (s, 2H, OH). ¹³C NMR (100 MHz, DMSO-d ₆): δ186.7 (CO), 180.6 (CO), 160.8 (ArC), 157.4 (ArC), 156.8 (ArC), 143.1 (ArC), 136.2 (ArC), 133.6 (ArC), 132.4 (ArC), 131.7 (ArC), 131.0 (ArC), 126.4 (ArC), 124.1 (ArC), 120.2 (ArC), 119.8 (ArC), 119.2 (ArC), 118.5 (ArC), 118.1 (ArC), 115.8 (ArC), 113.5 (ArC), 65.6 (CH₂), 45.9 (CH₂)。

The crystal structure is shown in the attached figure 1:

example 1 crystals of bis-benzimidazolate compound (IV) having the following crystal structure parameters:

crystal data and structure refinement parameters are included in the supporting information. Performed on a Bruker APEX II CCD diffractometer at an experimental temperature of 150 (10) K, operated with Mo-Ka radiation (0.71073 a) at 50kV and 20mA, and data collection and reduction were performed with SMART and SAINT software, q ranging from 1.8 < q < 25 °. The SADABS program was applied for empirical absorption correction. The crystal structure is solved by a direct method, and the SHELXTL package is used for carrying out full matrix least square correction on all non-hydrogen atom coordinate anisotropic thermal parameters.

Application example 1

Adding different kinds of nitrates as objects (different kinds of nitrates, e.g. Li) into acetonitrile as solvent of bis-benzimidazole hexafluorophosphate compound (IV) at 25 ℃⁺, Na⁺, K⁺, NH₄ ⁺, Ca²⁺, Co²⁺, Ni²⁺, Cu² ⁺, Zn²⁺, Cd²⁺, Cr³⁺, Al³⁺, Pb²⁺ and Hg²⁺) Referring to FIG. 2, it can be seen from FIG. 2 that the body (IV) is coupled to the Co²⁺Having selective recognition capability;

the fluorescence titration was measured by a Cary Eclipse fluorescence spectrophotometer using a 1cm path length quartz cell. The titration was carried out by subjecting the bulk (5X 10)^-6mol/L) into a 4 mL cuvette and adding a solution of cobalt nitrate (0-20X 10) of increasing concentration using a microsyringe^-6mol L^-1). The excitation wavelength of the host solution is 410 nm, and the emission spectrum has an emission peak at 488-710 nm. After each addition, reaction equilibrium was reached 8-10 minutes before the corresponding fluorescence spectra could be recorded, and data analysis used Origin 8.0, see FIG. 3, from which it can be seen that: with Co²⁺The fluorescence of the host gradually decreases as the concentration increases, when Co²⁺After the concentration reaches a certain value, the fluorescence is not obviously reduced.

In summary, the content of the present invention is not limited to the examples, and those skilled in the art can easily suggest other examples within the technical teaching of the present invention, but such examples are included in the scope of the present invention.

Claims

1. A bis-benzimidazole salt compound having the structure:

IV。

2. the process for preparing bis-benzimidazole salts according to claim 1, wherein the process comprises the following steps:

(1) 1, 8-dihydroxy-9, 10-anthraquinone is used as a raw material in an organic solvent and reacts with 1, 2-dibromoethane to obtain 1- (2-bromoethoxy-) -8-hydroxy-9, 10-anthraquinone and 1, 8-di (2-bromoethoxy) -9, 10-anthraquinone; wherein the molar ratio of the 1, 8-dihydroxy-9, 10-anthraquinone to the 1, 2-dibromoethane is 1:1 and 1: 2;

(2) reacting the obtained 1, 8-bis (2-bromoethoxy) -9, 10-anthraquinone with benzimidazole in an organic solvent under an alkaline condition to obtain 1, 8-bis [2- (benzimidazole-1-yl) ethoxy ] -9, 10-anthraquinone, wherein the molar ratio of the 1, 8-bis (2-bromoethoxy) -9, 10-anthraquinone to the benzimidazole is 1: 2;

(3) 1, 8-di [2- (benzimidazole-1-yl) ethoxy]Reacting-9, 10-anthraquinone with 1- (2-bromoethoxy) -8-hydroxy-9, 10-anthraquinone to obtain bromide, and reacting with NH₄PF₆Adding the mixture into a reaction vessel according to the molar ratio of 1:1.5, dissolving the mixture by using an organic solvent, reacting the mixture for 1 day at room temperature, filtering and washing the reaction product to obtain:

anthraquinone hexafluorophosphate.

3. The preparation method of claim 2, wherein the organic solvent is selected from one or more of dichloromethane, acetone, methanol, diethyl ether, acetonitrile and ethyl acetate.

4. The crystal of the bis-benzimidazole salt compound IV of claim 1, having the following crystal structure parameters:

。

5. the process for producing the bis-benzimidazolium compound IV crystal according to claim 4, wherein the bis-benzimidazolium compound IV is dissolved in acetonitrile, and then placed in a test tube, and the solution is diffused in a non-benign solvent to slowly crystallize the compound IV to obtain a yellow crystal; the non-benign solvent is diethyl ether.

6. Use of the bis-benzimidazole hexafluorophosphate compound IV of claim 1 for the preparation of fluorescent recognition; the fluorescence recognition refers to the recognition of Co²⁺Identification of (1).

7. Use of the crystal of bis-benzimidazolium salt IV according to claim 4 for the preparation of a fluorescent probe; the fluorescence recognition refers to the recognition of Co²⁺Identification of (1).