CN111848699A - Application of a Derivative - Google Patents

Abstract

The invention discloses application of a derivative, and belongs to the field of compounds. The preparation method of the compound comprises the following steps: the first step is as follows: reacting amino ferrocene with chloroacetyl chloride in the presence of an alkaline reagent to prepare a compound II; the second step is that: and reacting the compound II with m-phenylenediamine in the presence of an alkaline reagent to obtain a compound III. The ferrocene derivative provided by the invention has the advantages of simple preparation method, high yield, high responsiveness to metal ions and easy realization of industrial application.

Description

Application of a Derivative

This application is a divisional application for an invention patent with the application date: 2019-12-20, the application number: 201911330235.6, and the name: a novel ferrocene derivative and its synthesis method and application.

technical field

The present invention relates to the field of compounds, in particular to the application of a derivative.

Background technique

Copper is the third largest trace element necessary for organisms. Due to its redox properties, copper can participate in the metabolism of various enzymes such as tyrosinase and superoxide dismutase, and play a vital role in animals and plants. The daily intake of copper in the human body should be controlled within the range of 0.6-1.6 mg. When the intake of copper is too high, it will damage the liver and kidney; when there is a lack of copper in the body, it will cause anemia, brittle bones, cardiovascular disorders and other diseases. If the metabolism of copper in the body is abnormal, it will cause Alzheimer's disease, Wilson's disease and so on. Therefore, it is of great significance to detect copper ions and track their role in life activities.

Ferrocene is an organic transition metal compound with aromatic properties. As a building block, ferrocene has the following two advantages: 1. Good chemical stability and derivative substitution activity, and the two ferrocene rings of the ferrocene molecule can be freely rotated to form different torsion angles, which enables the design and synthesis of organic chemistry methods. Metal-macrocyclic compounds of polyferrocene become possible; 2. The good redox properties make the metal-macrocyclic complexes containing multiple ferrocene produce multiple electrochemical responses to the guest in the process of inclusion and dissociation, showing high sensitivity probe function. On this basis, we derivatized ferrocene to obtain a new type of ferrocene derivative, which has multiple electrochemical and photochemical responses to copper ions.

SUMMARY OF THE INVENTION

The present invention provides a novel ferrocene derivative, a synthetic method and an application for the above-mentioned existing technical problems.

The object of the present invention can be realized through the following technical solutions:

A novel ferrocene derivative, the structural formula of the derivative is as follows:

A preparation method of above-mentioned novel ferrocene derivative, reaction scheme is as follows:

In some specific technical solutions, the method includes the following steps:

The first step: aminoferrocene reacts with chloroacetyl chloride in the presence of an alkaline reagent to prepare compound II;

The second step: compound II is reacted with m-phenylenediamine in the presence of an alkaline reagent to obtain compound III.

In the above-mentioned method: the solvent used in the first step reaction is at least one of methylene chloride, tetrahydrofuran and toluene; the basic reagent used in the first step is 4-dimethylaminopyridine, triethylamine and pyridine. at least one.

In the above method: the molar ratio of aminoferrocene to the alkaline reagent is 1:1-6.

In the above-mentioned method: solvent acetonitrile, dichloromethane and ethanol used in the second step reaction, the basic reagent used in the second step is potassium iodide, N, N-diisopropylethylamine, triethylamine and anhydrous carbonic acid at least one of potassium.

In the above method: the molar ratio of m-phenylenediamine to the alkaline reagent is 1:2-3.

In the technical scheme of the present invention: the application of the ferrocene derivative as a fluorescent chemical sensor in the detection of Cu ²⁺ .

Beneficial effects of the present invention:

The preparation method of the ferrocene derivative provided by the invention is simple, the yield is high, and the responsivity to metal ions is high, and the industrial application is easy to be realized.

Description of drawings

FIG. 1 is an absorption spectrum diagram of the selective recognition of Cu ²⁺ by the ferrocene derivative FcmP (Example 1).

FIG. 2 is an absorption spectrum titration diagram of Cu ²⁺ p-ferrocene derivative FcmP (Example 1).

Figure 3 is a DPV diagram of the selective recognition of Cu ²⁺ by the ferrocene derivative FcmP (Example 1).

Figure 4 is a graph of the DPV titration of Cu ²⁺ p-ferrocene derivative FcmP (Example 1).

Detailed ways

Below in conjunction with embodiment, the present invention is further described, but protection scope of the present invention is not limited to this:

Example 1

Add aminoferrocene (3.02 g, 15 mmol), 200 mL of dichloromethane and 4-dimethylaminopyridine (1.83 g, 15 mmol) to a 500 mL three-necked flask in sequence, fully cool in an ice-salt bath, and then use a constant pressure funnel 50mL of the dichloromethane solution dissolved with chloroacetyl chloride (1.7g, 15mmol) was slowly added dropwise to the fully stirred three-necked flask, and the temperature of the reaction solution in the three-necked flask was controlled not to exceed 0°C. After the dropwise addition was completed, Continue to react in ice-salt bath for 4h. After the reaction was completed, the pH value of the reaction solution was adjusted to about 9 with 0.1 mol/L NaOH solution. The reaction was then extracted with dichloromethane (3 x 25 mL), the organic phases were combined and washed with water (3 x 25 mL) and dried over anhydrous Na ₂ SO ₄ overnight. After filtration, the filtrate was rotary evaporated to remove the organic solvent to obtain 3.88 g of dark red solid product II, yield: 93.3%, purity: 99.27%. Elemental analysis: (%) for C12H12NOClFe: Calculated: C 51.93; H 4.36; N 5.05, found: C 51.84; H 4.33; N 5.11.

¹ H NMR (500 MHz, CDCl ₃ , TMS): δ=10.82 (s, 1H), 4.88-4.83 (m, 5H), 4.76 (t, J=7.2, 2H), 4.62 (d, J=7.2, 2H) ),4.17(s,2H)ppm.

In a 250 mL flask, m-phenylenediamine (0.54 g, 5 mmol), potassium iodide (1.66 mg, 0.01 mmol) and N,N-diisopropylethylamine (10 mmol) were dissolved in 100 mL of acetonitrile, and the Under the conditions of N ₂ , reflux and stirring, a solution of compound II (2.77 g, 10 mmol) in 50 mL of acetonitrile was slowly added dropwise with a constant pressure funnel, and the drop was controlled within 1 h. After the completion of the dropwise addition, the reflux reaction was continued for 24 hours. After the reaction was completed, the reaction solution was cooled to room temperature, and the reaction solution was poured into water. It was then extracted with dichloromethane (3 x 25 mL) and the organic phases were combined and washed with saturated NaCl solution (3 x 25 mL). The organic phase was dried _over anhydrous _Na2SO4 overnight. After filtration, the filtrate was rotary evaporated to remove the organic solvent to obtain 2.73 g of brown-red solid product III (FcmP), yield: 92.5%, purity: 99.21%.

Elemental analysis: (%) for C30H30N4O2Fe2: Calculated: C 61.04; H 5.12; N 9.49, found: C60.92; H5.15; N 9.52.

¹ H NMR (500 MHz, CDCl ₃ , TMS): δ=10.33 (s, 2H), 6.98 (t, J=7.2, 1H), 6.37 (d, J=7.2, 2H), 6.14 (s, 1H), 4.81-4.78(m,10H),4.71(t,J=7.2,4H),4.60(d,J=7.2,4H),4.31(m,2H),3.88(d,J=7.2,4H)ppm.

Example 2

Add aminoferrocene (3.02 g, 15 mmol), 200 mL of tetrahydrofuran and 8 mL of triethylamine in sequence to a 250 mL three-necked flask, fully cool in an ice-salt water bath, and then use a constant pressure funnel to dissolve 50 mL of chloroacetyl chloride (1.7 g , 15mmol) tetrahydrofuran solution was slowly added dropwise to a fully stirred three-necked flask, and the temperature of the reaction solution in the three-necked flask was controlled not to exceed 0°C. After the reaction was completed, the pH value of the reaction solution was adjusted to about 9 with 0.1 mol/L NaOH solution. The reaction was then extracted with dichloromethane (3 x 25 mL), the organic phases were combined and washed with water (3 x 25 mL) and dried over anhydrous Na ₂ SO ₄ overnight. After filtration, the filtrate was rotary evaporated to remove the organic solvent to obtain 3.76 g of dark red solid product II, yield: 90.4%, purity: 99.08%.

In a 250 mL flask, m-phenylenediamine (0.54 g, 5 mmol), potassium iodide (1.66 mg, 0.01 mmol), and triethylamine (10 mmol) were dissolved in 100 mL of dichloromethane, under _N2 , reflux and Under stirring, a solution of compound II (2.77 g, 10 mmol) in 50 mL of dichloromethane was slowly added dropwise with a constant pressure funnel, and the drop was completed within 1 h. After the completion of the dropwise addition, the reflux reaction was continued for 20 hours. After the reaction was completed, the reaction solution was cooled to room temperature, and the reaction solution was poured into water. It was then extracted with dichloromethane (3 x 25 mL) and the organic phases were combined and washed with saturated NaCl solution (3 x 25 mL). The organic phase was dried _over anhydrous _Na2SO4 overnight. After filtration, the filtrate was rotary evaporated to remove the organic solvent to obtain 2.68 g of brown-red solid product III (FcmP), yield: 90.8%, purity: 99.18%.

Example 3

Add aminoferrocene (3.02 g, 15 mmol), 200 mL of toluene and 5 mL of pyridine in sequence to a 250 mL three-necked flask, fully cool in an ice-salt bath, and then use a constant pressure funnel to dissolve 50 mL of chloroacetyl chloride (1.7 g, 15 mmol) ) of toluene solution was slowly added dropwise to a fully stirred three-necked flask, and the temperature of the reaction solution in the three-necked flask was controlled not to exceed 0°C. After the reaction was completed, the pH value of the reaction solution was adjusted to about 9 with 0.1 mol/L NaOH solution. The reaction was then extracted with dichloromethane (3 x 25 mL), the organic phases were combined and washed with water (3 x 25 mL) and dried over anhydrous Na ₂ SO ₄ overnight. After filtration, the filtrate was rotary evaporated to remove the organic solvent to obtain 3.65 g of dark red solid product II, yield: 87.7%, purity: 99.13%.

In a 250 mL flask, m-phenylenediamine (0.54 g, 5 mmol), potassium iodide (1.66 mg, 0.01 mmol) and anhydrous potassium carbonate (10 mmol) were dissolved in 100 mL of ethanol, under _N2 , reflux and stirring 50 mL of ethanol solution dissolved with compound II (2.77 g, 10 mmol) was slowly added dropwise with a constant pressure funnel under the condition of , and the dripping was controlled to be completed within 1 h. After the completion of the dropwise addition, the reflux reaction was continued for 24 hours. After the reaction was completed, the reaction solution was cooled to room temperature, and the reaction solution was poured into water. It was then extracted with dichloromethane (3 x 25 mL) and the organic phases were combined and washed with saturated NaCl solution (3 x 25 mL). The organic phase was dried over anhydrous _Na2SO4 overnight. After filtration, the filtrate was rotary evaporated to remove the organic solvent to obtain 2.61 g of brown-red solid product III (FcmP), yield: 88.5%, purity: 99.04%.

nature experiment

1. Absorption Spectroscopy Experiment

Figure 1 shows the absorption spectrum of the selective recognition of Cu ²⁺ by the ferrocene derivative FcmP. In the mixed solution of 10 μmol/L ferrocene derivative FcmP (Example 1) in acetonitrile/water (3:1, v:v), 2 times the amount of metal ions (Ag ⁺ , Mg ^{2 +} , Ca ^{2 +} , Co ²⁺ , Cd ²⁺ , Cu ²⁺ , Na ⁺ , Ni ²⁺ , Pb ²⁺ , Fe ²⁺ , Al ³⁺ , Zn ²⁺ ). The absorption spectrum was measured on a Shimadzu UV2450 UV-Vis spectrophotometer.

It can be seen from Figure 1 that after adding Cu ²⁺ to the solution system, the absorption curve of the solution changes significantly. The original absorption peak intensity at 300nm decreases, and the absorption peak intensity at 405nm decreases and red-shifts (105nm) to 510nm. . However, after adding other metal ions, the absorption curve of the solution did not change significantly. This indicates that the ferrocene derivative FcmP can selectively recognize Cu ²⁺ in solution.

FIG. 2 is an absorption spectrum titration diagram of Cu ²⁺ p-ferrocene derivative FcmP (Example 1). 0, 0.1, 0.2, 0.3, 0.4, 0.5, 0.6, 0.7, 0.8, 0.9 were added to the mixed solution of 10 μmol/L ferrocene derivative FcmP in acetonitrile/water (3:1, v:v), respectively. , 1.0, 1.5 and 2.0 times the amount of Cu ²⁺ . The absorption spectrum was measured on a Shimadzu UV2450 UV-Vis spectrophotometer.

As can be seen from Figure 2, in the process of titration, the original absorption peak intensity at 300nm gradually decreased, and the absorption peak intensity at 405nm decreased and shifted (105nm) to 510nm. At the same time, the color of the solution gradually changed from yellow to red, indicating that the ferrocene derivative FcmP can be used to detect Cu ²⁺ with naked eyes.

2. Electrochemical experiments

Figure 3 is a DPV diagram of selective recognition of Cu ²⁺ by the ferrocene derivative FcmP (Example 1). 10 μL of metal ion solutions (Ag ⁺ , Mg ²⁺ , Ca ²⁺ , Co ²⁺ , Cd) with a concentration of 0.2 mol/L (1-fold molar amount) were added to 10 mL of the probe FcJD solution with a concentration of 0.2 mmol/L. ²⁺ , Cu ²⁺ , Na ⁺ , Ni ²⁺ , Pb ²⁺ , Fe ²⁺ , Al ³⁺ , Zn ²⁺ ). The solution systems used in the experiments are all mixed solutions of acetonitrile/water (3:1, v:v), n-Bu ₄ NPF ₆ (0.1mol/L) as the supporting electrolyte, and the three-electrode system uses a platinum disk electrode as Working electrode, platinum wire electrode as auxiliary electrode, Ag/AgCl electrode as reference electrode, the measurement temperature is 25°C, and the solution is measured after 30 minutes of nitrogen flow. Conventional differential pulse voltammetry (DPV) was measured on a CHI660C electrochemical workstation.

Conventional differential pulse voltammetry (DPV) response shows a reversible one-electron oxidation process with an oxidation peak at 0.51 V (vs AgNO ₃ /Ag) for the ferrocene derivative FcmP ascribed to the ferrocene group , after adding a double amount of different metal ions under the above experimental conditions, it was found that only after the addition of Cu ²⁺ was enough to make the ferrocene potential move significantly forward (about 40mV), but after the addition of other metal ions, it was not This phenomenon indicates that the ferrocene derivative FcmP has a unique electrochemical response to Cu ²⁺ .

Figure 4 is a graph of the DPV titration of Cu ²⁺ p-ferrocene derivative FcmP (Example 1). 0.1, 0.2, 0.3, 0.4, 0.5, 0.6, 0.7, 0.8, 0.9, 1.0, 1.5, 2.0 times the amount of Cu ²⁺ was sequentially added to 10 mL of a 0.2 mmol/L ferrocene derivative FcmP solution. The solution systems used in the experiments are all mixed solutions of acetonitrile/water (3:1, v:v), n-Bu ₄ NPF ₆ (0.1mol/L) as the supporting electrolyte, and the three-electrode system uses a platinum disk electrode as Working electrode, platinum wire electrode as auxiliary electrode, Ag/AgCl electrode as reference electrode, the measurement temperature is 25°C, and the solution is measured after 30 minutes of nitrogen flow. Conventional differential pulse voltammetry (DPV) was measured on a CHI660C electrochemical workstation.

It can be seen from Fig. 4 that with the addition of Cu ²⁺ , the oxidation peak of the ferrocene derivative FcmP at 0.51 V, which is attributed to the ferrocene group, gradually moved towards the anode and moved to 0.55 V. When Cu ²⁺ When the added amount of ⁺ reaches 1 times the molar amount, the oxidation peak of the ferrocene group no longer moves, and the intensity of the peak is basically unchanged. This indicates that the ferrocene derivative FcmP is 1:1 coordinated with Cu ²⁺ .

Claims (3)

1. A derivative is used as a fluorescent chemical sensor for the diagnosis and treatment of non-diseases in the detection of Cu ²⁺ , characterized in that: the structural formula of the derivative is as follows:

The preparation method of the derivative is:

The first step: aminoferrocene reacts with chloroacetyl chloride in the presence of an alkaline reagent to prepare compound II; The second step: compound II reacts with m-phenylenediamine in the presence of an alkaline reagent to obtain compound III; Wherein: solvent acetonitrile, dichloromethane or ethanol used in the second step reaction; The alkaline reagent used in the second step is at least one of potassium iodide, N,N-diisopropylethylamine, triethylamine and anhydrous potassium carbonate; The molar ratio of m-phenylenediamine to alkaline reagent is 1:2-3. 2. application according to claim 1 is characterized in that: the solvent used in the first step reaction is at least one in methylene dichloride, tetrahydrofuran and toluene; the basic reagent used in the first step is 4-dichloromethane At least one of methylaminopyridine, triethylamine and pyridine. 3 . The application according to claim 1 , wherein the molar ratio of aminoferrocene to the alkaline reagent is 1:1 to 6. 4 .

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