CN107043344B - Preparation, structure and the purposes of 4-acetylbiphenyl hydrazone-N- methyl -3- indolecarboxaldehyde Schiff base - Google Patents

Abstract

The present invention relates to the structure, preparation method and partial properties of a Schiff base compound. The compound has golden yellow bulk crystal in appearance, melting point is 168.5-169.0℃, molecular formula C ₂₄ H ₂₁ N ₃ , chemical name: 3-((E)-((E)-(1-(biphenyl-4-yl) ) ethylene)-hydrazide)-methyl)-1-methyl-1-H indole, the structure is as follows: Its crystal is monoclinic, P2 ₁ /c space group, β=90.252(2)°, Z=4. The compound has a simple preparation method and has a strong fluorescence emission peak in the range of 300-500 nm. In addition, the IC50 (50% inhibitory concentration) of the sifrbase on lung cancer cell A549 was 108.5 μM, and the IC50 on breast cancer cell 4T1 was 112.0 μM, which indicated that the compound had a certain inhibitory effect on these two cancer cells.

Description

Preparation, structure and application of biacetophenone hydrazone-N-methyl-3-indolecarboxaldehyde Schiff base

Technical field:

The invention relates to the fields of organic synthesis, optical materials and medicinal chemistry, and uses relatively simple raw materials and methods to synthesize target products in one step.

Background technique:

Schiffer base is a compound with a relatively special structure, and different types of Schiffer bases can be synthesized according to the different groups introduced. Schiffer bases have important applications in medicine, catalysis, analytical chemistry, corrosion, and photochromism. For example, in the medical field, schiff base has antibacterial, bactericidal, antitumor, and antiviral biological activities; in the field of optical materials, due to its electron-rich and rigid plane characteristics, it has good fluorescence properties and nonlinear optics. nature.

Biacetophenone hydrazone-like Schiff bases are rarely reported, but these compounds have a large conjugated system, which makes it easier to produce special properties in the field of optical materials; in the field of drug design, the biphenyl ring system stabilizes the drug The aromatic and hydrophobic interactions of molecules are therefore often used in the construction of drug molecules.

SUMMARY OF THE INVENTION

The content of the present invention is to synthesize a biacetophenone hydrazone-N-methyl-3-indolecarboxaldehyde schiff base compound, the compound appearance is golden yellow bulk crystal, the melting point is 168.5-169.0°C, and the molecular formula is C ₂₄ H ₂₁ N ₃ , chemical name: 3-((E)-((E)-(1-(biphenyl-4-yl)ethylene)-hydrazide)-methyl)-1-methyl-1 -H indole, [English system name: 3-((E)-((E)-(1-(biphenyl-4-yl)ethylidene)hydrazono)methyl)-1-methyl-1H-indole], abbreviation is 3-BEHMI; the structure is as follows.

1. Structure identification.

Elemental analysis shows that the percentages of C, H and N are 82.08%, 6.06% and 11.98% respectively (the theoretical values based on the molecular formula C ₂₄ H ₂₁ N ₃ are 82.02%, 6.02% and 11.96% respectively); single crystal Structural analysis shows that its crystal is monoclinic with space group P2 ₁ /c, β=90.252(2)°, Z=4, the relevant ¹ HNMR spectrum and ¹³ CNMR spectrum are shown in Figure 1 and Figure 2, respectively; Figure 3 and Figure 4 are the thermal ellipsoid crystal structure diagram and the crystal structure stacking diagram of the compound, respectively.

2. Synthesis method.

The synthetic method of the compound is characterized in that: using biacetophenone hydrazone and N-methyl-3-indole carboxaldehyde as raw materials, solution synthesis or solid phase synthesis method is adopted. Proceed as follows:

1) Dissolve biacetophenone hydrazone and N-methyl-3-indole carboxaldehyde in suitable organic solvent respectively, then mix by a certain molar ratio, and stir and react for a certain time at a certain temperature; solvent, directly mix the two reactants, and triturate the reaction.

2) During the liquid phase reaction, a certain method is used to remove most of the solvent from the obtained solution, and powder or crystals can be obtained, which is the target product; during the solid phase reaction, the target product can be obtained by grinding for a certain period of time.

3) The target product can be recrystallized in a suitable organic solvent to purify the product.

Preferably, the above reaction solvent or organic solvent for recrystallization is selected from methanol, ethyl acetate, dichloromethane, ethanol, acetonitrile, acetone, chloroform, and tetrahydrofuran.

Preferably, the reaction molar ratio of biacetophenone hydrazone and N-methyl-3-indolecarbaldehyde is 1:4 to 4:1.

Preferably, the reaction temperature is from room temperature to heating to reflux.

Preferably, the reaction time is: 0.5-12 hours.

Preferably, the method for removing the solvent is natural volatilization or atmospheric/vacuum distillation.

The beneficial effects of the present invention are that complex functional molecular materials can be synthesized in one step with relatively simple steps and reactants, and the separation method is simple.

3. Ultraviolet and fluorescent properties.

The ultraviolet spectrum of this compound was tested in ^10-6 mol/L ethanol solution, and it was found that it has four main ultraviolet absorption peaks at 203nm, 222nm, 282nm and 348nm. The ultraviolet spectrum diagram is shown in Figure 5.

In 10 ^-5 mol/L ethanol solution, the fluorescence properties of this compound were tested, and it was found that it has strong fluorescence emission in the range of 300-500 nm, and the fluorescence spectrum is shown in Figure 6.

4. In vitro antitumor activity:

A549 lung cancer cells or 4T1 mouse breast cancer cells in log phase growth were digested with 0.25% trypsin to make them into single cells, and the concentration was 1.25×10 using F12K medium containing 10% fetal bovine serum. ⁷ cells/L of single cell suspension, the cells were seeded in a 96-well culture plate, 200 μL per well (2.5×10 ³ cells per well). The 96-well cell culture plate was placed in a CO ₂ incubator for 48 h at 37°C, 5% CO ₂ .

When the cells in the wells are full (90% full), different doses of Bensifer base solution (200 μL/well) are added according to the experimental groups, so that the final concentrations of the compounds to be tested are 5 μM, 10 μM, 30 μM, 50 μM, 100μM, 150μM, 200μM, each group set 3 replicate wells, and cultured for 96h.

20 μL of MTT at a concentration of 0.5 g/L was added to each well, and the culture was continued for 4 h to reduce MTT to Formazan. After all the supernatant was sucked out, 200 μL of DMSO was added to each well, shaken for 15 min, and after the formazan was fully dissolved, the absorbance at 490 nm (OD value) was measured by enzyme-linked immunosorbent assay. Then calculate according to the following formula:

Cell inhibition rate%=(OD value of control group - OD value of experimental group)/OD value of control group × 100%

The test results showed that the IC50 (the half inhibitory concentration of the drug) of the sifrbase on lung cancer cells A549 was 108.5 μM, and the IC50 (the half inhibitory concentration of the drug) on breast cancer cells 4T1 was 112.0 μM, which indicated that the compound was effective against these two drugs. cancer cells have a certain inhibitory effect.

Detailed ways

In order to better understand the content of the present invention, the technical scheme of the present invention is further described below through two specific embodiments:

Example 1.

Dissolve 0.20 g (0.95 mmol) of biacetophenone hydrazone in 30 mL of anhydrous methanol, heat and stir until all dissolved, add 0.15 g (0.95 mmol) of N-methyl-3-indole carboxaldehyde, heat under reflux and stir for 6 hours , then filtered to obtain the filtrate, placed in a beaker to stand for volatilization, a large amount of crystalline precipitates can be obtained, and the resulting precipitates were filtered to obtain the initial product (the yield was about 70%), and the initial product could be recrystallized with ethanol to obtain golden yellow blocks The crystals are 3-BEHMI Schiff base.

Example 2.

Weigh 0.40g (1.9mmol) of biacetophenone hydrazone into a mortar, add 0.30g (1.9mmol) of N-methyl-3-indolecarboxaldehyde, grind for 3 hours to obtain the target product crude product; Recrystallize with ethanol to obtain golden yellow block crystals, which is 3-BEHMI Schiff base.

Description of drawings

Figure 1 is the ¹ H NMR spectrum of biacetophenone hydrazone-N-methyl-3-indolecarboxaldehyde Schiff base.

Figure 2 is a ¹³ CNMR spectrum of biacetophenone hydrazone-N-methyl-3-indolecarboxaldehyde Schiff base.

Figure 3 is a crystal structure diagram of biacetophenone hydrazone-N-methyl-3-indolecarboxaldehyde Schiff base, the probability of ellipsoid is 30%.

Figure 4 is a crystal structure stacking diagram of biacetophenone hydrazone-N-methyl-3-indolecarboxaldehyde Schiff base, with an ellipsoid probability of 5%.

Accompanying drawing 5 is the ultraviolet spectrum of biacetophenone hydrazone-N-methyl-3-indolecarboxaldehyde Schiff base ( ^10-6 mol/L ethanol solution).

Figure 6 is the fluorescence spectrum of biacetophenone hydrazone-N-methyl-3-indolecarboxaldehyde Schiff base (10 ^-5 mol/L ethanol solution).

Claims (5)

1. A compound, the appearance is golden yellow bulk crystal, the melting point is 168.5-169.0 ° C, the molecular formula is C ₂₄ H ₂₁ N ₃ , the chemical name is: 3-((E)-((E)-(1-(biphenyl) -4-yl)ethylene)-hydrazide)-methyl)-1-methyl-1-H indole, the structure is as follows: Its crystal is monoclinic, P2 ₁ /c space group, β=90.252(2)°, Z=4. 2. the preparation method of compound crystal as described in claim 1, is characterized in that: take biacetophenone hydrazone and N-methyl-3-indole carboxaldehyde as raw material, adopt solution synthesis method, and step is as follows: 1) Dissolve biacetophenone hydrazone and N-methyl-3-indolecarbaldehyde in methanol, ethyl acetate, dichloromethane, ethanol, acetonitrile, acetone, chloroform or tetrahydrofuran organic solvent respectively, and then press 1:4 To 4:1 molar ratio mixing, stirring and reacting at room temperature to reflux temperature for 0.5-12 hours; 2) adopt natural volatilization or atmospheric/vacuum distillation method to remove most solvent by the solution obtained, can obtain powder or crystalline substance, be the target product; 3) The target product can be recrystallized in methanol, ethyl acetate, dichloromethane, ethanol, acetonitrile, acetone, chloroform or tetrahydrofuran organic solvent to purify the product and grow a single crystal. 3. the preparation method of compound crystal as described in claim 1, is characterized in that: take biacetophenone hydrazone and N-methyl-3-indole carboxaldehyde as raw material, adopt solid-phase synthesis method, and step is as follows: 1) Biacetophenone hydrazone and N-methyl-3-indole carbaldehyde are mixed in a mol ratio of 1:4 to 4:1, and the reaction is ground for 0.5-12 hours at room temperature, and the obtained powder is the initial product of the target product; 2) The target product The primary product can be recrystallized in methanol, ethyl acetate, dichloromethane, ethanol, acetonitrile, acetone, chloroform or tetrahydrofuran organic solvent to purify the product and grow single crystals. 4. The purposes of the compound as claimed in claim 1 in the fields of organic pigments, optical brighteners, photo-oxidants, coatings, chemical and biochemical analysis, solar energy collectors, anti-counterfeiting marks, drug tracers and lasers, based on its fluorescence nature. 5. The use of the compound or a pharmaceutically acceptable salt thereof in claim 1 in the preparation of a medicament for preventing and/or treating tumors, wherein the tumor is lung cancer or breast cancer.