CN105462576A - Near infrared BODIPY fluorescence dye and preparation method thereof - Google Patents

Abstract

The invention relates to a near-infrared BODIPY fluorescent dye and a preparation method thereof, which is synthesized by Knoevenagel condensation reaction of 2-formyl tripolyindene and BODIPY derivatives under the catalysis of p-toluenesulfonic acid and piperidine, and the maximum absorption and emission wavelengths Above 650nm in organic solvents. The preparation method has the advantages of simple reaction steps, mild reaction conditions, good selectivity and the like. This type of fluorescent dye has excellent photophysical properties such as high molar extinction coefficient, good solubility and photostability, and has good application prospects in cell imaging and biomarking.

Description

A kind of near-infrared BODIPY type fluorescent dye and preparation method thereof

technical field

The invention belongs to the technical field of organic compound synthesis, and in particular relates to a near-infrared BODIPY fluorescent dye and a preparation method thereof.

Background technique

Fluoroboron dipyrrole dye (BODIPY) is a new type of fluorescent dye that has emerged in recent years, and it is a complex formed by dipyrromethene and boron trifluoride. The dye molecule has high photothermal stability, which can avoid the rapid degradation of the dye structure caused by the irradiation of the excitation light, the rise of temperature or the change of the detection environment of the dye itself during the fluorescence analysis process, ensuring the stability of the spectral analysis signal sex. In addition, BODIPY fluorescent dyes have high molar absorptivity, high fluorescence quantum yield, fluorescence signal is insensitive to solvent polarity and pH, narrow fluorescence spectrum peak, long fluorescence lifetime, moderate redox potential, and negligible triplet state. and other advantages; and the BODIPY fluorescent molecular core is relatively stable and has a certain chemical activity, the structure is easy to modify, and the absorption and emission wavelengths can be adjusted to the near-infrared region. Based on the above advantages, BODIPY fluorescent dyes have attracted more and more attention.

Near-infrared absorbing and fluorescently emitting dye molecules show great application prospects in many fields such as optical imaging, tumor diagnosis, infrared camouflage, nonlinear optical materials, and fluorescent labeling. In the near-infrared region, the emission wavelength of the dye is longer, the light penetration is strong, and the background interference is small; especially, the near-infrared light has a strong penetration ability in biological tissues and has little damage to the organism. Therefore, in recent years, the research on BODIPY dyes tends to synthesize near-infrared BODIPY dyes, which can be well applied in the fields of biological analysis and biological imaging.

At present, most near-infrared BODIPY dyes have many synthesis steps, high difficulty, low yield, and poor solubility, which limit their further application in the fields of biology and environment. The invention designs and synthesizes a novel near-infrared BODIPY fluorescent dye with novel structure, simple preparation method and excellent performance.

Contents of the invention

Purpose of the invention: Aiming at the deficiencies in the prior art, the purpose of the invention is to provide a near-infrared BODIPY fluorescent dye. Another object of the present invention is to provide a method for preparing the above-mentioned near-infrared BODIPY fluorescent dye.

Technical solution: In order to realize the above-mentioned purpose of the invention, the technical solution adopted in the present invention is:

Near-infrared BODIPY class fluorescent dye and derivative thereof of the present invention, its structural formula is as follows:

In the formula, R is H or I.

A preparation method for preparing the above-mentioned near-infrared BODIPY fluorescent dye, the steps are as follows:

1) In a round bottom flask equipped with a Dean-Stark apparatus, add BODIPY derivatives, 2-formyl tripolyindene and p-toluenesulfonic acid, then dissolve in 25 mL of toluene and 2 mL of piperidine, heat the mixture to reflux at 140 ° C, TCL The starting material was checked for complete reaction, and the solvent was collected until evaporated to dryness. Wherein, the molar ratio of tripolyindene formaldehyde, p-toluenesulfonic acid and BODIPY derivative is 4:1:1.

2) The reactant was cooled to room temperature, the solvent was removed under reduced pressure, and the residue was subjected to silica gel column chromatography to obtain the target product as a blue-green solid.

The specific chemical reaction formula is as follows:

In the above step (1), the molar ratio of terpolyindene formaldehyde, p-toluenesulfonic acid and BODIPY derivative is 4:1:1.

In above-mentioned step (1), the consumption of the added toluene and piperidine is respectively 25mL and 2mL.

In the above step (1), the catalyst is p-toluenesulfonic acid and piperidine.

In the above step (2), the column chromatography separation eluent is petroleum ether:dichloromethane=6:4～8:2.

Beneficial effects of the present invention

Compared with the prior art, the near-infrared BODIPY fluorescent dye and the preparation method thereof of the present invention have the following advantages: (1) the 3,5-position structure modification of the BODIPY dye by the trisinene group, the fluorescent dye The absorption and emission wavelengths are red-shifted to the near-infrared region (above 650nm); (2) the molar absorptivity is high, the fluorescence emission spectrum is narrow, the fluorescence quantum efficiency is high, the photostability is good and the solubility is good; (3) the preparation method is easy to operate The advantages of economy, good reaction selectivity, high yield and less pollution make it easy to popularize and apply in the field of cell imaging, fluorescent probe or laser dye.

Description of drawings

Fig. 1 is the ESI-MS spectrogram of compound A;

Fig. 2 is the proton nuclear magnetic resonance spectrogram of compound A;

Fig. 3 is the ultraviolet-visible absorption spectrogram of compound A;

Fig. 4 is the fluorescence emission spectrogram of compound A;

Fig. 5 is the ESI-MS spectrogram of compound B;

Fig. 6 is the proton nuclear magnetic resonance spectrogram of compound B;

Fig. 7 is the ultraviolet-visible absorption spectrogram of compound B;

FIG. 8 is a graph of the fluorescence emission spectrum of compound B.

detailed description

The present invention will be further described below in conjunction with specific drawings.

The structures of near-infrared BODIPY fluorescent dyes were characterized and confirmed by ¹ H-NMR, UV-Vis spectrum and ESIMASS. The instruments used for detection are: Bruker ARX600 nuclear magnetic resonance instrument (TMS is internal standard, deuterated chloroform is solvent), Shimadzu UV-3100 ultraviolet-visible spectrophotometer (scanning range 300～900nm, optical path slit 2nm), X- 4 digital micro-melting point instrument, American ThermoELECTRONCORPORATION mass spectrometer workstation, fluorescence spectrum is tested by American AmicoBowmanSeries2LuminescenceSpectrometer.

Example 1

Equipped with a water trap in the single-neck round bottom flask, 1,3,5,7-tetramethyl-8(2,4,6-trimethylbenzene)-BODIPY (146.4mg, 0.40mmol), 2-formyl Indene (0.862g, 1.60mmol) and p-toluenesulfonic acid (68mg) were dissolved in 25mL toluene and 2mL piperidine, the mixture was heated to reflux at 140°C, TLC was followed to detect the complete reaction of the raw materials, and the solvent was collected until evaporated to dryness. The reactant was concentrated and subjected to silica gel column chromatography with eluent (petroleum ether/CH ₂ Cl ₂ =6:4) to obtain dark green solid A (182.0 mg, 32.33%). Esi-MS: calcdforC ₁₀₂ H ₁₀₆ BF ₂ N ₂ 1407.8417, found: 1407.8459 (M+H ⁺ ) (Figure 1); ¹ HNMR: (600MHz, CDCl ₃ ) δ8.46 (d, J=4.20Hz, 2H) , 8.40(d, J=7.20Hz, 4H), 7.93(d, J=16.2Hz, 2H), 7.83(d, J=8.40Hz, 2H), 7.67(s, 1H), 7.54-7.52(m, 2H), 7.50-7.48(m, 2H), 7.46-7.42(m, 6H), 7.38-7.33(m, 4H), 7.03(s, 2H), 6.74(s, 2H), 3.15-3.03(m, 12H), 2.40(s, 3H), 2.31-2.18(m, 18H), 1.53(s, 6H), 0.33-0.25(m, 36H) (Figure 2); UV-vis: 348nm, 404nm, 613nm, 667nm (FIG. 3); Emission Wavelength: 691 nm (FIG. 4).

Example 2

Equipped with a water trap in the round bottom flask, 1,3,5,7-tetramethyl-2,6-diiodo-8(2,4,6-trimethylbenzene)-BODIPY (247.2mg, 0.40mmol) , tripolyindene formaldehyde (0.862g, 1.60mmol) and p-toluenesulfonic acid (68mg) were dissolved in 25mL toluene and 2mL piperidine, the mixture was heated to reflux at 140 ° C, TLC traced and detected that the reaction of the raw materials was complete, and the solvent was collected until evaporated to dryness. The reactant was concentrated and subjected to silica gel column chromatography with eluent (petroleum ether/CH ₂ Cl ₂ =8:2) to obtain green solid B (196.2 mg, 29.54%). Esi-MS: calcdforC ₁₀₂ H ₁₀₃ BF ₂ I ₂ N ₂ 1658.6272, found: 1658.6218 (M ⁺ ) (Fig. 5); ¹ HNMR: (600MHz, CDCl ₃ ) δ8.46 (d, J=8.40Hz, 2H) , 8.39(t, J=8.40Hz, 6H), 7.95(d, J=16.2Hz, 2H), 7.88(d, J=7.20Hz, 2H), 7.69(s, 2H), 7.49-7.33(m, 12H), 7.06(s, 2H), 3.14-2.99(m, 12H), 2.43(s, 3H), 2.33-2.13(m, 18H), 1.56(s, 6H), 0.34-0.23(m, 36H) (Figure 6); UV-vis: 356nm, 410nm, 483nm, 682nm (Figure 7); EmissionWavelength: 718nm (Figure 8).

Claims (7)

1. A near-infrared BODIPY class fluorescent dye and preparation method thereof, is characterized in that, its general structural formula is as follows: In the formula, R is H or I. 2. A kind of near-infrared BODIPY class fluorescent dye and preparation method thereof described in claim 1, is characterized in that: take 2-formyl tripolyindene and BODIPY derivative as raw material, in the catalysis of p-toluenesulfonic acid and piperidine To generate the target object, the steps are as follows: 1) Under anhydrous conditions, add BODIPY, terpolyindene formaldehyde and p-toluenesulfonic acid in a round bottom flask equipped with a Dean-Stark apparatus, then dissolve in 25 mL of toluene and 2 mL of piperidine, and heat the mixture to reflux at 140 °C, TLC detects that the starting point of the reaction disappears, and the solvent is collected until evaporated to dryness. Wherein, the molar ratio of tripolyindene formaldehyde, p-toluenesulfonic acid and BODIPY derivative is 4:1:1. 2) Cool the reactant to room temperature, evaporate the solvent to dryness under reduced pressure, and perform silica gel column chromatography to obtain the target product as a blue-green solid. 3. the preparation method of near-infrared BODIPY fluorescent dye according to claim 2, is characterized in that, in step 1), needs to be equipped with Dean-Stark device. 4. the preparation method of near-infrared BODIPY class fluorescent dye according to claim 2, is characterized in that, in step 1), the mol ratio of 2-formyl tripolyindene, p-toluenesulfonic acid and BODIPY derivative is 4: 1:1. 5. the preparation method of near-infrared BODIPY class fluorescent dye according to claim 2 is characterized in that, in step 1), catalyst is the p-toluenesulfonic acid that recrystallization crosses. 6. The preparation method of near-infrared BODIPY class fluorescent dye according to claim 2, is characterized in that, in step 1), the consumption of toluene and piperidine is respectively 25mL and 2mL. 7. the preparation method of near-infrared BODIPY class fluorescent dye according to claim 2 is characterized in that, in step 2), column chromatography separation eluent is sherwood oil: dichloromethane=6: 4～8: 2.