WO2023065506A1

WO2023065506A1 - Malachite green boronate and derivative and use thereof, and preparation method therefor

Info

Publication number: WO2023065506A1
Application number: PCT/CN2021/138133
Authority: WO
Inventors: 张鹏飞; 罗媛; 蔡林涛
Original assignee: 深圳先进技术研究院
Priority date: 2021-10-18
Filing date: 2021-12-15
Publication date: 2023-04-27
Also published as: CN115991717A

Abstract

Provided in the present invention are a malachite green boronate and a derivative and the use thereof, and a preparation method therefor. The method mainly comprises: firstly, generating a crude product from 4-bromobenzaldehyde and N,N-disubstituted aniline, and reacting the crude product with pinacol boronate in the presence of a catalyst to obtain a malachite green borate. The malachite green borate and the derivative thereof provided in the present invention can be used as dye precursors for fluorescent dyes capable of realizing aggregation-induced emission, and provide new synthesis blocks for fluorescent dyes capable of realizing aggregation-induced emission.

Description

A kind of malachite green borate and its derivatives, preparation method and application

technical field

The invention belongs to the technical field of fluorescent dyes, and in particular relates to malachite green borate ester and its derivatives, preparation method and application.

Background technique

Most traditional fluorescent dyes emit strong fluorescence as isolated molecules, but when aggregated or solid-state, the strong intermolecular π-π interactions cause strong aggregation-induced quenching (ACQ) effects without emitting light or with greatly increased fluorescence intensity. weakened. In order to solve this problem, Academician Tang Benzhong proposed a new aggregation-induced emission (AIE) concept in 2001. AIE emitters (AIEgens) adopt a twisted structure and exhibit excellent aggregation-induced emission by limiting the π-π interaction between molecules. performance. Although AIE has received extensive attention as a cutting-edge technology with wide application, the molecular design of novel AIEgens is still full of challenges. Due to the excellent optical properties and rich diversity of most conventional fluorescent molecules, the ACQ properties severely limit their applications. Therefore, converting traditional dyes into AIE active molecules provides another way to design high-brightness dyes.

So far, the design of AIEgens usually adopts the design guideline of backbone torsion + molecular rotor, and adopts the concept of restricted intramolecular motion (RIM). In general, ACQ-AIE conversion can be achieved by incorporating twisted AIEgens, propeller molecules, or bulky substituents into planar ACQ molecules to prevent tight coplanar packing.

Currently widely used propeller molecular building blocks include tetraphenylethylene, triethylamine and other very similar compounds, but it has been proved that such building blocks are not versatile when modifying traditional ACQ dyes. Therefore, it is of great significance to develop and synthesize new synthetic building blocks as precursors for the development of AIE dyes.

technical problem

In order to solve the deficiencies of the existing technology and develop a universal AIE dye precursor, the present invention proposes a new type of aggregation-induced luminescent fluorescent precursor dye-malachite green borate (MG-B) and Its derivatives, and the preparation method and application of malachite green borate and its derivatives. The fluorescent precursor dye can provide a new synthetic building block for the development of aggregation-induced luminescent fluorescent dyes, and has broad application prospects.

technical solution

Specifically, it is realized through the following technical solutions:

A malachite green borate ester, the structural formula is as shown in formula (1):

Formula 1)

Wherein, each R ₁ is independently methyl, ethyl, tert-butyl or julolidinyl.

The present invention also provides the preparation method of above-mentioned malachite green borate, comprising the following steps:

S1: react 4-bromobenzaldehyde and N, N-disubstituted aniline under the first catalyst, remove unreacted N, N-disubstituted aniline after the reaction, and extract the crude product;

S2: Dissolve the crude product obtained in step S1, pinaborate and potassium acetate in N, N-dimethylformamide, add a second catalyst for reaction, and extract and purify after the reaction to obtain malachite green Borates;

The structural formula of the N, N-disubstituted aniline is as follows:

Wherein, each R ₁ is independently methyl, ethyl, tert-butyl or julolidinyl.

Further, in step S1, the molar ratio of 4-bromobenzaldehyde to N, N-disubstituted aniline is 1:3.

Further, in step S1, the first catalyst is anhydrous zinc chloride.

Further, in step S1, the reaction temperature is 80°C-100°C, and the reaction time is 8-12h.

Further, in step S2, the second catalyst is [1,1'-bis(diphenylphosphino)ferrocene]palladium(II) dichloride.

Further, in step S2, the reaction temperature is 80°C-100°C, and the reaction time is 8-12h.

Further, in step S2, dichloromethane is added for extraction.

Further, in step S2, a silica gel column is used for purification.

A malachite green borate derivative, characterized in that the structural formula is shown in formula (2) or formula (3), wherein, formula (2) is:

Wherein, R is methyl, ethyl, methoxy or tert-butyl; each _R is independently methyl, ethyl, tert-butyl or julolidinyl;

Formula (3) is:

Wherein, each R ₁ is independently methyl, ethyl, tert-butyl or julolidinyl.

The present invention also provides the preparation method of above-mentioned malachite green borate derivative, comprising the following steps:

S2: Dissolve the crude product obtained in step S1, pina borate and potassium acetate in N, N-disubstituted aniline, add a second catalyst to react, and extract and purify after the reaction to obtain malachite green boric acid ester;

S3: The malachite green borate ester obtained in step S2 is subjected to Suzuki coupling reaction with reactant A to obtain malachite green borate ester derivatives;

Wherein, the structural formula of the N, N-disubstituted aniline is as follows:

The structural formula of the reactant A is:

or

Wherein, R is methyl, ethyl, methoxy or tert-butyl.

Further, in step S1, the first catalyst is anhydrous zinc chloride.

Further, in step S2, dichloromethane is added for extraction.

Further, in step S2, a silica gel column is used for purification.

The present invention also provides the application of the above-mentioned malachite green borate in synthesizing aggregation-induced luminescent fluorescent dyes as precursor dyes.

The present invention also provides the application of the above-mentioned malachite green borate derivatives in synthesizing aggregation-induced luminescent fluorescent dyes as precursor dyes.

Beneficial effect

The beneficial effects of the present invention are as follows:

The present invention proposes a new type of malachite green borate and its derivatives, preparation method and application. Malachite green borate and its derivatives can be used as the dye precursor of aggregation-induced luminescent fluorescent dyes to provide aggregation-induced luminescence Fluorescent dyes provide new crafting blocks.

Description of drawings

In order to more clearly illustrate the technical solutions in the embodiments of the present application, the drawings that need to be used in the description of the embodiments will be briefly introduced below. Obviously, the drawings in the following description are only some embodiments of the present application. For those skilled in the art, other drawings can also be obtained based on these drawings without creative effort.

Fig. 1 is the nuclear magnetic proton spectrum figure of MG-Br among the embodiment 1;

Fig. 2 is the carbon nuclear magnetic spectrogram of MG-Br in embodiment 1;

Fig. 3 is the high-resolution mass spectrogram of MG-Br in embodiment 1;

Fig. 4 is the NMR spectrum figure of MG-B in embodiment 1;

Fig. 5 is the carbon nuclear magnetic spectrogram of MG-B in embodiment 1;

FIG. 6 is a high-resolution mass spectrum of MG-B in Example 1.

Embodiments of the present invention

The following will clearly and completely describe the technical solutions in the embodiments of the present invention. Obviously, the described embodiments are only some of the embodiments of the present invention, rather than all the embodiments. Based on the embodiments of the present invention, all other embodiments obtained by persons of ordinary skill in the art without making creative efforts belong to the protection scope of the present invention.

Formula 1)

Wherein, each R ₁ is independently methyl, ethyl, tert-butyl or julolidinyl.

Wherein the structural formula of N, N-disubstituted aniline is as follows:

Wherein, each R ₁ is independently methyl, ethyl, tert-butyl or julolidinyl.

Further, in step S1, the first catalyst is anhydrous zinc chloride.

Further, in step S1, the reaction temperature is 80-100°C , the reaction time is 8-12h.

Further, in step S2, the reaction temperature is 80-100°C , the reaction time is 8-12h.

Further, in step S2, dichloromethane is added for extraction.

Further, in step S2, a silica gel column is used for purification.

The present invention also provides a malachite green borate derivative, characterized in that the structural formula is represented by formula (2) or formula (3), wherein, formula (2) is:

Formula (3) is:

Wherein, each R ₁ is independently methyl, ethyl, tert-butyl or julolidinyl.

The structural formula of the reactant A is:

or

Wherein, R is methyl, ethyl, methoxy or tert-butyl.

The synthetic route involved in preparing malachite green borate derivatives is as follows:

The present invention also provides the application of the above-mentioned malachite green borate and its derivatives in the synthesis of aggregation-induced luminescent fluorescent dyes as precursor dyes.

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

Example 1

A kind of malachite green borate, its structural formula is:

The synthetic routes involved are:

The preparation method is as follows:

(1) 4-bromobenzaldehyde (22.1 mg, A mixture of anhydrous zinc chloride (28.1 mg, 0.2 mmol), N, N-dimethylaniline (36.2 mg, 0.3 mmol) and absolute ethanol (1 mL) was stirred overnight at 100°C. After cooling to room temperature, the mixture was concentrated to remove remaining N,N-dimethylaniline. The crude product was extracted with water (4 mL) and ethyl acetate (3-5 mL). The combined organic phases were dried with anhydrous sodium sulfate, and the crude product was purified by silica gel column (n-hexane: ethyl acetate = 10:1) to obtain bromomalachite green (MG-Br) as a white powder.

(2) Dissolve MG-Br (40.8 mg, 0.1 mmol), pinaborate (80 mg, 0.3 mmol) and potassium acetate (49 mg, 0.125 mmol) in N,N-dimethylformamide (3 mL). [1,1'-bis(diphenylphosphino)ferrocene]palladium(II) dichloride (10 mg, 0.012 mmol, 10 %) was dissolved in N,N-dimethyl Dimethylformamide (1 mL) was added to the reaction mixture, and stirred at 80°C for 12 hours. Then the mixture was cooled, dichloromethane (10 mL) was added, extracted with 30 mL of water in a separatory funnel, the organic phase was collected, dried over anhydrous sodium sulfate, and dried by rotary evaporation. The crude product was purified by silica gel column chromatography, the solvent was removed, and the target product malachite green borate (MG-B) was obtained as a white solid after vacuum drying.

The intermediate MG-Br and the obtained target compound MG-B were systematically characterized, including H NMR, C NMR, and high-resolution mass spectrometry.

The hydrogen spectrum of MG-Br is shown in Figure 1, and the hydrogen spectrum data are: ¹ H NMR (400 MHz, CDCl ₃ ) δ (ppm) 7.48 (t, J = 6.3 Hz, 2H), 7.11 (dd, J = 18.5 , 8.5 Hz, 6H), 6.78 (t, J = 6.3 Hz, 4H), 5.44 (d, J = 5.2 Hz, 1H), 3.04 - 2.99 (m, 12H).

The carbon spectrum of MG-Br is shown in Figure 2, and the carbon spectrum data is: ¹³ C NMR (100 MHz, CDCl ₃ ) δ (ppm) 149.1, 144.7, 132.2, 131.2, 130.0, 129.5, 119.8, 113.2, 112.6, 54.5 , 40.8.

The high-resolution mass spectrum of MG-Br is shown in Figure 3. The mass spectrum data is: HRMS (ESI) calcd. for C ₂₃ H ₂₆ BrN ₂ [M + H] ⁺ 409.12794, found: 409.12741.

The hydrogen spectrum of MG-B is shown in Figure 4, and the hydrogen spectrum data are: ¹ H NMR (400 MHz, CDCl ₃ ) δ (ppm) 7.76 (d, J = 7.3 Hz, 2H), 7.20 (d, J = 7.6 Hz, 2H), 7.01 (d, J = 8.3 Hz, 4H), 6.70 (d, J = 8.2 Hz, 4H), 5.43 (s, 1H), 2.94 (s, 12H), 1.37 (s, 12H).

The carbon spectrum of MG-B is shown in Figure 5, and the carbon spectrum data is: ¹³ C NMR (100 MHz, CDCl ₃ ) δ (ppm) 148.9, 148.8, 134.7, 132.7, 130.0, 128.9, 112.6, 83.6, 83.5, 55.2 , 40.8, 25.1, 24.9.

The high-resolution mass spectrum of MG-B is shown in Figure 6. The mass spectrum data is: HRMS (ESI) calcd. for C ₂₉ H ₃₈ BN ₂ O ₂ [M + H] ⁺ 457.30263, found: 457.30215.

It can be seen from the H NMR spectrum, C NMR spectrum and high resolution mass spectrum of Figures 1-6 that the compound finally prepared by this application is the target compound MG-B, the preparation method is feasible, and the target compound obtained is correct.

The target product malachite green borate (MG-B) prepared in this example is a new precursor of aggregation-induced luminescence dyes, which is versatile and provides a new synthetic building block for aggregation-induced luminescence fluorescent dyes.

Example 2

A malachite green borate derivative, the structural formula is:

The preparation method is as follows:

(2) Dissolve MG-Br (40.8 mg, 0.1 mmol), pinaborate (80 mg, 0.3 mmol) and potassium acetate (49 mg, 0.125 mmol) in N,N-dimethylformamide (3 mL). [1,1'-bis(diphenylphosphino)ferrocene]palladium(II) dichloride (10 mg, 0.012 mmol, 10 %) was dissolved in N,N-dimethyl Dimethylformamide (1 mL) was added to the reaction mixture, and stirred at 80°C for 12 hours. Then the mixture was cooled, dichloromethane (10 mL) was added, extracted with 30 mL of water in a separatory funnel, the organic phase was collected, dried over anhydrous sodium sulfate, and dried by rotary evaporation. The crude product was purified by silica gel column chromatography, the solvent was removed, and malachite green borate (MG-B) was obtained as a white solid after vacuum drying.

(3) Dissolve MG-B (0.1 mmol), methyl-substituted p-bromoborate (0.3 mmol) and potassium acetate (49 mg, 0.125 mmol) in N,N-dimethylformamide (3 mL) middle. [1,1'-bis(diphenylphosphino)ferrocene]palladium(II) dichloride (10 mg, 0.012 mmol, 10 %) was dissolved in N,N-dimethyl Dimethylformamide (1 mL) was added to the reaction mixture, and stirred at 80°C for 12 hours. Then the mixture was cooled, dichloromethane (10 mL) was added, extracted with 30 mL of water in a separatory funnel, the organic phase was collected, dried over anhydrous sodium sulfate, and dried by rotary evaporation. The crude product was purified by silica gel column chromatography, the solvent was removed, and the target product malachite green borate derivative was obtained as a white solid after vacuum drying.

The target product malachite green borate derivative prepared in this example is a new precursor of aggregation-induced luminescence dyes, which is versatile and provides a new synthetic building block for aggregation-induced luminescence fluorescent dyes.

Example 3

A malachite green borate derivative, the structural formula is:

The preparation method is as follows:

(1) 4-bromobenzaldehyde (22.1 mg, A mixture of anhydrous zinc chloride (28.1 mg, 0.2 mmol), N, N-dimethylaniline (36.2 mg, 0.3 mmol) and absolute ethanol (1 mL) was stirred overnight at 100°C. After cooling to room temperature, the mixture was concentrated to remove remaining N,N-dimethylaniline. The crude product was extracted with water (4 mL) and ethyl acetate (3-5 mL). The organic phases were combined and dried with anhydrous sodium sulfate. The crude product was purified by silica gel column (n-hexane: ethyl acetate = 10:1) to obtain the pure product bromomalachite green (MG-Br) as a white powder.

(3) Dissolve MG-B (0.1 mmol), phenyl-substituted p-bromoborate (0.3 mmol) and potassium acetate (49 mg, 0.125 mmol) in N,N-dimethylformamide (3 mL) middle. [1,1'-bis(diphenylphosphino)ferrocene]palladium(II) dichloride (10 mg, 0.012 mmol, 10 %) was dissolved in N,N-dimethyl Dimethylformamide (1 mL) was added to the reaction mixture, and stirred at 80°C for 12 hours. Then the mixture was cooled, dichloromethane (10 mL) was added, extracted with 30 mL of water in a separatory funnel, the organic phase was collected, dried over anhydrous sodium sulfate, and dried by rotary evaporation. The crude product was purified by silica gel column chromatography, the solvent was removed, and the target product malachite green borate derivative was obtained as a white solid after vacuum drying.

In summary, the present invention proposes a novel malachite green borate and its derivatives, preparation method and application, malachite green borate and its derivatives can be used as dye precursors of aggregation-induced luminescent fluorescent dyes , providing a new synthetic building block for aggregation-induced luminescent fluorescent dyes.

The above descriptions are only preferred embodiments of the present invention, and are not intended to limit the present invention. Any modifications, equivalent replacements, improvements, etc. made within the spirit and principles of the present invention shall be included in the protection of the present invention. within range.

Claims

A kind of malachite green borate, is characterized in that, structural formula is as shown in formula (1):

Formula 1)

Wherein, each R 1 is independently methyl, ethyl, tert-butyl or julolidinyl.
A preparation method of malachite green borate according to claim 1, is characterized in that, comprises the following steps:

S1: react 4-bromobenzaldehyde and N, N-disubstituted aniline under the first catalyst, remove unreacted N, N-disubstituted aniline after the reaction, and extract the crude product;

S2: Dissolve the crude product obtained in step S1, pinaborate and potassium acetate in N, N-dimethylformamide, add a second catalyst for reaction, and extract and purify after the reaction to obtain malachite green Borates;

The N, The structural formula of N-disubstituted aniline is as follows:

Wherein, each R 1 is independently methyl, ethyl, tert-butyl or julolidinyl.
The preparation method of malachite green borate according to claim 2, is characterized in that, in step S1, the mol ratio of described 4-bromobenzaldehyde and N, N-disubstituted aniline is 1:3.
The preparation method of malachite green borate according to claim 2 is characterized in that, in step S1, the first catalyst is anhydrous zinc chloride, and the second catalyst is [1,1'-bis (Diphenylphosphine)ferrocene]palladium(II) dichloride.
The preparation method of malachite green borate according to claim 2, characterized in that, in step S1, the reaction temperature is 80°C-100°C, and the reaction time is 8-12h.
The preparation method of malachite green borate according to claim 2, characterized in that, in step S2, the reaction temperature is 80°C-100°C, and the reaction time is 8-12h.
A malachite green borate derivative, characterized in that the structural formula is shown in formula (2) or formula (3), wherein, formula (2) is:

Wherein, R is methyl, ethyl, methoxy or tert-butyl; each R is independently methyl, ethyl, tert-butyl or julolidinyl;

Formula (3) is:

Wherein, each R 1 is independently methyl, ethyl, tert-butyl or julolidinyl.
A preparation method of malachite green borate derivatives according to claim 7, is characterized in that, comprises the following steps:

S1: react 4-bromobenzaldehyde and N, N-disubstituted aniline under the first catalyst, remove unreacted N, N-disubstituted aniline after the reaction, and extract the crude product;

S2: Dissolve the crude product obtained in step S1, pina borate and potassium acetate in N, N-disubstituted aniline, add a second catalyst to react, and extract and purify after the reaction to obtain malachite green boric acid ester;

S3: The malachite green borate ester obtained in step S2 is subjected to Suzuki coupling reaction with reactant A to obtain malachite green borate ester derivatives;

Among them, the N, The structural formula of N-disubstituted aniline is as follows:

The structural formula of the reactant A is:

or

Wherein, R is methyl, ethyl, methoxy or tert-butyl.
The malachite green borate according to claim 1 or the malachite green borate prepared according to the preparation method of the malachite green borate according to any one of claims 2-6 is synthesized and aggregated to induce luminescent fluorescence Use of dyes as precursor dyes.
The malachite green borate derivatives according to claim 7 or the malachite green borate derivatives prepared according to the preparation method of the malachite green borate derivatives according to claim 8 are synthesized and aggregated to induce luminescence Application of fluorescent dyes as precursor dyes.