CN118005498A - Anthracene fluorescent dye and synthesis method thereof - Google Patents

Anthracene fluorescent dye and synthesis method thereof Download PDF

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Publication number
CN118005498A
CN118005498A CN202410174533.5A CN202410174533A CN118005498A CN 118005498 A CN118005498 A CN 118005498A CN 202410174533 A CN202410174533 A CN 202410174533A CN 118005498 A CN118005498 A CN 118005498A
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intermediate product
fluorescent dye
anthracene fluorescent
anthracene
synthesizing
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张朋乐
段海峰
朱建发
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Dyna Technology Beijing Co ltd
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Dyna Technology Beijing Co ltd
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    • C—CHEMISTRY; METALLURGY
    • C07—ORGANIC CHEMISTRY
    • C07C—ACYCLIC OR CARBOCYCLIC COMPOUNDS
    • C07C49/00—Ketones; Ketenes; Dimeric ketenes; Ketonic chelates
    • C07C49/587—Unsaturated compounds containing a keto groups being part of a ring
    • C07C49/703—Unsaturated compounds containing a keto groups being part of a ring containing hydroxy groups
    • C07C49/747—Unsaturated compounds containing a keto groups being part of a ring containing hydroxy groups containing six-membered aromatic rings
    • C—CHEMISTRY; METALLURGY
    • C09—DYES; PAINTS; POLISHES; NATURAL RESINS; ADHESIVES; COMPOSITIONS NOT OTHERWISE PROVIDED FOR; APPLICATIONS OF MATERIALS NOT OTHERWISE PROVIDED FOR
    • C09B—ORGANIC DYES OR CLOSELY-RELATED COMPOUNDS FOR PRODUCING DYES, e.g. PIGMENTS; MORDANTS; LAKES
    • C09B1/00—Dyes with anthracene nucleus not condensed with any other ring
    • C—CHEMISTRY; METALLURGY
    • C09—DYES; PAINTS; POLISHES; NATURAL RESINS; ADHESIVES; COMPOSITIONS NOT OTHERWISE PROVIDED FOR; APPLICATIONS OF MATERIALS NOT OTHERWISE PROVIDED FOR
    • C09K—MATERIALS FOR MISCELLANEOUS APPLICATIONS, NOT PROVIDED FOR ELSEWHERE
    • C09K11/00—Luminescent, e.g. electroluminescent, chemiluminescent materials
    • C09K11/06—Luminescent, e.g. electroluminescent, chemiluminescent materials containing organic luminescent materials
    • C—CHEMISTRY; METALLURGY
    • C09—DYES; PAINTS; POLISHES; NATURAL RESINS; ADHESIVES; COMPOSITIONS NOT OTHERWISE PROVIDED FOR; APPLICATIONS OF MATERIALS NOT OTHERWISE PROVIDED FOR
    • C09K—MATERIALS FOR MISCELLANEOUS APPLICATIONS, NOT PROVIDED FOR ELSEWHERE
    • C09K2211/00—Chemical nature of organic luminescent or tenebrescent compounds
    • C09K2211/10—Non-macromolecular compounds
    • C09K2211/1003—Carbocyclic compounds
    • C09K2211/1007—Non-condensed systems
    • C—CHEMISTRY; METALLURGY
    • C09—DYES; PAINTS; POLISHES; NATURAL RESINS; ADHESIVES; COMPOSITIONS NOT OTHERWISE PROVIDED FOR; APPLICATIONS OF MATERIALS NOT OTHERWISE PROVIDED FOR
    • C09K—MATERIALS FOR MISCELLANEOUS APPLICATIONS, NOT PROVIDED FOR ELSEWHERE
    • C09K2211/00—Chemical nature of organic luminescent or tenebrescent compounds
    • C09K2211/10—Non-macromolecular compounds
    • C09K2211/1003—Carbocyclic compounds
    • C09K2211/1011—Condensed systems

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  • Engineering & Computer Science (AREA)
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Abstract

The embodiment of the disclosure discloses an anthracene fluorescent dye and a synthesis method thereof. The anthracene fluorescent dye has a structure shown in a general formula (a), wherein R is selected from aryl, substituted aryl, C1-C6 alkyl, substituted C1-C6 alkyl, C1-C6 ether and substituted C1-C6 ether. The synthesis method comprises the following steps: reducing o-halogenated benzophenone to obtain a first intermediate product; converting halogen in the first intermediate product into carboxyl to obtain a second intermediate product; dehydrating and closing the ring of the second intermediate product to obtain a third intermediate product; oxidizing the third intermediate product to obtain a fourth intermediate product; removing the phenolic hydroxyl protecting group from the fourth intermediate to obtain a fifth intermediate; protecting two phenolic hydroxyl groups of the fifth intermediate product to obtain a sixth intermediate product; and (3) carrying out an anthrone addition reaction on the sixth intermediate product to obtain the anthracene fluorescent dye. The anthracene fluorescent dye can have a longer excitation wavelength.

Description

Anthracene fluorescent dye and synthesis method thereof
Technical Field
The present disclosure relates to the technical field of biochemical fluorescent dyes, and in particular relates to an anthracene fluorescent dye and a synthesis method thereof.
Background
Anthracene fluorescent dyes belong to a class of fluorescent compounds containing an anthracene nucleus (carbon bridge substitution). The compound has the characteristics of long wavelength, fluorescence switching, high molar absorption coefficient and the like. Such compounds and methods for their synthesis are also disclosed in patent CN201510155218.9, which was previously filed by the applicant.
In high throughput sequencing techniques, the fluorescent (fluorogenic) nature of the anthracene fluorescent dye can be used to label deoxynucleotides. The marking process specifically comprises the following steps: different fluorescent marker groups are linked to specific positions of deoxynucleotides through cleavable long phosphate chains, and after DNA has been identified and fluorescent signals recorded, the fluorescent marker groups are removed by additional chemical means, thereby preparing for the next round of deoxynucleotide introduction.
The inventor finds that the existing anthracene fluorescent dye has the problem of short excitation wavelength, and has the problems of larger spontaneous background, larger light damage and shallower tissue permeability of biological tissues in the high-flux sequencing process, so that development of the anthracene fluorescent dye with longer excitation wavelength is needed.
Disclosure of Invention
In view of this, the embodiments of the present disclosure provide an anthracene fluorescent dye and a synthesis method thereof, which can have a longer excitation wavelength.
In a first aspect, an embodiment of the present disclosure provides an anthracene fluorescent dye, which adopts the following technical scheme:
the anthracene fluorescent dye has a structure shown in a general formula (a):
wherein R is selected from the group consisting of aryl, substituted aryl, C1-C6 alkyl, substituted C1-C6 alkyl, C1-C6 ether, and substituted C1-C6 ether.
Alternatively, it has a structure represented by the general formula (b):
in a second aspect, an embodiment of the present disclosure provides a method for synthesizing an anthracene fluorescent dye, which adopts the following technical scheme:
The synthesis method of the anthracene fluorescent dye comprises the following steps:
S1, reducing o-halogenated benzophenone to obtain a first intermediate product;
s2, converting halogen in the first intermediate product into carboxyl to obtain a second intermediate product;
s3, dehydrating and closing the ring of the second intermediate product to obtain a third intermediate product;
s4, oxidizing the third intermediate product to obtain a fourth intermediate product;
S5, removing the phenolic hydroxyl protecting group from the fourth intermediate product to obtain a fifth intermediate product;
S6, protecting phenolic hydroxyl groups of the fifth intermediate product to obtain a sixth intermediate product;
s7, carrying out an anthrone addition reaction on the sixth intermediate product to obtain an anthracene fluorescent dye;
wherein the first intermediate product is a diphenylmethane derivative; the second intermediate product is a carboxyl derivative of diphenylmethane; the fourth intermediate product is an anthrone compound.
Optionally, in the step S1, the o-halogenated benzophenone is reduced by a reducing agent, where the reducing agent is one or more of activated iron powder, triethylsilane and hypophosphorous acid.
Optionally, at least one of the 3,4 positions of the o-halobenzophenone has a methoxy group.
Optionally, in step S2, the halogen in the first intermediate product is converted to a carboxyl group by a grignard reagent or an alkyl lithium.
Optionally, in step S3, the second intermediate product is subjected to a dehydration and ring-closing reaction by using a ring-closing reagent to obtain a third intermediate product, where the ring-closing reagent is one or more of oxalyl chloride/boron tribromide, concentrated sulfuric acid, and polyphosphoric acid.
Optionally, in the step S3, the second intermediate product is subjected to dehydration and ring closure reaction at 20-50 ℃ for a period of time not more than 1 hour.
Optionally, in the step S4, the methylene in the third intermediate product is oxidized to carbonyl by an oxidizing agent at 60-70 ℃, and the oxidizing agent is one or more of chromium trioxide, potassium dichromate and potassium permanganate.
Optionally, in step S7, an anthrone addition reaction is performed on the sixth intermediate product by an addition reagent, where the addition reagent is a halogenated aromatic compound or a halogenated alkyl compound.
The embodiment of the disclosure provides an anthracene fluorescent dye and a synthesis method thereof, wherein the anthracene fluorescent dye has a structure shown in a general formula (a), and the synthesis method comprises the following steps: reducing o-halogenated benzophenone to obtain a first intermediate product; converting halogen in the first intermediate product into carboxyl to obtain a second intermediate product; dehydrating and closing the ring of the second intermediate product to obtain a third intermediate product; oxidizing the third intermediate product to obtain a fourth intermediate product; removing the phenolic hydroxyl protecting group from the fourth intermediate to obtain a fifth intermediate; protecting two phenolic hydroxyl groups of the fifth intermediate product to obtain a sixth intermediate product; and (3) carrying out an anthrone addition reaction on the sixth intermediate product to obtain the anthracene fluorescent dye. The anthracene fluorescent dye has hydroxyl, and lone pair electrons on hydroxyl oxygen enhance the conjugation property of the anthracene fluorescent dye, so that the anthracene fluorescent dye has longer excitation wavelength, and further solves the problems of larger spontaneous background, larger photodamage and shallower tissue permeability of biological tissues in the prior art.
The foregoing description is only an overview of the disclosed technology, and may be implemented in accordance with the disclosure of the present disclosure, so that the above-mentioned and other objects, features and advantages of the present disclosure can be more clearly understood, and the following detailed description of the preferred embodiments is given with reference to the accompanying drawings.
Drawings
In order to more clearly illustrate the technical solutions of the embodiments of the present disclosure, the drawings that are needed in the embodiments will be briefly described below, and it is obvious that the drawings in the following description are only some embodiments of the present disclosure, and other drawings may be obtained according to these drawings without inventive effort to a person of ordinary skill in the art.
FIG. 1 is a flow chart of a method for synthesizing an anthracene fluorescent dye according to an embodiment of the present disclosure;
FIG. 2 is a graph showing fluorescence absorption height statistics of anthracene fluorescent dyes at different pH values according to an embodiment of the present disclosure;
fig. 3 is a graph of excitation and emission spectra of anthracene fluorescent dyes provided in an embodiment of the present disclosure.
Detailed Description
The present disclosure is described in further detail below with reference to the drawings and the embodiments. It is to be understood that the specific embodiments described herein are merely illustrative of the relevant content and not limiting of the present disclosure. It should be further noted that, for convenience of description, only a portion relevant to the present disclosure is shown in the drawings.
In addition, embodiments of the present disclosure and features of the embodiments may be combined with each other without conflict. The technical aspects of the present disclosure will be described in detail below with reference to the accompanying drawings in conjunction with embodiments.
Unless otherwise indicated, the exemplary implementations/embodiments shown are to be understood as providing exemplary features of various details of some ways in which the technical concepts of the present disclosure may be practiced. Thus, unless otherwise indicated, features of the various implementations/embodiments may be additionally combined, separated, interchanged, and/or rearranged without departing from the technical concepts of the present disclosure.
The terminology used herein is for the purpose of describing particular embodiments only and is not intended to be limiting. As used herein, the singular forms "a", "an" and "the" are intended to include the plural forms as well, unless the context clearly indicates otherwise. Furthermore, when the terms "comprises" and/or "comprising," and variations thereof, are used in the present specification, the presence of stated features, integers, steps, operations, elements, components, and/or groups thereof is described, but the presence or addition of one or more other features, integers, steps, operations, elements, components, and/or groups thereof is not precluded. It is also noted that, as used herein, the terms "substantially," "about," and other similar terms are used as approximation terms and not as degree terms, and as such, are used to explain the inherent deviations of measured, calculated, and/or provided values that would be recognized by one of ordinary skill in the art.
The embodiment of the disclosure provides an anthracene fluorescent dye, specifically, the anthracene fluorescent dye has a structure shown in a general formula (a):
wherein R is selected from the group consisting of aryl, substituted aryl, C1-C6 alkyl, substituted C1-C6 alkyl, C1-C6 ether, and substituted C1-C6 ether.
The anthracene fluorescent dye according to the embodiments of the present disclosure refers to a fluorescent dye having a triphenylanthracene-like structure. C1-C6 means having 1 to 6 carbon atoms, and others are similar.
In one example, the anthracene fluorescent dye in embodiments of the present disclosure has a structure represented by general formula (b):
The anthracene fluorescent dye provided by the embodiment of the disclosure has hydroxyl, and lone pair electrons on hydroxyl oxygen enhance the conjugation property of the anthracene fluorescent dye, so that the anthracene fluorescent dye has a longer excitation wavelength, specifically, the excitation wavelength of the anthracene fluorescent dye provided by the embodiment of the disclosure is red shifted, the excitation wavelength is 570-580 nm, the emission wavelength is 590-610 nm, and the quantum yield is about 93%. Compared with fluorescent dyes (such as FAM, TG, PO and the like) in the prior art, the fluorescent dye has longer excitation wavelength, further solves the problems of larger spontaneous background, larger light damage and shallower tissue permeability of biological tissues in the prior art, is more suitable for excitation light sources with lower cost, and has important significance for the sequencing field. The excitation wavelength of the fluorescent dye such as FAM, TG, PO in the prior art is usually concentrated at 490-550 nm, and the excitation wavelength of the hydrophilic anthracene fluorescent dye disclosed in patent CN112300599B is 460-540nm.
In addition, an embodiment of the present disclosure provides a method for synthesizing an anthracene fluorescent dye, as shown in fig. 1, the method for synthesizing an anthracene fluorescent dye includes:
And S1, reducing o-halogenated benzophenone to obtain a first intermediate product.
Optionally, in step S1, the o-halogenated benzophenone is reduced by a reducing agent, where the reducing agent is one or more of activated iron powder, triethylsilane, and hypophosphorous acid. The first intermediate is a diphenylmethane derivative. Taking the reducing agent as triethylsilane as an example, 1.5-3 equivalents of triethylsilane are required when step S1 is performed at room temperature, and 3-5 equivalents of hypophosphorous acid are required when step S1 is performed at 60 ℃.
Optionally, at least one of the 3,4 positions of the o-halogenated benzophenone has a methoxy group, which can be used as a power supply group to increase the electron cloud density of the conjugated structure, thereby increasing the excitation wavelength of the anthracene fluorescent dye.
And S2, converting halogen in the first intermediate product into carboxyl to obtain a second intermediate product.
The second intermediate is a carboxy derivative of diphenylmethane. Alternatively, in step S2, the halogen in the first intermediate is converted into a carboxyl group by a grignard reagent, and illustratively, the grignard reagent converts the halogen in the first intermediate into a carboxyl group at 0 ℃ and the reaction requires 1.5 to 3 equivalents of the grignard reagent, which may be methyl magnesium bromide, isopropyl magnesium bromide, or the like. Or converting the halogen in the first intermediate product into carboxyl group by alkyl lithium, and illustratively, converting the halogen in the first intermediate product into carboxyl group by n-butyl lithium at-78 ℃, the reaction requires 1.0 to 1.5 equivalents of n-butyl lithium.
And S3, dehydrating and closing the ring of the second intermediate product to obtain a third intermediate product.
Optionally, in step S3, the second intermediate is subjected to a dehydration ring-closing reaction by a ring-closing reagent to obtain a third intermediate. The ring-closing reagent can be one or more of oxalyl chloride/boron tribromide, concentrated sulfuric acid and polyphosphoric acid.
Optionally, in step S3, the second intermediate product is subjected to dehydration and ring closure reaction at 20-50 ℃ for a period of time not more than 1 hour, so as to avoid that the reaction temperature is too high and/or the reaction time is too long, which leads to the increase of byproducts.
Taking the ring-closing reagent as polyphosphoric acid as an example, step S3 may specifically be adding 10 times of mass equivalent of polyphosphoric acid to the second intermediate product, and stirring at room temperature for 1 hour, thereby obtaining a third intermediate product.
And S4, oxidizing the third intermediate product to obtain a fourth intermediate product.
The fourth intermediate product is an anthrone compound.
Optionally, in step S4, the methylene in the third intermediate product is oxidized to carbonyl by an oxidizing agent, where the oxidizing agent is one or more of chromium trioxide, potassium dichromate, and potassium permanganate. Alternatively, the methylene group in the third intermediate product is oxidized to a carbonyl group by an oxidizing agent at 60 to 70 ℃. Taking the oxidant as chromium trioxide as an example, step S4 may specifically be adding 3 equivalents of chromium trioxide and 10 times the volume of acetic acid to the third intermediate product, and heating at 60 ℃ for 2 hours.
And S5, removing the phenolic hydroxyl protecting group from the fourth intermediate product to obtain a fifth intermediate product.
Illustratively, 3 equivalents of boron tribromide are added to the fourth intermediate, and a demethylation reaction occurs at room temperature for 2 hours, resulting in the fourth intermediate being stripped of phenolic hydroxyl protecting groups to yield a fifth intermediate.
And S6, protecting phenolic hydroxyl groups of the fifth intermediate product to obtain a sixth intermediate product.
Illustratively, the phenolic hydroxyl groups in the fifth intermediate are protected with 2.5 to 3.0 equivalents of TBSCl to the fifth intermediate to afford a sixth intermediate.
S7, carrying out an anthrone addition reaction on the sixth intermediate product to obtain an anthracene fluorescent dye;
optionally, in step S7, an anthrone addition reaction is performed on the sixth intermediate product by an addition reagent, where the addition reagent is a halogenated aromatic compound or a halogenated alkyl compound.
In step S7, 1.5 equivalents of n-butyllithium were added to the sixth intermediate, reacted at-78℃for 1 hour, and a solution of 1.0 equivalent of tetrahydrofuran was added dropwise while maintaining at-78 ℃.
It should be noted that, among the steps mentioned in the embodiments of the present disclosure, some steps may have other products, and those skilled in the art can obtain the target product on the basis of the embodiments of the present disclosure, and the specific structure of the other products is not core in the embodiments of the present disclosure, which is not described herein.
The synthesis method of the anthracene fluorescent dye can synthesize the fluorescent dye with longer excitation wavelength, has the advantages of cheap and easily available raw materials, simple preparation of intermediates, high yield, simple and easy operation synthesis, and can effectively improve the yield, increase the derivatization feasibility, reduce the large-scale synthesis cost and facilitate the application of the anthracene fluorescent dye in the aspect of molecular marking.
Examples
The synthetic route of the anthracene fluorescent dye with the structure shown in the general formula (b) is as follows:
The specific synthesis process comprises the following steps:
(1) Synthesis of Compound 1-bromo-4-methoxy-2- (3-methoxybenzyl) benzene 2:
20g of compound 1 is added into 200ml of dichloromethane solution, 37ml of triethylsilane is added under ice bath, 25ml of trifluoroacetic acid is added into the solution, after the addition, 2ml of trifluoromethanesulfonic acid is added into the mixed solution dropwise, stirring is continued under ice bath for 10min, the temperature is raised to room temperature, stirring is continued for two hours, after TCL monitors that the raw materials are completely converted, the reaction system is added into 200ml of pure water, the solution is separated, the organic phase is washed once with 200ml of pure water, and the compound 2 (15 g, YIeld: 78%) is obtained after the organic phase is concentrated and purified by a column. Yield is Yield.
The one-dimensional nuclear magnetic resonance hydrogen spectrum and mass spectrometer test results are as follows:
1H NMR(500MHz,CDCl3)7.39(d,J＝7.5Hz,1H),7.21(t,J＝7.5Hz,1H),7.01–6.95(m,1H),6.82(ddd,J＝7.6,6.2,1.5Hz,2H),6.70(q,J＝1.1Hz,1H),6.66(p,J＝1.2Hz,1H),3.95(q,J＝0.9Hz,2H),3.82(d,J＝3.1Hz,6H).
LCMS:C15H15BrO2,(M+H):307.0255/309.0235。
(2) Synthesis of 4-methoxy-2- (3-methoxybenzyl) benzoic acid:
15g of compound 2 is dissolved in 150ml of ultra-dry tetrahydrofuran, stirred until the solution is clear, cooled to-78 ℃,20 ml of n-hexane solution (2.4M) of n-butyllithium is dripped into a reaction system, the mixture is kept at-78 ℃ after dripping, stirring is continued for 30min, ultra-dry carbon dioxide gas is introduced into the reaction system, the mixture is kept at-78 ℃ for 10min, the temperature is slowly raised to room temperature, the reaction is continued for 30min, after TLC detection reaction is completed, the reaction system is added into 150ml of 1M hydrochloric acid aqueous solution, 100ml of ethyl acetate is added into the reaction system, the mixture is separated, an organic phase is washed once by 100ml of saturated saline, and the organic phase is concentrated until the mixture is dried to obtain a crude product of the compound 3 (14 g, YIeld:100 percent), and the crude product is directly used for the next reaction.
The one-dimensional nuclear magnetic resonance hydrogen spectrum and mass spectrometer test results are as follows:
1H NMR(500MHz,Chloroform-d)δ7.79(d,J＝7.4Hz,1H),7.21(t,J＝7.5Hz,1H),6.97(dq,J＝7.5,1.2Hz,1H),6.81(dt,J＝7.5,1.5Hz,1H),6.75–6.68(m,2H),6.63(p,J＝1.2Hz,1H),4.25(q,J＝0.9Hz,2H),3.87(s,3H),3.80(s,3H).
LCMS:C16H16O4，(M+H):273.1082。
(3) Synthesis of Compound 3,6-dimethoxyanthracen-9 (10H) -one 4:
14g of compound 3 is dissolved in 30ml of dichloromethane solution, then the dichloromethane solution of the compound 3 is added into 140g of PPA, the reaction system is stirred at room temperature until the TLC is monitored to be completely reacted, ice water is added into the system, the glass rod is stirred until the PPA is completely hydrolyzed, then 150ml of dichloromethane is added into a quenching system for extraction once, liquid separation is carried out, and the aqueous phase is extracted once again with 150ml of dichloromethane, and liquid separation is carried out. The combined organic phases were concentrated to dryness, the concentrated dry system was slurried with 50ml MTBE and filtered to give compound 4 (8 g, yield: 61%) which was used directly in the next reaction.
The one-dimensional nuclear magnetic resonance hydrogen spectrum and mass spectrometer test results are as follows:
1H NMR(500MHz,Chloroform-d)δ7.88(d,J＝7.4Hz,2H),6.92–6.84(m,4H),4.36(t,J＝1.0Hz,2H),3.85(s,5H).
LCMS:C16H14O3，(M+H):255.0976。
(4) Synthesis of Compound 2,7-dimethoxyanthracene-9,10-dione 5:
Dissolving 4g of compound into 40ml of glacial acetic acid solution, adding 9.4g of chromium trioxide, heating the system to 50 ℃, stirring for 1 hour, cooling the reaction system to room temperature after TLC monitoring reaction is complete, adding 150ml of pure water, continuously stirring for 30min, and filtering to obtain 5 (8 g, YIeld: 95%).
The one-dimensional nuclear magnetic resonance hydrogen spectrum and mass spectrometer test results are as follows:
1H NMR(500MHz,Chloroform-d)δ8.15(d,J＝7.4Hz,2H),7.58(d,J＝1.5Hz,2H),7.12(dd,J＝7.5,1.5Hz,2H),3.82(s,5H).
LCMS:C16H12O4，(M+H):269.0769。
(5) Synthesis of Compound 2,7-dihydroxyanthracene-9,10-dione 6:
Dissolving 5g of compound into 80ml of obtained dichloromethane solution, cooling to 0 ℃, dropwise adding 6.6ml of obtained boron tribromide into the solution, after the dropwise addition, slowly heating to room temperature, continuously stirring for 2 hours, dropwise adding 150ml of pure water into a reaction system after TLC monitoring reaction is complete, adding 150ml of ethyl acetate into the reaction system, separating liquid, extracting the aqueous phase once with 50ml of ethyl acetate, merging organic phases, washing once with 50ml of saturated saline solution, separating liquid, and concentrating the organic phases until the organic phases are dried to obtain the compound 6 (6 g, YIeld: 84%).
The one-dimensional nuclear magnetic resonance hydrogen spectrum and mass spectrometer test results are as follows:
1H NMR(500MHz,Chloroform-d)δ9.04(s,2H),8.08(d,J＝7.5Hz,2H),7.54(d,J＝1.4Hz,2H),7.29(dd,J＝7.5,1.5Hz,2H).
LCMS:C14H8O4，(M+H):241.0456。
(6) Synthesis of 2,7-bis (tert-butyldimethylsilyl) oxy) anthraquinone-9, 10-dione 7:
6g of the compound was added to 30ml of DMF, 5.1g of imidazole and 9.4g of TBSCl were added thereto and stirred at room temperature for 2 hours, after completion of the TLC monitoring reaction, the reaction system was added to 90ml of pure water, 90ml of MTBE was further added thereto, the solution was separated, the organic phase was washed once with 60ml of saturated brine, the solution was separated, the organic phase was concentrated to dryness, the concentrated dry matter was slurried with 30ml of methanol, and compound 7 (10 g, yield: 85%) was obtained by filtration.
The one-dimensional nuclear magnetic resonance hydrogen spectrum and mass spectrometer test results are as follows:
1H NMR(500MHz,Chloroform-d)δ8.03(d,J＝7.5Hz,2H),7.44(d,J＝1.6Hz,3H),7.26(dd,J＝7.5,1.5Hz,2H),1.01(s,17H),0.21(s,11H).
LCMS:C26H36O4Si2，(M+H):469.2186
(7) Synthesis of the Compound 10-bis (2, 4-DIMETHYLPHENYL) -7,9-dihydroxyanthracen-2 (9H) -one target 1:
Dissolving 7.2 g of compound into 10ml of ultra-dry tetrahydrofuran, stirring until the solution is clear, sealing the solution for later use, dissolving 2.4g of compound 1-bromo-2,4-dimethylbenzene into 10ml of ultra-dry tetrahydrofuran, cooling to-78 ℃, dropwise adding 5.4ml of n-hexane solution of n-butyllithium into the solution, keeping-78 ℃, continuously stirring for 30min, dropwise adding the prepared tetrahydrofuran solution of the compound 7 into a low-temperature system, keeping-78 ℃, stirring for 10min, then slowly heating to room temperature, continuously stirring for 30min, adding 20ml of 5M hydrochloric acid aqueous solution into the reaction system after TLC monitoring reaction is complete, stirring for 1 hour at room temperature, and filtering to obtain a compound target 1 (1.3 g, YIeld: 70%).
The one-dimensional nuclear magnetic resonance hydrogen spectrum and mass spectrometer test results are as follows:
1H NMR(500MHz,Chloroform-d)δ8.87(s,1H),7.54–7.46(m,2H),7.22(dd,J＝7.5,4.4Hz,2H),7.17(ddd,J＝7.5,1.5,0.8Hz,1H),7.11–7.04(m,2H),6.93(d,J＝1.5Hz,1H),6.86(t,J＝1.0Hz,1H),6.76(dd,J＝7.5,1.7Hz,1H),6.62(d,J＝2.3Hz,1H),6.58(dd,J＝11.0,2.2Hz,1H),4.79(s,1H),2.35(d,J＝4.0Hz,6H),2.30(d,J＝1.5Hz,6H).
LCMS:C30H26O3，(M+H)：435.1915。
As shown in FIG. 2, the anthracene fluorescent dye having a structure represented by a general formula (b) has a small fluorescence absorption height at pH less than 8, and a significant increase in fluorescence absorption height at pH 8 < 10, and the fluorescence absorption height remains substantially stable after pH > 10.
The spectral properties of compound target1 were measured by fluorescence spectroscopy in a ph=8 TEAA buffer solution, as shown in fig. 3, with excitation wavelength of 576nm and emission wavelength of 594nm.
In the description of the present specification, reference to the terms "one embodiment/manner," "some embodiments/manner," "example," "a particular example," "some examples," etc., means that a particular feature, structure, material, or characteristic described in connection with the embodiment/manner or example is included in at least one embodiment/manner or example of the application. In this specification, the schematic representations of the above terms are not necessarily for the same embodiment/manner or example. Furthermore, the particular features, structures, materials, or characteristics described may be combined in any suitable manner in any one or more embodiments/modes or examples. Furthermore, the various embodiments/modes or examples described in this specification and the features of the various embodiments/modes or examples can be combined and combined by persons skilled in the art without contradiction.
Furthermore, the terms "first," "second," and the like, are used for descriptive purposes only and are not to be construed as indicating or implying a relative importance or implicitly indicating the number of technical features indicated. Thus, a feature defining "a first" or "a second" may explicitly or implicitly include at least one such feature. In the description of the present application, the meaning of "plurality" means at least two, for example, two, three, etc., unless specifically defined otherwise.
It will be appreciated by those skilled in the art that the above-described embodiments are merely for clarity of illustration of the disclosure, and are not intended to limit the scope of the disclosure. Other variations or modifications will be apparent to persons skilled in the art from the foregoing disclosure, and such variations or modifications are intended to be within the scope of the present disclosure.

Claims (10)

1. An anthracene fluorescent dye characterized by having a structure represented by a general formula (a):
wherein R is selected from the group consisting of aryl, substituted aryl, C1-C6 alkyl, substituted C1-C6 alkyl, C1-C6 ether, and substituted C1-C6 ether.
2. The anthracene fluorescent dye according to claim 1, having a structure represented by a general formula (b):
3. a method for synthesizing anthracene fluorescent dye, which is characterized by comprising the following steps:
S1, reducing o-halogenated benzophenone to obtain a first intermediate product;
s2, converting halogen in the first intermediate product into carboxyl to obtain a second intermediate product;
s3, dehydrating and closing the ring of the second intermediate product to obtain a third intermediate product;
s4, oxidizing the third intermediate product to obtain a fourth intermediate product;
S5, removing the phenolic hydroxyl protecting group from the fourth intermediate product to obtain a fifth intermediate product;
S6, protecting phenolic hydroxyl groups of the fifth intermediate product to obtain a sixth intermediate product;
s7, carrying out an anthrone addition reaction on the sixth intermediate product to obtain an anthracene fluorescent dye;
wherein the first intermediate product is a diphenylmethane derivative; the second intermediate product is a carboxyl derivative of diphenylmethane; the fourth intermediate product is an anthrone compound.
4. The method for synthesizing anthracene fluorescent dye according to claim 3, wherein in the step S1, the o-halogenated benzophenone is reduced by a reducing agent, wherein the reducing agent is one or more of activated iron powder, triethylsilane and hypophosphorous acid.
5. The method for synthesizing an anthracene fluorescent dye according to claim 3, wherein at least one of the 3,4 positions of the o-halogenated benzophenone has a methoxy group.
6. The method for synthesizing an anthracene fluorescent dye according to claim 3, wherein in the step S2, halogen in the first intermediate product is converted into carboxyl by a grignard reagent or an alkyl lithium.
7. The method for synthesizing anthracene fluorescent dye according to claim 3, wherein in the step S3, the second intermediate product is subjected to dehydration and ring closure reaction by a ring closure reagent to obtain a third intermediate product, and the ring closure reagent is one or more of oxalyl chloride/boron tribromide, concentrated sulfuric acid and polyphosphoric acid.
8. The method for synthesizing anthracene fluorescent dye according to claim 7, wherein in the step S3, the second intermediate product is subjected to dehydration and ring closure reaction at 20-50 ℃ for not more than 1 hour.
9. The method for synthesizing anthracene fluorescent dye according to claim 3, wherein in the step S4, methylene in the third intermediate product is oxidized into carbonyl by an oxidizing agent, and the oxidizing agent is one or more of chromium trioxide, potassium dichromate and potassium permanganate.
10. The method for synthesizing an anthracene fluorescent dye according to claim 3, wherein in the step S7, an anthrone addition reaction is performed on the sixth intermediate product by an addition reagent, wherein the addition reagent is a halogenated aromatic compound or a halogenated alkyl compound.
CN202410174533.5A 2024-02-07 2024-02-07 Anthracene fluorescent dye and synthesis method thereof Pending CN118005498A (en)

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