CN111825634A - Novel compounds, process for their preparation and their use - Google Patents
Novel compounds, process for their preparation and their use Download PDFInfo
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Abstract
The invention discloses a novel compound, a preparation method and application thereof; specifically, the invention provides 2- (2' -hydroxyphenyl) benzoxazole compounds with excited intramolecular proton transfer and aggregation-induced emission characteristics, which have a skeleton structure shown in a general formula I: in the formula I, R2 is independently selected from hydrogen, aldehyde group or an electron-withdrawing unit conjugated with a benzene ring through a double bond; the invention provides a preparation method of 2- (2' -hydroxyphenyl) benzoxazole compounds; in addition, the invention also provides application of the 2- (2' -hydroxyphenyl) benzoxazole compound containing the nitrogen positive ion structure in living cell mitochondrial imaging; the 2- (2' -hydroxyphenyl) benzoxazole compound with the excited intramolecular proton transfer and aggregation induced luminescence effects has good application prospects in the fields of photoelectricity, sensing, biomedicine and the like.
Description
Technical Field
The invention belongs to the field of functional fluorescence molecule synthesis for biomedicine, and particularly relates to a 2- (2' -hydroxyphenyl) benzoxazole compound with excited intramolecular proton transfer and aggregation-induced emission effects, a preparation method of the compound and application of the compound in mitochondrion targeted fluorescence imaging.
Background
Conventional organic light emitting materials generally have a planar aromatic ring, generally have higher light emitting efficiency in dilute solution, but pi-pi accumulation occurs in concentrated solution or aggregation state, increasing non-radiative energy loss, showing that the light emitting efficiency is reduced or even no light is emitted, i.e. aggregation induced emission quenching phenomenon (ACQ) is generated, and the ACQ effect limits their application in fields such as Organic Light Emitting Diode (OLED) and biological detection and imaging. In 2001, Down's academy et al first proposed a novel concept of "aggregation-induced emission" (AIE). Unlike traditional ACQ dyes, AIE fluorophores exhibit weak or negligible fluorescence emission in dilute solutions, but have strong fluorescence emission in the aggregate or solid state. The phenomenon of AIE is completely opposite to that of ACQ, so that the fluorescent molecule with the AIE effect can effectively solve the problem of the traditional fluorescent dye ACQ. Currently, AIE molecules are widely used in the fields of optoelectronics, sensing, biomedicine, and the like, and exhibit unique advantages over conventional luminescent materials. Therefore, how to prepare fluorescent molecules with AIE effect is a hot and difficult problem of current research.
The currently developed classes of fluorescent molecules with ESIPT and AIE effects are quite limited, mainly including salicylaldydrazines. However, the compounds are single in type, short in emission wavelength and low in fluorescence quantum yield. Therefore, the development of fluorescent molecules with various structures, easily-controlled emission wavelength and AIE and ESIPT effects is urgently needed.
Disclosure of Invention
The invention aims to provide a 2- (2' -hydroxyphenyl) benzoxazole compound with a novel structure and excited-state intramolecular proton transfer and aggregation-induced emission effects, and also provides a preparation method and application thereof in mitochondrion targeted fluorescence imaging.
In order to achieve the technical purpose, the invention provides a 2- (2' -hydroxyphenyl) benzoxazole compound with excited state intramolecular proton transfer and aggregation induced luminescence effects, which has a structure shown in formula I:
in formula I, X is selected from-O-, -S-, -NH-or-C (O) NH-,
R1is an aromatic conjugated structural unit with molecular rotor characteristics,
R2selected from hydrogen, aldehyde groups or electron-withdrawing units conjugated with the benzene ring via double bonds.
A compound having a structure represented by the formula II,
in formula II, X is selected from-O-, -S-, -NH-or-C (O) NH-,
r1 is an aromatic hydrocarbon conjugated structural unit with molecular rotor characteristics.
A compound having the structure described by formula III,
in the formula (III), the reaction solution is,
x is selected from-O-, -S-, -NH-or-C (O) NH-,
r1 is an aromatic hydrocarbon conjugated structural unit with molecular rotor characteristics.
In some forms, R1Is selected from any one of the following items,
in some forms, R2Is selected from any one of the following items,
wherein R4 is selected from I-，Br-，ClO4 -Or PF6 -Any of them.
A process for the preparation of a compound of formula i comprising the steps of:
s1, dissolving borated aromatic hydrocarbon and 2- (2' -hydroxyphenyl) benzoxazole in an organic solvent, adding a strong base solution, reacting under the protection of inert gas, extracting an organic phase, combining the organic phase, concentrating, and separating and purifying by silica gel column chromatography to obtain a product;
s2, dissolving the product S1 in trifluoroacetic acid solution, adding hexamethyl-hydroxylamine, heating and refluxing, adjusting the pH value of the system to 6 +/-0.5 (6 in one case) by using sodium hydroxide solution after the reaction is finished, filtering to obtain a filter cake, and separating and purifying by silica gel column chromatography to obtain the product;
s3, dissolving the S2 product and an electron acceptor containing active hydrogen in ethanol or acetonitrile solution, adding piperidine into a mixed system, heating and refluxing, separating and purifying by silica gel column chromatography after the reaction is finished to obtain a product shown in the formula IV,
r1 is an aromatic hydrocarbon conjugated structural unit with molecular rotor characteristics,
r3 is selected from electron withdrawing units conjugated to the benzene ring via a double bond.
A process for preparing the compound of formula II includes such steps as dissolving arylhydrocarbon borate and 2- (2' -hydroxy phenyl) benzoxazole in organic solvent, adding strong alkali solution, reacting under the protection of nitrogen or argon gas, extracting organic phase, merging organic phases, concentrating, and purifying by silica gel column chromatography to obtain the product of formula II
In one mode, in a molar ratio, the ratio of the borated aromatic hydrocarbon to the 2- (2' -hydroxyphenyl) benzoxazole in step S1 is 1.0 to 1.5, and the ratio of the hexamethyl-nitril and the product of formula III added in step S2 is 5 to 7.
In one mode, the catalyst in step S1 is selected from Pd (PPh)3)4、PdCl2、Pd(OAc)2、Pd(Pph2)Cl2、Pd(dppf)Cl2、Ph2P(CH2)2PPh(dppe)Ph2P(CH2)3PPh2(dppe)、Ph2P(CH2)3PPh2(dpp) the amount of catalyst used is 0.1 to 0.3 equivalent, calculated as 2- (2' -hydroxyphenyl) benzoxazole, in particular 0.1 to 0.3 equivalent of the benzoxazole compound.
In one mode, the alkali solution in step S1 includes Na2CO3Solution, CsCO3Solution, CH3COOK solution, K2CO3Solutions, KOH solutions, or NaOH solutions.
The preparation method of the compound shown in the formula II comprises the following steps of dissolving borated aromatic hydrocarbon and 2- (2' -hydroxyphenyl) benzoxazole in an organic solvent, adding a strong base solution, reacting under the protection of inert gas, extracting an organic phase, combining the organic phase, concentrating, separating and purifying to obtain a product shown in the formula II.
The compound of formula I is used as fluorescent dye in living cell mitochondrion targeting imaging.
Use of a compound of formula II as a reactant in the preparation of a compound of formula IV; the preparation difficulty is reduced.
The invention has the beneficial effects that:
the novel compound is provided, the emission wavelength is longer, the fluorescence quantum yield is higher, and the structure is more various; meanwhile, a reaction raw material for preparing the 2- (2' -hydroxyphenyl) benzoxazole compound with excited intramolecular proton transfer and aggregation induced luminescence effects is also provided.
Drawings
Figure 1 is a high resolution mass spectrum diagram of compound HBTTAP,
figure 2 is a high resolution mass spectrum of compound hbtpip,
FIG. 3 is a high-resolution mass spectrum of compound HBTTEP,
figure 4 shows mitochondrially targeted fluorescence imaging of compound hbtpap,
figure 5 is mitochondrially targeted fluorescence imaging of compound hbtpip,
figure 6 shows mitochondrially targeted fluorescence imaging of compound hbttep.
Detailed Description
The following embodiments are intended to further illustrate the present invention and are not intended to limit the present invention.
A2- (2' -hydroxyphenyl) benzoxazole compound having excited intramolecular proton transfer and aggregation-induced emission effects, has the structure of formula I:
wherein X is independently selected from-O-, -S-, -NH-or-C (O) NH-,
R1is an aromatic conjugated structural unit with molecular rotor characteristics, R2Independently selected from hydrogen, aldehyde group or electron-withdrawing unit conjugated with benzene ring through double bond.
The 2- (2' -hydroxyphenyl) benzoxazole compound is a molecule with an Excited State Intramolecular Proton Transfer (ESIPT) effect, has large Stokes shift and higher solid-state luminous efficiency, but the luminous efficiency is easily interfered by a polar solvent and a protic solvent. However, fluorescent molecules with AIE effect can avoid interference of polar or protic solvents when forming an aggregate or solid state, which facilitates the occurrence of ESIPT effect. In addition, the ESIPT molecules can effectively inhibit intramolecular movement when forming intramolecular hydrogen bonds, and contribute to the occurrence of AIE effect. Therefore, the fluorescent molecule with both ESIPT and AIE effects has the excellent properties of large Stokes shift, no quenching of fluorescence at high concentration and the like, and can be used as an ideal luminescent material to be applied to different fields of biological imaging, chemical biological sensing and the like.
The structural units, electronic units, described herein generally refer to groups, which can be combined with their aforementioned groups.
The inert gas is generally nitrogen or argon.
In the preparation step, the intermediate product has a plurality of types, but is not limited to one type, and is determined according to reactants and reaction conditions and obtained according to a reaction formula.
Example 1 (HBTPA)
The 2- (2' -hydroxyphenyl) benzoxazole compound 3- (benzo [ d ] of the invention has the effects of proton transfer and aggregation induced luminescence in excited state molecules]Thiazol-2-yl) -4'- (bis (4-methoxyphenyl) amino) - [1,1' -biphenyl]-4-ol (hbtpa) (X-S, R in the examples)1＝
R2H), the synthetic route is as follows:
synthesis of compound HBTBr: 5-Bromosalicylaldehyde (301.5mg,1.5mmol) and o-aminothiophenol (187.8mg, 1.5mmol) were each weighed out and dissolved in 5mL of an ethanol solution, and 1mL of concentrated hydrochloric acid was added thereto with stirring at room temperature, followed by 40. mu.L of 30% aqueous hydrogen peroxide solution and reacted with stirring at room temperature for 30 min. After the reaction is finished, filtering is carried out, and ethanol is recrystallized to obtain a compound HBTBR with the yield of 83.7%.
1H NMR(400MHz,CDCl3),(ppm):12.55(s,1H),7.99-8.01(d,1H),7.92-7.94(d,1H),7.79-7.80(d,1H),7.51-7.55(m,1H),7.43-7.47(m,2H)；13C NMR(100MHz,CDCl3),(ppm):167.77,157.01,151.63,135.31,132.61,130.48,126.93,125.95,122.37,121.63,119.81,111.02。
Synthesis of Compound HBTPA: compound HBTBR (100mg,0.33mmol) and compound (4- (bis (4-methoxyphenyl) amino) phenyl) boronic acid (114mg,0.33mmol) were weighed out and dissolved in 5mL DMF, and they were thoroughly stirred at room temperature, followed by addition of 1mL of a solution containing 200mg of K2CO3And 20mg of catalyst Pd (PPh) was added3)4. The reaction system is fully refluxed and reacted for 12 hours at 75 ℃ under the protection of nitrogen, after the TLC plate monitors that the reaction is complete, the solvent is removed by reduced pressure distillation, and the product HBTPA is obtained by silica gel column chromatography separation. The yield was 24.3%.
1H NMR(400MHz,CDCl3),(ppm):12.41(s,1H),8.02-8.04(d,2H),7.93-7.95(d,2H),7.85-7.86(d,2H),7.59-7.61(dd,2H),7.52-7.66(m,1H),7.42-7.47(m,3H),7.11-7.18(m,5H),7.02-7.06(d,2H),6.86-6.90(m,4H),3.84(s,6H)；13C NMR(100MHz,CDCl3),(ppm):169.43,156.89,155.89,151.89,148.01,140.91,132.70,132.64,132.05,131.18,127.13,126.72,126.54,126.05,125.56,122.21,121.55,120.95,118.23,116.87,114.73,55.52。
Example 2 (HBTTAQ)
The 2- (2' -hydroxyphenyl) benzoxazole compound 5- (benzo [ d ] of the invention with the effects of proton transfer and aggregation-induced luminescence in excited state molecules]Thiazol-2-yl) -4'- (bis (4-methoxyphenyl) amino) -4-hydroxy- [1,1' -biphenyl]-3-carboxaldehyde (hbtpaq) (in the example X-S, R1＝
R2The synthetic route of — CHO) is as follows:
synthesis of compound HBTBr: 5-Bromosalicylaldehyde (301.5mg,1.5mmol) and o-aminothiophenol (187.8mg, 1.5mmol) were each weighed out and dissolved in 5mL of an ethanol solution, and 1mL of concentrated hydrochloric acid was added thereto with stirring at room temperature, followed by 40. mu.L of 30% aqueous hydrogen peroxide solution and reacted with stirring at room temperature for 30 min. After the reaction is finished, filtering is carried out, and ethanol is recrystallized to obtain a compound HBTBR with the yield of 83.7%.
1H NMR(400MHz,CDCl3),(ppm):12.55(s,1H),7.99-8.01(d,1H),7.92-7.94(d,1H),7.79-7.80(d,1H),7.51-7.55(m,1H),7.43-7.47(m,2H)；13C NMR(100MHz,CDCl3),(ppm):167.77,157.01,151.63,135.31,132.61,130.48,126.93,125.95,122.37,121.63,119.81,111.02。
Synthesis of compound HBTBrQ: the compound HBTBR (100mg,0.33mmol) was dissolved in 8mL of trifluoroacetic acid, and hexamethylenamine (300mg,2.14mmol) was added to the mixture, and the mixture was stirred well and then refluxed at 120 ℃ for 12 hours. After the reaction is finished, pouring the reaction system into 200mL of aqueous solution, adjusting the pH of the system to be about 6 by using NaOH solution, carrying out suction filtration to obtain a filter cake, drying, and carrying out column chromatography purification to obtain a compound HBTBBQ with the yield of 63.7%.
1H NMR(400MHz,CDCl3),(ppm):10.48(s,1H),8.13(s,1H),7.95-8.06(m,4H),7.55-7.59(t,1H),7.55-7.59(t,1H)；13C NMR(100MHz,CDCl3),(ppm):159.38,151.25,136.39,127.20,126.38,122.62,121.73,111.64。
Synthesis of compound HBTTAQ: the compound HBTBBrQ (62mg,0.19mmol) and the compound (4- (bis (4-methoxyphenyl) amino) phenyl) boronic acid (66mg,0.19mmol) were weighed out and dissolved in 4mL of DMF, and they were thoroughly stirred at room temperature, followed by addition of 1mL of a solution containing 200mg of K to the reaction system2CO3And 20mg of catalyst Pd (PPh) was added3)4. And (3) fully refluxing and reacting the reaction system at 75 ℃ for 12 hours under the protection of nitrogen, monitoring the reaction by a TLC plate, removing the solvent by reduced pressure distillation, and separating by silica gel column chromatography to obtain the HBTTAQ product. The yield was 32.4%.
1H NMR(400MHz,CDCl3),(ppm):10.58(s,1H),8.26(s,1H),8.08-8.10(m,2H),7.95-7.97(d,1H),7.54-7.58(t,1H),7.44-7.49(m,3H),7.01-7.12(m,6H),6.85-6.88(m,6H)。
Example 3 (HBTTI)
The molecular endoplasmic of the invention having an excited state2- (2' -hydroxyphenyl) benzoxazole compound 3- (benzo [ d ] for inducing luminescence effect by proton transfer and aggregation]Thiazol-2-yl) -4'- (4, 5-bis (4-methoxyphenyl) -1-phenyl-1H-imidazol-2-yl) - [1,1' -biphenyl]-4-ol (hbtpi) (in the example X-S, R1＝
R2The synthetic route of ═ H) is as follows:
synthesis of compound HBTBr: 5-Bromosalicylaldehyde (301.5mg,1.5mmol) and o-aminothiophenol (187.8mg, 1.5mmol) were each weighed out and dissolved in 5mL of an ethanol solution, and 1mL of concentrated hydrochloric acid was added thereto with stirring at room temperature, followed by 40. mu.L of 30% aqueous hydrogen peroxide solution and reacted with stirring at room temperature for 30 min. After the reaction is finished, filtering is carried out, and ethanol is recrystallized to obtain a compound HBTBR with the yield of 83.7%.
1H NMR(400MHz,CDCl3),(ppm):12.55(s,1H),7.99-8.01(d,1H),7.92-7.94(d,1H),7.79-7.80(d,1H),7.51-7.55(m,1H),7.43-7.47(m,2H)；13C NMR(100MHz,CDCl3),(ppm):167.77,157.01,151.63,135.31,132.61,130.48,126.93,125.95,122.37,121.63,119.81,111.02.
Synthesis of Compound HBTTPI: compound HBTBR (40mg,0.13mmol) and compound (4- (4, 5-bis (4-methoxyphenyl) -1-phenyl-1H-imidazol-2-yl) phenyl) boronic acid (63mg,0.13mmol) were weighed out and dissolved in 5mL DMF, and the solution was sufficiently stirred at room temperature, followed by addition of 1mL of a solution containing 100mg of K to the reaction system2CO3And 15mg of catalyst Pd (PPh) was added3)4. And (3) fully refluxing and reacting the reaction system at 75 ℃ for 12 hours under the protection of nitrogen, monitoring the reaction by a TLC plate, removing the solvent by reduced pressure distillation, and separating by silica gel column chromatography to obtain the HBTPI product. The yield was 25.6%.
1H NMR(400MHz,CDCl3),(ppm):12.62(s,1H),8.02-8.04(d,1H),7.88-7.95(m,2H),7.34-7.63(m,12H),7.07-7.19(m,5H),6.78-6.86(dd,4H),3.81-3.82(d 6H)；13C NMR(100MHz,CDCl3),(ppm):169.21,159.18,158.44,157.61,151.83,146.05,139.48,138.00,137.34,132.62,132.38,132.07,131.47,129.30,129.19,128.54,128.28,126.78,126.54,126.21,125.66,122.84,122.24,121.58,118.38,116.96,113.86,113.65,55.21,55.14。
Example 4(HBT TPIQ)
The 2- (2' -hydroxyphenyl) benzoxazole compound 5- (benzo [ d ] of the invention with the effects of proton transfer and aggregation-induced luminescence in excited state molecules]Thiazol-2-yl) -4'- (4, 5-bis (4-methoxyphenyl) -1-phenyl-1H-imidazol-2-yl) -4-hydroxy- [1,1' -biphenyl]-3-carbaldehyde (hbtpiq) (X-S, R in the example)1 
R2The synthetic route of — CHO) is as follows:
synthesis of compound HBTBr: 5-Bromosalicylaldehyde (301.5mg,1.5mmol) and o-aminothiophenol (187.8mg, 1.5mmol) were each weighed out and dissolved in 5mL of an ethanol solution, and 1mL of concentrated hydrochloric acid was added thereto with stirring at room temperature, followed by 40. mu.L of 30% aqueous hydrogen peroxide solution and reacted with stirring at room temperature for 30 min. After the reaction is finished, filtering is carried out, and ethanol is recrystallized to obtain a compound HBTBR with the yield of 83.7%.
1H NMR(400MHz,CDCl3),(ppm):12.55(s,1H),7.99-8.01(d,1H),7.92-7.94(d,1H),7.79-7.80(d,1H),7.51-7.55(m,1H),7.43-7.47(m,2H)；13C NMR(100MHz,CDCl3),(ppm):167.77,157.01,151.63,135.31,132.61,130.48,126.93,125.95,122.37,121.63,119.81,111.02.
Synthesis of compound HBTBrQ: the compound HBTBR (100mg,0.33mmol) was dissolved in 8mL of trifluoroacetic acid, and hexamethylenamine (300mg,2.14mmol) was added to the mixture, and the mixture was stirred well and then refluxed at 120 ℃ for 12 hours. After the reaction is finished, pouring the reaction system into 200mL of aqueous solution, adjusting the pH of the system to be about 6 by using NaOH solution, carrying out suction filtration to obtain a filter cake, drying, and carrying out column chromatography purification to obtain a compound HBTBBQ with the yield of 63.7%.
1H NMR(400MHz,CDCl3),(ppm):10.48(s,1H),8.13(s,1H),7.95-8.06(m,4H),7.55-7.59(t,1H),7.55-7.59(t,1H)；13C NMR(100MHz,CDCl3),(ppm):159.38,151.25,136.39,127.20,126.38,122.62,121.73,111.64.
Synthesis of compound hbtpiq: the compound HBTBBrQ (40mg,0.19mmol) and the compound (4- (bis (4-methoxyphenyl) amino) phenyl) boronic acid (66mg,0.19mmol) were weighed out and dissolved in 4mL of DMF, and they were thoroughly stirred at room temperature, followed by addition of 1mL of a solution containing 200mg of K to the reaction system2CO3And 20mg of catalyst Pd (PPh) was added3)4. And (3) fully refluxing and reacting the reaction system at 75 ℃ for 12 hours under the protection of nitrogen, monitoring the reaction by a TLC plate, removing the solvent by reduced pressure distillation, and separating by silica gel column chromatography to obtain the HBTTAQ product. The yield was 32.4%.
The results of the nmr analysis were:1H NMR(400MHz,CDCl3),(ppm):10.57(s,1H),8.23(s,1H),8.10(s,1H),8.04-8.05(d,1H),7.94-7.96(d,1H),7.51-7.57(m,8H),7.45-7.48(t,1H),7.30-7.35(m,3H),7.09-7.11(m,2H),7.05-7.06(d,2H),6.82-6.84(d,2H),6.76-6.78(d,2H),3.78-3.80(d 6H)；13C NMR(150MHz,CDCl3),(ppm):159.98,159.22,158.48,151.49,145.85,138.22,137.29,132.39,129.42,129.25,128.55,128.52,128.39,126.27,122.79,122.50,121.69,113.88,113.67,55.22,55.15。
example 5(HBTTPEQ)
The 2- (2' -hydroxyphenyl) benzoxazole compound 5- (benzo [ d ] of the invention with the effects of proton transfer and aggregation-induced luminescence in excited state molecules]Thiazol-2-yl) -4-hydroxy-4 '- (1,2, 2-triphenyltoluene) - [1,1' -biphenyl]-3-carbaldehyde (hbtpeq) (in the example X-S, R1＝
R2The synthetic route of — CHO) is as follows:
synthesis of compound HBTBr: 5-Bromosalicylaldehyde (301.5mg,1.5mmol) and o-aminothiophenol (187.8mg, 1.5mmol) were each weighed out and dissolved in 5mL of an ethanol solution, and 1mL of concentrated hydrochloric acid was added thereto with stirring at room temperature, followed by 40. mu.L of 30% aqueous hydrogen peroxide solution and reacted with stirring at room temperature for 30 min. After the reaction is finished, filtering is carried out, and ethanol is recrystallized to obtain a compound HBTBR with the yield of 83.7%.
1H NMR(400MHz,CDCl3),(ppm):12.55(s,1H),7.99-8.01(d,1H),7.92-7.94(d,1H),7.79-7.80(d,1H),7.51-7.55(m,1H),7.43-7.47(m,2H)；13C NMR(100MHz,CDCl3),(ppm):167.77,157.01,151.63,135.31,132.61,130.48,126.93,125.95,122.37,121.63,119.81,111.02.
Synthesis of compound HBTBrQ: the compound HBTBR (100mg,0.33mmol) was dissolved in 8mL of trifluoroacetic acid, and hexamethylenamine (300mg,2.14mmol) was added to the mixture, and the mixture was stirred well and then refluxed at 120 ℃ for 12 hours. After the reaction is finished, pouring the reaction system into 200mL of aqueous solution, adjusting the pH of the system to be about 6 by using NaOH solution, carrying out suction filtration to obtain a filter cake, drying, and carrying out column chromatography purification to obtain a compound HBTBBQ with the yield of 63.7%.
1H NMR(400MHz,CDCl3),(ppm):10.48(s,1H),8.13(s,1H),7.95-8.06(m,4H),7.55-7.59(t,1H),7.55-7.59(t,1H)；13C NMR(100MHz,CDCl3),(ppm):159.38,151.25,136.39,127.20,126.38,122.62,121.73,111.64.
Synthesis of compound HBTTPEQ: the compounds HBTBBQ (108.8mg,0.33mmol) and 4,4,5, 5-tetramethyl-2- (4- (1,2, 2-triphenylvinyl) phenyl) -1,3, 2-dioxaborane (149.8mg,0.33mmol) were weighed out and dissolved in 5mLDMF, and then, the mixture was sufficiently stirred at room temperature, and 600. mu.L of a solution containing 250mg of K was added to the reaction system2CO3And 33mg of catalyst Pd (PPh) was added3)4. And (3) fully refluxing and reacting the reaction system at 75 ℃ for 12 hours under the protection of nitrogen, monitoring the reaction by a TLC plate, removing the solvent by reduced pressure distillation, and separating by silica gel column chromatography to obtain the HBTTEQ product. The yield was 33.6%.
The results of the nmr analysis were:1H NMR(400MHz,CDCl3),(ppm):10.56(s,1H),8.25(s,1H),8.09(s,1H),8.05-8.06(d,1H),7.94-7.95(d,1H),7.54-7.57(t,1H),7.45-7.48(t,1H),7.39-7.40(d,2H),7.08-7.13(m,15H),6.88-6.90(d,2H),6.56-6.58(d,2H)；13C NMR(150MHz,CDCl3),(ppm):159.78,154.10,151.37,144.01,143.92,143.90,143.66,143.63,143.35,141.47,140.46,140.25,140.18,136.49,136.33,132.74,132.54,132.08,131.41,131.38,131.35,131.34,127.89,127.79,127.72,127.69,127.62,127.04,126.68,126.60,126.53,126.39,126.27,126.06,125.86,122.46,121.69,114.61。
example 6 (HBTTAP)
The 2- (2' -hydroxyphenyl) benzoxazole compound hbtpap according to the present invention having the effect of excited intramolecular proton transfer and aggregation-induced emission (in the example, X ═ S, R)1＝
R2 
) The synthetic route of (2) is as follows:
synthesis of compound HBTBr: 5-Bromosalicylaldehyde (301.5mg,1.5mmol) and o-aminothiophenol (187.8mg, 1.5mmol) were each weighed out and dissolved in 5mL of an ethanol solution, and 1mL of concentrated hydrochloric acid was added thereto with stirring at room temperature, followed by 40. mu.L of 30% aqueous hydrogen peroxide solution and reacted with stirring at room temperature for 30 min. After the reaction is finished, filtering is carried out, and ethanol is recrystallized to obtain a compound HBTBR with the yield of 83.7%.
1H NMR(400MHz,CDCl3),(ppm):12.55(s,1H),7.99-8.01(d,1H),7.92-7.94(d,1H),7.79-7.80(d,1H),7.51-7.55(m,1H),7.43-7.47(m,2H)；13C NMR(100MHz,CDCl3),(ppm):167.77,157.01,151.63,135.31,132.61,130.48,126.93,125.95,122.37,121.63,119.81,111.02.
Synthesis of compound HBTBrQ: the compound HBTBR (100mg,0.33mmol) was dissolved in 8mL of trifluoroacetic acid, and hexamethylenamine (300mg,2.14mmol) was added to the mixture, and the mixture was stirred well and then refluxed at 120 ℃ for 12 hours. After the reaction is finished, pouring the reaction system into 200mL of aqueous solution, adjusting the pH of the system to be about 6 by using NaOH solution, carrying out suction filtration to obtain a filter cake, drying, and carrying out column chromatography purification to obtain a compound HBTBBQ with the yield of 63.7%.
1H NMR(400MHz,CDCl3),(ppm):10.48(s,1H),8.13(s,1H),7.95-8.06(m,4H),7.55-7.59(t,1H),7.55-7.59(t,1H)；13C NMR(100MHz,CDCl3),(ppm):159.38,151.25,136.39,127.20,126.38,122.62,121.73,111.64.
Synthesis of compound HBTTAQ: the compound HBTBBrQ (62mg,0.19mmol) and the compound (4- (bis (4-methoxyphenyl) amino) phenyl) boronic acid (66mg,0.19mmol) were weighed out and dissolved in 4mL of DMF, and they were thoroughly stirred at room temperature, followed by addition of 1mL of a solution containing 200mg of K to the reaction system2CO3And 20mg of catalyst Pd (PPh) was added3)4. And (3) fully refluxing and reacting the reaction system at 75 ℃ for 12 hours under the protection of nitrogen, monitoring the reaction by a TLC plate, removing the solvent by reduced pressure distillation, and separating by silica gel column chromatography to obtain the HBTTAQ product. The yield was 32.4%.
1H NMR(400MHz,CDCl3),(ppm):10.58(s,1H),8.26(s,1H),8.08-8.10(m,2H),7.95-7.97(d,1H),7.54-7.58(t,1H),7.44-7.49(m,3H),7.01-7.12(m,6H),6.85-6.88(m,6H).
Synthesis of Compound HBTTAP: compound HBTTAQ (31.3mg,0.056mmol) and compound 1-ethyl-4-methylpyridine-1-iodide (36mg,0.14mmol) were weighed out and dissolved in 6mL of anhydrous ethanol, and stirred well at room temperature, followed by addition of 10. mu.L of piperidine to the reaction system. The reaction system is fully refluxed and reacted for 8 hours at the temperature of 95 ℃, after the TLC plate monitors that the reaction is complete, the solvent is removed by reduced pressure distillation, and the product HBTTAP is obtained by silica gel column chromatography separation. The yield was 57.4%.
HRMS(ESI):m/z 662.2457[(M-I)+,calcd for 689.2472]。
Example 7 (HBTTIP)
The 2- (2' -hydroxyphenyl) benzoxazole compound HBTTPIP (X-S, R in the example) with the effects of proton transfer in excited state and aggregation induced luminescence1＝
R2＝
) The synthetic route of (2) is as follows:
synthesis of compound HBTBr: 5-Bromosalicylaldehyde (301.5mg,1.5mmol) and o-aminothiophenol (187.8mg, 1.5mmol) were each weighed out and dissolved in 5mL of an ethanol solution, and 1mL of concentrated hydrochloric acid was added thereto with stirring at room temperature, followed by 40. mu.L of 30% aqueous hydrogen peroxide solution and reacted with stirring at room temperature for 30 min. After the reaction is finished, filtering is carried out, and ethanol is recrystallized to obtain a compound HBTBR with the yield of 83.7%.
1H NMR(400MHz,CDCl3),(ppm):12.55(s,1H),7.99-8.01(d,1H),7.92-7.94(d,1H),7.79-7.80(d,1H),7.51-7.55(m,1H),7.43-7.47(m,2H)；13C NMR(100MHz,CDCl3),(ppm):167.77,157.01,151.63,135.31,132.61,130.48,126.93,125.95,122.37,121.63,119.81,111.02。
Synthesis of compound HBTBrQ: the compound HBTBR (100mg,0.33mmol) was dissolved in 8mL of trifluoroacetic acid, and hexamethylenamine (300mg,2.14mmol) was added to the mixture, and the mixture was stirred well and then refluxed at 120 ℃ for 12 hours. After the reaction is finished, pouring the reaction system into 200mL of aqueous solution, adjusting the pH of the system to be about 6 by using NaOH solution, carrying out suction filtration to obtain a filter cake, drying, and carrying out column chromatography purification to obtain a compound HBTBBQ with the yield of 63.7%.
1H NMR(400MHz,CDCl3),(ppm):10.48(s,1H),8.13(s,1H),7.95-8.06(m,4H),7.55-7.59(t,1H),7.55-7.59(t,1H)；13C NMR(100MHz,CDCl3),(ppm):159.38,151.25,136.39,127.20,126.38,122.62,121.73,111.64。
Synthesis of compound hbtpiq: the compound HBTBBrQ (40mg,0.19mmol) and the compound (4- (bis (4-methoxyphenyl) amino) phenyl) boronic acid (66mg,0.19mmol) were weighed out and dissolved in 4mL of DMF, and they were thoroughly stirred at room temperature, followed by addition of 1mL of a solution containing 200mg of K to the reaction system2CO3Water of (2)Solution and 20mg of catalyst Pd (PPh) was added3)4. And (3) fully refluxing and reacting the reaction system at 75 ℃ for 12 hours under the protection of nitrogen, monitoring by a TLC plate to complete the reaction, distilling under reduced pressure to remove the solvent, and separating by silica gel column chromatography to obtain the HBTTIQ product. The yield was 32.4%.
The results of the nmr analysis were:1H NMR(400MHz,CDCl3),(ppm):10.57(s,1H),8.23(s,1H),8.10(s,1H),8.04-8.05(d,1H),7.94-7.96(d,1H),7.51-7.57(m,8H),7.45-7.48(t,1H),7.30-7.35(m,3H),7.09-7.11(m,2H),7.05-7.06(d,2H),6.82-6.84(d,2H),6.76-6.78(d,2H),3.78-3.80(d 6H)；13C NMR(150MHz,CDCl3),(ppm):159.98,159.22,158.48,151.49,145.85,138.22,137.29,132.39,129.42,129.25,128.55,128.52,128.39,126.27,122.79,122.50,121.69,113.88,113.67,55.22,55.15.
synthesis of HBTTIP compound: compound HBTTIQ (21mg,0.031mmol) and compound 1-ethyl-4-methylpyridine-1-iodide (11.4mg,0.046mmol) were weighed out and dissolved in 6mL of anhydrous ethanol, and stirred well at room temperature, followed by addition of 10. mu.L of piperidine to the reaction system. The reaction system is fully refluxed and reacted for 8 hours at the temperature of 95 ℃, after the TLC plate monitors that the reaction is complete, the solvent is removed by reduced pressure distillation, and the product HBTTAP is obtained by silica gel column chromatography separation. The yield was 60.3%.
HRMS(ESI):m/2z 395.1478[(M-I)+,calcd for 789.2894]。
Example 8 (HBTTAP mitochondrial Targeted imaging)
The 2- (2' -hydroxyphenyl) benzoxazole compound hbtpap according to the present invention having the effect of excited intramolecular proton transfer and aggregation-induced emission (in the example, X ═ S, R)1＝
R2 
) Application to mitochondrial targeting imaging:
selecting colon cancer cell line CT-26, and mixing 2 × 105Inoculating CT-26 cells to a confocal dish containing 1mL of culture medium, culturing in 5% CO2 at 37 deg.CCulturing in a box for 12h, adding 10 μ M HBTTAP, incubating for 1h, washing with PBS for 3 times for 3-5min, and adding 100nM mitochondrial dye (MitoTracker)TMGreen FM) for 20min, washing with PBS for 3 times, 3-5min each time, adding 1mL of culture medium, and performing mitochondria co-localization analysis under laser confocal condition.
Example 9(HBTTPIP mitochondrial Targeted imaging)
The 2- (2' -hydroxyphenyl) benzoxazole compound HBTTPIP (X-S, R in the example) with the effects of proton transfer in excited state and aggregation induced luminescence1＝
R2 
) Application to mitochondrial targeting imaging:
selecting colon cancer cell line CT-26, and mixing 2 × 105Inoculating CT-26 cells into a confocal dish containing 1mL of culture medium, culturing in 5% CO2 at 37 deg.C for 12h, adding 10 μ M HBTTPIP, incubating for 1h, washing with PBS for 3 times for 3-5min, and adding 100nM mitochondrial dye (MitoTracker)TMGreen FM) for 20min, washing with PBS for 3 times, 3-5min each time, adding 1mL of culture medium, and performing mitochondria co-localization analysis under laser confocal condition.
Example 10 (HBTTEP targeted mitochondrial imaging)
HBTTEP (X-S, R in the example) of 2- (2' -hydroxyphenyl) benzoxazole compound with excited state intramolecular proton transfer and aggregation induced luminescence effect1＝
R2＝
) Application to mitochondrial targeting imaging:
selecting colon cancer cell line CT-26, and mixing 2 × 105The individual CT-26 cells were seeded in a confocal dish containing 1mL of medium and placed at 5% CO2, incubated at 37 deg.C for 12h in a incubator, incubated for 1h with 10 μ M HBTTEP, washed 3 times with PBS for 3-5min each, and then 100nM mitochondrial dye (MitoTracker) was addedTMGreen FM) for 20min, washing with PBS for 3 times, 3-5min each time, adding 1mL of culture medium, and performing mitochondria co-localization analysis under laser confocal condition.
Example 11
The 2- (2' -hydroxyphenyl) benzoxazole compound of the present invention having an excited state intramolecular proton transfer and aggregation-induced emission effect (in the example, X-S, R1 ═
R2
) The synthetic route of (2) is as follows:
synthesis of compound HBTBr: 5-Bromosalicylaldehyde (301.5mg,1.5mmol) and o-aminothiophenol (187.8mg, 1.5mmol) were each weighed out and dissolved in 5mL of an ethanol solution, and 1mL of concentrated hydrochloric acid was added thereto with stirring at room temperature, followed by 40. mu.L of 30% aqueous hydrogen peroxide solution and reacted with stirring at room temperature for 30 min. After the reaction is finished, filtering, and recrystallizing with ethanol to obtain the compound HBTBR.
Synthesis of compound HBTBrQ: the compound HBTBR (100mg,0.33mmol) was dissolved in 8mL of trifluoroacetic acid, and hexamethylenamine (300mg,2.14mmol) was added to the mixture, and the mixture was stirred well and then refluxed at 120 ℃ for 12 hours. After the reaction is finished, pouring the reaction system into 200mL of aqueous solution, adjusting the pH of the system to be about 6 by using NaOH solution, carrying out suction filtration to obtain a filter cake, drying, and carrying out column chromatography purification to obtain the compound.
The compound HBTBBrQ (40mg,0.19mmol) and the compound (4- (bis (4-methoxyphenyl) amino) phenyl) boronic acid (66mg,0.19mmol) were weighed out and dissolved in 4mL of DMF, and they were thoroughly stirred at room temperature, followed by addition of 1mL of a solution containing 200mg of K to the reaction system2CO3And 20mg of catalyst Pd (PPh) was added3)4. And (3) fully refluxing and reacting the reaction system at 75 ℃ for 12 hours under the protection of nitrogen, monitoring by a TLC plate to complete the reaction, distilling under reduced pressure to remove the solvent, and separating by silica gel column chromatography to obtain the HBTTIQ product.
Synthesis of the Compounds: compound HBTTIQ (21mg,0.031mmol) and compound 1-ethyl-4-methylpyridine-1-perchlorate (0.046mmol) were weighed out and dissolved in 6mL of anhydrous ethanol, and stirred well at room temperature, followed by addition of 10. mu.L of piperidine to the reaction system. The reaction system is fully refluxed and reacted for 8 hours at the temperature of 95 ℃, after the TLC plate monitors that the reaction is complete, the solvent is removed by reduced pressure distillation, and the product is obtained by silica gel column chromatography separation.
It will be apparent to those skilled in the art that various modifications may be made to the above embodiments without departing from the general spirit and concept of the invention. All falling within the scope of protection of the present invention. The protection scheme of the invention is subject to the appended claims.
Claims (12)
1. A compound having the structure shown in formula I:
in the formula I, the compound has the following structure,
x is selected from-O-, -S-, -NH-or-C (O) NH-,
R1is an aromatic conjugated structural unit with molecular rotor characteristics,
R2selected from any one of hydrogen ions, aldehyde groups or electron-withdrawing units conjugated with benzene rings through double bonds.
2. The compound of claim 1, wherein: r2Is an electron-withdrawing unit conjugated with the benzene ring through a double bond.
3. The compound of claim 1, wherein: r2Is a hydrogen ion.
4. The method according to any one of claims 1 to 3A compound of (a), characterized in that: r1Is selected from any one of the following
5. The compound of claim 1, wherein: r2Is selected from any one of the following
Wherein R is4Is selected from I-，Br-，ClO4 -Or PF6 -Any of them.
6. A process for preparing a compound according to claim 2, comprising the steps of:
s1, dissolving borated aromatic hydrocarbon and 2- (2' -hydroxyphenyl) benzoxazole in an organic solvent, adding an alkali solution, reacting under the protection of inert gas, extracting organic phases, combining the organic phases, concentrating, separating and purifying to obtain an intermediate product;
s2, dissolving the product S1 in a trifluoroacetic acid solution, adding hexamethyl-hydroxylamine, heating and refluxing, adjusting the pH value of the system to 6 +/-0.5 by using a sodium hydroxide solution, and separating and purifying to obtain an intermediate product;
s3, dissolving the S2 product and an electron acceptor containing active hydrogen in ethanol or acetonitrile solution, adding piperidine into a mixed system, heating and refluxing, separating and purifying after the reaction is finished to obtain a product shown in the formula IV,
r1 is an aromatic hydrocarbon conjugated structural unit with molecular rotor characteristics,
r3 is selected from electron withdrawing units conjugated to the benzene ring via a double bond.
7. A process for preparing a compound of formula ii as defined in claim 3, characterized in that: comprises the following steps of (a) carrying out,
dissolving borated aromatic hydrocarbon and 2- (2' -hydroxyphenyl) benzoxazole in an organic solvent, adding an alkali solution, reacting under the protection of inert gas, extracting an organic phase, combining the organic phases, concentrating, separating and purifying to obtain a product shown in a formula II
8. The production method according to claim 6 or 7, characterized in that: the ratio of borated aromatic hydrocarbon to 2- (2' -hydroxyphenyl) benzoxazole is 1.0-1.5.
9. The method of claim 6, wherein: the molar ratio of the hexamethyl-hydroxylamine to the product of formula III added in step S2 is 5-7.
10. The production method according to claim 6 or 7, characterized in that: the catalyst in step S1 is selected from Pd (PPh)3)4、PdCl2、Pd(OAc)2、Pd(Pph2)Cl2、Pd(dppf)Cl2、Ph2P(CH2)2PPh(dppe)Ph2P(CH2)3PPh2(dppe)、Ph2P(CH2)3PPh2(dpp) the catalyst is used in an amount of 0.1 to 0.3 equivalents, calculated as 2- (2' -hydroxyphenyl) benzoxazole.
11. Use of a compound according to any one of claims 1 to 5 as a fluorescent dye in mitochondrial targeting imaging of living cells.
12. Use of a compound of formula II as a reactant in the preparation of a compound of formula IV.
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Cited By (4)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN112402628A (en) * | 2020-11-16 | 2021-02-26 | 华中科技大学同济医学院附属协和医院 | Preparation method of bionic targeted macrophage optical imaging agent and application of bionic targeted macrophage optical imaging agent in diagnosis of macrophage-related diseases |
| CN112521383A (en) * | 2020-12-11 | 2021-03-19 | 三峡大学 | Benzothiazole derivatives and their use as fluorescent dyes |
| CN113563325A (en) * | 2021-05-24 | 2021-10-29 | 南京邮电大学 | ESIPT luminescent material with high exciton utilization rate and preparation method and application thereof |
| CN114456161A (en) * | 2022-02-16 | 2022-05-10 | 长春海谱润斯科技股份有限公司 | Imidazole derivative and organic electroluminescent device thereof |
Citations (10)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN104974745A (en) * | 2014-04-07 | 2015-10-14 | 香港科技大学深圳研究院 | Amphiphilic illuminant with aggregation induced emission characteristics and applications thereof |
| CN105623645A (en) * | 2014-10-29 | 2016-06-01 | 香港科技大学深圳研究院 | Aggregation-induced emission principle-based fluorescent probe, its preparation method and use and endotoxin detection method |
| WO2017080413A1 (en) * | 2015-11-10 | 2017-05-18 | The Hong Kong University Of Science And Technology | Aie bioprobes emitting red or yellow fluorescence |
| CN106749094A (en) * | 2016-12-09 | 2017-05-31 | 南京邮电大学 | 42 (2` hydroxy phenyls) benzoxazole compounds and its preparation method and purposes containing substituted base |
| CN107001927A (en) * | 2014-11-21 | 2017-08-01 | 香港科技大学 | AIE illuminophores and its production method for bacterium imaging, killing, photodynamic therapy and antibiotic-screening |
| CN107849441A (en) * | 2015-06-24 | 2018-03-27 | 香港科技大学 | AIE illuminators for visualization and the treatment of cancer |
| CN108055852A (en) * | 2015-07-16 | 2018-05-18 | 香港科技大学 | Emit red or yellow fluorescent aggregation inducing emitting biological probe |
| CN109970630A (en) * | 2019-04-23 | 2019-07-05 | 四川大学 | A kind of two-photon fluorescence probe and its preparation method and application of energy targetted mitochondria |
| CN111057008A (en) * | 2019-12-31 | 2020-04-24 | 华南理工大学 | D-A type excited state proton transfer high-efficiency fluorescent material and preparation method and application thereof |
| CN111440129A (en) * | 2020-03-06 | 2020-07-24 | 齐鲁工业大学 | 2- (2-hydroxyphenyl) benzothiazole derivative HTPA, preparation method thereof and application thereof in fluorescence anti-counterfeiting |
-
2020
- 2020-08-02 CN CN202010764255.0A patent/CN111825634B/en active Active
Patent Citations (10)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN104974745A (en) * | 2014-04-07 | 2015-10-14 | 香港科技大学深圳研究院 | Amphiphilic illuminant with aggregation induced emission characteristics and applications thereof |
| CN105623645A (en) * | 2014-10-29 | 2016-06-01 | 香港科技大学深圳研究院 | Aggregation-induced emission principle-based fluorescent probe, its preparation method and use and endotoxin detection method |
| CN107001927A (en) * | 2014-11-21 | 2017-08-01 | 香港科技大学 | AIE illuminophores and its production method for bacterium imaging, killing, photodynamic therapy and antibiotic-screening |
| CN107849441A (en) * | 2015-06-24 | 2018-03-27 | 香港科技大学 | AIE illuminators for visualization and the treatment of cancer |
| CN108055852A (en) * | 2015-07-16 | 2018-05-18 | 香港科技大学 | Emit red or yellow fluorescent aggregation inducing emitting biological probe |
| WO2017080413A1 (en) * | 2015-11-10 | 2017-05-18 | The Hong Kong University Of Science And Technology | Aie bioprobes emitting red or yellow fluorescence |
| CN106749094A (en) * | 2016-12-09 | 2017-05-31 | 南京邮电大学 | 42 (2` hydroxy phenyls) benzoxazole compounds and its preparation method and purposes containing substituted base |
| CN109970630A (en) * | 2019-04-23 | 2019-07-05 | 四川大学 | A kind of two-photon fluorescence probe and its preparation method and application of energy targetted mitochondria |
| CN111057008A (en) * | 2019-12-31 | 2020-04-24 | 华南理工大学 | D-A type excited state proton transfer high-efficiency fluorescent material and preparation method and application thereof |
| CN111440129A (en) * | 2020-03-06 | 2020-07-24 | 齐鲁工业大学 | 2- (2-hydroxyphenyl) benzothiazole derivative HTPA, preparation method thereof and application thereof in fluorescence anti-counterfeiting |
Non-Patent Citations (1)
| Title |
|---|
| BIJIN LI, ET AL.: "Rhodium(III)-Catalyzed ortho-Heteroarylation of Phenols through Internal Oxidative C¢H Activation: Rapid Screening of Single-Molecular White-Light-Emitting Materials", 《ANGEW. CHEM. INT. ED.》 * |
Cited By (6)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN112402628A (en) * | 2020-11-16 | 2021-02-26 | 华中科技大学同济医学院附属协和医院 | Preparation method of bionic targeted macrophage optical imaging agent and application of bionic targeted macrophage optical imaging agent in diagnosis of macrophage-related diseases |
| CN112521383A (en) * | 2020-12-11 | 2021-03-19 | 三峡大学 | Benzothiazole derivatives and their use as fluorescent dyes |
| CN113563325A (en) * | 2021-05-24 | 2021-10-29 | 南京邮电大学 | ESIPT luminescent material with high exciton utilization rate and preparation method and application thereof |
| CN113563325B (en) * | 2021-05-24 | 2023-07-04 | 南京邮电大学 | ESIPT luminescent material with high exciton utilization rate and preparation method and application thereof |
| CN114456161A (en) * | 2022-02-16 | 2022-05-10 | 长春海谱润斯科技股份有限公司 | Imidazole derivative and organic electroluminescent device thereof |
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