Benzothiazole compound as well as preparation method and application thereof

Abstract

The invention discloses a benzothiazole compound as well as a preparation method and application thereof. The compound has a structure as shown in a formula I. The invention provides a series of benzothiazole compounds with novel structures. The compound has an aggregation-induced emission property; the emission reaches near-infrared region emission from conventional short wavelength; the fluorescent probe has the characteristics of large Stokes displacement, long emission wavelength and high fluorescence quantum yield.

Description

Technical Field

[0001] This invention relates to the field of organic synthesis technology, and in particular to a benzothiazole compound, its preparation method, and its application. Background Technology

[0002] The emission wavelength of 2-(2-hydroxybenzene)benzothiazole is relatively short, and aggregation can easily lead to fluorescence quenching, which limits the application of this type of compound in fields such as fluorescent labeling, fluorescent probes, photodynamic therapy, bioimaging, and organic light-emitting diodes, becoming a bottleneck in the development of 2-(2-hydroxybenzene)benzothiazole compounds.

[0003] Therefore, it is necessary to develop a benzothiazole compound with a novel structure, long emission wavelength, large Stokes shift, and high fluorescence quantum yield. Summary of the Invention

[0004] The present invention aims to at least solve one of the technical problems existing in the prior art. To this end, the first aspect of the present invention proposes a benzothiazole compound, which has the characteristics of long emission wavelength, large Stokes shift and high fluorescence quantum yield.

[0005] A second aspect of the present invention also provides a method for preparing benzothiazole compounds.

[0006] A third aspect of the present invention also provides a fluorescent probe.

[0007] The fourth aspect of the present invention also provides an application of benzothiazole compounds.

[0008] According to a first aspect of the present invention, a benzothiazole compound is provided having the structure shown in Formula I:

[0009]

[0010] Among them, R1 is selected from C 1～10 alkyl, oxygen-substituted C 2～8 cycloalkyl, C 1～10 alkoxy, C 1～6 Halogenated alkyl groups, halogens, diphenylamine groups, C 1～6 Alkoxy-substituted diphenylamino, phenyl or phenyl-substituted, triphenylamino, diphenylamino, C 1～22 Alkoxy-substituted phenyl or thiophene group;

[0011] R2 is selected from the following groups:

[0012]

[0013] According to a preferred embodiment of the present invention, the benzothiazole compound has the structure shown in Formula II:

[0014]

[0015] Among them, R1 is selected from C 1～10 alkyl, oxygen-substituted C 2～8 cycloalkyl, C 1～10 alkoxy, C 1～6 Halogenated alkyl groups, halogens, diphenylamine groups, C 1～6 Alkoxy-substituted diphenylamino, phenyl or phenyl-substituted, triphenylamino, diphenylamino, C 1～22 Alkoxy-substituted phenyl and thiophene groups.

[0016] According to a preferred embodiment of the present invention, R1 is selected from C. 1～6 alkyl, oxygen-substituted C 1～6 cycloalkyl, C 1～6 alkoxy, C 1～6 Halogenated alkyl groups, halogens, diphenylamine groups, C 1～3 Alkoxy-substituted diphenylamino, phenyl or phenyl-substituted, triphenylamino, diphenylamino, C 1～10 Alkoxy-substituted phenyl and thiophene groups.

[0017] According to a preferred embodiment of the present invention, R1 is selected from C. 1～6 alkyl,

[0018]

[0019] n is 0 to 21.

[0020] According to a preferred embodiment of the present invention, the benzothiazole compound is selected from the following structural formulas:

[0021]

[0022] The benzothiazole compounds according to embodiments of the present invention have at least the following beneficial effects:

[0023] This invention provides a series of novel benzothiazole compounds; these compounds exhibit aggregation-induced emission properties; their emission ranges from conventional short wavelengths to near-infrared emission; and they are characterized by large Stokes shift (~250 nm), long emission wavelength (~640 nm), and high fluorescence quantum yield.

[0024] According to a second aspect of the present invention, a method for preparing benzothiazole compounds as described in the first aspect of the present invention is provided, comprising the following steps:

[0025] The product is obtained by reacting a mixture of compound 1, compound 2, solvent, and base.

[0026] The structural formulas of compounds 1 and 2 are as follows:

[0027]

[0028] According to a preferred embodiment of the present invention, the solvent includes at least one selected from ethanol, trifluoroacetic acid, tetrahydrofuran, acetonitrile, and toluene.

[0029] According to a preferred embodiment of the present invention, the alkali includes at least one of piperidine, potassium carbonate, and cesium carbonate.

[0030] According to a preferred embodiment of the present invention, the molar ratio of compound 1 to compound 2 is 1:(1 to 1.5).

[0031] A third aspect of the present invention provides a fluorescent probe comprising the benzothiazole compounds described in the first aspect of the present invention.

[0032] A fourth aspect of the present invention provides an application of the above-described benzothiazole compounds in fluorescence imaging detection.

[0033] Definitions and general terms

[0034] “C 1～6 "alkyl" refers to an alkyl group with a total number of 1 to 6 carbon atoms, including C64. 1-6 straight-chain alkyl, C 1-6 Branched alkyl groups and C 3-6 The cycloalkyl group can be, for example, a straight-chain alkyl group with a total number of carbon atoms of 1, 2, 3, 4, 5, or 6; a branched-chain alkyl group with a total number of carbon atoms of 1, 2, 3, 4, 5, or 6; or a cycloalkyl group with a total number of carbon atoms of 3, 4, 5, or 6; for example, it can be methyl, ethyl, n-propyl, isopropyl, n-butyl, isobutyl, tert-butyl, n-pentyl, isopentyl, n-hexyl, cyclopropyl, methylcyclopropyl, ethylcyclopropyl, cyclopentyl, methylcyclopentyl, cyclohexyl, etc. Regarding "C1~ 10 "alkyl" has a similar interpretation, except that the number of carbon atoms is different.

[0035] “C 1～6 "Alkoxy" refers to alkoxy groups with a total number of carbon atoms of 1 to 6, including straight-chain alkoxy groups with 1 to 6 carbon atoms and branched-chain alkoxy groups with 1 to 6 carbon atoms; for example, it can be a straight-chain alkoxy group with a total number of carbon atoms of 1, 2, 3, 4, 5, or 6, or a branched-chain alkoxy group with a total number of carbon atoms of 1, 2, 3, 4, 5, or 6. Examples include methoxy, ethoxy, n-propoxy, isopropoxy, etc. Regarding "C..." 1-10 alkoxy group, C 1～3 alkoxy group, C 1-22The "alkoxy group" has a similar explanation, except that the number of carbon atoms is different.

[0036] “C 1～6 "halogenated alkyl" and "C" 1-6 The definition of "alkyl" is similar, except that it is composed of "C". 1～6 In the haloalkyl group, at least one H atom is substituted by any halogen.

[0037] "Halogen" includes any one or more of fluorine, chlorine, bromine, and iodine.

[0038] "C with oxygen atom substitution" 2～8 "Cycloalkyl" refers to a cycloalkyl group with a total number of carbon atoms of 2 to 8, and at least one oxygen atom replaces a carbon atom in the ring. For example, it can be...

[0039] Other features and advantages of the invention will be set forth in the description which follows, and will be apparent in part from the description, or may be learned by practicing the invention. Attached Figure Description

[0040] The above and / or additional aspects and advantages of the present invention will become apparent and readily understood from the description of the embodiments taken in conjunction with the following drawings, in which:

[0041] Figure 1 The 1H NMR spectrum of compound 4 of this invention;

[0042] Figure 2 This is the high-resolution mass spectrum of compound 4 of the present invention;

[0043] Figure 3 The 1H NMR spectrum of compound 5 of this invention;

[0044] Figure 4 This is the high-resolution mass spectrum of compound 5 of the present invention;

[0045] Figure 5 The 1H NMR spectrum of compound 6 of this invention;

[0046] Figure 6 This is the high-resolution mass spectrum of compound 6 of the present invention.

[0047] Figure 7 The 1H NMR spectrum of compound 7 of this invention;

[0048] Figure 8 This is the high-resolution mass spectrum of compound 7 of the present invention;

[0049] Figure 9 The 1H NMR spectrum of compound 8 of this invention;

[0050] Figure 10This is the high-resolution mass spectrum of compound 8 of the present invention;

[0051] Figure 11 The fluorescence intensity diagrams are for compounds 4-8 of this invention.

[0052] Figure 12 The fluorescence intensity diagrams of compound 4 of the present invention at different THF / H2O ratios are shown.

[0053] Figure 13 The fluorescence intensity diagrams of compound 5 of the present invention at different THF / H2O ratios are shown.

[0054] Figure 14 The fluorescence intensity diagrams of compound 6 of the present invention at different THF / H2O ratios are shown.

[0055] Figure 15 The fluorescence intensity diagrams of compound 7 of the present invention at different THF / H2O ratios are shown.

[0056] Figure 16 The fluorescence intensity diagrams of compound 8 of the present invention at different THF / H2O ratios are shown. Detailed Implementation

[0057] The following are specific embodiments of the present invention, and the technical solutions of the present invention will be further described in conjunction with the embodiments, but the present invention is not limited to these embodiments.

[0058] Unless otherwise specified, the reagents, methods and equipment used in this invention are all conventional reagents, methods and equipment in this technical field.

[0059] Example 1

[0060] This example provides a benzothiazole compound, the reaction equation and preparation method of which are as follows:

[0061]

[0062] S1. Dissolve 2-hydroxy-5-methylbenzaldehyde (2000 mg, 14.7 mmol) and 2-aminobenzylthiophenol (1838 mg, 14.7 mmol) in anhydrous ethanol (50 mL); then add HCl (7%, 4 mL) and H2O2 (30%, 10 mL). After 1 h, a precipitate is formed. Filter and wash the precipitate with anhydrous ethanol. After drying, a yellow powder (2280 mg, 64%) is obtained.

[0063] S2, yellow powder (500 mg, 6.21 mmol) and hexamethylenetetramine (1043 mg, 7.45 mmol) were dissolved in trifluoroacetic acid (10 mL) and reacted for 12 h to give compound 1 (491 mg, 29%).

[0064] S3, compound 1 (50 mg, 0.13 mmol) and acetyltetraphenylene (45 mg, 0.13 mmol) were dissolved in ethanol (6 mL), and piperidine (100 μL) was added dropwise in small amounts several times to give compound 4 (18.10 mg, 16%).

[0065] Compound 4 was subjected to 1H NMR and mass spectrometry tests, and the results are as follows: Figure 1 and Figure 2 As shown, the data is as follows:

[0066] 1 H NMR(500MHz,Chloroform-d)δ13.31(s,1H),8.06(d,J=15.7Hz,1H),8.01(d,J=8.1Hz,1H),7.92(d,J=8.1Hz,1H),7.87(d,J=15.7Hz,1 H),7.84(d,J=8.1Hz,2H),7.55–7.51(m,2H),7.48(s,1H),7.43(t,J=7.6Hz,1H),7.19–7.11(m,11H),7.08–7.02(m,6H),2.38(s,3H).

[0067] HR-ESI-MS for C 43 H 31 NO2S([M+H] + )Calcd:626.2148,Found:626.2145.

[0068] Example 2

[0069] This example provides a benzothiazole compound, the reaction equation and preparation method of which are as follows:

[0070]

[0071] S1, 2-hydroxy-5-bromobenzaldehyde (2000 mg, 10 mmol) and o-aminothiophenol (1250 mg, 10 mmol) were dissolved in ethanol (30 mL), and hydrochloric acid (7%, 4 mL) and hydrogen peroxide (30%, 10 mL) were added dropwise. The reaction was carried out for 2 h, and the green powder (1436 mg, 46%) was obtained by filtration.

[0072] S2. Green powder (500 mg, 1.63 mmol) and hexamethylenetetramine (347 mg, 2.48 mmol) were dissolved in trifluoroacetic acid (10 mL) and reacted for 12 h to obtain compound 2 (432 mg, 79%).

[0073] S3, compound 2 (43 mg, 0.13 mmol) and acetyltetraphenylene (50 mg, 0.13 mmol) were dissolved in ethanol (13 mL), and piperidine (300 μL) was added dropwise in small amounts several times to give compound 5 (34 mg, 43%).

[0074] Compound 5 was subjected to 1H NMR and mass spectrometry tests, and the results are as follows: Figure 3 and Figure 4 As shown, the data is as follows:

[0075] 1 H NMR(400MHz,Chloroform-d)δ13.53(s,1H),8.03(d,J=4.0Hz,1H),8.00(d,J=12.2Hz,1H),7.94(d,J=6.8Hz,1H),7 .85–7.79(m,4H),7.75(d,J=2.3Hz,1H),7.58–7.53(m,1H),7.47(t,J=7.7Hz,1H),7.20–7.10(m,11H),7.05(m,6H).

[0076] HR-ESI-MS for C 42 H 29 NO2BrS([M+H)) + )Calcd:690.1097,Found:690.1087.

[0077] Example 3

[0078] This example provides a benzothiazole compound, the reaction equation and preparation method of which are as follows:

[0079]

[0080] S1, 2-hydroxy-5-fluorobenzaldehyde (1222 mg, 7.99 mmol) and o-aminothiophenol (1000 mg, 7.99 mmol) were dissolved in ethanol (30 mL), hydrochloric acid (2 mL) and hydrogen peroxide (5 mL) were added dropwise, the reaction was carried out for 2 h, and the green powder (1200 mg, 61%) was obtained by filtration.

[0081] S2. Green powder (1200 mg, 4.89 mmol) and hexamethylenetetramine (2057 mg, 14.69 mmol) were dissolved in trifluoroacetic acid (20 mL) and reacted for 12 h to obtain compound 3 (589 mg, 44%).

[0082] S3, compound 3 (100 mg, 0.36 mmol) and acetyltetraphenylene (127 mg, 0.36 mmol) were dissolved in ethanol (20 mL), and piperidine (200 μL) was added dropwise in small amounts several times to give compound 6 (21 mg, 14%).

[0083] Compound 6 was subjected to 1H NMR and mass spectrometry tests, and the results are as follows: Figure 5 and Figure 6 As shown, the data is as follows:

[0084] 1 H NMR(400MHz,Chloroform-d)δ13.32(s,1H),8.06(d,J=7.8Hz,1H),8.03(s,1H),7.94(d,J=8.0Hz,1H),7.85–7.79(m,3H), 7.56(t,J=7.7Hz,1H),7.49–7.46(m,1H),7.46–7.43(m,1H),7.39(dd,J=8.9,3.0Hz,1H),7.19–7.12(m,11H),7.05(m,6H).

[0085] HR-ESI-MS for C 42 H 48 FNO2S([M+H)) + )Calcd:630.1898,Found:630.1896.

[0086] Example 4

[0087] This example provides a benzothiazole compound, the reaction equation and preparation method of which are as follows:

[0088]

[0089] Compound 5 (23 mg, 0.033 mmol) and [1-(4-boronylphenyl)-1,2,2-triphenyl]ethylene (33 mg, 0.09 mmol) were added to tetrahydrofuran (15 mL) solvent with tetratriphenylphosphine palladium (3 mg, 1.6% mmol) and potassium carbonate (230 μL, 0.12 mmol), and column chromatography was performed to obtain compound 7 (15 mg, 48%).

[0090] Compound 7 was subjected to 1H NMR and mass spectrometry tests, and the results are as follows: Figure 7 and Figure 8 As shown, the data is as follows:

[0091] 1H NMR(400MHz,Chloroform-d)δ13.57(s,1H),8.14(d,J=15.8Hz,1H),8.06(d,J=8.1Hz,1H),7.98–7.89(m,3H),7.89 –7.84(m,3H),7.57(t,J=7.7Hz,1H),7.48(t,J=7.6Hz,1H),7.40(d,J=8.1Hz,2H),7.22–7.10(m,26H),7.07(m,8H).

[0092] HR-ESI-MS for C 68 H 48 NO2S([M+H] + )Calcd:942.3400,Found:942.3381.

[0093] Example 5

[0094] This example provides a benzothiazole compound, the reaction equation and preparation method of which are as follows:

[0095]

[0096] Compound 5 (30 mg, 0.043 mmol) and 4-(diphenylamino)phenylboronic acid (50 mg, 0.17 mmol) were added to tetrahydrofuran (15 mL) solvent with tetratriphenylphosphine palladium (3 mg, 1.3%) and potassium carbonate (130 μL, 0.26 mmol), and column chromatography was performed to obtain compound 8 (20 mg, 55%).

[0097] Compound 8 was subjected to 1H NMR and mass spectrometry tests, and the results are as follows: Figure 9 and Figure 10 As shown, the data is as follows:

[0098] 1 H NMR (400MHz, Chloroform-d) δ13.53(s,1H),8.13(d,J=15.8Hz,1H),8.02(d,J=8.1Hz,1H),7.96–7.90(m,2H),7.88–7.85(m,2H),7.84(d,J =4.7Hz,2H),7.53(t,J=7.7Hz,1H),7.50–7.45(m,2H),7.43(d,J=7.5Hz,1H),7.30(t,J=7.9Hz,4H),7.22–7.10(m,17H),7.09–7.02(m,8H).

[0099] HR-ESI-MS for C 60 H43 N₂O₂S([M+H)) + )Calcd:855.3039,Found:855.3014.

[0100] Performance testing

[0101] First, the benzothiazole compounds 4-8 prepared in Examples 1-5 of this invention were dissolved in N,N-dimethylformamide solvent, and their fluorescence intensity was tested. The results are as follows: Figure 11 As shown, from Figure 11 It can be observed that the fluorescence intensity of the benzothiazole compounds of the present invention gradually undergoes a red shift.

[0102] Furthermore, to test whether compounds 4-8 are aggregation-induced emission materials, compounds 4-8 prepared in this invention were dissolved in the good solvent THF, and their fluorescence intensity was tested as the poor solvent H2O was added. The results are as follows: Figure 12 , Figure 13 , Figure 14 , Figure 15 and Figure 16 As shown, the fluorescence intensity of compounds 4, 5, and 7 first increases and then decreases with the addition of a poor solvent; the fluorescence intensity of compound 8 first decreases and then increases with the addition of a poor solvent. This indicates that compounds 4-5 and compounds 7-8 prepared in this invention are all aggregation-induced emission materials.

[0103] The present invention has been described in detail above with reference to the embodiments of the present invention. However, the present invention is not limited to the above embodiments. Within the scope of knowledge possessed by those skilled in the art, various changes can be made without departing from the spirit of the present invention.

Claims

1. A benzothiazole compound, characterized in that, It has the structure shown in Equation I: Among them, R1 is selected from C 1～10 alkyl, oxygen-substituted C 2～8 cycloalkyl, C 1～10 alkoxy, C 1～6 Halogenated alkyl groups, halogens, diphenylamine groups, C 1～6 Alkoxy-substituted diphenylamino, phenyl or phenyl-substituted, triphenylamino, diphenylamino, C 1～22 Alkoxy-substituted phenyl or thiophene group; R2 is selected from the following groups:

2. The benzothiazole compound according to claim 1, characterized in that, It has the structure shown in Formula II: Among them, R1 is selected from C 1～10 alkyl, oxygen-substituted C 2～8 cycloalkyl, C 1～10 alkoxy, C 1～6 Halogenated alkyl groups, halogens, diphenylamine groups, C 1～6 Alkoxy-substituted diphenylamino, phenyl or phenyl-substituted, triphenylamino, diphenylamino, C 1～22 Alkoxy-substituted phenyl and thiophene groups.

3. The benzothiazole compound according to claim 1 or 2, characterized in that, R1 is selected from C 1～6 alkyl, oxygen-substituted C 1～6 cycloalkyl, C 1～6 alkoxy, C 1～6 Halogenated alkyl groups, halogens, diphenylamine groups, C 1～3 Alkoxy-substituted diphenylamino, phenyl or phenyl-substituted, triphenylamino, diphenylamino, C 1～10 Alkoxy-substituted phenyl and thiophene groups.

4. The benzothiazole compound according to any one of claims 1 to 3, characterized in that, The benzothiazole compounds are selected from the following structural formulas:

5. A method for preparing benzothiazole compounds as described in any one of claims 1 to 4, characterized in that, Includes the following steps: The product is obtained by reacting a mixture of compound 1, compound 2, solvent, and base. The structural formulas of compounds 1 and 2 are as follows:

6. The preparation method according to claim 5, characterized in that, The solvent includes at least one of ethanol, trifluoroacetic acid, tetrahydrofuran, acetonitrile, and toluene.

7. The preparation method according to claim 5, characterized in that, The base includes at least one of piperidine, potassium carbonate, and cesium carbonate.

8. The preparation method according to claim 5, characterized in that, The molar ratio of compound 1 to compound 2 is 1:(1 to 1.5).

9. A fluorescent probe, characterized in that, Includes the benzothiazole compounds as described in any one of claims 1 to 4.

10. The use of the benzothiazole compounds according to any one of claims 1 to 4 in fluorescence imaging detection.

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