Benzocarbazole derivative as well as synthesis method and application thereof

Abstract

The invention relates to the technical field of organic synthesis, and particularly discloses a benzocarbazole derivative, the structural formula of the benzocarbazole derivative is # imgabs0, and R1 and R2 are hydrogen atoms, fluorine, chlorine, bromine, iodine, methyl, phenyl, alkoxy, benzyloxy or dimethyl tert-butyl siloxy. According to the benzocarbazole derivative, ultraviolet absorption is located in a blue-violet light range, and the benzocarbazole derivative has large absorption wavelength and fluorescence quantum yield, is mild in synthesis reaction condition, safe and simple to operate, short in synthesis route and high in synthesis yield, and has certain application value in the field of fluorescent probes.

Description

Technical Field

[0001] The invention relates to the technical field of organic synthesis, and in particular to a benzocarbazole derivative and a synthesis method and application thereof. Background Art

[0002] With the development of modern organic synthetic chemistry, heterocyclic compounds play an increasingly important role in organic synthesis. In particular, nitrogen heterocyclic compounds are one of the most important and widely used synthetic intermediates in organic synthesis. Generally, substituted benzocarbazole compounds can be synthesized by cyclization reaction of indole with olefins or alkynes, for example, indole and olefins are synthesized by cycloaddition reaction in DMF (N,N-dimethylformamide) / DMSO (dimethyl sulfoxide) mixed solvent by palladium catalysis. In addition, indole and diphenyl conjugated alkynes can also be synthesized by [4+2]-cycloaddition reaction in DCE by gold catalysis. Such methods of synthesizing benzocarbazole compounds by cycloaddition reaction of indole and relatively simple olefins or alkynes have many disadvantages: 1) low reaction yield; 2) harsh reaction conditions; 3) limited substrate range; 4) the reaction has certain risks. It has been found through testing that the ultraviolet absorption of benzocarbazole compounds is in the blue-violet light range. Therefore, the development of an efficient synthesis method for benzocarbazole compounds has very important theoretical significance and practical application value in the field of dyes and fluorescent probes.

[0003] At present, there are many synthetic methods for benzocarbazole compounds reported (Chem. Commun. 2019, 55, 3339-3342; Chin. J. Org. Chem. 2012, 32, 1217-1231), but most of the methods reported in the literature are relatively complicated, with low yields and poor substrate adaptability. Therefore, it is of great significance to develop an efficient synthesis method for benzocarbazole compounds with high yield, safe reaction process and good substrate adaptability for the promotion and application of benzocarbazole compounds. Summary of the invention

[0004] In view of the above shortcomings, the present invention provides a benzocarbazole derivative and a synthesis method and application thereof, which can be used in the field of fluorescent probes, has mild synthesis reaction conditions, safe and simple operation, high synthesis yield, and good substrate adaptability. The specific technical scheme is as follows:

[0005] A benzocarbazole derivative, the structural formula of the benzocarbazole derivative is:

[0006]

[0007] Wherein, R1 and R2 are hydrogen atom, fluorine, chlorine, bromine, iodine, methyl, phenyl, alkoxy, benzyloxy or dimethyl-tert-butylsilyloxy.

[0008] A method for synthesizing the above-mentioned benzocarbazole derivatives comprises the following steps:

[0009] (1) mixing a (2-ethynyl)aryl aziridine diester and a substituted indole in an organic solvent, adding a gold catalyst and a Lewis acid catalyst, stirring and reacting under a dual catalytic system, extracting after the reaction, and collecting an organic phase;

[0010] (2) drying the organic phase obtained in step (1), concentrating under reduced pressure, and separating by silica gel column chromatography to obtain a benzocarbazole derivative;

[0011] The synthetic route of the benzocarbazole derivatives is as follows:

[0012]

[0013] Preferably, in the above-mentioned method for synthesizing benzocarbazole derivatives, the reaction temperature is 10 to 30° C., and the reaction time is 10 to 15 hours.

[0014] Preferably, in the above-mentioned method for synthesizing benzocarbazole derivatives, the organic solvent is dichloromethane or acetonitrile.

[0015] Preferably, in the above-mentioned method for synthesizing benzocarbazole derivatives, the organic solvent is dichloromethane.

[0016] Preferably, in the above-mentioned method for synthesizing benzocarbazole derivatives, the dual catalytic system is PPh3AuNTf2 / Sc(OTf)3, PPh3AuNTf2 / Ni(OTf)3, PPh3AuNTf2 / Y(OTf)3 or PPh3AuNTf2 / Yb(OTf)3.

[0017] Preferably, in the above-mentioned method for synthesizing benzocarbazole derivatives, the bimetallic catalyst system is PPh3AuNTf2 / Sc(OTf)3.

[0018] Preferably, in the above-mentioned synthesis method of benzocarbazole derivatives, the molar ratio of the (2-ethynyl) aryl aziridine diester to the substituted indole is 1:1 to 1.5, the molar amount of the gold catalyst is 3 to 10% of the molar amount of the (2-ethynyl) aryl aziridine diester, and the molar amount of the Lewis acid catalyst is 5 to 12% of the molar amount of the (2-ethynyl) aryl aziridine diester; the ratio of the (2-ethynyl) aryl aziridine diester to the organic solvent is 1 mmol:1 to 1.5 ml.

[0019] Preferably, in the above-mentioned synthesis method of benzocarbazole derivatives, the molar ratio of the (2-ethynyl)aryl aziridine diester to the substituted indole is 1:1.2, the molar amount of the gold catalyst is 5% of the molar amount of the (2-ethynyl)aryl aziridine diester, and the molar amount of the Lewis acid catalyst is 10% of the molar amount of the (2-ethynyl)aryl aziridine diester.

[0020] Preferably, in the above-mentioned synthesis method of benzocarbazole derivatives, the extraction is extraction with ethyl acetate; the eluent in the silica gel column chromatography is petroleum ether and ethyl acetate, and the volume ratio of petroleum ether to ethyl acetate is 19:1 to 5:1.

[0021] Application of the above-mentioned benzocarbazole derivatives in fluorescent probes.

[0022] Compared with the prior art, the present invention has the following beneficial effects:

[0023] 1. The benzocarbazole derivatives of the present invention have ultraviolet absorption in the blue-violet range, have a large absorption wavelength and fluorescence quantum yield, and have certain application value in the field of fluorescent probes.

[0024] 2. The method for synthesizing benzocarbazole derivatives of the present invention uses a dual catalyst system to catalyze the cycloisomerization reaction of (2-ethynyl)arylaziridine diester and indole to synthesize benzocarbazole derivatives. The synthesis reaction conditions are mild, the operation is safe and simple, the synthesis route is short, and the synthesis yield is high. It can be applied to the synthesis of different substituted benzocarbazole derivatives. BRIEF DESCRIPTION OF THE DRAWINGS

[0025] In order to more clearly illustrate the technical solutions of the embodiments of the present invention, the following briefly introduces the drawings required for describing the embodiments. Obviously, the drawings described below are some embodiments of the present invention, and for ordinary technicians in this field, other drawings can be obtained based on these drawings without creative work.

[0026] Figure 1 It is the ultraviolet absorption spectrum of benzocarbazole derivatives 3l, 3g, 3n, 3m, 3o and 3p in the application example of the present invention.

[0027] Figure 2 3 is the fluorescence emission diagram of benzocarbazole derivatives 3l, 3g, 3n, 3m, 3o and 3p in the application examples of the present invention. DETAILED DESCRIPTION

[0028] The specific embodiments of the present invention are described in detail below, but it should be understood that the protection scope of the present invention is not limited by the specific embodiments. Unless otherwise defined, all professional terms used hereinafter have the same meaning as those generally understood by those skilled in the art. The professional terms used herein are only for the purpose of describing specific embodiments and are not intended to limit the protection scope of the present invention. Unless otherwise specifically stated, various raw materials, reagents, instruments and equipment used in the present invention, etc. can be purchased from the market or can be prepared by existing methods.

[0029] In the following examples and comparative examples, the reactant (2-ethynyl) aryl aziridine diester was prepared by the following method. The preparation of other (2-ethynyl) aryl aziridine diesters with different substituents was carried out according to the following method, except that there is an R1 substituent on the benzene ring of S1.

[0030] The synthetic route of (2-ethynyl)aryl aziridine diester is:

[0031]

[0032] The preparation method of (2-ethynyl) aryl aziridine diester specifically comprises:

[0033] The first step: 2-iodoimine S1 (5.1 g, 13.2 mmol, 1.0 equivalent) was dissolved in acetonitrile and stirred at 0 ° C for 5 minutes; diethyl bromomalonate S2 (3.8 g, 15.9 mmol, 1.2 equivalent) and NaH (0.64 g, 15.9 mmol, 1.2 equivalent, 60% dispersed in mineral oil) were added and reacted at 0 ° C for 30 minutes. TLC monitored the reaction to be complete. The aqueous phase was adjusted to pH = 4-5, extracted with ethyl acetate (2 × 100 mL), and washed with saturated brine (2 × 100 mL). The combined organic layer was dried, concentrated and purified by flash silica gel chromatography using (90: 10 to 85: 15 petroleum ether: ethyl acetate) to obtain 2-iodoaryl aziridine diester S3.

[0034] Step 2: Trimethylsilyl acetylene S4 (1.71 g, 17.46 mmol, 1.2 equivalents), Pd(PPh3)2Cl2 (0.2 g, 0.3 mmol), cuprous iodide (0.14 g, 0.73 mmol) and triethylamine (50 mL) were added to a tetrahydrofuran solution of S3. The reaction mixture was stirred at room temperature for 12 hours in an argon atmosphere. The pH of the aqueous phase was then adjusted to 4-5, extracted with ethyl acetate (2×100 mL) and washed with saturated brine (2×100 mL). The combined organic layer was dried, concentrated and purified with (90:10 to 85:15 petroleum ether: ethyl acetate) to obtain (2-trimethylsilyl acetylene) aryl aziridine diester S5.

[0035] Step 3: (2-trimethylsilyl acetylene) aryl aziridine diester S5 (5.0 g, 9.75 mmol, 1.0 equivalent) was dissolved in anhydrous ethanol, anhydrous potassium carbonate (4.0 g, 29.25 mmol, 3.0 equivalent) was added, and the reaction mixture was stirred at room temperature for 12 hours, and then the aqueous phase was adjusted to pH = 4-5, extracted with ethyl acetate (2 × 100 mL), and washed with saturated brine (2 × 100 ml). The combined organic layer was dried, concentrated and purified with (90:10 to 85:15 petroleum ether: ethyl acetate) to obtain (2-ethynyl) aryl aziridine diester 1.

[0036] Example 1

[0037] A benzocarbazole derivative, the structural formula is:

[0038]

[0039] The synthesis route of the benzocarbazole derivatives of this embodiment is:

[0040]

[0041] The synthesis method of the benzocarbazole derivative of this embodiment specifically comprises the following steps:

[0042] (1) (2-ethynyl)aryl aziridine diester 1a (44.1 mg, 0.1 mmol, 1.0 equivalent) and indole 2a (14.0 mg, 0.12 mmol, 1.2 eq) were added to a reaction flask, dissolved with dichloromethane (1.0 mL), and Ph3PAuNTf2 (3.7 mg, 0.005 mmol) and Sc(OTf)3 (4.9 mg, 0.01 mmol) were added respectively. The reactants were stirred at room temperature for 12 hours; the mixture was diluted with brine (2.0 mL), extracted with ethyl acetate (2.0 mL×2), and the organic phase was collected;

[0043] (2) The organic phase was dried, concentrated under reduced pressure, and purified and separated using silica gel chromatography (19:1-5:1 petroleum ether:ethyl acetate) to obtain the benzocarbazole derivative 3a with a yield of 88% (49.1 mg, 0.088 mmol).

[0044] The nuclear magnetic resonance data of the benzocarbazole derivative 3a in this example are:

[0045] 1H NMR(DMSO-d6,400MHz)δ10.38(s,1H),8.36(d,J=7.6Hz,1H),8.25(d,J=8.4Hz,1H),7.86(d,J=8.4Hz,1H),7.53–7.48(m,2H),7.36–7.3 1(m,3H),7.27–7.24(m,1H),7.18–7.12(m,3H),5.86(s,1H),4.08–3.94(m,4H),3.18(s,3H),2.24(s,3H),0.91(dt,J=21.2,6.8Hz,6H);

[0046] 13 C NMR (101MHz, CDCl3) δ167.9,166.3,143.9,142.0,140.0(s),135.9,132.0,131.2,128.8,128.5,127.6,126.9,125.2,1 24.6, 124.1, 123.6 (d, J = 5.4Hz), 122.9, 122.4, 119.2, 110.9, 110.4, 68.5, 62.8 (d, J = 10.3Hz), 21.4, 15.8, 14.0, 13.3;

[0047] HRMS (TOF-ESI + )m / z:calcd for C 31 H 30 N2O6SNa[M+Na] + 581.1717, found 581.1727.

[0048] Example 2

[0049] A benzocarbazole derivative, the structural formula is:

[0050]

[0051] The synthesis route of the benzocarbazole derivatives of this embodiment is:

[0052]

[0053] The synthesis method of the benzocarbazole derivative of this embodiment is the same as that of Example 1, except that: in step (1), 4-fluoro-2-ethynylaryl aziridine diester 1b (45.9 mg, 0.1 mmol, 1.0 equivalent) is used to replace (2-ethynyl) aryl aziridine diester 1a to obtain 4-fluorobenzocarbazole derivative 3b with a yield of 63% (36.3 mg, 0.063 mmol).

[0054] The nuclear magnetic resonance data of the benzocarbazole derivative 3b in this example are:

[0055] 1 H NMR(DMSO-d6,400MHz)δ10.47(s,1H),8.36(d,J=8.0Hz,1H),7.99–7.95(m,2H),7.52(d,J=3.6Hz,2H),7.33(d,J=8.4Hz,2H),7.28–7.24(m,1H) ,7.15–7.07(m,3H),5.93(s,1H),4.14–4.02(m,2H),3.96–3.92(m,2H), 3.13(s,3H),2.24(s,3H),0.99(t,J=6.8Hz,3H),0.81(t,J=7.2Hz,3H);

[0056] 13 C NMR(DMSO-d6,101MHz)δ166.9,166.4,144.5,142.3,139.7,135.9,131.4,129.6,128.8,128.5,128.8,128.5,126. 2,125.4,124.2,122.7,119.8,115.4,115.2,111.2,110.9,108.0,107.8,67.8,62.9,62.6,21.4,16.2,13.9,13.7;

[0057] HRMS (TOF-ESI + )m / z:calcd for C 31 H 29 FN2O6SK[M+K] + 615.1362, found 615.1371.

[0058] Example 3

[0059] A benzocarbazole derivative, the structural formula is:

[0060]

[0061] The synthesis route of the benzocarbazole derivatives of this embodiment is:

[0062]

[0063] The synthesis method of the benzocarbazole derivative of this embodiment is the same as that of Example 1, except that: in step (1), 4-chloro-2-ethynylaryl aziridine diester 1c (47.5 mg, 0.1 mmol, 1.0 equivalent) is used to replace (2-ethynyl) aryl aziridine diester 1a to obtain 4-chlorobenzocarbazole derivative 3c with a yield of 68% (40.1 mg, 0.068 mmol).

[0064] The nuclear magnetic resonance data of the benzocarbazole derivative 3c in this example are:

[0065] 1 H NMR(DMSO-d6,400MHz)δ10.56(s,1H),8.37(d,J=8.0Hz,1H),8.27(d,J=2.0Hz ,1H),7.94(d,J=9.2Hz,1H),7.53(d,J=4.0Hz,2H),7.33(d,J=8.0Hz,2H),7.29 –7.25(m,1H),7.17–7.13(m,3H),5.94(s,1H),4.15–4.02(m,2H),3.97–3.89( m,2H),3.15(s,3H),2.24(s,3H),0.99(t,J=6.8Hz,3H),0.79(t,J=7.2Hz,3H);

[0066] 13 C NMR(DMSO-d6,101MHz)δ166.9,166.3,144.6,142.3,140.2,135.8,131.5,130.1,129.6,128.6,127.9(d,J=19.6Hz ),127.6,125.6,125.4(d,J=5.6Hz),124.3,123.4,122.8,112.0,111.1,67.7,62.9,62.6,21.4,16.0,13.9,13.7;

[0067] HRMS (TOF-ESI + )m / z:calcd for C 31 H 29 ClN2O6SK[M+K] + 631.1066, found 631.1072.

[0068] Example 4

[0069] A benzocarbazole derivative, the structural formula is:

[0070]

[0071] The synthesis route of the benzocarbazole derivatives of this embodiment is:

[0072]

[0073] The synthesis method of the benzocarbazole derivative of this embodiment is the same as that of Example 1, except that: in step (1), 5-bromo-2-ethynylaryl aziridine diester 1d (51.9 mg, 0.1 mmol, 1.0 equivalent) is used to replace (2-ethynyl) aryl aziridine diester 1a to obtain 5-bromobenzocarbazole compound 3d with a yield of 60% (38.2 mg, 0.060 mmol).

[0074] The nuclear magnetic resonance data of the benzocarbazole derivative 3c in this example are:

[0075] 1 H NMR(DMSO-d6,400MHz)δ10.76(s,1H),8.37(d,J=8.0Hz,1H),8.17(d,J=9.1H z,1H),7.86(d,J=2.0Hz,1H),7.61–7.52(m,2H),7.38–7.34(m,3H),7.30–7.2 6(m,1H),7.16(d,J=8.0Hz,2H),5.96(s,1H),4.17–4.03(m,2H),3.95–3.89(m ,2H),3.16(s,3H),2.29(s,3H),1.05(t,J=6.8Hz,3H),0.80(t,J=7.2Hz,3H);

[0076] 13 C NMR (DMSO-d6, 101MHz) δ166.9, 166.3, 144.7, 142.3, 140.8, 135.8, 132.6 (d, J = 1.7Hz), 129.7, 128.4, 127.9, 127.0, 125. 5(d,J=6.7Hz),125.0,124.8,124.2,123.0,120.0(d,J=10.5Hz),111.2,110.0,67.6,62.9,62.7,21.5,16.0,14.0,13.7;

[0077] HRMS (TOF-ESI + )m / z:calcd for C 31 H 29 BrN2O6SNa[M+Na] + 659.0822, found 659.0834.

[0078] Example 5

[0079] A benzocarbazole derivative, the structural formula is:

[0080]

[0081] The synthesis route of the benzocarbazole derivatives of this embodiment is:

[0082]

[0083] The synthesis method of the benzocarbazole derivative of this embodiment is the same as that of embodiment 1, except that: in step (1), 5-fluoro-2-ethynyl aryl aziridine diester 1e (45.9 mg, 0.1 mmol, 1.0 equivalent) is used to replace (2-ethynyl) aryl aziridine diester 1a to obtain 5-fluorobenzocarbazole compound 3e. The yield is 65% (37.4 mg, 0.065 mmol).

[0084] The nuclear magnetic resonance data of the benzocarbazole derivative 3e in this example are:

[0085] 1 H NMR(DMSO-d6,400MHz)δ10.58(s,1H),8.36–8.30(m,2H),7.57–7.50(m,3H),7.35(d,J=8.4Hz,2H),7.29–7.24(m,1H),7.22–7.13( m,3H),5.94(s,1H),4.20–4.04(m,2H),3.98–3.86(m,2H),3.17(s,3H),2.24(s,3H),1.04(t,J=7.2Hz,3H),0.78(t,J=7.2Hz,3H);

[0086] 13 C NMR(DMSO-d6,101MHz)δ167.1,166.2,144.5,142.0,141.0,136.0,133.2(d,J=10.0Hz),132.7,129.5,128.5,127.9,127.8,127.6,124.4,124 .0,123.1,112.0,112.8,112.6,111.0,110.4,106.6,106.4,67.7,62.9 ,62.6,40.6,40.4,40.2,34.0,39.8,39.5,39.3,21.3,16.2,13.,13.6;

[0087] HRMS (TOF-ESI + )m / z:calcd for C 31 H 29FN2O6SK[M+K] + 615.1362, found 615.1371.

[0088] Example 6

[0089] A benzocarbazole derivative, the structural formula is:

[0090]

[0091] The synthesis route of the benzocarbazole derivatives of this embodiment is:

[0092]

[0093] The synthesis method of the benzocarbazole derivative of this embodiment is the same as that of Example 1, except that: in step (1), 5-methyl-2-ethynylaryl aziridine diester 1f (45.5 mg, 0.1 mmol, 1.0 equivalent) is used to replace (2-ethynyl) aryl aziridine diester 1a to obtain 5-methylbenzocarbazole compound 3f with a yield of 70% (40.0 mg, 0.070 mmol).

[0094] The 3f NMR data of the benzocarbazole derivatives of this example are:

[0095] 1 H NMR(DMSO-d6,400MHz)δ10.48(s,1H),8.34(d,J=8.0Hz,1H),8.12(d,J=8.8Hz,1H ),7.57(d,J=7.6Hz,1H),7.50(t,J=7.6Hz,1H),7.39(d,J=8.0Hz,2H),7.34(s,1H) ,7.25(t,J=7.6Hz,1H),7.18–7.12(m,3H),5.83(s,1H),4.08–4.02(m,3H),3.93– 3.89(m,1H),3.14(s,3H),2.28(s,3H),2.14(s,3H),0.93(dd,J=15.6,7.2Hz,6H);

[0096] 13C NMR(DMSO-d6,101MHz)δ167.0,166.6,144.4,142.0,140.3,136.4,134.5,131.9,131.4,129.5,128.6,127.3,125.7,124. 9,124.6,123.9,123.6,123.4,122.0,119.7,110.9,110.4,67.9,62.7(d,J=4.5Hz),21.6,21.3,16.0,13.8(d,J=10.8Hz);

[0097] HRMS (TOF-ESI + )m / z:calcd for C 31 H 31 N2O6S[M+H] + 573.2054, found 573.2045.

[0098] Example 7

[0099] A benzocarbazole derivative, the structural formula is:

[0100]

[0101] The synthesis route of the benzocarbazole derivatives of this embodiment is:

[0102]

[0103] The synthesis method of the benzocarbazole derivative of this embodiment is the same as that of embodiment 1, except that: in step (1), 5-fluoroindole 2b (16.2 mg, 0.12 mmol, 1.2 equivalents) is used to replace indole 2a to obtain 5'-fluorobenzocarbazole compound 3g with a yield of 61% (34.3 mg, 0.061 mmol).

[0104] The nuclear magnetic resonance data of the benzocarbazole derivative 3g in this example are:

[0105] 1H NMR(DMSO-d6,400MHz)δ10.46(s,1H),8.26(d,J=8.8Hz,1H),8.15–8.12(m,1H),7.85(d,J=8.4Hz,1H),7.57–7.53(m,1H),7.40–7.35(m,2H), 7.34–7.31(m,2H),7.18–7.12(m,3H),5.87(s,1H),4.10–3.94(m,4H), 3.15(s,3H),2.24(s,3H),0.95(t,J=6.8Hz,3H),0.85(t,J=6.8Hz,3H);

[0106] 13 C NMR(CDCl3,101MHz)δ168.0,166.2,158.3,155.9,143.9,140.8,138.2,135.8,132.5,131.5,128.8,128.4,127.4,125.5,12 4.2,122.9,122.5,114.3,114.1,111.1,110.6(d,J=8.9Hz),109.8,109.6,68.4,62.9(d,J=11.6Hz),21.4,15.7,14.0,13.3; 19 F NMR(377MHz,DMSO)δ-124.15(s);

[0107] HRMS (TOF-ESI + )m / z:calcd for C 30 H 27 FN2O6SNa[M+Na] + 599.1623, found599.1633.

[0108] Example 8

[0109] A benzocarbazole derivative, the structural formula is:

[0110]

[0111] The synthesis route of the benzocarbazole derivatives of this embodiment is:

[0112]

[0113] The synthesis method of the benzocarbazole derivative of this embodiment is the same as that of embodiment 1, except that: in step (1), 5-benzyloxyindole 2c (26.8 mg, 0.12 mmol, 1.2 equivalents) is used to replace indole 2a to obtain 5'-benzyloxybenzocarbazole compound 3h with a yield of 52% (33.8 mg, 0.052 mmol).

[0114] The 3h NMR data of the benzocarbazole derivatives of this example are:

[0115] 1 H NMR(DMSO-d6,400MHz)δ10.40(s,1H),8.12(d,J=8.8Hz,1H),7.81(d,J=8.4Hz,1H),7.58(d ,J=8.0Hz,2H),7.47–7.41(m,4H),7.34(d,J=8.4Hz,2H),7.28–7.24(m,1H),7.14(t,J=8.0 Hz,4H),7.05(d,J=7.6Hz,1H),6.89(d,J=8.4Hz,1H),5.84(s,1H),5.38(s,2H),4.07–4.02 (m,3H),3.96–3.92(m,1H),3.21(s,3H),2.23(s,3H),0.94–0.93(m,3H),0.92–0.90(m,3H);

[0116] 13 C NMR(DMSO-d6,101MHz)δ167.0,166.7,154.4,144.4,144.0,140.2,137.1,136.2,132.3,131.0,129.5,128.9(d,J=12.6Hz),128.5(d,J=5.6H z),128.0,125.1(d,J=20.3Hz),122.9,122.6,111.8,110.7,104.1,103.5,70.7,68.0,62.8(d,J=16.1Hz),21.4(s),19.2,13.8(d,J=7.3Hz);

[0117] HRMS (TOF-ESI + )m / z:calcd for C 37 H 34 N2O7SNa[M+Na] + 687.2135, found 687.2148.

[0118] Example 9

[0119] A benzocarbazole derivative, the structural formula is:

[0120]

[0121] The synthesis route of the benzocarbazole derivatives of this embodiment is:

[0122]

[0123] The synthesis method of the benzocarbazole derivative of this embodiment is the same as that of embodiment 1, except that: in step (1), 5-chloroindole 2d (18.1 mg, 0.12 mmol, 1.2 equivalents) is used to replace indole 2a to obtain 5'-chlorobenzocarbazole compound 3i with a yield of 50% (29.6 mg, 0.050 mmol).

[0124] The nuclear magnetic resonance data of the benzocarbazole derivative 3i in this example are:

[0125] 1 H NMR(DMSO-d6,400MHz)δ10.61(s,1H),8.33–8.26(m,2H),7.86(d,J=8.8Hz,1H),7.59–7.52(m,2H),7.35–7.32(m,3H),7. 19–7.12(m,3H),5.89(s,1H),4.10–3.91(m,4H),3.16(s,3H),2.24(s,3H),0.96(t,J=7.2Hz,3H),0.81(t,J=7.2Hz,3H);

[0126] 13 C NMR(CDCl3,101MHz)δ168.0,166.1,144.0,140.3(d,J=9.4Hz),135.8,132.6,131.5,128.9,128.4,127.6,126.8,125.6, 124.7,124.4,124.2,123.7,123.3,123.0,122.7,111.2(d,J=9.2Hz),68.4,62.9(d,J=13.4Hz),21.4,15.8,14.0,13.3;

[0127] HRMS (TOF-ESI + )m / z:calcd for C 30 H 28 ClN2O6S[M+H] + 593.1508, found 593.1500.

[0128] Example 10

[0129] A benzocarbazole derivative, the structural formula is:

[0130]

[0131] The synthesis route of the benzocarbazole derivatives of this embodiment is:

[0132]

[0133] The synthesis method of the benzocarbazole derivative of this embodiment is the same as that of embodiment 1, except that in step (1), 5-bromoindole 2e (23.4 mg, 0.12 mmol, 1.2 equivalents) is used to replace indole 2a to obtain 5'-bromobenzocarbazole compound 3j with a yield of 55% (34.2 mg, 0.055 mmol).

[0134] The nuclear magnetic resonance data of the benzocarbazole derivative 3j in this example are:

[0135] 1 H NMR(CDCl3,400MHz)δ9.87(s,1H),8.30–8.21(m,3H),7.59–7.57(m,1H),7.45– 7.42(m,1H),7.38(d,J=8.4Hz,2H),7.26(s,1H),7.10(t,J=8.4Hz,1H),6.97(d ,J=8.4Hz,2H),5.46(s,1H),4.47–4.37(m,2H),4.00–3.92(m,1H),3.82–3.73( m,1H),3.20(s,3H),2.22(s,3H),1.37(t,J=7.2Hz,3H),0.84(t,J=7.2Hz,3H).

[0136] 13 C NMR(CDCl3,101MHz)δ168.0,165.9,144.0,140.6,139.2,135.7,132.7,131.9,129.1(d,J=8.9Hz),128.4,128.0,125 .8,124.8,124.5,124.1,123.7,123.0,122.4,120.2,111.5,103.7,68.1,62.9(d,J=14.7Hz),21.4,15.8,14.0,13.3;

[0137] HRMS (TOF-ESI + )m / z:calcd for C 30 H 27 BrN2O6SNa[M+Na] +659.0822, found 659.0833.

[0138] Embodiment 11

[0139] A benzocarbazole derivative, the structural formula is:

[0140]

[0141] The synthesis route of the benzocarbazole derivatives of this embodiment is:

[0142]

[0143] The synthesis method of the benzocarbazole derivative of this embodiment is the same as that of embodiment 1, except that: in step (1), 5-iodoindole 2f (29.2 mg, 0.12 mmol, 1.2 equivalents) is used to replace indole 2a to obtain 5'-iodobenzocarbazole compound 3k with a yield of 68% (45.6 mg, 0.068 mmol).

[0144] The 3k nuclear magnetic resonance data of the benzocarbazole derivatives of this example are:

[0145] 1 H NMR (DMSO-d6, 400MHz) δ10.59 (s, 1H), 8.60 (s, 1H), 8.26 (d, J = 8.8Hz, 1H), 7.88 (d, J=8.8Hz,1H),7.78(d,J=8.8Hz,1H),7.42(d,J=8.4Hz,1H),7.34(t,J=8.0Hz,3H),7 .18(d,J=8.4Hz,1H),7.13(d,J=8.0Hz,2H),5.89(s,1H),4.12–4.00(m,2H),3.95–3 .91(m,2H),3.15(s,3H),2.24(s,3H),0.96(t,J=7.2Hz,3H),0.81(t,J=6.8Hz,3H);

[0146] 13 C NMR(DMSO-d6,101MHz)δ166.7,166.4,144.4,141.4,139.9,136.1,135.6,132.8,131.9,129.5,128.6,127.4,12 5.8,125.6,124.7,123.4,123.0,113.4,111.2,82.4,67.8,62.7(d,J=19.1Hz),21.4,16.0,13.8(d,J=15.3Hz);

[0147] HRMS (TOF-ESI+ )m / z:calcd for C 30 H 27 IN2O6SK[M+K] + 723.0423, found 723.0430.

[0148] Example 12

[0149] A benzocarbazole derivative, the structural formula is:

[0150]

[0151] The synthesis route of the benzocarbazole derivatives of this embodiment is:

[0152]

[0153] The synthesis method of the benzocarbazole derivative of this embodiment is the same as that of Example 1, except that in step (1), 2 g of 5-methylindole (15.7 mg, 0.12 mmol, 1.2 equivalents) is used to replace indole 2a to obtain 5'-methylbenzocarbazole compound 31 with a yield of 75% (42.9 mg, 0.075 mmol).

[0154] The nuclear magnetic resonance data of the benzocarbazole derivative 31 in this example are:

[0155] 1 H NMR (CDCl3, 400MHz) δ9.71 (s, 1H), 8.20 (d, J = 8.0Hz, 1H), 8.10 (s, 1H), 7.98 (d ,J=8.0Hz,1H),7.41(d,J=8.4Hz,2H),7.32–7.24(m,4H),6.96(d,J=8.0Hz,2H) ,5.30(s,1H),4.45–4.36(m,2H),4.03–3.95(m,1H),3.85–3.77(m,1H),3.20( s,3H),2.55(s,3H),2.22(s,3H),1.36(t,J=7.2Hz,3H),0.87(t,J=7.2Hz,3H);

[0156] 13C NMR(CDCl3,101MHz)δ167.9,166.3,143.8,140.2(d,J=12.4Hz),136.0,131.9,131.1,128.8,128.4(d,J=9.3Hz),128.0,127.5 ,125.2,124.6,124.1,123.8(d,J=10.5Hz),122.8,122.2,110.9,110.1,68.6,62.8(d,J=8.2Hz),21.7,21.4,15.9,14.0,13.4;

[0157] HRMS (TOF-ESI + )m / z:calcd for C 31 H 30 N2O6SK[M+K] + 611.1613, found 611.1618.

[0158] Embodiment 13

[0159] A benzocarbazole derivative, the structural formula is:

[0160]

[0161] The synthesis route of the benzocarbazole derivatives of this embodiment is:

[0162]

[0163] The synthesis method of the benzocarbazole derivative of this embodiment is the same as that of embodiment 1, except that: in step (1), 5-methoxyindole 2h (17.6 mg, 0.12 mmol, 1.2 equivalents) is used to replace indole 2a to obtain 5'-methoxybenzocarbazole compound 3m with a yield of 80% (45.9 mg, 0.080 mmol).

[0164] The 3m NMR data of the benzocarbazole derivatives of this example are:

[0165] 1 H NMR(DMSO-d6,400MHz)δ10.17(s,1H),8.24(d,J=8.4Hz,1H),7.86–7.84(m,2H),7.44(d,J=8.8Hz,1H),7.36–7.28(m ,3H),7.18–7.12(m,4H),5.82(s,1H),4.07–3.93(m,4H),3.90(s,3H),3.17(s,3H),2.24(s,3H),0.94–0.89(m,6H);

[0166] 13 C NMR(CDCl3,101MHz)δ167.9,166.3,153.5,143.8,140.7,136.8,135.9,132.1,131.2,128.8,128.5,127.2,125.3 ,124.6,124.1,122.8,122.2,114.5,110.9,110.7,108.6,68.5,62.8(d,J=8.0Hz),56.4,21.4,15.8,14.0,13.4;

[0167] HRMS (TOF-ESI + )m / z:calcd for C 31 H 30 N2O7SNa[M+Na] + 611.1822, found 611.1835.

[0168] Embodiment 14

[0169] A benzocarbazole derivative, the structural formula is:

[0170]

[0171] The synthesis route of the benzocarbazole derivatives of this embodiment is:

[0172]

[0173] The synthesis method of the benzocarbazole derivative of this embodiment is the same as that of embodiment 1, except that in step (1), 5-phenylindole 2i (23.2 mg, 0.12 mmol, 1.2 equivalents) replaces indole 2a to obtain 5'-phenylbenzocarbazole compound 3n with a yield of 68% (42.2 mg, 0.068 mmol).

[0174] The 3n NMR data of the benzocarbazole derivatives of this example are:

[0175] 1H NMR(DMSO-d6,400MHz)δ10.50(s,1H),8.55(d,J=0.8Hz,1H),8.28(d,J=8.4Hz ,1H),7.88(d,J=8.4Hz,1H),7.83–7.80(m,3H),7.62(d,J=8.4Hz,1H),7.51(t, J=7.6Hz,2H),7.38–7.32(m,4H),7.19–7.14(m,3H),5.89(s,1H),4.10–3.96( m,4H),3.25(s,3H),2.25(s,3H),0.95(t,J=7.2Hz,3H),0.88(t,J=7.2Hz,3H);

[0176] 13 C NMR(CDCl3,101MHz)δ167.9,166.2,143.9,142.3,141.5,140.4,135.9,132.8,132.2,131.3,128.9,128.5,127.6,127.4,126.5 (d,J=9.4Hz),125.4,124.6,124.2,122.9,122.4(d,J=9.7Hz),111.1,110.6,68.5,62.9(d,J=11.6Hz),21.4,16.0,14.0,13.4;

[0177] HRMS (TOF-ESI + )m / z:calcd for C 36 H 32 N2O6SK[M+K] + 673.1769, found 673.1770.

[0178] Embodiment 15

[0179] A benzocarbazole derivative, the structural formula is:

[0180]

[0181] The synthesis route of the benzocarbazole derivatives of this embodiment is:

[0182]

[0183] The synthesis method of the benzocarbazole derivative of this example is the same as that of Example 1, except that in step (1), 5-OTBS indole 2j (29.6 mg, 0.12 mmol, 1.2 equivalents) replaces indole 2a to obtain 5'-OTBS benzocarbazole compound 3o with a yield of 72% (48.5 mg, 0.072 mmol).

[0184] The nuclear magnetic resonance data of the benzocarbazole derivative 3o in this example are:

[0185] 1 H NMR(DMSO-d6,400MHz)δ10.24(s,1H),8.23(d,J=8.4Hz,1H),7.81(d,J=8.8Hz,1 H),7.75(d,J=2.0Hz,1H),7.42(d,J=8.8Hz,1H),7.36–7.29(m,3H),7.14(t,J=8 .8Hz,3H),7.08–7.05(m,1H),5.83(s,1H),4.08–3.95(m,4H),3.12(s,3H),2.24 (s,3H),1.02(s,9H),0.95(t,J=7.2Hz,3H),0.91(t,J=7.2Hz,3H),0.26(s,6H);

[0186] 13 C NMR(DMSO-d6,101MHz)δ166.7(d,J=11.2Hz),148.6,144.3,140.7,137.2,136.2,132.1,131.6,129.5,128.5,127.0,125.2,1 24.6,124.2,123.7,123.1,122.6,120.3,114.5,111.3,110.9,67.9,62.7(d,J=15.5Hz),26.2,21.4,18.6,15.8,13.8,-3.9;

[0187] HRMS (TOF-ESI + )m / z:calcd for C 36 H 42 N2O7SSiK[M+K] + 727.2270, found 727.2274.

[0188] Example 16

[0189] A benzocarbazole derivative, the structural formula is:

[0190]

[0191] The synthesis route of the benzocarbazole derivatives of this embodiment is:

[0192]

[0193] The synthesis method of the benzocarbazole derivative of this embodiment comprises the following steps:

[0194] (1) 5'-OTBS benzocarbazole 3o (68.8 mg, 0.1 mmol, 1.0 equivalent) obtained in Example 15 was dissolved in tetrahydrofuran, filled with argon at 0°C and tetrabutylammonium fluoride (40.0 mg, 0.15 mmol, 1.5 equivalent) was added, the reactants were stirred for 2 hours, and the reaction was completed after monitoring by TLC. The mixture was diluted with brine (2.0 mL), extracted with ethyl acetate (2.0 mL×2), and the organic phase was collected;

[0195] (2) The combined organic layers were dried, concentrated and purified by flash silica gel chromatography using (petroleum ether:ethyl acetate 19:1 to 5:1) to give 5'-OH benzocarbazole derivative 3p in 86% yield (45.0 mg, 0.086 mmol).

[0196] The 3p NMR data of the benzocarbazole derivatives in this example are:

[0197] 1 H NMR (400MHz, CDCl3) δ9.67(s,1H),8.14(d,J=8.4Hz,1H),7.91(d,J=8.4Hz,1H),7.67(d,J=2.0 Hz,1H),7.43(d,J=8.0Hz,2H),7.30(t,J=7.2Hz,1H),7.24(d,J=8.8Hz,1H),7.13(d,J=8.4Hz, 1H),6.98–6.92(m,3H),5.32(s,1H),4.45–4.37(m,2H),4.03–3.99(m,1H),3.84–3.80(m,1H), 3.02(d,J=3.6Hz,3H),2.23(s,3H),2.05(s,1H),1.36(t,J=7.2Hz,3H),0.90(t,J=7.2Hz,3H);

[0198] 13 C NMR (101MHz, CDCl3) δ167.9,166.4,149.2,144.0,140.7,136.5,135.9,132.2,131.2,128.9,128.5,127.2,12 5.3,124.6,124.1,124.0,122.7,122.2,115.4,110.7,110.6,109.7,68.6,62.9,60.5,21.4,15.6,14.0,13.4;

[0199] HRMS (TOF-ESI + )m / z:calcd for C31 H 30 N2O7SH[M+H] + 575.1846, found 575.1854.

[0200] Examples 17 to 20 and Comparative Examples 1 to 10

[0201] The synthetic routes of Examples 17 to 20 and Comparative Examples 1 to 10 are:

[0202]

[0203] The difference between Examples 17 to 20 and Comparative Examples 1 to 10 and Example 1 is that the dual catalyst system is different or the organic solvent is different. The specific information of the dual catalyst system and the organic solvent is shown in Table 1. The yield of the obtained benzocarbazole derivative is shown in Table 1. It can be seen from Table 1 that the catalyst system and the organic solvent will affect the progress of the synthesis reaction and the yield of the benzocarbazole derivative.

[0204] Table 1 Catalyst systems, organic solvents and yield data of Examples 17 to 20 and Comparative Examples 1 to 10

[0205] Serial number LA [Au] / [Ag] solvent yield(%) Example 1 <![CDATA[Sc(OTf)3]]> <![CDATA[Ph3PAuNTf2]]> <![CDATA[CH2Cl2]]> 88 Embodiment 17 <![CDATA[Ni(OTf)2]]> <![CDATA[Ph3PAuNTf2]]> <![CDATA[CH2Cl2]]> 60 Embodiment 18 <![CDATA[Y(OTf)3]]> <![CDATA[Ph3PAuNTf2]]> <![CDATA[CH2Cl2]]> 54 Embodiment 19 <![CDATA[Yb(OTf)3]]> <![CDATA[Ph3PAuNTf2]]> <![CDATA[CH2Cl2]]> 41 Embodiment 20 <![CDATA[Sc(OTf)3]]> <![CDATA[Ph3PAuNTf2]]> MeCN 43 Comparative Example 1 <![CDATA[Cu(OTf)2]]> <![CDATA[Ph3PAuNTf2]]> <![CDATA[CH2Cl2]]> trace Comparative Example 2 <![CDATA[In(OTf)3]]> <![CDATA[Ph3PAuNTf2]]> <![CDATA[CH2Cl2]]> 23 Comparative Example 3 <![CDATA[Sc(OTf)3]]> <![CDATA[(ArO)3PAu(PhCN)SbF6 b ]]> <![CDATA[CH2Cl2]]> 39 Comparative Example 4 <![CDATA[Sc(OTf)3]]> <![CDATA[PPh3AuCl / AgSbF6]]> <![CDATA[CH2Cl2]]> 25 Comparative Example 5 <![CDATA[Sc(OTf)3]]> <![CDATA[JohnphosAuCl / AgSbF6]]> <![CDATA[CH2Cl2]]> 14 Comparative Example 6 <![CDATA[Sc(OTf)3]]> <![CDATA[IPrAuCl / AgSbF6]]> <![CDATA[CH2Cl2]]> trace Comparative Example 7 <![CDATA[Sc(OTf)3]]> <![CDATA[Ph3PAuNTf2]]> <![CDATA[CH2ClCH2Cl]]> 18 Comparative Example 8 <![CDATA[Sc(OTf)3]]> <![CDATA[Ph3PAuNTf2]]> THF 9 Comparative Example 9 <![CDATA[Sc(OTf)3]]> <![CDATA[Ph3PAuNTf2]]> Toluene 22 Comparative Example 10 <![CDATA[Sc(OTf)3]]> <![CDATA[Ph3PAuNTf2]]> MeOH nd

[0206] Application Examples

[0207] Figure 1 is the UV absorption spectra of benzocarbazole derivatives 3g, 3l, 3n, 3m, 3o and 3p, Figure 2 is the fluorescence emission spectrum of benzocarbazole derivatives 3g, 3l, 3n, 3m, 3o and 3p, and Table 1 is the spectrum data of benzocarbazole derivatives 3g, 3l, 3n, 3m, 3o and 3p. Figure 1 , Figure 2 From the data in Table 1, we can see that 3g, 3l, 3n, 3m, 3o and 3p have large absorption peaks at 404-418nm ultraviolet wavelengths, and the benzocarbazole derivatives have fluorescence signals at 447-471nm after ultraviolet excitation at the maximum absorption peak wavelength, among which compound 3l has strong fluorescence at 447nm, and the compound also has a certain Stokes shift (43nm) and a high fluorescence quantum yield (71%). The above results show that these benzocarbazole derivatives can be used in the field of fluorescent probes and fluorescent imaging.

[0208] Table 1 Spectral data of benzocarbazole derivatives 3g, 3l, 3n, 3m, 3o and 3p

[0209] Compound <![CDATA[λ abs (nm)]]> <![CDATA[λ em (nm)]]> <![CDATA[Φ F(x) (%)]]> <![CDATA[SS a (nm)]]> 3g 408 449 55 41 3l 404 447 71 43 3n 405 448 45 43 3m 415 466 36 51 3o 413 461 43 48 3p 418 471 32 53

[0210] The foregoing description of specific exemplary embodiments of the present invention is for the purpose of illustration and demonstration. These descriptions are not intended to limit the present invention to the precise form disclosed, and it is clear that many changes and variations can be made based on the above teachings. The purpose of selecting and describing the exemplary embodiments is to explain the specific principles of the present invention and its practical application, so that those skilled in the art can realize and utilize various different exemplary embodiments of the present invention and various different selections and changes. The scope of the present invention is intended to be limited by the claims and their equivalents.

Claims

1. A benzocarbazole derivative, characterized in that The structural formula of the benzocarbazole derivative is: Wherein, R1 and R2 are hydrogen atom, fluorine, chlorine, bromine, iodine, methyl, phenyl, alkoxy, benzyloxy or dimethyl-tert-butylsilyloxy.

2. A method for synthesizing the benzocarbazole derivative according to claim 1, characterized in that: The following steps are involved: (1) mixing a (2-ethynyl)aryl aziridine diester and a substituted indole in an organic solvent, adding a gold catalyst and a Lewis acid catalyst, stirring and reacting under a dual catalytic system, extracting after the reaction, and collecting an organic phase; (2) drying the organic phase obtained in step (1), concentrating under reduced pressure, and separating by silica gel column chromatography to obtain a benzocarbazole derivative; The synthetic route of the benzocarbazole derivatives is as follows:

3. The method for synthesizing a benzocarbazole derivative according to claim 2, characterized in that: The reaction temperature is 10-30° C., and the reaction time is 10-15 hours.

4. The method for synthesizing a benzocarbazole derivative according to claim 2, characterized in that: The organic solvent is dichloromethane or acetonitrile.

5. The method for synthesizing a benzocarbazole derivative according to claim 2, characterized in that: The dual catalytic system is PPh3AuNTf2 / Sc(OTf)3, PPh3AuNTf2 / Ni(OTf)3, PPh3AuNTf2 / Y(OTf)3 or PPh3AuNTf2 / Yb(OTf)3.

6. The method for synthesizing a benzocarbazole derivative according to claim 5, characterized in that: The dual catalytic system is PPh3AuNTf2 / Sc(OTf)3.

7. The method for synthesizing a benzocarbazole derivative according to claim 2, characterized in that: The molar ratio of the (2-ethynyl)aryl aziridine diester to the substituted indole is 1:1-1.5, the molar amount of the gold catalyst is 3-10% of the molar amount of the (2-ethynyl)aryl aziridine diester, and the molar amount of the Lewis acid catalyst is 5-12% of the molar amount of the (2-ethynyl)aryl aziridine diester.

8. The method for synthesizing a benzocarbazole derivative according to claim 2, characterized in that: The extraction is performed by using ethyl acetate; the eluents in the silica gel column chromatography are petroleum ether and ethyl acetate, and the volume ratio of petroleum ether to ethyl acetate is 19:1 to 5:

1.

9. Use of the benzocarbazole derivative as claimed in claim 1 in a fluorescent probe.

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