A nitrogen and oxygen condensed ring aromatic hydrocarbon and its synthesis method and application

Abstract

The present invention proposes a nitrogen and oxygen condensed aromatic hydrocarbon and a synthesis method and application thereof, in order to solve the technical problems such as the single synthesis method of existing condensed heterocyclic aromatic hydrocarbons, the complex synthesis of substrates and the limited product structure. The synthesis method of the present invention comprises the following steps: adding an oxazine compound 1, a diazo compound 2, a catalyst and an additive to a solvent under an inert atmosphere, reacting in an inert atmosphere, and obtaining a condensed aromatic hydrocarbon compound 3 after the reaction. The present invention provides a simple and effective synthesis method for the synthesis of condensed aromatic hydrocarbons containing multiple heteroatoms, and the method has the characteristics of mild reaction conditions, simple operation, atom economy, step economy, strong functional group tolerance and good yield. The obtained product has broad industrial application prospects, and at the same time provides a new idea and new method for the fields of medicine, natural product synthesis and luminescent materials.

Description

Technical Field

[0001] The invention belongs to the technical field of organic synthetic chemistry, and in particular relates to nitrogen and oxygen condensed ring aromatic hydrocarbons and a synthesis method and application thereof. Background Art

[0002] Polycyclic aromatic hydrocarbons refer to polycyclic aromatic hydrocarbon compounds composed of two or more aromatic hydrocarbons, which are widely used in the pharmaceutical, dye and other industries. The crystal arrangement of polycyclic aromatic hydrocarbons has π-π interactions, and the molecules form an orderly stacking. They have broad application prospects in organic optoelectronic devices (including organic field-effect transistors (OFET), organic solar cells (OSC) and organic light-emitting diodes (OLED), etc.), organic semiconductor materials, etc. (Chem. Rev., 2007, 107, 926; Chem. Soc. Rev., 2010, 39, 1489; Chem. Soc. Rev., 2012, 41, 4245; Nature, 2004, 428, 911). Compared with traditional inorganic optoelectronic materials, large-sized conjugated molecules have the advantages of molecular-level structural adjustment, good solubility, easy processing, light weight, flexibility, and large-area device preparation. Therefore, designing and synthesizing new organic polycyclic aromatic hydrocarbons, and studying their properties and applications, have always been one of the research hotspots for scientists in the fields of chemistry, materials, and biology. In particular, replacing some carbon atoms in polycyclic compounds with heteroatoms to form heteroatom-containing conjugated skeleton molecules, namely heteropolycyclic aromatic hydrocarbons, can significantly improve the stability and assembly performance of materials, thereby significantly improving the optoelectronic properties and multifunctionality of organic optoelectronic materials (Angew. Chem., Int. Ed., 2010, 49, 8209; Chem. Mater., 2015, 28, 3). At the same time, multifunctional modification of polycyclic aromatic hydrocarbons is also an important means to give organic optoelectronic molecules controllability and diversity.

[0003] Due to the advantages of high atom economy and step economy, the direct functionalization reaction of inert CH bonds has now become an undisputed ideal synthetic method pursued by chemists. It was once called the "holy grail of chemistry". In the past 20 years, transition metal-catalyzed CH activation reactions have indeed achieved very remarkable results, realizing many transformations that cannot be completed by traditional chemistry. Among them, the synthesis of polycyclic aromatic hydrocarbons constructed by 1:2 coupling directed by rhodium catalysis for CH bond activation has developed rapidly, and a large number of new polycyclic aromatic hydrocarbon skeletons with important application prospects in the fields of organic optoelectronic materials and drugs have been prepared. As an important intermediate in organic synthesis, the application of diazo compounds in the construction of polycyclic heterocyclic aromatic hydrocarbons by transition metal catalysis 1:2 coupling is still in its infancy. So far, there has been only one report on the construction of polycyclic aromatic hydrocarbon molecules by 1:2 coupling directed by rhodium catalysis for CH activation, and the research is relatively slow. The above method uses strongly coordinated pyridine compounds as directing groups, and achieves 1:2 coupling with diazo compounds under the action of rhodium catalyst, constructing a series of naphthoxyquinoline skeletons.

[0004] On the one hand, the directing group used in the existing synthesis method is pyridine with strong coordination ability, the substrate synthesis is complex, the product type is single, and the obtained skeleton is only nitrogen-containing condensed aromatic hydrocarbons. On the other hand, benzoxazine-type imines are key intermediates in organic synthesis, which are simple to synthesize and have a wide range of sources. There are no reports on the application of them as weak directing groups in rhodium-catalyzed carbene 1:2 coupling. According to existing literature reports, hetero-condensed aromatic hydrocarbons can significantly improve the stability and assembly performance of materials, thereby significantly improving the photoelectric properties and multifunctionality of organic optoelectronic materials (Angew. Chem., Int. Ed., 2010, 49, 8209; Chem. Mater., 2015, 28, 3). The application of hetero-condensed aromatic hydrocarbons in organic optoelectronic materials has broad prospects; therefore, it is urgent to find a new method for synthesizing hetero-condensed aromatic hydrocarbons. Summary of the invention

[0005] In view of the technical problems such as the single synthesis method of existing condensed heterocyclic aromatic hydrocarbons, complex substrate synthesis and product structure limitations, the present invention proposes a nitrogen and oxygen condensed heterocyclic aromatic hydrocarbon and a synthesis method and application thereof. The present invention provides a simple and effective synthesis method for the synthesis of condensed heterocyclic aromatic hydrocarbons containing multiple heteroatoms, and the method has the characteristics of mild reaction conditions, simple operation, atom economy, step economy, strong functional group tolerance and good yield.

[0006] In order to achieve the above object, the technical solution of the present invention is achieved as follows:

[0007] A nitrogen and oxygen condensed aromatic hydrocarbon, the structural formula is as follows:

[0008]

[0009] wherein R is any one of H, Me, OMe, F, Cl or Br; R 1 is any one of Me, n-Pr or Ph; R 2 n-Am or i Pr; Ar is a benzene ring substituted by any one of Me, OMe, F, Cl, Br, Ph or CF3.

[0010] The above-mentioned method for synthesizing nitrogen and oxygen hetero-condensed aromatic hydrocarbons comprises the following steps: adding an oxazine compound 1, a diazo compound 2, a catalyst, and an additive to a solvent under an inert atmosphere and reacting the oxazine compound 1, and obtaining a hetero-condensed aromatic hydrocarbon compound 3 after the reaction is completed. The reaction equation is:

[0011]

[0012] wherein R is any one of H, Me, OMe, F, Cl or Br; R 1 is any one of Me, n-Pr or Ph; R 2 n-Am or i Pr; Ar is a benzene ring substituted by any one of Me, OMe, F, Cl, Br, Ph or CF3; wherein Rh(III) is a catalyst.

[0013] After the reaction is completed, the resulting solution is separated and purified to obtain the hetero-condensed aromatic compound 3.

[0014] During the reaction, the reaction temperature is 80-120° C. and the reaction time is 6-12 hours.

[0015] The catalyst includes a rhodium catalyst and a silver salt; the molar ratio of the rhodium catalyst to the silver salt is 1:4; the rhodium catalyst is any one or a combination of dichloro(pentamethylcyclopentadienyl)rhodium dimer, pentamethylcyclopentadienyl rhodium acetate or di(hexafluoroantimonate)triacetonitrile(pentamethylcyclopentadienyl)rhodium; the silver salt is any one or a combination of silver hexafluoroantimonate, silver tetrafluoroborate, bistrifluoromethanesulfonyl silver imide, silver trifluoromethanesulfonate, silver sulfate, silver acetate, and silver trifluoroacetate.

[0016] The catalyst consists of dichloro(pentamethylcyclopentadienyl)rhodium dimer and silver hexafluoroantimonate; the molar ratio of dichloro(pentamethylcyclopentadienyl)rhodium dimer to silver hexafluoroantimonate is 1:4.

[0017] The additive is any one or a combination of 2,4,6-trimethylbenzoic acid, pivalic acid, acetic acid, 1-adamantanecarboxylic acid, zinc acetate, sodium carbonate, potassium acetate or potassium carbonate.

[0018] The solvent is any one or a combination of dichloroethane (DCE), methanol (MeOH), acetonitrile (MeCN), 1,4-dioxane or toluene.

[0019] The inert atmosphere is a nitrogen atmosphere, and may also be a gas atmosphere such as helium, neon, and argon.

[0020] The molar ratio of the oxazine compound 1, the diazo compound 2, the catalyst, the additive and the solvent is: 1:(2-3):(0.02-0.04):(0.08-0.16).

[0021] The concentration of the reaction system in the solvent is 0.05M-0.2M.

[0022] The application of nitrogen and oxygen condensed aromatic hydrocarbons as fluorescent probes for identifying exogenous HSO3 in living cells - .

[0023] The reaction mode of this reaction is as follows: Fig.31 As shown: first, the substrate 1a reacts with the catalyst to obtain a cyclometallated intermediate A, then the nitrogen-filled compound reacts with intermediate A to obtain intermediate B, followed by carbene migration and insertion of intermediate B to obtain intermediate C, and then metal removal occurs to obtain intermediate D, intermediate D undergoes the above process again to obtain a dialkylated intermediate E, intermediate E quickly interconverts to the enol form F, the hydroxyl group in intermediate F attacks the imine bond to obtain intermediate G, and the NH of intermediate G undergoes nucleophilic addition-elimination to the carbonyl group of another molecule to obtain intermediate I, and then intermediate I undergoes acidification-ring opening-ring closing-dehydration and other continuous transformations to give the target nitrogen, oxygen-containing condensed aromatic hydrocarbon 3aa.

[0024] Beneficial effects of the present invention: The present invention innovatively selects simple and easily available oxazine compounds and diazo compounds as reactants, and under the action of metal rhodium catalyst, uses imine in oxazine compounds as weak reactive directing group, and realizes the construction of new nitrogen and oxygen hetero-condensed aromatic hydrocarbon skeleton in one step through continuous [4+2] tandem strategy. The method is simple to operate, has significant atom economy and step economy, and provides a simple and effective method for the synthesis of hetero-condensed aromatic hydrocarbons. The reaction conditions of the method are mild, and the reaction temperature is only 80-120°C; in addition, the yield of the prepared nitrogen and oxygen hetero-condensed aromatic hydrocarbons is good, and the yield is generally above 80%, and the highest reaches 98%. The obtained product has broad industrial application prospects, and at the same time provides a new idea and new method for the fields of medicine, natural product synthesis and luminescent materials. BRIEF DESCRIPTION OF THE DRAWINGS

[0025] In order to more clearly illustrate the embodiments of the present invention or the technical solutions in the prior art, the drawings required for use in the embodiments or the description of the prior art will be briefly introduced below. Obviously, the drawings described below are only some embodiments of the present invention. For ordinary technicians in this field, other drawings can be obtained based on these drawings without paying creative work.

[0026] Figure 1 This is the NMR of compound 3aa 1 H spectrum; Figure 2 This is the NMR of compound 3aa 13 C spectrum.

[0027] Figure 3 This is the NMR of compound 3ba 1 H spectrum; Figure 4 This is the NMR of compound 3ba 13 C spectrum.

[0028] Figure 5 This is the NMR of compound 3ca 1 H spectrum; Figure 6 This is the NMR of compound 3ca 13 C spectrum.

[0029] Figure 7 The NMR of compound 3da 1 H spectrum; Figure 8 The NMR of compound 3da 13 C spectrum.

[0030] Fig. 9 This is the NMR of compound 3ea 1 H spectrum; Fig.10 This is the NMR of compound 3ea 13 C spectrum.

[0031] Fig.11 This is the NMR of compound 3fa 1 H spectrum; Fig.12 This is the NMR of compound 3fa 13 C spectrum.

[0032] Fig.13 This is the NMR of compound 3ga 1 H spectrum; Fig.14 This is the NMR of compound 3ga 13 C spectrum.

[0033] Fig.15 This is the NMR of compound 3ha 1 H spectrum; Fig.16 This is the NMR of compound 3ha 13 C spectrum.

[0034] Fig.17 This is the NMR of compound 3ia 1 H spectrum; Fig.18 This is the NMR of compound 3ia 13 C spectrum.

[0035] Fig.19 This is the NMR of compound 3ja 1 H spectrum; Fig. 20 This is the NMR of compound 3ja 13 C spectrum.

[0036] Fig.21 The NMR of the compound 3ka 1 H spectrum; Fig. 22 The NMR of the compound 3ka 13 C spectrum.

[0037] Fig.23 This is the NMR of compound 3ab 1 H spectrum; Fig.24 This is the NMR of compound 3ab 13 C spectrum.

[0038] Fig.25 This is the NMR of compound 3ac 1 H spectrum; Fig.26 This is the NMR of compound 3ac 13 C spectrum.

[0039] Fig. 27 This is the NMR of compound 3ad 1 H spectrum; Fig.28 This is the NMR of compound 3ad 13 C spectrum.

[0040] Fig.29 This is the NMR of compound 3ae 1 H spectrum; Fig.30 This is the NMR of compound 3ae 13 C spectrum.

[0041] Fig.31 It is the reaction mechanism diagram of the present invention.

[0042] Fig.32 are the UV-visible absorption spectra of the five compounds.

[0043] Fig.33 are the liquid fluorescence emission spectra of the five compounds.

[0044] Fig.34 are the solid-state fluorescence emission spectra of the five compounds.

[0045] Fig.35 This is a fluorescence photograph of compound 3fa in Paulownia root cells. DETAILED DESCRIPTION

[0046] The following will be combined with the drawings in the embodiments of the present invention to clearly and completely describe the technical solutions in the embodiments of the present invention. Obviously, the described embodiments are only part of the embodiments of the present invention, not all of the embodiments. Based on the embodiments of the present invention, all other embodiments obtained by ordinary technicians in this field without creative work are within the scope of protection of the present invention.

[0047] Example 1

[0048]

[0049] Under nitrogen conditions, 3-arylbenzoxazine compound 1a (0.20mmol), diazo compound 2a (0.44mmol), [Cp*RhCl2]2 (4mol%), AgSbF6 (16mol%), MesCOOH (0.4mmol) and solvent DCE (2.0mL) were added to a 10mL sealed tube and reacted in a reaction module at 80 degrees for 10h. After the reaction, the solvent was removed under reduced pressure and the target product 5,12-dimethylisoquinoline [2,1,8-mna] phenoxazine-4,13-dicarboxylic acid diethyl ester (3aa) was obtained by separation with a silica gel column. All eluents were prepared from petroleum ether, ethyl acetate and dichloromethane in a ratio of 30:1:1. Product data characterization: yellow-brown liquid, 78% yield. The NMR spectrum of the product is shown in Figure 1 and 2 As shown, 1 H NMR(400MHz, CDCl3) δ7.23(d,J=8.6Hz,1H),7.11(t,J=8.0Hz,1H),7.03–6.97(m,1H),6.94(t,J=7.6Hz,1H),6.89 (d,J=7.7Hz,1H),6.82(d,J=7.9Hz,1H),6.77(d,J=7.3Hz,1H),4.49–4.38(m,4H),2.33(s,6H),1.45–1.40(m,6H). 13 C NMR (101MHz, CDCl3) δ168.6,167.7,150.6,138.6,137.1,131.2,130.2,129.1,128.4,127.7,125.8,125.7 ,125.0,123.9,123.6,120.1,119.6,117.1,116.8,115.2,61.1,61.0,19.0,14.4,14.3,13.2.HRMS: [M+H] + calculated for C 26 H24 NO5 + :430.1649,found:430.1635.

[0050] Example 2

[0051]

[0052] Under nitrogen conditions, 3-arylbenzoxazine compound 1b (0.20mmol), diazo compound 2a (0.44mmol), [Cp*RhCl2]2 (4mol%), AgSbF6 (16mol%), MesCOOH (0.4mmol) and solvent DCE (2.0mL) were added to a 10mL sealed tube and reacted in a reaction module at 80 degrees for 10h. After the reaction, the solvent was removed under reduced pressure and the target product 7-bromo-5,12-dimethylisoquinoline [2,1,8-mna] phenoxazine-4,13-dicarboxylic acid diethyl ester (3ba) was obtained by separation with a silica gel column. All eluents were prepared from petroleum ether, ethyl acetate and dichloromethane in a ratio of 30:1:1. Product data characterization: yellow-brown solid, 98% yield, melting range: 119-120℃. The NMR spectrum of the product is as follows Figure 3 and 4 As shown, 1 H NMR (400MHz, CDCl3) δ7.26(t,J=8.3Hz,2H),7.14(t,J=8.0Hz,1H),6.86(t,J=8.0Hz,1H),6 .79(dd,J=7.5,4.6Hz,2H),4.49–4.39(m,4H),2.44(s,3H),2.33(s,3H),1.45–1.40(m,6H). 13 C NMR (101MHz, CDCl3) δ168.6,167.6,147.7,138.0,137.1,132.0,131.0,129.2,128.8,128.7,128.0,126.3 ,124.7,124.6,124.0,120.6,118.5,117.6,115.7,111.2,61.3,61.2,19.0,14.4,14.4,13.5.HRMS: [M+H] + calculated for C 26 H 23 BrNO5 + :508.0754,found:508.0717.

[0053] Example 3

[0054]

[0055] Under nitrogen conditions, 3-arylbenzoxazine compound 1c (0.20mmol), diazo compound 2a (0.44mmol), [Cp*RhCl2]2 (4mol%), AgSbF6 (16mol%), MesCOOH (0.4mmol) and solvent DCE (2.0mL) were added to a 10mL sealed tube and reacted in a reaction module at 80 degrees for 10h. After the reaction, the solvent was removed under reduced pressure and the target product 8-fluoro-5,12-dimethylisoquinoline [2,1,8-mna] phenoxazine-4,13-dicarboxylic acid diethyl ester (3ca) was obtained by separation with a silica gel column. All eluents were prepared from petroleum ether, ethyl acetate and dichloromethane in a ratio of 30:1:1. Product data characterization: yellow solid, 89% yield, melting range: 104-105℃. The NMR spectrum of the product is shown in Figure 5 and 6 As shown, 1 H NMR (400MHz, CDCl3) δ7.26(t,J=8.3Hz,2H),7.14(t,J=8.0Hz,1H),6.86(t,J=8.0Hz,1H),6 .79(dd,J=7.5,4.6Hz,2H),4.49–4.39(m,4H),2.44(s,3H),2.33(s,3H),1.45–1.40(m,6H). 13 C NMR (101MHz, CDCl3) δ168.6,167.6,147.7,138.0,137.1,132.0,131.0,129.2,128.8,128.7,128.0,126.3 ,124.7,124.6,124.0,120.6,118.5,117.6,115.7,111.2,61.3,61.2,19.0,14.4,14.4,13.5.HRMS: [M+Na] + calculated for C 26 H 22 FNnO5 + :470.1374,found:470.1371.

[0056] Example 4

[0057]

[0058] Under nitrogen conditions, 3-arylbenzoxazine compound 1d (0.20mmol), diazo compound 2a (0.44mmol), [Cp*RhCl2]2 (4mol%), AgSbF6 (16mol%), MesCOOH (0.4mmol) and solvent DCE (2.0mL) were added to a 10mL sealed tube and reacted in a reaction module at 80 degrees for 10h. After the reaction, the solvent was removed under reduced pressure and the target product 8-chloro-5,12-dimethylisoquinoline [2,1,8-mna] phenoxazine-4,13-dicarboxylic acid diethyl ester (3da) was obtained by separation with a silica gel column. All eluents were prepared from petroleum ether, ethyl acetate and dichloromethane in a ratio of 30:1:1. Product data characterization: yellow-brown solid, 82% yield, melting range: 127-128℃. The NMR spectrum of the product is as follows Figure 7 and 8 As shown, 1 H NMR (400MHz, CDCl3) δ7.21 (d, J = 8.6Hz, 1H), 7.15–7.06 (m, 1H), 6.98–6.89 (m, 2H), 6. 74(t,J=7.6Hz,2H),4.46–4.36(m,4H),2.30(s,3H),2.29(s,3H),1.43-1.38(m,6H). 13 C NMR (101MHz,CDCl3) 13 C NMR (101MHz, CDCl3) δ168.6,167.7,151.2,138.0,136.8,131.1,130.9,129.2,128.9,128.6,128.0,125.9 ,124.9,124.0,123.9,120.4,119.9,117.7,117.3,115.6,61.4,61.2,19.0,14.5,14.4,13.3.HRMS: [M+H] + calculated for C 26 H 23 ClNO5 + :464.1259,found:464.1244.

[0059] Example 5

[0060]

[0061] Under nitrogen conditions, 3-arylbenzoxazine compound 1e (0.20mmol), diazo compound 2a (0.44mmol), [Cp*RhCl2]2 (4mol%), AgSbF6 (16mol%), MesCOOH (0.4mmol) and solvent DCE (2.0mL) were added to a 10mL sealed tube and reacted in a reaction module at 80 degrees for 10h. After the reaction, the solvent was removed under reduced pressure and the target product 8-bromo-5,12-dimethylisoquinoline [2,1,8-mna] phenoxazine-4,13-dicarboxylic acid diethyl ester (3ea) was obtained by separation with a silica gel column. All eluents were prepared from petroleum ether, ethyl acetate and dichloromethane in a ratio of 30:1:1. Product data characterization: yellow solid, 89% yield, melting range: 144-145℃. The NMR spectrum of the product is shown in Fig. 9 and 10 As shown, 1 H NMR(400MHz, CDCl3)δ7.20(d,J=8.6Hz,1H),7.13–7.00(m,3H),6.74(d,J=7.2Hz,1H),6.64 (d,J=8.4Hz,1H),4.46–4.35(m,4H),2.28(s,3H),2.27(s,3H),1.40(td,J=7.1,5.2Hz,6H). 13 C NMR (101MHz, CDCl3) δ168.5,167.6,151.2,137.9,136.8,130.8,129.6,128.8,128.5,127.9,126.9,125.8 ,124.8,123.9,120.4,120.4,120.2,118.3,117.3,115.6,61.3,61.2,18.9,14.4,14.4,13.2.HRMS: [M+Na] + calculated for C 26 H 22 BrNNaO5 + =530.0574, found: 530.0564.

[0062] Example 6

[0063]

[0064] Under nitrogen conditions, 3-arylbenzoxazine compound 1f (0.20mmol), diazo compound 2a (0.44mmol), [Cp*RhCl2]2 (4mol%), AgSbF6 (16mol%), MesCOOH (0.4mmol) and solvent DCE (2.0mL) were added to a 10mL sealed tube and reacted in a reaction module at 80 degrees for 10h. After the reaction, the solvent was removed under reduced pressure and the target product 8-methyl-5,12-dimethylisoquinoline [2,1,8-mna] phenoxazine-4,13-dicarboxylic acid diethyl ester (3fa) was obtained by separation with a silica gel column. All eluents were prepared from petroleum ether, ethyl acetate and dichloromethane in a ratio of 30:1:1. Product data characterization: yellow solid, 77% yield, melting range: 100-101°C. The NMR spectrum of the product is shown in Fig.11 and 12 As shown, 1 H NMR(400MHz, CDCl3)δ7.18(d,J=8.6Hz,1H),7.08(t,J=8.0Hz,1H),6.78–6.68(m,4H), 4.48–4.34(m,4H),2.31(s,3H),2.31(s,3H),2.26(s,3H),1.40(td,J=7.1,3.7Hz,6H). 13 C NMR (101MHz, CDCl3) δ168.8,168.0,150.6,139.0,137.1,136.1,131.4,129.3,128.4,127.8,127.5,125.9,12 5.1,124.4,123.4,120.0,119.4,117.9,116.2,115.1,61.2,61.0,20.7,19.2,14.5,14.4,13.3.HRMS: [M+Na] + calculated for C 27 H 25 NNaO5 + =466.1625, found: 466.1617.

[0065] Example 7

[0066]

[0067] Under nitrogen conditions, 1g (0.20mmol) of 3-arylbenzoxazine compound, diazo compound 2a (0.44mmol), [Cp*RhCl2]2 (4mol%), AgSbF6 (16mol%), MesCOOH (0.4mmol) and solvent DCE (2.0mL) were added to a 10mL sealed tube and reacted in a reaction module at 80 degrees for 10h. After the reaction, the solvent was removed under reduced pressure and the target product 9-bromo-5,12-dimethylisoquinoline [2,1,8-mna] phenoxazine-4,13-dicarboxylic acid diethyl ester (3ga) was obtained by separation with a silica gel column. All eluents were prepared from petroleum ether, ethyl acetate and dichloromethane in a ratio of 30:1:1. Product data characterization: yellow solid, 91% yield, melting range: 132-133℃. The NMR spectrum of the product is shown in Fig.13 and 14 As shown, 1 H NMR(400MHz, CDCl3)δ7.21(d,J=8.6Hz,1H),7.13–7.08(m,2H),6.94(d,J=1.6Hz,1H) ,6.77–6.74(m,2H),4.45–4.37(m,4H),2.31(s,3H),2.30(s,3H),1.43–1.39(m,6H). 13 C NMR (101MHz, CDCl3) δ168.6,167.6,149.8,137.6,137.1,131.8,130.7,128.7,128.4,128.4,128.0,125.9 ,124.8,124.2,122.3,120.6,118.3,117.9,116.3,115.8,61.4,61.3,18.9,14.5,14.4,13.3.HRMS: [M+H] + calculated for C 26 H 23 BrNO5 + =508.0754, found: 508.0747.

[0068] Example 8

[0069]

[0070] Under nitrogen conditions, 3-arylbenzoxazine compound 1h (0.20mmol), diazo compound 2a (0.44mmol), [Cp*RhCl2]2 (4mol%), AgSbF6 (16mol%), MesCOOH (0.4mmol) and solvent DCE (2.0mL) were added to a 10mL sealed tube and reacted in a reaction module at 80 degrees for 10h. After the reaction, the solvent was removed under reduced pressure and the target product 9-methoxy-5,12-dimethylisoquinoline [2,1,8-mna] phenoxazine-4,13-dicarboxylic acid diethyl ester (3ha) was obtained by separation with a silica gel column. All eluents were prepared from petroleum ether, ethyl acetate and dichloromethane in a ratio of 30:1:1. Product data characterization: yellow solid, 53% yield, melting range: 162-163℃. The NMR spectrum of the product is as follows Fig.15 and 16 As shown, 1 H NMR (400MHz, CDCl3) δ7.20(d,J=8.3Hz,1H),7.14–7.04(m,1H),6.80(d,J=8.8Hz,1H),6.74(d,J=7.0Hz,1H),6.5 2(dd,J=8.8,2.6Hz,1H),6.39(d,J=2.7Hz,1H),4.46–4.36(m,4H),2.34(s,3H),2.31(s,3H),1.42–1.38(m,6H). 13 C NMR (101MHz, CDCl3) δ168.7,167.8,156.2,144.2,138.4,137.6,131.0,130.9,128.9,128.2,127.6,125. 9,125.0,123.7,120.3,117.0,115.3,109.4,106.6,61.2,61.1,55.9,19.2,14.4,14.4,13.3.HRMS: [M+H] + calculated for C 27 H 26 NO6 + =460.1755, found: 460.1753.

[0071] Example 9

[0072]

[0073] Under nitrogen conditions, 3-arylbenzoxazine compound 1i (0.20mmol), diazo compound 2a (0.44mmol), [Cp*RhCl2]2 (4mol%), AgSbF6 (16mol%), MesCOOH (0.4mmol) and solvent DCE (2.0mL) were added to a 10mL sealed tube and reacted in a reaction module at 80 degrees for 10h. After the reaction, the solvent was removed under reduced pressure and the target product 2-fluoro-5,12-dimethylisoquinoline [2,1,8-mna] phenoxazine-4,13-dicarboxylic acid diethyl ester (3ia) was obtained by separation with a silica gel column. All eluents were prepared from petroleum ether, ethyl acetate and dichloromethane in a ratio of 30:1:1. Product data characterization: yellow solid, 82% yield, melting range: 162-163℃. The NMR spectrum of the product is shown in Fig.17 and 18 As shown, 1 H NMR (400MHz, CDCl3) δ7.07–7.03(m,1H),7.00–6.96(m,1H),6.92(dd,J=7.9,1.5Hz,1H),6.88(dd,J=11.4,2.0Hz,1H),6. 85(dd,J=8.0,1.2Hz,1H),6.61(dd,J=10.2,2.0Hz,1H),4.46–4.37(m,4H),2.37(s,3H),2.32(s,3H),1.43–1.39(m,6H). 13 C NMR (101MHz, CDCl3) δ168.2, 167.1, 162.6 (d, J = 243.1Hz), 150.7, 140.8, 136.6, 131.9 (d, J = 11.2Hz), 131.3, 129.6, 129.5, 127.3, 126.2, 123. 9,122.8(d,J=5.4Hz),122.2,120.0,117.3,115.5,105.4(d,J=29.2Hz),103.8(d,J=24.6Hz),61.2,61.2,19.4,14.4,14.3,13.4.HRMS: [M+H] + calculated for C 26 H 23 FNO5 + =448.1555, found: 448.1539.

[0074] Example 10

[0075]

[0076] Under nitrogen conditions, 3-arylbenzoxazine compound 1j (0.20mmol), diazo compound 2a (0.44mmol), [Cp*RhCl2]2 (4mol%), AgSbF6 (16mol%), MesCOOH (0.4mmol) and solvent DCE (2.0mL) were added to a 10mL sealed tube and reacted in a reaction module at 80 degrees for 10h. After the reaction, the solvent was removed under reduced pressure and the target product 2-bromo-5,12-dimethylisoquinoline [2,1,8-mna] phenoxazine-4,13-dicarboxylic acid diethyl ester (3ja) was obtained by separation with a silica gel column. All eluents were prepared from petroleum ether, ethyl acetate and dichloromethane in a ratio of 30:1:1. Product data characterization: yellow solid, 87% yield, melting range: 142-143℃. The NMR spectrum of the product is shown in Fig.19 and 20 As shown, 1 H NMR (400MHz, CDCl3) δ7.39d, J=1.5Hz, 1H), 7.10–7.05 (m, 1H), 7.03–7.01 (m, 1H), 6.94 (dd, J=7.8 ,1.5Hz,1H),6.89–6.84(m,2H),4.49–4.39(m,4H),2.38(s,3H),2.34(s,3H),1.45–1.42(m,6H). 13 C NMR (101MHz, CDCl3) δ168.1,167.2,150.7,140.5,137.4,131.3,131.0,129.7,129.4,127.0,126.3,124. 2,123.6,122.8,122.1,120.0,118.4,117.4,115.4,77.2,61.4,61.3,19.4,14.4,14.4,13.4.HRMS: [M+H] + calculated for C 26 H 23 BrNO5 + =508.0754, found: 508.0742.

[0077] Embodiment 11

[0078]

[0079] Under nitrogen conditions, 3-arylbenzoxazine compound 1k (0.20mmol), diazo compound 2a (0.44mmol), [Cp*RhCl2]2 (4mol%), AgSbF6 (16mol%), MesCOOH (0.4mmol) and solvent DCE (2.0mL) were added to a 10mL sealed tube and reacted in a reaction module at 80 degrees for 10h. After the reaction, the solvent was removed under reduced pressure and the target product 2-methoxy-5,12-dimethylisoquinoline [2,1,8-mna] phenoxazine-4,13-dicarboxylic acid diethyl ester (3ka) was obtained by separation with a silica gel column. All eluents were prepared from petroleum ether, ethyl acetate and dichloromethane in a ratio of 30:1:1. Product data characterization: red solid, 77% yield, melting range: 172-173℃. The NMR spectrum of the product is shown in Fig.21 and 22 As shown, 1 H NMR(400MHz, CDCl3)δ7.52(s,1H),7.08(t,J=7.7Hz,1H),7.03–6.99(m,1H),6.95–6.93(m,2H),6.88–6.86( d,J=7.4Hz,1H),4.49(q,J=7.1Hz,1H),4.43(q,J=7.2Hz,1H),2.39(s,3H),2.36(s,3H),1.45–1.41(m,6H). 13 C NMR (101MHz, CDCl3) δ167.9,167.2,150.5,140.9,138.7,131.1,130.7,129.7(q,J=31.8Hz),129.5,127.3,126.3,126.2,124.7,124.3,124.2( q,J=272.7Hz),120.0,117.7(dd,J=9.2),117.7(d,J=4.7Hz),117.4,115.7,110.8(d,J=3.2Hz).61.5,61.3,19.5,14.3,14.3,13.3.HRMS: [M+H] + calculated for C 27 H 23 F3NO5 + =498.1523, found: 498.1508.

[0080] Example 12

[0081]

[0082] Under nitrogen conditions, 3-arylbenzoxazine compound 1a (0.20mmol), diazo compound 2b (0.44mmol), [Cp*RhCl2]2 (4mol%), AgSbF6 (16mol%), MesCOOH (0.4mmol) and solvent DCE (2.0mL) were added to a 10mL sealed tube and reacted in a reaction module at 80 degrees for 10h. After the reaction, the solvent was removed under reduced pressure and the target product 5,12-dimethylisoquinoline [2,1,8-mna] phenoxazine-4,13-dicarboxylic acid dipentyl ester (3ab) was obtained by separation with a silica gel column. All eluents were prepared from petroleum ether, ethyl acetate and dichloromethane in a ratio of 30:1:1. Product data characterization: yellow liquid, 96% yield. The NMR spectrum of the product is shown in Fig.23 and 24 As shown, 1 H NMR (400MHz, CDCl3) δ7.23–7.15(m,1H),7.09(t,J=7.9Hz,1H),7.03(t,J=7 .4Hz,1H),6.99–6.95(m,1H),6.91(dd,J=7.7,1.6Hz,1H),6.84(d,J=7.7Hz, 1H),6.79–6.67(m,1H),4.36(t,J=6.7Hz,3H),4.31(t,J=6.8Hz,3H),2.32(s ,3H),2.31(s,3H),1.80–1.73(m,4H),1.43–1.36(m,8H),0.95–0.90(m,6H). 13 C NMR (101MHz, CDCl3) δ168.9,168.0,150.7,138.6,137.2,131.3,130.3,129.2,128.4,127.8,125.9,125.8,125.1,124.0,12 3.7,120.2,119.7,117.2,116.9,115.3,65.4,65.3,28.5,28.4,28.3,28.3,22.4,22.4,19.1,14.1,14.1,13.3.HRMS: [M+H] + calculated for C 32 H 36 NO5 + =514.2588, found: 514.2577.

[0083] Example 13

[0084]

[0085] Under nitrogen conditions, 3-arylbenzoxazine compound 1a (0.20mmol), diazo compound 2c (0.44mmol), [Cp*RhCl2]2 (4mol%), AgSbF6 (16mol%), MesCOOH (0.4mmol) and solvent DCE (2.0mL) were added to a 10mL sealed tube and reacted in a reaction module at 80 degrees for 10h. After the reaction, the solvent was removed under reduced pressure and the target product 5,12-dimethylisoquinoline [2,1,8-mna] phenoxazine-4,13-dicarboxylic acid diisopropyl ester (3ac) was obtained by separation with a silica gel column. All eluents were prepared from petroleum ether, ethyl acetate and dichloromethane in a ratio of 30:1:1. Product data characterization: red liquid, 80% yield. The NMR spectrum of the product is shown in Fig.25 and 26 As shown, 1 H NMR (400MHz, CDCl3) δ7.24 (d, J = 23.1Hz, 1H), 7.16–7.07 (m, 1H), 7.02–6.89 (m, 3H), 6.8 4–6.80(m,1H),6.75–6.70(m,1H),5.39–5.28(m,2H),2.33(s,6H),1.44–1.36(m,12H). 13 C NMR(101MHz,CD Cl3)δ168.1,167.2,150.5,137.9,137.1,131.1,130.2,129.1,128.2,127.7,125.6,125.4 ,125.0,123.9,119.9,119.5,117.1,114.9,68.8,68.7,22.0,21.9,18.9,13.1.HRMS:[M+H] + calculated for C 28 H 28 NO5 + =458.1962, found: 458.1943.

[0086] Embodiment 14

[0087]

[0088] Under nitrogen conditions, 3-arylbenzoxazine compound 1a (0.20mmol), diazo compound 2d (0.44mmol), [Cp*RhCl2]2 (4mol%), AgSbF6 (16mol%), MesCOOH (0.4mmol) and solvent DCE (2.0mL) were added to a 10mL sealed tube and reacted in a reaction module at 80 degrees for 10h. After the reaction, the solvent was removed under reduced pressure and the target product 5,12-diethylisoquinoline [2,1,8-mna] phenoxazine-4,13-dicarboxylic acid dimethyl ester (3ad) was obtained by separation with a silica gel column. All eluents were prepared from petroleum ether, ethyl acetate and dichloromethane in a ratio of 30:1:1. Product data characterization: yellow liquid, 60% yield. The NMR spectrum of the product is shown in Fig. 27 and 28 As shown, 1 H NMR (400MHz, CDCl3) δ7.17(t,J=8.5Hz,1H),7.13–7.08(m,1H),7.07–7.03(m,1H),7.01–6.95(m,1H),6.94–6.88(m,2H),6.70(d,J=7.1Hz,1H ),3.94(s,3H),3.91(s,3H),2.81–2.74(m,2H),2.69(dd,J=8.7,6.8Hz,2H),1.71–1.52(m,4H),0.99(t,J=7.4Hz,3H),0.94(t,J=7.3Hz,3H). 13 C NMR (101MHz, CDCl3) δ169.3,168.5,150.7,142.8,137.4,132.2,131.6,130.9,129.0,128.5,127.8,125.7,124. 9,124.1,123.1,120.8,119.3,118.2,117.3,115.6,52.2,52.2,32.4,30.2,23.9,22.8,14.5,13.9.HRMS: [M+H] + calculated for C 28 H 28 NO5 + =458.1962, found: 458.1949.

[0089] Embodiment 15

[0090]

[0091] Under nitrogen conditions, 3-arylbenzoxazine compound 1a (0.20mmol), diazo compound 2e (0.44mmol), [Cp*RhCl2]2 (4mol%), AgSbF6 (16mol%), MesCOOH (0.4mmol) and solvent DCE (2.0mL) were added to a 10mL sealed tube and reacted in a reaction module at 80 degrees for 10h. After the reaction, the solvent was removed under reduced pressure and the target product 5,12-dipropylisoquinoline [2,1,8-mna] phenoxazine-4,13-dicarboxylic acid dimethyl ester (3ae) was obtained by separation with a silica gel column. All eluents were prepared from petroleum ether, ethyl acetate and dichloromethane in a ratio of 30:1:1. Product data characterization: yellow liquid, 63% yield. The NMR spectrum of the product is shown in Fig.29 and 30 As shown, 1 H NMR(400MHz, CDCl3)δ7.19(dd,J=8.6,0.7Hz,1H),7.13–7.09(m,1H),7.07–7.03(m,1H),7 .00–6.96(m,1H),6.93(dd,J=7.8,1.5Hz,0H),6.90(dd,J=7.9,1.4Hz,1H),6.70(dd,J=7.2 ,0.7Hz,1H),3.94(s,3H),3.91(s,3H),2.82–2.79(m,2H),2.76–2.65(m,2H),1.65–1.51( m,4H),1.48–1.39(m,2H),1.37–1.32(m,2H),0.96(t,J=7.3Hz,3H),0.85(t,J=7.3Hz,3H). 13 C NMR (101MHz, CDCl3) δ169.3,168.5,150.7,143.1,137.4,132.2,131.6,131.2,129.1,128.5,127.7,125.7,124.8,124 .1,123.0,120.7,119.3,118.1,117.2,115.5,52.2,52.1,32.7,31.5,30.1,27.9,23.0,22.4,14.1,13.8.HRMS: [M+H] + calculated for C 30 H 32 NO5 + =486.2275, found: 486.2266.

[0092] The spectral properties of the five compounds 3aa, 3ja, 3ia, 3fa and 3ea synthesized in the examples were studied, and their structures are shown in the following formula: The UV-visible absorption spectrum and fluorescence emission spectrum in liquid state and the fluorescence emission spectrum in solid state were tested. First, the UV-visible spectrum was measured in dichloromethane solution ( Fig.32 ), the solution concentration is 10-5mmol / mL. The five compounds all have a certain absorption of light at 250-600nm, the maximum absorption wavelength appears at 410nm, and the molar absorption coefficient is 4.0×10 5 L·mol -1 cm -1 -1.2×10 6 L·mol -1 cm -1 In addition, the fluorescence emission spectra of the above five compounds were also tested in solution. The maximum emission wavelength of compound 3ea appeared at 505nm, while compounds 3aa, 3ia and 3fa showed a certain degree of red shift under the same conditions ( Fig.33 ), all five compounds showed good fluorescence optical properties, and the peaks of the spectra were symmetrical and the fluorescence properties were stable, so they can be used as fluorescent probes. The solid-state fluorescence emission spectra of the above five compounds were also tested ( Fig.34 ), it is not difficult to see that in the solid state, the emission spectra of the five compounds have undergone different degrees of red shift, indicating that 3aa, 3ja, 3ia, 3fa and 3ea have good photostability and potential value for application in biological systems. In summary, the developed nitrogen and oxygen condensed ring aromatics and their derivatives have excellent nonlinear optical properties due to the presence of a large conjugated system in their molecules. Good biological activity and thermal stability make them have good application value in the fields of biological imaging, fluorescent probes and optoelectronic functional materials, laying a solid theoretical and practical foundation for the development and application research of new nonlinear optical materials.

[0093] Subsequently, compound 3fa was used to track exogenous HSO3 in living cells. - and hexachlorocyclohexane. For biological applications, the probe should minimize the effect on the normal function of living cells. During the 3-day co-culture of compound 3fa and Paulownia root cells, the cells grew well and no cell death or decreased activity was found. Therefore, compound 3fa can be used for cell imaging in plant cell systems. The above studies show that compound 3fa has a strong effect on HSO3 in the solution system. - The recognition ability was outstanding and the specificity was reversible enough when HCH was added. We then tried to confirm the recognition ability of HSO3 in living cells. -The recognition performance and reversibility of hexachlorocyclohexane. Fig.35 As shown in A, there is no fluorescence background in normal Paulownia root cells. After being treated with 10 μM 3fa solution and incubated at room temperature for 2 hours, the root cells showed strong near-infrared fluorescence ( Fig.35 B). This indicates that 3fa can effectively enter root cells and produce good bioimaging. To reveal its location accumulation in the cells, the cells were stained with Mito Tracker Green, a commercially available mitochondrial indicator. Due to the positive charge of 3fa, it also localizes to the same location as Mito Tracker Green ( Fig.35 C). The merged image of the green and red channels showed good overlap between the red and green fluorescence signals. Therefore, these results confirmed its ability to accurately localize to mitochondria. However, after adding 2.0 equivalents of NaHSO3 solution (20 μM), the near-infrared fluorescence disappeared rapidly, indicating that HSO3 - Destroys the π-conjugated system of 3fa ( Fig.35 D). After incubation with 100 μM HCH for 30 min, near-infrared fluorescence ( Fig.35 E). Similarly, after adding hexachlorocyclohexane and irradiating with ultraviolet light (365 nm) for 2 minutes, the fluorescence can be fully and quickly restored ( Fig.35 F).

[0094] The above description is only a preferred embodiment of the present invention and is not intended to limit the present invention. Any modifications, equivalent substitutions, improvements, etc. made within the spirit and principle of the present invention should be included in the protection scope of the present invention.

Claims

1. A nitrogen-oxygen condensed aromatic hydrocarbon, characterized in that: The structural formula is as follows: wherein R is any one of H, Me, OMe, F, Cl or Br; R 1 is any one of Me, n-Pr or Ph; R 2 for n -Am or i Pr; Ar is a benzene ring substituted by any one of Me, OMe, F, Cl, Br, Ph or CF3.

2. The method for synthesizing nitrogen and oxygen condensed aromatic hydrocarbons according to claim 1, characterized in that: The following steps are involved: Under an inert atmosphere, an oxazine compound 1, a diazo compound 2, a catalyst, and an additive are added to a solvent and reacted. After the reaction, a hetero-condensed aromatic compound 3 is obtained. The reaction equation is: wherein R is any one of H, Me, OMe, F, Cl or Br; R 1 is any one of Me, n-Pr or Ph; R 2 for n -Am or i Pr; Ar is a benzene ring substituted by any one of Me, OMe, F, Cl, Br, Ph or CF3; During the reaction, the reaction temperature is 80-120°C and the reaction time is 6-12 h; The catalyst consists of a rhodium catalyst and a silver salt; The rhodium catalyst is any one of dichloro(pentamethylcyclopentadienyl)rhodium dimer, pentamethylcyclopentadienyl rhodium acetate or di(hexafluoroantimonate)triacetonitrile(pentamethylcyclopentadienyl)rhodium; the silver salt is any one of silver hexafluoroantimonate, silver tetrafluoroborate, silver bistrifluoromethanesulfonyl imide, silver trifluoromethanesulfonate, silver sulfate, silver acetate, and silver trifluoroacetate; The additive is any one or a combination of 2,4,6-trimethylbenzoic acid, pivalic acid, acetic acid, 1-adamantanecarboxylic acid, zinc acetate, sodium carbonate, potassium acetate or potassium carbonate.

3. The method for synthesizing nitrogen and oxygen condensed aromatic hydrocarbons according to claim 2, characterized in that: The molar ratio of the rhodium catalyst to the silver salt is 1:

4.

4. The method for synthesizing nitrogen and oxygen condensed aromatic hydrocarbons according to claim 3, characterized in that: The catalyst consists of dichloro(pentamethylcyclopentadienyl)rhodium dimer and silver hexafluoroantimonate; the molar ratio of dichloro(pentamethylcyclopentadienyl)rhodium dimer to silver hexafluoroantimonate is 1:

4.

5. The method for synthesizing nitrogen and oxygen condensed aromatic hydrocarbons according to claim 4, characterized in that: The solvent is any one or a combination of ethylene dichloride, methanol, acetonitrile, 1,4-dioxane or toluene.

6. The method for synthesizing nitrogen and oxygen condensed aromatic hydrocarbons according to any one of claim 5, characterized in that: The inert atmosphere is a nitrogen atmosphere.

7. The method for synthesizing nitrogen and oxygen condensed aromatic hydrocarbons according to claim 6, characterized in that: The molar ratio of the oxazine compound 1, the diazo compound 2, the catalyst, the additive and the solvent is: 1:(2-3):(0.02-0.04):(0.08-0.16); the concentration of the reaction system in the solvent is 0.05 M-0.2 M.

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