Alpha-hydrazino-substituted aza-boron dipyrrole compound as well as preparation method and application thereof

Abstract

The invention relates to the technical field of organic synthesis and the technical field of fine chemical engineering, in particular to an alpha-hydrazino-substituted aza-boron dipyrrole compound and a preparation method thereof. The alpha-hydrazino-substituted aza-boron dipyrrole compound is as shown in a formula (I) which is described in the specification. Wherein R1 is selected from one of aryl, heterocyclic aryl and alkyl, and R2 is selected from halogen atoms or oxygen-containing groups. According to the alpha-hydrazino-substituted aza-boron dipyrrole compound, active hydrazino is introduced into the alpha-site of aza-boron dipyrrole for the first time, efficient chemical modification and metal coordination sites can be provided, and the alpha-hydrazino-substituted aza-boron dipyrrole compound has wide application prospects in the fields of chemical sensing, biomarkers, photo-thermal therapy and the like. Meanwhile, the alpha-hydrazino-substituted aza-boron dipyrrole compound disclosed by the invention is synthesized by an efficient'one-pot method ', and the preparation method has the advantages of easily available raw materials, simple steps and good functional group tolerance, is suitable for industrial large-scale production, and has a wide application prospect.

Description

Technical Field

[0001] This invention relates to the fields of organic synthesis technology and fine chemical technology, specifically to an α-hydrazine-substituted nitrogen boron dipyrrole compound, its preparation method, and its application. Background Technology

[0002] Benzoboron dipyrroles, as an important class of functional dyes, have attracted widespread research interest in organic optoelectronic materials and biomedicine due to their stable π-conjugated framework, excellent near-infrared absorption properties, and good photostability. Among these, the synthesis methods of benzoboron dipyrroles typically rely on multi-step reactions of starting materials such as phthalonitriles or isoindole, for example, the route developed by Lukyanets and Shen et al. (…). Tetrahedron Lett. 2008, 49 , 6152; Angew. Chem. Int. Ed. 2015, 54 Their functionalization strategies mainly focus on halogenation, arylation, and other modifications to the α-aryl ring of the pyrrole ring. However, these methods have obvious limitations: First, the synthetic routes are usually lengthy, involving multiple steps and intermediate separation, resulting in low overall yields; second, and more importantly, it is difficult to introduce functional groups with high reactivity or strong coordination ability at key sites of the molecule, thus limiting their further development and application as targeted probe precursors or functional chelating ligands.

[0003]

[0004] The hydrazine group, as an important chemical functional group, is an ideal site for constructing bioconjugated molecules and chemical probes due to its unique nucleophilicity, reducing properties, and specific condensation ability with carbonyl compounds. Simultaneously, the hydrazine group is also an excellent metal ion ligand, which can be used to design metal ion sensors. However, due to the high reactivity of the hydrazine group, its direct and efficient introduction into the potentially acid-, base-, and oxygen-sensitive azirone dipyrrole conjugated framework has always presented a significant synthetic challenge. Existing synthetic methods cannot achieve this goal, resulting in the lack of reports on azirone dipyrrole dyes possessing both near-infrared properties and active hydrazine functional groups.

[0005] Therefore, developing a novel synthetic method with readily available raw materials, simple steps, and good functional group tolerance for the efficient construction of novel benzozaborine dipyrrole derivatives would not only fill the structural gap in this class of functional dyes, but also provide a crucial material basis for the development of novel targeted biomarker tools, highly selective chemical sensing platforms, and photothermal therapeutic agents. Summary of the Invention

[0006] To address the shortcomings of existing technologies, this invention provides a novel α-hydrazyl-substituted azaboron dipyrrole compound. This compound, for the first time, introduces an active hydrazine group into the α-position of azaboron dipyrrole, providing a highly efficient chemical modification and metal coordination site, and holds broad application prospects in fields such as chemical sensing, biolabeling, and photothermal therapy. Furthermore, the α-hydrazyl-substituted azaboron dipyrrole compound of this invention is synthesized via a highly efficient one-pot method. This preparation method utilizes readily available raw materials, involves simple steps, exhibits good functional group tolerance, and is suitable for large-scale industrial production, thus possessing broad application potential.

[0007] To achieve the above objectives, in a first aspect, the present invention provides an α-hydrazyl-substituted azaboron dipyrrole compound, said α-hydrazyl-substituted azaboron dipyrrole compound as shown in formula (I);

[0008] R1 is selected from aryl, heterocyclic aryl, and alkyl groups, and R2 is selected from halogen atoms or oxygen-containing groups.

[0009] Preferably, R1 is selected from one of monocyclic aryl, fused-ring aryl, haloaryl, or alkyl-substituted aryl, and R2 is selected from one of C1-C16 alkoxy, siloxy, F, and Cl.

[0010] Preferably, R1 is selected from one of phenyl, 4-bromophenyl, 4-trifluoromethylphenyl, 1-naphthyl, tert-butyl, 1,1-diphenyl, 2-pyridyl, 6-chloropyridyl and 6-bromopyridyl, and R2 is selected from one of methoxy, trimethylsiloxy, n-butoxy, ethoxy and F.

[0011] Secondly, the present invention provides a method for preparing an α-hydrazine-substituted azaboron dipyrrole compound, the method comprising: 1) In the presence of a solvent and a Lewis acid, 1-amino-1H-isoindole-3-imine of formula A is condensed with a hydrazine derivative of formula B to obtain an intermediate; 2) Add borate ester and / or boron trifluoride complexing agent as shown in formula C to the reaction system of step 1) to carry out a coordination reaction to obtain α-hydrazine-substituted azaborine dipyrrole compound; ; Wherein, R1 is selected from one of aryl, heterocyclic aryl and alkyl, and R2 is selected from halogen atoms or oxygen-containing groups.

[0012] Preferably, R1 is selected from one of monocyclic aryl, fused-ring aryl, haloaryl, or alkyl-substituted aryl, and R2 is selected from one of C1-C16 alkoxy, siloxy, F, and Cl.

[0013] Preferably, R1 is selected from one of phenyl, 4-bromophenyl, 4-trifluoromethylphenyl, 1-naphthyl, tert-butyl, 1,1-diphenyl, 2-pyridyl, 6-chloropyridyl and 6-bromopyridyl, and R2 is selected from one of methoxy, trimethylsiloxy, n-butoxy, ethoxy and F.

[0014] Preferably, in step 1), the solvent is selected from one or more of chlorobenzene, o-dichlorobenzene and toluene.

[0015] Preferably, in step 1), the Lewis acid is selected from one or more of acetic acid, p-toluenesulfonic acid, hydrochloric acid, nitric acid, and sulfuric acid.

[0016] Preferably, in step 1), the molar ratio of 1-amino-1H-isoindole-3-imine represented by Formula A, the hydrazine derivative represented by Formula B, and the Lewis acid is 1:1~1.1:0.01~0.3.

[0017] Preferably, in step 1), the conditions for the condensation reaction include: a temperature of 100~200℃ and a time of 0.5~20h.

[0018] Preferably, in step 2), the borate ester is selected from one or more of trimethyl borate, tri-n-butyl borate, and tris(trimethylsilyl)borate.

[0019] Preferably, in step 2), the molar ratio of 1-amino-1H-isoindole-3-imine represented by formula A to the borate ester or boron trifluoride ether represented by formula C is 1:5~30.

[0020] Preferably, in step 2), the conditions for the coordination reaction include: a temperature of 100~220℃ and a time of 12~48h.

[0021] Thirdly, the present invention provides an α-hydrazine-substituted azaborine dipyrrole compound prepared by the preparation method described herein.

[0022] Fourthly, the present invention provides the application of the α-hydrazine-substituted azaborine dipyrrole compound described herein in the preparation of highly selective chemical sensing products, photosensitizers, and photothermal reagents.

[0023] In the above technical solution, the present invention successfully introduces a highly reactive hydrazine group into the α-position of aziboron dipyrrole for the first time, breaking through the limitation of existing aziboron dipyrrole compounds that can only undergo simple modifications such as halogenation and arylation, and filling the structural gap of this type of functional dye.

[0024] Meanwhile, the method for preparing α-hydrazine-substituted azaborine dipyrrole compounds of the present invention is a highly efficient "one-pot" synthetic strategy. Starting from commercially available raw materials, it directly constructs complex molecules through continuous condensation-coordination reactions, avoiding cumbersome intermediate separation. It has high reaction efficiency, good substrate universality, and high yield (32%-59%), which is superior to traditional multi-step routes.

[0025] Furthermore, the α-hydrazine-substituted azaboron dipyrrole compounds of the present invention fundamentally alter the molecular properties and application potential due to the introduction of the hydrazine group, for example, for the development of highly selective metal ions (such as Cu). 2+ Hg 2+ Fluorescence / colorimetric sensors offer a novel platform molecule. These compounds have a maximum absorption wavelength of up to 615 nm, and although their fluorescence emission is weak, they are well-suited for absorption-based photothermal therapy or photoacoustic imaging.

[0026] Other features and advantages of the present invention will be described in detail in the following detailed description section. Attached Figure Description

[0027] The accompanying drawings are provided to further illustrate the invention and form part of the specification. They are used together with the following detailed description to explain the invention, but do not constitute a limitation thereof. In the drawings: Figure 1 This describes the synthetic route for the α-hydrazine-substituted azaboron dipyrrole compounds of the present invention.

[0028] Figure 2 Front and side views of the crystal structure of phenylhydrazine-modified azatrimethoxyboron dipyrrole 1b.

[0029] Figure 3 The crystal structure of bromophenylhydrazine-modified nitrogen-butoxyboron dipyrrole 1d is shown in front and side views.

[0030] Figure 4 Front and side views of the crystal structure of 1 g of tert-butylhydrazine-modified nitrogen-containing fluoroboron dipyrrole.

[0031] Figure 5 The front and side views of the crystal structure of chloropyridinium hydrazine modified nitrogen boron dipyrrole 1i. Detailed Implementation

[0032] The following provides a detailed description of specific embodiments of the present invention. It should be understood that the specific embodiments described herein are for illustrative and explanatory purposes only and are not intended to limit the scope of the invention.

[0033] The endpoints and any values ​​of the ranges disclosed herein are not limited to the precise ranges or values, and these ranges or values ​​should be understood to include values ​​close to these ranges or values. For numerical ranges, the endpoint values ​​of the various ranges, the endpoint values ​​of the various ranges and individual point values, and individual point values ​​can be combined with each other to obtain one or more new numerical ranges, which should be considered as specifically disclosed herein.

[0034] In a first aspect, the present invention provides an α-hydrazyl-substituted azaboron dipyrrole compound, the α-hydrazyl-substituted azaboron dipyrrole compound being as shown in formula (I);

[0035] R1 is selected from aryl, heterocyclic aryl, and alkyl groups, and R2 is selected from halogen atoms or oxygen-containing groups.

[0036] This invention is the first to successfully introduce a highly reactive hydrazine group into the α-position of aziboron dipyrrole, breaking through the limitation of existing aziboron dipyrrole compounds that can only undergo simple modifications such as halogenation and arylation, and filling the structural gap of this type of functional dye.

[0037] In a preferred embodiment of the present invention, R1 is selected from one of monocyclic aryl, fused-ring aryl, haloaryl, or alkyl-substituted aryl, and R2 is selected from one of C1-C16 alkoxy, siloxy, F, and Cl.

[0038] In a preferred embodiment of the present invention, R1 is selected from one of phenyl, 4-bromophenyl, 4-trifluoromethylphenyl, 1-naphthyl, tert-butyl, 1,1-diphenyl, 2-pyridyl, 6-chloropyridyl and 6-bromopyridyl, and R2 is selected from one of methoxy, trimethylsiloxy, n-butoxy, ethoxy and F.

[0039] Secondly, the present invention provides a method for preparing an α-hydrazine-substituted azaboron dipyrrole compound, the method comprising: 1) In the presence of a solvent and a Lewis acid, 1-amino-1H-isoindole-3-imine of formula A is condensed with a hydrazine derivative of formula B to obtain an intermediate; 2) Add borate ester and / or boron trifluoride complexing agent as shown in formula C to the reaction system of step 1) to carry out a coordination reaction to obtain α-hydrazine-substituted azaborine dipyrrole compound; ; Wherein, R1 is selected from one of aryl, heterocyclic aryl and alkyl, and R2 is selected from halogen atoms or oxygen-containing groups.

[0040] The method for preparing α-hydrazine-substituted azaborine dipyrrole compounds of the present invention is a highly efficient "one-pot" synthetic strategy. Starting from commercially available raw materials, it directly constructs complex molecules through continuous condensation-coordination reactions, avoiding cumbersome intermediate separation. It has high reaction efficiency, good substrate universality, and high yield (32%-59%), which is superior to traditional multi-step routes.

[0041] In a preferred embodiment of the present invention, R1 is selected from one of monocyclic aryl, fused-ring aryl, haloaryl, or alkyl-substituted aryl, and R2 is selected from one of C1-C16 alkoxy, siloxy, F, and Cl.

[0042] In a preferred embodiment of the present invention, R1 is selected from one of phenyl, 4-bromophenyl, 4-trifluoromethylphenyl, 1-naphthyl, tert-butyl, 1,1-diphenyl, 2-pyridyl, 6-chloropyridyl and 6-bromopyridyl, and R2 is selected from one of methoxy, trimethylsiloxy, n-butoxy, ethoxy and F.

[0043] In a preferred embodiment of the present invention, in step 1), the solvent is selected from one or more of chlorobenzene, o-dichlorobenzene and toluene.

[0044] In a preferred embodiment of the present invention, in step 1), the Lewis acid is selected from one or more of acetic acid, p-toluenesulfonic acid, hydrochloric acid, nitric acid, and sulfuric acid.

[0045] In a preferred embodiment of the present invention, in step 1), the molar ratio of 1-amino-1H-isoindole-3-imine represented by Formula A, the hydrazine derivative represented by Formula B, and the Lewis acid is 1:1 to 1.1:0.01 to 0.3, for example, it can be 1:1:0.01, 1:1:0.05, 1:1:0.10, 1:1:0.20, 1:1:0.30, 1:1.1:0.01, 1:1.1:0.05, 1:1.1:0.20, or 1:1.1:0.30.

[0046] In a preferred embodiment of the present invention, in step 1), the conditions for the condensation reaction include: a temperature of 100~200℃ and a time of 0.5~20h, for example, 200℃, 0.5h, 190℃, 1h, 100℃, 10h, 110℃, 15h, 120℃, 20h, 130℃, 5h, and 170℃, 12h.

[0047] In a preferred embodiment of the present invention, in step 2), the borate ester is selected from one or more of trimethyl borate, tri-n-butyl borate and tris(trimethylsilyl)borate.

[0048] In a preferred embodiment of the present invention, in step 2), the molar ratio of 1-amino-1H-isoindole-3-imine represented by Formula A to the borate ester represented by Formula C is 1:5 to 30, for example, it can be 1:5, 1:10, 1:15, 1:20, 1:25 or 1:30.

[0049] In a preferred embodiment of the present invention, in step 2), the conditions for the coordination reaction include: a temperature of 100~220℃ and a time of 12~48h, for example, 100℃, 12h, 110℃, 15h, 120℃, 13h, 130℃, 15h, 150℃, 20h, 150℃, 24h, or 200℃, 48h.

[0050] In a preferred embodiment of the present invention, the preparation method further includes separation and purification, wherein the separation is a conventional method in the art, and the purification is performed by silica gel column chromatography to purify the crude product.

[0051] In a preferred embodiment of the present invention, the developing solvent used in the silica gel column chromatography is a conventional developing solvent formulation in the art. For example, it can be obtained by mixing petroleum ether and dichloromethane in a volume ratio of 2:1, or by mixing hexane and ethyl acetate in a volume ratio of 9:1, or by mixing n-hexane and dichloromethane in a volume ratio of 1:1.

[0052] Thirdly, the present invention provides an α-hydrazine-substituted azaborine dipyrrole compound prepared by the preparation method described herein.

[0053] Fourthly, the present invention provides the application of the α-hydrazine-substituted azaborine dipyrrole compound described herein in highly selective chemical sensing products, photosensitizers, and photothermal reagents.

[0054] The α-hydrazine-substituted azaboron dipyrrole compounds of this invention fundamentally alter the molecular properties and application potential due to the introduction of the hydrazine group, for example, for the development of highly selective metal ions (such as Cu). 2+ Hg 2+ Fluorescence / colorimetric sensors offer a novel platform molecule. These compounds have a maximum absorption wavelength of up to 615 nm, and although their fluorescence emission is weak, they are well-suited for absorption-based photothermal therapy or photoacoustic imaging.

[0055] According to a preferred embodiment of the present invention, the room temperature is 25-35°C.

[0056] The present invention will be described in detail below through examples. In the following examples, the pharmaceuticals and agents are all conventional commercially available products.

[0057] Example 1 This example illustrates the synthesis of α-hydrazine-substituted azaboron dipyrrole compound 1a:

[0058] Using 1-amino-1H-isoindole-3-imine (290 mg, 2 mmol) and phenylhydrazine hydrochloride (334 mg, 2.2 mmol) as starting materials, glacial acetic acid (0.1 mL) was added to the reaction mixture in a high-pressure flask with chlorobenzene (20 mL) as solvent. The reaction mixture was refluxed in a metal bath at 140 °C for 0.5 h, and the reaction was monitored by thin-layer chromatography (TLC). After the 1-amino-1H-isoindole-3-imine reaction on the TLC plate disappeared, the corresponding trimethyl borate (0.45 mL, 4 mmol) was added. The reaction mixture was placed in a sealed high-pressure flask and stirred overnight at 150 °C. The residue was extracted with dichloromethane (50 mL) and water (100 mL). The corresponding aqueous phase was further extracted twice with dichloromethane (30 mL each time). The organic layers were combined, washed with water, dried on anhydrous Na₂SO₄, filtered, and evaporated to dryness under vacuum. The crude product was purified by silica gel column chromatography and recrystallized from dichloromethane and n-hexane to give 1a295 mg of black powder solid, with a yield of 28%.

[0059] The NMR and high-resolution mass spectrometry data of the recrystallization from dichloromethane and n-hexane are as follows: 1 H NMR (400 MHz, CDCl3) δ 11.63 (s, 2H), 8.63 (s, 2H), 8.14 (d, J = 7.8Hz, 2H), 7.74 (t, J = 7.5 Hz, 2H), 7.62 (t, J = 7.5 Hz, 2H), 7.52 – 7.40 (m, 8H), 7.07 (t, J = 7.1 Hz, 2H), 2.80 (s, 6H). 13 C NMR (126 MHz, CDCl3) δ 144.1, 137.4,132.5, 132.1, 129.5, 128.3, 123.4, 122.2, 120.6, 114.0, 49.5. 11 B NMR (128 MHz, CDCl3) δ 2.20. HRMS (ESI) Calcd. for C 30 H 27 BN7O2[M + H] +528.2319, found 528.2302. Example 2 This example illustrates the synthesis of α-hydrazine-substituted azaboron dipyrrole compound 1b:

[0060] The procedure was carried out according to Example 1, except that an equivalent amount of trimethyl borate was replaced with tris(trimethylsilane)borate (1.36 mL, 4 mmol), yielding 1b424 mg, with a yield of 33%.

[0061] The NMR and high-resolution mass spectrometry data of the recrystallization from dichloromethane and n-hexane are as follows: 1 H NMR (500 MHz, CDCl3) δ 11.14 (s, 2H), 8.37 (d, J = 7.9 Hz, 2H), 8.14(d, J = 7.6 Hz, 2H), 7.72 (t, J = 7.5 Hz, 2H), 7.60 (t, J = 7.4 Hz, 2H), 7.47 –7.43 (m, 8H), 7.108 – 7.05 (m, 1H), -0.42 (s, 9H). 13 C NMR (126 MHz, CDCl3) δ159.3, 143.9, 137.8, 132.9, 132.4, 130.3, 129.8, 128.8, 128.5, 126.6, 123.6,122.2, 120.8, 113.8, 0.42. 11 B NMR (128 MHz, CDCl3) δ 1.73. HRMS (ESI) Calcd.for C 34 H 39 BN7O2Si2[M + H] + 644.2797, found 644.2805. Example 3 This example illustrates the synthesis of α-hydrazine-substituted azaboron dipyrrole compound 1c:

[0062] The procedure was carried out according to Example 1, except that an equivalent amount of trimethyl borate was replaced with tributyl borate (1.1 mL, 4 mmol), yielding 1 c513 mg, with a yield of 42%.

[0063] The NMR and high-resolution mass spectrometry data of the recrystallization from dichloromethane and n-hexane are as follows: 1 H NMR (400 MHz, CDCl3) δ 11.68 (s, 2H), 8.27 (d, J = 7.7 Hz, 2H), 8.16– 8.13 (m, 2H), 7.71 (t, J = 7.5 Hz, 2H), 7.58 (t, J = 7.5 Hz, 2H), 7.48 – 7.44(m, 8H), 7.06 – 7.03 (m, 2H), 2.86 – 2.81 (m, 4H), 1.24 – 1.21 (m, 4H), 1.12– 1.08 (m, 4H), 0.60 – 0.55 (m, 6H). 13 C NMR (101 MHz, CDCl3) δ 161.3, 144.1,137.4, 132.5, 132.1, 130.4, 129.5, 128.1, 123.0, 121.8, 120.6, 113.7, 61.5,33.2, 18.9, 13.5. 11 B NMR (128 MHz, CDCl3) δ 1.74. HRMS (ESI) Calcd. forC 36 H 39 BN7O2[M + H] + 612.3258, found 612.3234. Example 4 This example illustrates the synthesis of α-hydrazine-substituted azaboron dipyrrole compound 1d:

[0064] The procedure was carried out according to Example 3, except that an equivalent amount of phenylhydrazine hydrochloride was replaced with 4-bromophenylhydrazine hydrochloride (494 mg, 2.2 mmol) to obtain 1d552 mg, with a yield of 36%.

[0065] The NMR and high-resolution mass spectrometry data of the recrystallization from dichloromethane and n-hexane are as follows: 1 H NMR (400 MHz, CDCl3) δ 11.66 (s, 2H), 8.28 (t, J= 6.5 Hz, 2H), 8.11(d, J = 7.8 Hz, 2H), 7.74 – 7.70 (m, 2H), 7.62 – 7.58 (m, 2H), 7.54 – 7.50 (m,4H), 7.30 (d, J = 8.8 Hz, 4H), 2.82 (t, J = 6.3 Hz, 4H), 1.24 – 1.17 (m, 4H), 1.13 – 1.04 (m, 4H), 0.58 (t, J = 7.3 Hz, 6H). 13 C NMR (126 MHz, CDCl3) δ 143.12,137.20, 133.04, 132.45, 132.41, 130.40, 128.45, 123.24, 123.19, 120.68,115.13, 113.96, 61.44, 33.12, 18.94, 13.45. 11 B NMR (128 MHz, CDCl3) δ 1.53.HRMS (ESI) Calcd. for C 36 H 37 BBr2N7O2[M + H] + 768.1649, found 768.1697. Example 5 This example illustrates the synthesis of α-hydrazine-substituted azaboron dipyrrole compound 1e:

[0066] The procedure was carried out according to Example 3, except that an equivalent amount of phenylhydrazine hydrochloride was replaced with 4-trifluoromethylphenylhydrazine hydrochloride (470 mg, 2.2 mmol) to obtain 1e597 mg, with a yield of 40%.

[0067] The NMR and high-resolution mass spectrometry data of the recrystallization from dichloromethane and n-hexane are as follows: 1 H NMR (500 MHz, CDCl3) δ 11.80 (s, 2H), 8.25 (d, J = 7.7 Hz, 2H), 8.14(d, J = 7.7 Hz, 2H), 7.76 – 7.73 (m, 2H), 7.68 (d, J= 8.4 Hz, 4H), 7.62 (t, J =7.4 Hz, 2H), 7.48 (d, J = 8.4 Hz, 4H), 2.86 (t, J = 6.4 Hz, 4H), 1.26 – 1.20 (m,4H), 1.14 – 1.07 (m, 4H), 0.58 (t, J = 7.4 Hz, 6H). 13 C NMR (126 MHz, CDCl3) δ163.0, 146.8, 137.4, 134.1, 132.9, 131.0, 129.0, 128.0, 127.1 ( J F-C = 3.8 Hz), 125.9, 124.8 ( J F-C = 272.2 Hz), 123.4, 123.4 ( J F-C = 31.5 Hz), 121.1, 113.3,61.7, 33.3, 19.1, 13.6. 11 B NMR (160 MHz, CDCl3) δ 1.61. HRMS (ESI) Calcd. forC 38 H 37 BF6N7O2[M + H] + 748.3006 was found; 748.3007 was also found. Example 6 This example illustrates the synthesis of α-hydrazine-substituted azaboron dipyrrole compound 1f:

[0068] The procedure was carried out according to Example 3, except that an equivalent amount of phenylhydrazine hydrochloride was replaced with naphthalenehydrazine hydrochloride (305 mg, 2.1 mmol) to obtain 1f583 mg, with a yield of 41%.

[0069] The NMR and high-resolution mass spectrometry data of the recrystallization from dichloromethane and n-hexane are as follows: 1 H NMR (400 MHz, CDCl3) δ 12.03 (s, 2H), 8.59 (s, 2H), 8.24 (d, J = 7.6Hz, 2H), 7.96 (d, J= 8.7 Hz, 2H), 7.92 – 7.82 (m, 6H), 7.81 – 7.71 (m, 4H),7.64 (t, J = 7.5 Hz, 2H), 7.53 (t, J = 7.5 Hz, 2H), 7.40 (t, J = 7.4 Hz, 2H), 2.90(t, J = 6.2 Hz, 4H), 1.25 (q, J = 6.6 Hz, 4H), 1.17 – 1.07 (m, 4H), 0.54 (t, J =7.2 Hz, 6H). 13 C NMR (126 MHz, CDCl3) δ 141.6, 137.2, 136.6, 134.6, 132.6,130.2, 129.7, 128.5, 128.0, 127.1, 126.9, 124.0, 123.9, 120.7, 115.5, 109.1,61.6, 33.1, 19.0, 13.4. 11 B NMR (128 MHz, CDCl3) 1.74. HRMS (ESI) Calcd. forC 44 H 43 BN7O2[M + H] + 712.3571, found 712.3587. Example 7 This example illustrates the synthesis of 1 g of an α-hydrazine-substituted azaboron dipyrrole compound:

[0070] Using 1-amino-1H-isoindole-3-imine (290 mg, 2 mmol) and tert-butylhydrazine hydrochloride (275 mg, 2.2 mmol) as starting materials, the reaction mixture was refluxed in a metal bath at 200 °C for 0.5 h in a high-pressure flask with chlorobenzene (20 mL) as solvent, and the reaction was monitored by thin-layer chromatography. After the 1-amino-1H-isoindole-3-imine reaction on the thin-layer plate disappeared, boron trifluoride diethyl ether (2.5 mL, 20.25 mmol) was used as a starting material, and the reaction mixture was placed in a sealed high-pressure flask in the presence of triethylamine and stirred overnight at 220 °C. The residue was extracted with dichloromethane (50 mL) and water (100 mL). The corresponding aqueous phase was further extracted twice with dichloromethane (30 mL each time). The organic layers were combined, washed with water, dried on anhydrous Na₂SO₄, filtered, and evaporated to dryness under vacuum. The crude product was purified by silica gel column chromatography and recrystallized from dichloromethane and n-hexane to give 1 g of red powder solid (454 mg), with a yield of 49%.

[0071] The NMR and high-resolution mass spectrometry data of the recrystallization from dichloromethane and n-hexane are as follows: 1 H NMR (400 MHz, CDCl3) δ 8.22 (t, J = 6.8 Hz, 2H), 7.95 (d, J = 7.8 Hz, 2H), 7.82 (t, J = 9.8 Hz, 2H), 7.64 (t, J = 7.5 Hz, 2H), 7.50 (t, J = 7.5 Hz, 2H), 1.44 (s, 18H). 13 C NMR (101 MHz, CDCl3) δ 160.1, 160.0, 137.7, 132.4, 130.0,129.4, 127.6, 123.2, 123.1, 120.0, 55.5, 28.6. 11 B NMR (128 MHz, CDCl3) δ 1.09(t, J = 36.5 Hz). 19 F NMR (377 MHz, CDCl3) δ -115.87 (dd, J = 50.9, 23.3 Hz). HRMS(ESI) Calcd. for C 24 H 29 BN7F2[M + H]+ 464.2546, found 464.2536. Example 8 This example illustrates the synthesis of α-hydrazine-substituted azaboron dipyrrole compound 1h:

[0072] The procedure was carried out according to Example 7, except that an equivalent amount of tert-butylhydrazine hydrochloride was replaced with 1,1-diphenylhydrazine hydrochloride (486 mg, 2.2 mmol) to obtain 1h651 mg, with a yield of 48%.

[0073] The NMR and high-resolution mass spectrometry data of the recrystallization from dichloromethane and n-hexane are as follows: 1 H NMR (400 MHz, CDCl3) δ 8.37 (d, J = 7.8 Hz, 2H), 8.24 (d, J = 6.0 Hz, 2H), 7.82 (d, J = 7.1 Hz, 4H), 7.73 – 7.66 (m, 4H), 7.52 – 7.45 (m, 6H), 7.41 –7.33 (m, 10H). 13 C NMR (101 MHz, CDCl3) δ 167.4, 163.8, 138.2, 134.4, 133.6,132.4, 131.5, 131.2, 130.4, 130.1, 129.8, 129.7, 129.7, 129.2, 128.9, 128.6,128.3, 128.3, 127.6, 126.4, 124.0. 11 B NMR (128 MHz, CDCl3) δ 1.15 – 0.46 (m). 19 F NMR (376 MHz, CDCl3) δ -128.32 (dd, J = 59.6, 30.2 Hz), -138.98. HRMS (ESI)Calcd. for C 42 H 29 BN7F2[M + H] + 680.2546, found 680.2555. Example 9 This example illustrates the synthesis of α-hydrazine-substituted azaboron dipyrrole compound 1i:

[0074] Using 1-amino-1H-isoindole-3-imine (290 mg, 2 mmol) and chloropyridinium hydrazine (286 mg, 2 mmol) as starting materials, glacial acetic acid (0.1 mL) was added to a high-pressure flask with chlorobenzene (20 mL) as solvent. The reaction mixture was refluxed in a metal bath at 200 °C for 0.5 h, and the corresponding tributyl borate (1.1 mL, 4 mmol) was added. The mixture was stirred at 200 °C for 6 h. Spot monitoring was performed. The residue was extracted with dichloromethane (50 mL) and water (100 mL). The corresponding aqueous phase was further extracted twice with dichloromethane (30 mL each time). The organic layers were combined, dried over anhydrous Na₂SO₄, filtered, and concentrated by rotary evaporation to remove the organic solvent. The crude product was purified by silica gel column chromatography to obtain product 11430 mg, with a yield of 59%.

[0075] The NMR and high-resolution mass spectrometry data of the recrystallization from dichloromethane and n-hexane are as follows: 1 H NMR (400 MHz, CDCl3) δ 12.09 (s, 2H), 8.25 – 8.17 (m, 4H), 7.74 (t, J = 7.5 Hz, 2H), 7.65 – 7.61 (m, 4H), 7.35 (d, J = 8.1 Hz, 2H), 6.92 (d, J = 7.5Hz, 2H), 2.88 (t, J = 6.1 Hz, 4H), 1.29 – 1.22 (m, 8H), 0.59 (t, J = 7.1 Hz, 6H). 13 C NMR (126 MHz, CDCl3) δ 163.5, 155.7, 150.3, 140.1, 137.3, 134.9, 132.8,131.1, 129.1, 123.3, 121.4, 116.6, 106.6, 61.6, 33.0, 18.9, 13.5. 11 B NMR (128MHz, CDCl3) δ 1.57. HRMS (ESI) Calcd. for C 34 H 35 BCl2N9O2[M + H] + : 682.2384, found 682.2362. Example 10 This example illustrates the synthesis of α-hydrazine-substituted azaboron dipyrrole compound 1j:

[0076] Using 1-amino-1H-isoindole-3-imine (290 mg, 2 mmol) and bromopyridinium hydrazine (382 mg, 2 mmol) as starting materials, glacial acetic acid (0.1 mL) was added to a high-pressure flask with chlorobenzene (20 mL) as solvent. The reaction mixture was refluxed in a metal bath at 200 °C for 0.5 h, and the corresponding tributyl borate (1.1 mL, 4 mmol) was added. The mixture was stirred at 200 °C for 6 h. Spot monitoring was performed. The residue was extracted with dichloromethane (50 mL) and water (100 mL). The corresponding aqueous phase was further extracted twice with dichloromethane (30 mL each time). The organic layers were combined, dried over anhydrous Na₂SO₄, filtered, and concentrated by rotary evaporation to remove the organic solvent. The crude product was purified by silica gel column chromatography to obtain product 1417 mg, with a yield of 58%.

[0077] The NMR and high-resolution mass spectrometry data of the recrystallization from dichloromethane and n-hexane are as follows: 1 H NMR (400 MHz, CDCl3) δ 12.11 (s, 2H), 8.23 ​​(d, J = 7.7 Hz, 2H), 8.17(d, J = 7.7 Hz, 2H), 7.74 (t, J = 7.3 Hz, 2H), 7.62 (t, J = 7.4 Hz, 2H), 7.53 (t, J =7.8 Hz, 2H), 7.38 (d, J = 8.1 Hz, 2H), 7.07 (d, J = 7.5 Hz, 2H), 2.87 (t, J = 6.0Hz, 4H), 1.25 – 1.14 (m, 8H), 0.60 (t, J = 7.0 Hz, 6H). 13 C NMR (126 MHz, CDCl3)δ 163.7, 155.9, 140.9, 140.0, 137.4, 135.1, 133.0, 131.3, 129.2, 123.4,121.5, 120.6, 107.0, 61.8, 33.1, 19.1, 13.7.11 B NMR (128 MHz, CDCl3) δ 1.87.HRMS (ESI) Calcd. for C 34 H 35 BBr2N9NaO2[M + Na] + : 794.1255, found 794.1216. Comparative Example 1 The method of Example 1 was followed, except that "reacting under reflux in a metal bath at 140°C for 0.5 h" was changed to "reacting under reflux in a metal bath at 80°C for 24 h".

[0078] The results showed that a large amount of raw material remained after 24 hours of reaction, and the reaction could not be completed, resulting in a yield of less than 5% for the final target product 1a. This indicates that the temperature of the condensation reaction, limited to 130-200°C as specified in this invention, is crucial for the formation of the α-hydrazine-substituted azaborine dipyrrole compounds of this invention.

[0079] Comparative Example 2 The method described in Example 5 was followed, except that "tributyl borate" was replaced with "phenylboronic acid" for the coordination reaction.

[0080] The target product 1e was not obtained; only the uncomplexed ligand intermediate was recovered. This indicates that the use of specific borate esters or boron trifluoride ethers is key to achieving the boron complexation of this invention.

[0081] Detection Example 1 The α-hydrazine-substituted azaboron dipyrrole compounds obtained in Examples 1-10 were characterized by X-ray single-crystal diffraction, and some results are shown below. Figure 2-5 As shown.

[0082] Figure 2 The molecular structure of compound 1b was shown. X-ray single-crystal diffraction analysis clearly confirmed that the hydrazine group was successfully bonded to the α-carbon atom at the pyrrole position of the nitrogen-boron dipyrrole framework, forming a unique molecular structure. The entire molecule exhibits high planarity, and the BN coordination bond lengths are within the normal range, demonstrating the stability of its structure.

[0083] Figure 3-5 The molecular structures of compounds 1d, 1g, and 1i are shown, collectively demonstrating that the synthetic method of this invention has good universality for different substituents (bromophenyl, fluorine atom, chloropyridyl), and can efficiently and specifically obtain the target product. These crystal structures provide direct and strong evidence for the general formula structure of this invention.

[0084] Detection Example 2 The photophysical properties of the α-hydrazyl-substituted azaboron dipyrrole compounds 1a-1e prepared in Examples 1-5 were tested in different organic solvents, such as the maximum absorption wavelength (λ). abs max / nm), molar absorptivity (lgε) max ), maximum emission wavelength (λ) em max / nm) and Stokes shift / cm -1 The results are shown in Table 1.

[0085] Table 1

[0086] As shown in Table 1, the α-hydrazine-substituted azaboron dipyrrole compounds (1a-1e) prepared in this invention exhibit strong absorption characteristics in various organic solvents, with the maximum absorption wavelength mainly distributed in the range of 559-615 nm, and the molar absorptivity is generally high, greater than 4.3, indicating their excellent light-harvesting ability. Simultaneously, these compounds show a very large Stokes shift (Stokes shift > 11000 cm⁻¹). -1 This helps reduce self-absorption interference. Notably, their fluorescence quantum yield (Φ) is generally low (<0.03), indicating that the main advantage of this series of compounds lies in their strong absorption properties and active functional groups, rather than their fluorescence emission performance, thus guiding their application towards fields such as photothermal therapy, chemisensing, and bioconjugation.

[0087] As demonstrated by the above embodiments and performance data, the "one-pot" synthesis strategy provided by this invention can efficiently and conveniently prepare a series of novel hydrazine-modified azirone dipyrrole compounds. The yield of this method is significantly higher than that of traditional multi-step routes, and it exhibits excellent substrate versatility. This invention is the first to introduce a hydrazine group structure into the azirone dipyrrole framework, utilizing the strong coordinating and reducing properties of the hydrazine group to endow these dyes with specific metal ions (such as Cu). 2+ Hg 2+ The high selectivity of these dyes, along with their potential as biomarker reaction sites, are features not found in traditional azirone dipyrrole dyes. These hydrazine-modified dyes exhibit weak near-infrared emission, making them particularly suitable for biotherapy and possessing irreplaceable value in photodynamic therapy and bioconjugated chemistry.

[0088] The preferred embodiments of the present invention have been described in detail above. However, the present invention is not limited to the specific details in the above embodiments. Within the scope of the technical concept of the present invention, various simple modifications can be made to the technical solution of the present invention, and these simple modifications all fall within the protection scope of the present invention.

[0089] It should also be noted that the various specific technical features described in the above specific embodiments can be combined in any suitable manner without contradiction. In order to avoid unnecessary repetition, the present invention will not describe the various possible combinations separately.

[0090] Furthermore, various different embodiments of the present invention can be combined in any way, as long as they do not violate the spirit of the present invention, they should also be regarded as the content disclosed by the present invention.

Claims

1. An α-hydrazyl-substituted azaboron dipyrrole compound, characterized in that, The α-hydrazine-substituted azaboron dipyrrole compound is shown in formula (I); R1 is selected from aryl, heterocyclic aryl, and alkyl groups, and R2 is selected from halogen atoms or oxygen-containing groups.

2. The α-hydrazine-substituted azaboron dipyrrole compound according to claim 1, characterized in that, R1 is selected from one of monocyclic aryl, fused aryl, haloaryl, or alkyl-substituted aryl, and R2 is selected from one of C1-C16 alkoxy, siloxy, F, and Cl. Preferably, R1 is selected from one of phenyl, 4-bromophenyl, 4-trifluoromethylphenyl, 1-naphthyl, tert-butyl, 1,1-diphenyl, 2-pyridyl, 6-chloropyridyl and 6-bromopyridyl, and R2 is selected from one of methoxy, trimethylsiloxy, n-butoxy, ethoxy and F.

3. A method for preparing an α-hydrazine-substituted azaboron dipyrrole compound, characterized in that, The preparation method includes: 1) In the presence of a solvent and a Lewis acid, 1-amino-1H-isoindole-3-imine of formula A is condensed with a hydrazine derivative of formula B to obtain an intermediate; 2) Add borate ester and / or boron trifluoride complexing agent as shown in formula C to the reaction system of step 1) to carry out a coordination reaction to obtain α-hydrazine-substituted azaborine dipyrrole compound; ； Wherein, R1 is selected from one of aryl, heterocyclic aryl and alkyl, and R2 is selected from halogen atoms or oxygen-containing groups.

4. The preparation method according to claim 3, characterized in that, R1 is selected from one of monocyclic aryl, fused aryl, haloaryl, or alkyl-substituted aryl, and R2 is selected from one of C1-C16 alkoxy, siloxy, F, and Cl. Preferably, R1 is selected from one of phenyl, 4-bromophenyl, 4-trifluoromethylphenyl, 1-naphthyl, tert-butyl, 1,1-diphenyl, 2-pyridyl, 6-chloropyridyl and 6-bromopyridyl, and R2 is selected from one of methoxy, trimethylsiloxy, n-butoxy, ethoxy and F.

5. The preparation method according to claim 3 or 4, characterized in that, In step 1), the solvent is selected from one or more of chlorobenzene, o-dichlorobenzene, and toluene; The Lewis acid is selected from one or more of acetic acid, p-toluenesulfonic acid, hydrochloric acid, nitric acid, and sulfuric acid; The molar ratio of the 1-amino-1H-isoindole-3-imine derivative shown in Formula A, the hydrazine derivative shown in Formula B, and the Lewis acid is 1:1~1.1:0.01~0.

3.

6. The preparation method according to any one of claims 3-5, characterized in that, In step 1), the conditions for the condensation reaction include: a temperature of 130~200℃ and a time of 0.5~20h.

7. The preparation method according to any one of claims 3-6, characterized in that, In step 2), the borate ester is selected from one or more of trimethyl borate, tri-n-butyl borate and tris(trimethylsilyl)borate; The molar ratio of 1-amino-1H-isoindole-3-imine represented by Formula A to the borate ester or boron trifluoride ether represented by Formula C is 1:5~30.

8. The preparation method according to any one of claims 3-7, characterized in that, In step 2), the conditions for the coordination reaction include: a temperature of 100~220℃ and a time of 12~48h.

9. An α-hydrazine-substituted azaboron dipyrrole compound prepared by the method according to any one of claims 3-8.

10. The use of an α-hydrazine-substituted azaboron dipyrrole compound as described in claim 1, 2, or 9 in the preparation of highly selective chemical sensing products, photosensitizers, and photothermal reagents.

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