A spiroxanthene compound, a preparation method and application thereof

Abstract

This invention relates to the field of organic compound synthesis technology, specifically to a spirocyclooxanthone compound, its preparation method, and its applications. 2-[4-(dihexylamino)-2-hydroxybenzoyl]benzoic acid is reacted with 4-bromo-3-methylphenol under concentrated sulfuric acid catalysis. The reaction product is post-treated to obtain a crude product, which is then separated and purified to obtain 2'-bromo-6'-(dihexylamino)-3'-methyl-3H-spiro[isobenzofuran-1,9'-xanthones]-3-one. This one-pot acid-catalyzed tandem cyclization method efficiently and selectively constructs complex spirocyclooxanthone skeletons in one step, solving key problems in traditional multi-step synthesis such as cumbersome steps, low yield, harsh conditions, and difficulty in controlling regioselectivity. It achieves the preparation of spirocyclooxanthone derivatives with high yield, high purity, and a simple process.

Description

Technical Field

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

[0002] Xanthones are among the most important core structures for classic and high-performance dyes. For example, the well-known fluorescein and rhodamine dye families are based on this backbone. Through structural modification, the absorption / emission wavelengths, molar extinction coefficients, fluorescence quantum yields, photostability, and solubility of these compounds can be precisely controlled. Introducing spirocyclic structures can further break planarity, regulate molecular aggregation behavior, and generate novel optical properties (such as solid-state fluorescence and mechanochromism), which are crucial for developing next-generation bioimaging probes, fluorescent sensors, high-end textile dyes, inkjet printing inks, and photostability stabilizers.

[0003] Meanwhile, these compounds are core chromophores and functional units for constructing high-performance organic optoelectronic functional materials. In organic light-emitting diodes (OLEDs), they can serve as highly efficient light-emitting materials (especially red and green light materials) or host materials; their rigid spirocyclic structure helps suppress concentration quenching and improve device efficiency. In dye-sensitized solar cells (DSSCs), xanthone-based dyes (such as xanthones) are widely studied due to their wide absorption, suitable energy levels, and good photostability. Furthermore, they are also promising p-type or n-type semiconductor materials in organic field-effect transistors (OFETs), whose planarity and modifiable electronic structure facilitate charge transport. In the field of fluorescence sensing and imaging, their derivatives are designed as high-brightness, high-stability fluorescent probes and biolabeling dyes with specific responses to pH, ions, and biomolecules.

[0004] Furthermore, the xanthonone skeleton is an important structural advantage for drug activity. Numerous natural and synthetic xanthonone derivatives have been proven to possess broad biological activities, including anticancer, anti-inflammatory, antibacterial, antiviral, antioxidant, and neuroprotective effects. Introducing a spirocyclic structure can significantly alter the molecule's three-dimensional conformation, lipid-water partition coefficient, and pharmacokinetic properties, thereby optimizing its binding affinity and selectivity to biological targets (such as enzymes and receptors). This is one of the key strategies for structural modification and optimization of lead compounds in current innovative drug development. The bromine atom in this reaction product also serves as a valuable synthetic handle, facilitating the further introduction of pharmacophores through reactions such as coupling.

[0005] Due to their complexity and rigidity, these structures are often used as challenging synthetic targets or key intermediates. Developing new methods for efficiently constructing such spirocyclooxanthone skeletons not only enriches the toolbox of synthetic chemists but also provides a material basis for rapidly constructing structurally diverse compound libraries for high-throughput screening (drug discovery, materials performance testing), thus possessing significant methodological implications.

[0006] In the field of organic synthesis, the traditional construction of xanthone skeletons mainly relies on acid-catalyzed condensation cyclization (such as Pechmann condensation) of phenol derivatives with o-hydroxybenzoic acid compounds. Although this method is widely used, its regioselectivity and functional group compatibility have significant limitations: when the substrate contains multiple substituents or sensitive groups, strong acid conditions easily trigger side reactions, and it is difficult to control the cyclization site, leading to difficulties in separation and purification.

[0007] When the synthetic target is upgraded to structurally complex spirocyclic xanthones, the core challenge lies in how to efficiently construct the spirocyclic quaternary carbon center connecting isobenzofuranone and xanthonone. Existing techniques mostly employ a "stepwise assembly" strategy: first, a functionalized xanthonone precursor is synthesized, then a spirocyclic fragment is introduced through multi-step functional group transformations, and finally cyclization is completed. This route suffers from three bottlenecks: lengthy reaction steps lead to low overall yields (often below 30%); steric hindrance of the spirocyclic quaternary carbon center makes its formation difficult under conventional conditions; and the synthetic process often relies on harsh conditions such as noble metal catalysis, anhydrous and oxygen-free environments, resulting in high operating costs. More importantly, existing methods lack universally applicable regioselectivity control strategies, making it difficult to efficiently synthesize structurally diverse derivatives. Summary of the Invention

[0008] The technical problem to be solved by the present invention is to provide a spirocyclooxanthone compound, its preparation method and its application.

[0009] The technical solution of the present invention to solve the above-mentioned technical problems is as follows: This invention provides a method for preparing spirocyclooxanthone compounds, wherein the spirocyclooxanthone compound is 2'-bromo-6'-(dihexylamino)-3'-methyl-3H-spiro[isobenzofuran-1,9'-xanthon]-3-one; The preparation method involves reacting 2-[4-(dihexylamino)-2-hydroxybenzoyl]benzoic acid with 4-bromo-3-methylphenol under concentrated sulfuric acid catalysis, post-treating the reaction product to obtain a crude product, and separating and purifying the crude product to obtain 2'-bromo-6'-(dihexylamino)-3'-methyl-3H-spiro[isobenzofuran-1,9'-xanthon]-3-one.

[0010] Based on the above technical solution, the present invention can be further improved as follows.

[0011] Furthermore, the concentrated sulfuric acid is an aqueous solution of sulfuric acid, with a mass percentage of 98%.

[0012] Furthermore, the reaction temperature is 10-40℃ and the time is 8-14 hours.

[0013] Furthermore, the molar ratio of 2-[4-(dihexylamino)-2-hydroxybenzoyl]benzoic acid to 4-bromo-3-methylphenol is 1:1 to 1:1.5.

[0014] Furthermore, before carrying out the reaction, 2-[4-(dihexylamino)-2-hydroxybenzoyl]benzoic acid is mixed with concentrated sulfuric acid, and then 4-bromo-3-methylphenol is added.

[0015] Furthermore, the reaction is carried out in an inert gas environment.

[0016] Furthermore, the post-processing involves quenching the reaction with an ice-water mixture, filtering to obtain a precipitate, washing the precipitate with alkali, and drying to obtain the crude product.

[0017] Further, the precipitate obtained by vacuum filtration is first mixed with dichloromethane, washed with water, and then subjected to alkaline washing. The alkaline washing method is to add a 10% sodium hydroxide aqueous solution to make the pH value 10 and stir for 0.5-1.5 hours. After the alkaline washing is completed, the dichloromethane layer is washed with water, dehydrated, and filtered to obtain the crude product.

[0018] Furthermore, the separation and purification are carried out by column chromatography using an eluent, wherein the eluent is a mixture of petroleum ether and ethyl acetate, and the volume ratio of petroleum ether to ethyl acetate is 2-4:1.

[0019] Furthermore, it also includes monitoring during the reaction process, wherein the monitoring method is TLC tracking.

[0020] The present invention also provides a spirocycloxanthone compound, wherein the spirocycloxanthone compound is 2'-bromo-6'-(dihexylamino)-3'-methyl-3H-spiro[isobenzofuran-1,9'-xanthon]-3-one prepared by the method described above.

[0021] The present invention also provides the application of the above-described spirocycloxanthone compounds in the preparation of high color density fluorane dyes.

[0022] The present invention also provides a high color density fluorane dye, which is prepared using spirocycloxanthone compounds as described above.

[0023] The beneficial effects of this invention are as follows: (1) The method for preparing spirocyclooxanthone compounds of the present invention uses a one-pot acid-catalyzed tandem cyclization method to efficiently and selectively construct a complex spirocyclooxanthone skeleton in one step. This method solves the key problems of cumbersome steps, low yield, harsh conditions and difficulty in controlling regioselectivity in traditional multi-step synthesis, and achieves the preparation of spirocyclooxanthone derivatives with high yield, high purity and simple process. (2) The method for preparing spirocycloxanthone compounds of the present invention uses concentrated sulfuric acid as a reaction medium and promoter, without the need for additional catalysts, which significantly improves the yield and purity of the target product. (3) The preparation method of the spirocycloxanthone compounds of the present invention avoids the tedious operation of separation and purification of intermediates, reduces material loss and human error, and improves production efficiency; (4) The preparation method of the spirocycloxanthone compounds of the present invention avoids the generation of a large amount of strong acid, strong base or metal ion-containing wastewater, reduces the environmental treatment burden, directly constructs complex spirocyclic structures, has short steps, few side reactions, and has high atom economy. (5) The preparation method of the spirocycloxanthone compounds of the present invention has mild reaction conditions, low equipment requirements, no need for special or high pressure devices, low energy consumption, and is easy to control, which is conducive to achieving stable large-scale production. (6) The method for preparing spirocycloxanthone compounds of the present invention successfully prepared 2'-bromo-6'-(dihexylamino)-3'-methyl-3H-spiro[isobenzofuran-1,9'-xanthon]-3-one, which is an important intermediate for the synthesis of high-performance fluorescent dyes. It is the key to the preparation of fluorescent dyes with high color density and excellent color development performance, and is of great significance for the development of high-end thermosensitive recording materials, pressure color-changing materials and other fields. Attached Figure Description

[0024] Figure 1 The UV-Vis absorption spectrum of the product in Example 1 of the present invention; Figure 2 The FTIR spectrum of the product in Example 1 of the present invention; Figure 3 In Embodiment 1 of the present invention, the product 1 H-NMR spectrum; Figure 4 In Embodiment 1 of the present invention, the product 13 C-NMR spectrum; Figure 5 The HSQC diagram of the product in Embodiment 1 of the present invention; Figure 6 The HMBC diagram of the product in Embodiment 1 of the present invention; Figure 7This is the HPLC chromatogram of the product in Example 1 of the present invention. Detailed Implementation

[0025] The principles and features of the present invention are described below. The examples given are only for explaining the present invention and are not intended to limit the scope of the present invention.

[0026] The present invention discloses a method for preparing a spirocycloxanthone compound, wherein the spirocycloxanthone compound is 2'-bromo-6'-(dihexylamino)-3'-methyl-3H-spiro[isobenzofuran-1,9'-xanthon]-3-one; the preparation method comprises reacting 2-[4-(dihexylamino)-2-hydroxybenzoyl]benzoic acid with 4-bromo-3-methylphenol under the catalysis of concentrated sulfuric acid, post-treating the reaction product to obtain a crude product, and separating and purifying the crude product to obtain 2'-bromo-6'-(dihexylamino)-3'-methyl-3H-spiro[isobenzofuran-1,9'-xanthon]-3-one.

[0027] The method for preparing spirocycloxanthone compounds of this invention uses inexpensive concentrated sulfuric acid as a catalyst, completely eliminating the dependence on precious metal catalysts such as palladium and rhodium. This not only significantly reduces raw material costs but also completely avoids the potential impact of precious metal residues on product quality (especially in the pharmaceutical and electronic materials fields). The reaction system exhibits good tolerance to oxygen and moisture in the air, eliminating the need for strict inert gas protection or anhydrous and oxygen-free operation, significantly simplifying the process. This feature allows the reaction to be carried out in conventional glassware, reducing the requirements for specialized equipment and making it easier to implement and promote in industrial production.

[0028] The reaction product was separated and purified to obtain a high-purity 2'-bromo-6'-(dihexylamino)-3'-methyl-3H-spiro[isobenzofuran-1,9'-xanthon]-3-one product.

[0029] The reaction formula for the preparation method of this invention is as follows: Using 2-[4-(dihexylamino)-2-hydroxybenzoyl]benzoic acid as substrate A and 4-bromo-3-methylphenol as substrate B, the specific mechanism of the above reaction is explained as follows: (1) Protonation and lactone formation of substrate A (forming a spirocyclic core) In concentrated sulfuric acid, the carboxylic acid of substrate A is first protonated, becoming a good electrophile (acyl cation equivalent). At the same time, the intramolecular ortho-phenolic hydroxyl group acts as an electron-rich nucleophile, attacking the protonated carboxyl carbon, undergoing intramolecular nucleophilic addition-elimination (esterification), and dehydration to form a five-membered lactone ring (isobenzofuran-3-one).

[0030] This step generates the left half of the product (isobenzofuran-3-one) and the central carbon atom of the spirocyclic ring of the entire molecule. At this point, the central carbon of the spirocyclic ring (the original carboxyl carbon) is attached to an oxygen atom (the oxygen atom of the lactone) and an aromatic ring (the aromatic ring of the salicylic acid moiety), and is connected to another aromatic ring (the dihexylaminophenol moiety) through a carbonyl group. This carbonyl group is the key electrophilic site for the next step.

[0031] (2) Electrophilic substitution of substrate B (Friedrich-K alkylation) In acid, the oxygen atom of the phenolic hydroxyl group of substrate B may be protonated, but more importantly, its benzene ring is highly electron-rich due to the strong electron-donating effect (+M effect) of -OH, making it an excellent nucleophile.

[0032] The carbonyl carbon of the dihexylaminophenol moiety from the intermediate in step (1) is protonated in a strong acid medium of concentrated sulfuric acid to form a highly electron-deficient electrophilic center with a quinone structure (which can be regarded as an oxonium ion or a protonated p-quinone methylate). The positive charge and electron deficiency of this electrophilic center can be significantly stabilized by the strong electron-donating group at the para position (dihexylamino, through its resonance effect).

[0033] The electron-rich benzene ring of substrate B (preferably at the para or ortho position of its hydroxyl group, but since the para position is occupied by bromine, the ortho position is attacked) acts as a nucleophile, attacking the electrophilic center mentioned above. Specifically, the attack site is the ortho position of the hydroxyl group on the benzene ring of substrate B (relative to the other ortho position of the methyl group).

[0034] The interpretation of region selectivity is as follows: Of the two ortho positions of the hydroxyl group, one is C-2 (para position of the carbon atom connecting to bromine) and the other is C-6 (ortho position of the carbon atom connecting to methyl). Due to the steric hindrance of the methyl group, nucleophilic attack tends to occur at the less sterically hindered position, i.e., the position farthest from the methyl group (C-2 position). This explains the relative positions of bromine and methyl in the product: bromine at the 2' position, methyl at the 3' position, and the newly formed C / C bond at the 1' position (connecting the spiro atom). This step is an intermolecular Friedel-Crafts alkylation reaction, forming a new C / C bond connecting the two aromatic rings (i.e., the connection between the 9-carbon and 1'-carbon of the future xanthonium ring).

[0035] (3) Dehydration and formation of oxygen heterocycles (pyran rings): The intermediate formed in the previous step is a triarylmethane derivative with the following structure attached to its central carbon (spiro atom): The oxygen atom in the isobenzofuranone ring; Aromatic rings derived from substrate A that have already undergone lactone formation; An aromatic ring with a dihexylamino group from substrate A (now part of an electrophilic center); Aromatic rings from substrate B; At this point, the phenolic hydroxyl oxygen atom from substrate B, acting as an intramolecular nucleophile, attacks the carbonyl carbon on the aromatic ring with a dihexylamino atom attached to the spiro atom (this carbonyl group still exists after the previous alkylation step). This addition process is specifically an intramolecular nucleophilic addition, followed by proton transfer and dehydration to form a six-membered oxygen heterocycle (pyran ring).

[0036] This process completed the construction of the xanthone skeleton. Specifically, it formed a dibenzo[γ]pyran-9-one structure, in which an aromatic ring (from the dihexylaminophenol moiety of substrate A) and an aromatic ring (from the bromomethylphenol moiety of substrate B) are connected by a carbonyl group and an oxygen bridge.

[0037] (4) Deprotonation and aromatization: In the above cyclization process, the intermediate undergoes keto-enol tautomerism and re-aromatization of the aromatic ring. Ultimately, under the reaction conditions, all aromatic rings regain their aromaticity, lose protons, and yield neutral, stable, and highly conjugated spirocyclic products.

[0038] As can be seen from the above explanation of the mechanism, this preparation method uses acid-catalyzed dehydration condensation as its core mechanism, with a clear and well-defined reaction pathway, fundamentally avoiding the problems of over-oxidation and poor selectivity commonly found in oxidation methods. The only byproduct is water, resulting in near-ideal atom economy and conforming to the principles of green chemistry. Compared with traditional oxidation methods, this method eliminates the need for expensive or toxic stoichiometric oxidants (such as periodates, heavy metal oxides, etc.), reducing waste generation and improving the safety of the production process. The reaction conditions are mild and controllable, the product has high purity, and the post-processing is simple, providing a new strategy for the efficient and environmentally friendly construction of carbon-carbon bonds.

[0039] Preferably, in the preparation method of the present invention, the mass percentage of concentrated sulfuric acid is 98%; the reaction temperature is 10-40℃, and the reaction time is 8-14 hours; the molar ratio of 2-[4-(dihexylamino)-2-hydroxybenzoyl]benzoic acid to 4-bromo-3-methylphenol is 1:1-1:1.5.

[0040] Regarding the molar ratio of 2-[4-(dihexylamino)-2-hydroxybenzoyl]benzoic acid to 4-bromo-3-methylphenol, if the ratio is too high, it will lead to excessive raw material residue, increased side reactions, and increased separation costs and difficulties; while if the ratio is too low, it will result in incomplete conversion of the main raw material, serious waste, and make the product extremely difficult to purify due to its similar structure.

[0041] Regarding reaction temperature, excessively high temperatures can exacerbate side reactions (such as sulfonation, coking, or excessive condensation), leading to increased product impurities and decreased yield. Conversely, excessively low temperatures can slow down the reaction rate, significantly prolong the reaction time, and even cause poor solubility of the raw materials and incomplete reaction.

[0042] For reaction time, too long a reaction time will lead to more side reactions, product degradation or polymerization, and reduced yield and purity; too short a reaction time will result in incomplete reaction and raw material residue, which will also lead to reduced yield and separation difficulties.

[0043] Preferably, the optimal reaction conditions of the present invention are a reaction temperature of 25°C and a reaction time of 12 hours; the molar ratio of 2-[4-(dihexylamino)-2-hydroxybenzoyl]benzoic acid to 4-bromo-3-methylphenol is 1:1.05; these optimal reaction conditions can effectively avoid raw material residues and side reactions, balance the reaction rate and control side reactions, ensure complete reaction, and avoid product degradation.

[0044] Preferably, the reaction of the present invention is carried out in an inert gas environment; the inert gas environment can prevent moisture and oxygen in the air from interfering with the reaction and ensure an anhydrous and oxygen-free environment.

[0045] Further preferably, the inert gas is nitrogen; experimental verification shows that under nitrogen protection, the yield can reach 90.25% and the purity is 98.38% (see Example 1), while under air conditions the yield is about 80-85% and the purity is about 94-96%; it can be seen that although the reaction of the present invention is still feasible in air, it is preferred to carry out under nitrogen protection to ensure a stable high yield and high purity.

[0046] Preferably, the 2-[4-(dihexylamino)-2-hydroxybenzoyl]benzoic acid used in the method of the present invention has a purity > 99.00% and can be prepared by a publicly disclosed method; the 4-bromo-3-methylphenol has a purity of 99% and is a commercially available product.

[0047] Preferably, the reaction is monitored by TLC. The developing solvent for TLC is petroleum ether and ethyl acetate in a volume ratio of 3:1. TLC allows for clear observation of the disappearance of the starting material and the formation of the product, ensuring complete reaction.

[0048] In the preparation method of this invention, the post-treatment involves quenching the reaction with an ice-water mixture, filtering to obtain a precipitate, washing the precipitate with alkali, and drying to obtain a crude product. Specifically, the reaction solution must be slowly poured into a large amount of stirred ice water to ensure safe dilution of concentrated sulfuric acid and complete precipitation of the product.

[0049] Preferably, the precipitate obtained by vacuum filtration is first mixed with dichloromethane (DCM), washed with water, and then subjected to alkaline washing. The alkaline washing method is to add a 10% sodium hydroxide aqueous solution to make the pH value 10, stir for 0.5-1.5 hours, and selectively remove unreacted acidic raw materials and other impurities. After alkaline washing, the DCM layer is washed with water, dehydrated and filtered to obtain the crude product.

[0050] Preferably, the DCM layer is fully dehydrated with sufficient anhydrous sodium sulfate; otherwise, residual moisture will seriously affect the subsequent column chromatography results.

[0051] In the preparation method of the present invention, separation and purification are carried out by column chromatography using an eluent. The eluent is a mixture of petroleum ether and ethyl acetate, and the volume ratio of petroleum ether to ethyl acetate is 2-4:1, with the optimum being 3:1.

[0052] Preferably, the eluent ratio can be finely adjusted, and high-purity fractions are accurately collected according to TLC results to ensure separation effect.

[0053] Preferably, after separation and purification, the product is subjected to final drying to completely remove trace solvents; the final drying method is vacuum drying, and the product is stored in the dark under nitrogen protection to prevent degradation.

[0054] The preparation method of the present invention comprises the following specific steps: S1. Mix the substrate thoroughly and stir: Under nitrogen protection, 98% H2SO4 was added to the reaction flask, and the mixture was stirred until homogeneous. 2-[4-(dihexylamino)-2-hydroxybenzoyl]benzoic acid was slowly added in portions to the reaction flask, and stirring continued until completely dissolved. Then, 4-bromo-3-methylphenol was added in portions to the reaction flask, and the mixture was kept warm and stirred until the reaction solution changed from dark red to black.

[0055] S2, Post-processing: After the reaction was complete, the reaction mixture was added to ice water, and the precipitate was obtained by vacuum filtration. The residue was dissolved in dichloromethane (DCM), washed once with deionized water, and a 10% sodium hydroxide aqueous solution was added to adjust the pH of the aqueous layer to 10. The mixture was stirred for 1 hour. The DCM layer was separated, washed with deionized water, and dehydrated with anhydrous sodium sulfate. The anhydrous sodium sulfate was removed by filtration, and the filtrate was concentrated under reduced pressure to remove the solvent, yielding the crude product.

[0056] S3. Separation and purification: The crude product was purified by silica gel column chromatography with petroleum ether:ethyl acetate as the eluent in a ratio of 3:1. The target product was collected and the solvent was removed under reduced pressure to obtain the pure product 2'-bromo-6'-(dihexylamino)-3'-methyl-3H-spiro[isobenzofuran-1,9'-xanthon]-3-one.

[0057] The preparation method of the present invention has the following specific advantages: (1) Significantly improves reaction efficiency and product purity: This method, under nitrogen protection, uses concentrated sulfuric acid as the reaction medium and promoter, and adopts a highly efficient and simple one-pot process without the need for additional catalysts, significantly improving the yield and purity of the target product. According to the results of the examples, the product yield is as high as 90.25% and the purity reaches 98.38%, which is significantly better than the prior art.

[0058] (2) Simplified process and high operational safety: The "one-pot" continuous feeding and reaction method avoids the cumbersome operations of intermediate separation and purification, reduces material loss and human error, and improves production efficiency. The reaction system does not require the large amount of hygroscopic and flammable metal halides (such as AlCl3) required by traditional Friedel-Crafts reactions, and also avoids the use of expensive and potentially residual transition metal catalysts, reducing operational hazards and the difficulty of post-processing of products.

[0059] (3) Environmentally friendly and in line with the concept of green chemistry: The reaction system uses concentrated sulfuric acid as a medium, and the separation is achieved by adjusting the pH with alkaline solution in the post-treatment, which avoids the generation of a large amount of strong acid, strong alkali or metal ion-containing wastewater and reduces the environmental treatment burden. The reaction directly constructs complex spirocyclic structures, with short steps, few side reactions, and high atom economy.

[0060] (4) The reaction conditions of this invention have good potential for industrial scale-up, the process conditions are mild, and it is easy to scale up production. The reaction is carried out under a nitrogen atmosphere at normal temperature and pressure, which requires low equipment, low energy consumption, and is easy to control. Only conventional stirred reactors, filtration and concentration equipment are needed, without the need for special or high-pressure devices, resulting in low investment costs. The reaction mechanism is clear, the heat and mass transfer process is simple, and the process window is wide, which is conducive to achieving stable large-scale production.

[0061] (5) Stable and reliable product quality. By precisely controlling the feed ratio, reaction temperature, and time, and effectively monitoring the reaction process using TLC, this invention ensures stable product quality; the process conditions are easy to control precisely, and the yield and purity of products are highly consistent between different batches; the crude product can be purified by simple extraction, pH adjustment, and silica gel column chromatography to obtain a high-purity product. The high yield and high purity directly reduce the unit consumption of raw materials and purification costs, improve the market competitiveness of the product, and lay a solid material and technical foundation for the development of related high-value-added fine chemicals. It is of great significance for the development of high-end thermal recording materials, pressure-sensitive color-changing materials, and other fields.

[0062] (6) The 2'-bromo-6'-(dihexylamino)-3'-methyl-3H-spiro[isobenzofuran-1,9'-xanthon]-3-one successfully prepared by this invention is an important intermediate for the synthesis of high-performance fluorescent dyes, filling the gap in preparation technology and providing an efficient and high-purity synthetic route, solving the problem that this specific structural intermediate is difficult to obtain or that existing methods are inefficient.

[0063] The spirocycloxanthone compounds of the present invention, having a purity greater than or equal to 98.00%, can be used to prepare high color density fluorane dyes.

[0064] The high color density fluorane dyes of the present invention are prepared using spirocycloxanthone compounds as described above.

[0065] The effects of the present invention will be illustrated below through specific embodiments and comparative examples.

[0066] Example 1 Under a nitrogen atmosphere and under nitrogen protection, 98% H2SO4 was added to the reaction flask, and the mixture was stirred at room temperature (25°C) until homogeneous. 2-[4-(dihexylamino)-2-hydroxybenzoyl]benzoic acid (425 mg) was slowly added in portions to the reaction flask, and stirring continued until completely dissolved. Then, 4-bromo-3-methylphenol (196 mg) was added in portions to the reaction flask, and the mixture was stirred and kept at this temperature for 12 hours until the reaction solution changed from dark red to black.

[0067] The reaction was monitored by TLC, and the developing solvent was petroleum ether: ethyl acetate: glacial acetic acid = 3:1.

[0068] After the reaction, post-processing was performed as follows: The reaction mixture was added to ice water, and the precipitate was obtained by vacuum filtration. The residue was dissolved in DCM, washed once with deionized water, and a 10% sodium hydroxide aqueous solution was added to adjust the pH of the aqueous layer to 10. The mixture was stirred for 1 hour. The DCM layer was separated, washed with deionized water, and dehydrated with anhydrous sodium sulfate. The anhydrous sodium sulfate was removed by filtration, and the filtrate was concentrated under reduced pressure to remove the solvent, yielding the crude product.

[0069] The crude product was purified by silica gel column chromatography using petroleum ether:ethyl acetate in a 3:1 eluent. The target product was collected and the solvent was removed under reduced pressure to obtain the pure product 2'-bromo-6'-(dihexylamino)-3'-methyl-3H-spiro[isobenzofuran-1,9'-xanthone]-3-one. The calculated product mass was 519 mg, with a yield of 90.25%.

[0070] The UV-Vis absorption spectra of the above products are as follows: Figure 1 As shown, according to Figure 1 It can be seen that the maximum absorption wavelength of the product is 275 nm, which is consistent with the expected characteristics of the target product.

[0071] The FTIR spectra of the above products are as follows: Figure 2 As shown in Table 1, the main absorption peaks and their functional group assignments are as follows: Table 1. Assignment of major absorption peaks and functional groups in FTIR spectra FTIR spectroscopy can yield the following results: (1) The main carbonyl peak of this product is 1753.86 cm⁻¹. -1This clearly supports the structural characteristics of spirolactone, verifying the correctness of the main functional group. The peak position is significantly higher than that of typical esters (1735-1750 cm⁻¹). -1 ) and ketones (1705-1725 cm) -1 This is a direct manifestation of the strain effect of five-membered ring lactones. If it is an open-ring rhodamine structure, the carbonyl peak should appear at 1680-1720 cm⁻¹. -1 .

[0072] (2) Aromatic ring C=C interval (1514-1608 cm) -1 The key absorptions of multiple CH2 / CH3 and CO clearly correspond to the presence of a polybenzene ring host and long-chain amines.

[0073] (3) The absorption intensity of C-Br, CN, N-alkyl, etc. in the low band is weak or overlaps with other bands, making it difficult to distinguish them individually, but the structure can still help in the inference.

[0074] The product 1 H-NMR spectrum as shown Figure 3 As shown, 1 The proton peak assignments for the H-NMR spectra are shown in Table 2.

[0075] Table 2 1 Proton peak assignment table for H-NMR spectra pass 1 As can be seen from the 1H-NMR spectrum and Table 2, the five aromatic hydrogens of the isobenzofuran ring (δ 7.19-8.05 ppm) exhibit a complete 1,2-ortho-substituted coupling mode, with chemical shifts gradually increasing from 8.05 ppm (ortho-carbonyl) to 7.19 ppm (ortho-spirocarbon). The coupling constants are all in the range of 7-8 Hz, which is consistent with the typical values ​​of ortho-coupled benzene rings.

[0076] The Xanthene rings (δ 6.35–6.91 ppm) exhibit a typical 1,2,4-trisubstituted mode. The coupling constant combination of H-5′ / H-3′ / H-4′ (J = 8.9–9.0 Hz adjacent, J = 2.5–2.6 Hz interposition) perfectly matches theoretical expectations. The single-peak signal of H-1′ further confirms the substitution mode.

[0077] The dihexylamine alkyl chain (δ 0.91-3.32 ppm) exhibits a typical chemical shift gradient distribution, gradually increasing from 3.24-3.32 ppm at the α-position to 0.91-0.94 ppm at the terminal methyl group. The integral sum is 26H, consistent with the total number of hydrogens in the two hexyl chains.

[0078] Total integral verification: Aromatic hydrogen 9H + aromatic methyl 3H + alkyl chain 26H = 38H, consistent with the theoretical molecular formula of the product C 33 H 38 BrNO3 is completely consistent.

[0079] The product 13 C-NMR spectrum as shown Figure 4 As shown, 13 The carbon peak assignments for the C-NMR spectra are shown in Table 3.

[0080] Table 3 13 Carbon peak assignment table for C-NMR spectra pass 13 As can be seen from the C NMR spectrum and Table 3: (1) The carbonyl carbon (169.44 ppm) and spiro carbon (83.40 ppm) together confirmed the closed-ring spironolactone structure, which is the fundamental difference from the open-ring rhodamine structure.

[0081] (2) The characteristic coupling splitting of C-Br (152.68 ppm, d, J=24.6 Hz) directly originates from 13 C- 79 Br / 81 Br coupling is direct evidence of bromine substitution. The coupling constant of 24.6 Hz is within the reported range of C-Br coupling (10-30 Hz).

[0082] (3) The characteristic coupling split of CN (118.91 ppm, d, J=4.3 Hz) originates from 13 C- 14 N-coupling is direct evidence of aromatic amine substitution. The coupling constant of 4.3 Hz conforms to the typical CN-coupling range (1–6 Hz).

[0083] (4) Stratified distribution of aromatic carbon regions: The CH carbons of the isobenzofuran ring are concentrated at 125-135 ppm, while the CH carbons of the xanthene ring are concentrated at 97-119 ppm. The higher chemical shift of the CH carbons in the xanthene ring reflects the strong influence of electron-donating groups such as ether oxygen and amine groups.

[0084] (5) The aliphatic carbon region exhibits a typical alkyl chain chemical shift gradient distribution, gradually increasing from 51.11 ppm for α-carbon to 14.09 ppm for terminal methyl.

[0085] (6) Carbon number statistics: 24 independent carbon signals were observed, fewer than the theoretical carbon number (33). This is reasonable because the two hexyl chains are symmetrical and many carbon atoms have the same overlapping chemical shift.

[0086] The HSQC spectra of the above products are as follows: Figure 5 As shown in Table 4, the key data tables for HSQC are as follows: Table 4 Key Data Table of HSQC The following key conclusions can be drawn from the HSQC graph and Table 4: (1) HC correspondence in the aromatic region: HSQC correlation peaks for all aromatic hydrogens and their corresponding carbons are clearly visible, confirming the complete structures of the isobenzofuran ring and the xanthene ring. HSQC data are consistent with the original... 1 H and 13 The C NMR data are highly consistent.

[0087] (2) The HSQC correlation peaks of the HC corresponding to the side chain region: N-αCH2 (δ3.28 / 51.20 ppm) and terminal CH3 (δ0.93 / 13.96 ppm) clearly confirmed the structure of dihexylamine.

[0088] (3) The bimodal effect at δ1.34 ppm: 1 Hδ 1.34 ppm (corresponding to) 13 The Cδ values ​​of 22.68 and 26.86 ppm reveal that the two hexyl chains are in different chemical environments, reflecting conformational differences or varying degrees of spatial proximity to the aromatic ring.

[0089] The HMBC spectra of the above products are as follows: Figure 6 As shown in Table 5, detailed information on key HMBC-related peaks is presented.

[0090] Table 5. Detailed information on key HMBC-related peaks The key findings of HMBC are as follows: (1) Decisive evidence of spirocyclic structure: The spirocarbon (δ83.37 ppm) and multiple aromatic hydrogens (H-5 / H-6, H-1′, H-3′, H-5′) of the two ring systems all have HMBC related peaks, which proves that the spirocarbon is indeed a shared connection point of the two ring systems. This is the decisive evidence of spirocyclic structure.

[0091] (2) Precise confirmation of the position of the substituent: The correlation peaks between the C-Br quaternary carbon (δ 152.76 ppm) and H-3′ / H-4′ confirmed that bromine was located at the 2′- position.

[0092] The strong correlation peak between CN quaternary carbon (δ 150.22 ppm) and N-αCH2 confirmed that dihexylamine was located at the 6′-position.

[0093] The correlation peak between the methyl carbon (δ23.06 ppm) and H-1′ confirmed that the methyl group was located at the 3′-position.

[0094] (3) Confirmation of carbonyl position: The carbonyl carbon (δ169.48 ppm) has a related peak with the H-5 / H-6 of the isobenzofuran ring, confirming that the lactone carbonyl is at the C-3 position.

[0095] In summary, all signals are highly consistent with the chemical shifts and integrals of each proton type in the structure of 2'-bromo-6'-(dihexylamino)-3'-methyl-3H-spiro[isobenzofuran-1,9'-xanthone]-3-one, therefore, this sample is confirmed as the expected target compound. Based on the above analysis, the chemical structure of the product of this embodiment is determined as follows: The yield and purity of the above products were determined by HPLC, and the test parameters are shown in Table 6. Table 6 HPLC detection parameters HPLC chromatogram as shown Figure 7 As shown in Table 7, the chromatographic peak information in the spectrum is as follows: Table 7 HPLC chromatographic peak information The purity of 2'-bromo-6'-(dihexylamino)-3'-methyl-3H-spiro[isobenzofuran-1,9'-xanthon]-3-one was calculated to be 98.38% based on the area normalization method.

[0096] Example 2 This embodiment optimizes the reaction temperature; the specific experimental procedure is as follows: Under nitrogen protection, 98% H2SO4 was added to the reaction flask, heated to 40°C, and stirred until homogeneous. 2-[4-(dihexylamino)-2-hydroxybenzoyl]benzoic acid (425 mg) was slowly added in portions to the reaction flask, and stirring continued until completely dissolved. Then, 4-bromo-3-methylphenol (196 mg) was added in portions to the reaction flask, and the reaction was maintained at this temperature with stirring for 12 hours until the reaction solution changed from dark red to black. Post-treatment was the same as in Example 1. 465 mg of the pure product 2'-bromo-6'-(dihexylamino)-3'-methyl-3H-spiro[isobenzofuran-1,9'-xanthon]-3-one was obtained, with a yield of 80.75% and a purity of 97.02%.

[0097] Example 3 This embodiment optimizes the reaction temperature; the specific experimental procedure is as follows: 98% H2SO4 was added to the reaction flask, and the temperature was controlled to 10°C in an ice bath. Stirring was started and the mixture was stirred until homogeneous. 2-[4-(dihexylamino)-2-hydroxybenzoyl]benzoic acid (425 mg) was slowly added in portions to the reaction flask, and stirring continued until completely dissolved. Then, 4-bromo-3-methylphenol (196 mg) was added in portions to the reaction flask, and the mixture was stirred and kept at this temperature for 12 hours until the reaction solution changed from dark red to black. Post-treatment was the same as in Example 1. 480 mg of the pure product 2'-bromo-6'-(dihexylamino)-3'-methyl-3H-spiro[isobenzofuran-1,9'-xanthon]-3-one was obtained, with a yield of 83.42% and a purity of 97.16%.

[0098] Example 4 This embodiment optimizes the reaction time; the specific experimental procedure is as follows: Add 98% H2SO4 to the reaction flask and stir until homogeneous at room temperature (25°C). Slowly add 425 mg of 2-[4-(dihexylamino)-2-hydroxybenzoyl]benzoic acid to the reaction flask in portions, and continue stirring until completely dissolved. Then add 196 mg of 4-bromo-3-methylphenol to the reaction flask in portions, and keep the mixture at this temperature with stirring for 8 hours until the reaction solution changes from dark red to black. Post-treatment is the same as in Example 1. 432 mg of the pure product 2'-bromo-6'-(dihexylamino)-3'-methyl-3H-spiro[isobenzofuran-1,9'-xanthon]-3-one was obtained, with a yield of 75.15% and a purity of 90.55%.

[0099] Example 5 This embodiment optimizes the reaction time; the specific experimental procedure is as follows: Add 98% H2SO4 to the reaction flask and stir until homogeneous at room temperature (25°C). Slowly add 425 mg of 2-[4-(dihexylamino)-2-hydroxybenzoyl]benzoic acid to the reaction flask in portions, and continue stirring until completely dissolved. Then add 196 mg of 4-bromo-3-methylphenol to the reaction flask in portions, and keep the mixture at this temperature with stirring for 14 h until the reaction solution changes from dark red to black. Post-treatment is the same as in Example 1. 451 mg of the pure product 2'-bromo-6'-(dihexylamino)-3'-methyl-3H-spiro[isobenzofuran-1,9'-xanthon]-3-one was obtained, with a yield of 78.38% and a purity of 88.26%.

[0100] Comparative Example 1 This comparative example was prepared using the Friedel-Crafts cyclization method.

[0101] Friedel-Crafts cyclization is one of the most direct and classic methods for constructing spirocyclic compounds. Its core principle involves using Lewis or Brønsted acid catalysis to induce a pre-designed side chain to electrophilically attack the aromatic ring of anthrone or similar compounds, forming a new C-C bond and closing the ring.

[0102] The general reaction mechanism is as follows: a side chain with a carbonyl group (aldehyde, ketone, acid) or an alkene is introduced at an appropriate position in anthrone or xanthone (usually ortho- or para-position of the phenolic hydroxyl group). Under acidic conditions, the carbocation or acyl cation intermediate of the side chain undergoes an electrophilic substitution reaction with the electron-rich aromatic ring, thereby forming a spirocyclic ring.

[0103] This method is typically carried out under harsh conditions, often requiring strong Lewis acid catalysts (such as AlCl3 and BF3) and high temperatures, resulting in poor tolerance of functional groups. Many sensitive functional groups are prone to decomposition or side reactions during the reaction. Furthermore, the reaction often exhibits regioselectivity issues, particularly with substitution on the aromatic ring, which easily generates a mixture of multiple isomers, complicating product separation and purification. From an environmental perspective, the post-reaction treatment is complex, generating large amounts of acidic wastewater containing metal salts, placing a significant burden on the environment and contradicting the development direction of green chemistry.

[0104] The specific process of this comparative example is as follows: 2-[4-(dihexylamino)-2-hydroxybenzoyl]benzoic acid (425 mg) and 4-bromo-3-methylphenol (196 mg) were dissolved in dry dichloromethane. Under nitrogen protection, 1-ethyl-(3-dimethylaminopropyl)carbodiimide hydrochloride (EDCI) and a catalytic amount of 4-dimethylaminopyridine (DMAP) were added. The mixture was then heated to room temperature and stirred for 12-24 hours.

[0105] After the reaction was complete, the organic phase was washed with water and saturated brine, dried over anhydrous sodium sulfate, and concentrated under reduced pressure. The ester-linked precursor compound was then purified by column chromatography.

[0106] The precursor compound obtained in the previous step was dissolved in dry dichloromethane and cooled to 0°C. Under nitrogen protection, trifluoromethanesulfonic acid (TfOH) was slowly added dropwise. After the addition was complete, the temperature was raised to 40°C and the reaction was carried out for 1-4 hours.

[0107] After the reaction was complete, the reaction solution was quenched extremely slowly in ice water and extracted with dichloromethane. The organic phase was washed with saturated sodium bicarbonate solution, water, and brine, dried, and concentrated. Purification by column chromatography yielded 295 mg of the pure product 2'-bromo-6'-(dihexylamino)-3'-methyl-3H-spiro[isobenzofuran-1,9'-xanthon]-3-one, with a yield of 51.33% and a purity of 68.26%.

[0108] Comparative Example 2 This comparative example was prepared using a transition metal catalysis method. Transition metal catalysis utilizes the catalytic power of transition metals such as palladium and copper to efficiently construct spirocyclic rings through one-step or multi-step cascade reactions. It typically offers better atom economy and step economy.

[0109] The general reaction mechanism is as follows: it usually involves an intramolecular Sonogashira coupling, Heck reaction, or CH bond activation / cyclization process. The metal catalyst first mediates a cross-coupling reaction to form a key intermediate, which then undergoes intramolecular cyclization under reaction conditions (or through functional group conversion) to form a spirocycle.

[0110] While this method is highly efficient, it typically relies on expensive transition metal catalysts (such as palladium and rhodium) and complex organic ligands, resulting in high overall synthesis costs. The reaction process often requires strictly anhydrous and oxygen-free conditions, placing high demands on experimental equipment and operational techniques, which hinders large-scale applications. Furthermore, metal ions from the catalytic system may remain in the product, affecting not only the purity standards of the drug or material but also adding extra costs and difficulties to subsequent purification, limiting its widespread application in fine chemicals and pharmaceuticals.

[0111] The specific process of this comparative example is as follows: Add 2-[4-(dihexylamino)-2-hydroxybenzoyl]benzoic acid (425 mg), 4-bromo-3-methylphenol (196 mg), and cesium carbonate (Cs₂CO₃) to a pressure-resistant tube. Purge the tube with nitrogen three times. Add anhydrous toluene / 1,4-dioxane mixed solvent, followed by tris(dibenzylacetone)dipalladium (Pd₂(dba)₃) and 2-dicyclohexylphosphine-2',4',6'-triisopropylbiphenyl (XPhos). Purge with nitrogen again, seal the reaction tube, and heat to 110-130°C with stirring for 24-48 hours.

[0112] After cooling, the solid was removed by filtration, and the filtrate was concentrated under reduced pressure. Purification by column chromatography yielded 205 mg of the pure product 2'-bromo-6'-(dihexylamino)-3'-methyl-3H-spiro[isobenzofuran-1,9'-xanthon]-3-one, with a yield of 35.75% and a purity of 38.26%.

[0113] Comparative Example 3 This comparative example uses a different solvent based on the preparation method of the present invention. The specific process is as follows: Under nitrogen protection, 85% H3PO4 was added to the reaction flask, heated to 40°C, and stirred until homogeneous. 2-[4-(dihexylamino)-2-hydroxybenzoyl]benzoic acid (425 mg) was slowly added in portions to the reaction flask, and stirring continued until completely dissolved. Then, 4-bromo-3-methylphenol (196 mg) was added in portions to the reaction flask, and the reaction was maintained at this temperature with stirring for 12 hours. The color change of the reaction solution was slow, and a large amount of raw material remained unreacted after 12 hours. The crude product was purified by column chromatography to obtain 177 mg of pure 2'-bromo-6'-(dihexylamino)-3'-methyl-3H-spiro[isobenzofuran-1,9'-xanthon]-3-one, with a yield of 30.75% and a purity of 80.62%.

[0114] Comparative Example 4 This comparative example changes the order of feeding materials based on the preparation method of the present invention. The specific process is as follows: Under a nitrogen atmosphere, 4-bromo-3-methylphenol (196 mg) was first dissolved in 98% H2SO4, heated to 25°C and stirred, and then 2-[4-(dihexylamino)-2-hydroxybenzoyl]benzoic acid (425 mg) was added in batches, and the rest was the same as in Example 1.

[0115] Purification by column chromatography yielded 397 mg of the pure product 2'-bromo-6'-(dihexylamino)-3'-methyl-3H-spiro[isobenzofuran-1,9'-xanthon]-3-one, with a yield of 69.07% and a purity of 75.19%.

[0116] Comparative Example 5 This comparative example differs from the preparation method of the present invention by changing the acid concentration of the reaction medium. The specific process is as follows: Under nitrogen protection, a 70% aqueous solution of H₂SO₄ was added to the reaction flask, heated to 25°C, and stirred until homogeneous. 2-[4-(dihexylamino)-2-hydroxybenzoyl]benzoic acid (425 mg) was slowly added in portions to the reaction flask, and stirring continued until completely dissolved. Then, 4-bromo-3-methylphenol (196 mg) was added in portions to the reaction flask, and the reaction was maintained at this temperature with stirring for 12 hours. TLC showed residual reactants, and unreacted reactants and a small amount of unknown byproducts were separated. No target product was formed.

[0117] The reaction conditions, yields, and purities of the above-described embodiments and comparative examples are shown in Table 8. Table 8 Reaction conditions, yields, and purity of the examples and comparative examples As can be seen from the data in Table 1, Example 1 used 98% concentrated sulfuric acid as the reaction medium and reacted at 25°C for 12 hours, achieving the best results with a yield of 90.25% and a purity of 98.38%, which fully demonstrates the superiority of the process conditions.

[0118] Example 2, increasing the temperature to 40°C, resulted in a yield decrease to 80.75% and a purity decrease to 97.02%, indicating that excessively high temperatures exacerbate side reactions such as sulfonation, coking, or excessive condensation, leading to increased product impurities. Example 3, decreasing the temperature to 10°C, yielded a yield of 83.42% and a purity of 97.16%, slightly better than the high-temperature conditions but still lower than room temperature conditions, indicating that excessively low temperatures slow down the reaction rate, prolong the reaction time, and may even lead to decreased solubility of the raw materials and incomplete reaction. Example 4, shortening the reaction time to 8 hours, resulted in a yield decrease to 75.15% and a purity of only 90.55%, indicating that insufficient reaction time leads to incomplete conversion of the raw materials. Example 5, extending the reaction time to 14 hours, instead resulted in a yield decrease to 78.38% and a purity decrease to 88.26%, indicating that excessively long reaction times lead to increased side reactions, product degradation, or polymerization.

[0119] Comparative Example 1 uses the traditional Friedel-Crafts cyclization method, which involves esterification with EDCI and DMAP followed by cyclization catalyzed by trifluoromethanesulfonic acid. After multiple steps, the yield is only 51.33% and the purity is 68.26%, which is far lower than the one-pot method of this invention, demonstrating the inefficiency of the stepwise strategy.

[0120] Comparative Example 2 used a transition metal catalysis method, reacting Pd2(dba)3 and XPhos at a high temperature of 110-130℃ for 24-48 hours, with a yield of only 35.75% and a purity of 38.26%. This method not only required harsh conditions and was costly, but also produced extremely poor results, indicating that noble metal catalysis is not suitable for this system.

[0121] Comparative Example 3 replaced the acid medium with 85% phosphoric acid and reacted at 40°C for 12 hours. The yield was only 30.75% and the purity was 80.62%, which was much lower than that of the sulfuric acid system. This proves that the acid strength of phosphoric acid is insufficient to effectively catalyze this tandem cyclization reaction.

[0122] Comparative Example 4 changed the order of addition, adding 4-bromo-3-methylphenol first and then 2-[4-(dihexylamino)-2-hydroxybenzoyl]benzoic acid, resulting in a yield of 69.07% and a purity of 75.19%. This indicates that the order of addition has a significant impact on the reaction. Allowing the carboxylic acid to fully dissolve in concentrated sulfuric acid first and undergo lactone formation to form a spirocyclic core before adding the phenolic substrate for subsequent reactions is a more reasonable feeding strategy.

[0123] Comparative Example 5 used a 70% sulfuric acid aqueous solution, and no target product was obtained. The yield was 0% and the purity was 0%. This clearly shows that the presence of water severely disrupted the strongly acidic environment required for the reaction, causing the dehydration condensation reaction to be unable to proceed.

[0124] In summary, the yield and purity of all embodiments were significantly higher than those of the comparative examples, and the combination of conditions in Example 1 (98% concentrated sulfuric acid, 25°C, 12 hours, molar ratio 1:1.05, carboxylic acid added first and phenol added later) was determined to be the optimal process.

[0125] This invention presents a one-pot acid-catalyzed tandem cyclization strategy that rapidly constructs a spirocyclic core through intramolecular esterification, utilizes protonated carbonyl groups to form an electrophilic center for intermolecular Friedel-Crafts alkylation, and finally completes the construction of the xanthonone skeleton through intramolecular etherification. This strategy achieves simplified steps, mild conditions, and controllable selectivity, providing an efficient, economical, and environmentally friendly synthetic route for the preparation of key intermediates in high-density fluorane dyes. Compared to the existing Friedel-Crafts cyclization method (yield 51.33%, purity 68.26%), this invention improves the yield by 38.92 percentage points and the purity by 30.12 percentage points. Compared to the existing transition metal catalytic method (yield 35.75%, purity 38.26%), this invention improves the yield by 54.50 percentage points and the purity by 60.12 percentage points.

[0126] In addition, oxidative coupling is also a common method in existing technologies. This method generates free radicals or highly reactive intermediates through oxidation, thereby initiating coupling and cyclization reactions. It is particularly suitable for constructing complex polycyclic spirocyclic systems. The general reaction mechanism is as follows: using chemical oxidants (such as DDQ, CAN, FeCl3, peroxy acids, etc.) or electrochemical oxidation, phenols or electron-rich aromatic ring precursors lose electrons, generating phenoxy radicals or quinone-type intermediates. These highly reactive intermediates then undergo intramolecular radical addition or nucleophilic attack, leading to the dearomatization of the aromatic ring and the formation of new C-C bonds, thereby constructing a spirocyclic system.

[0127] The main drawbacks of this method are: The primary challenge of this type of reaction is its poor chemoselectivity, which easily leads to peroxidation or the formation of multiple byproducts due to the difficulty in precisely controlling the oxidation process. The regioselectivity of the functional groups on the aromatic ring is also difficult to control, often resulting in mixed products and reducing the yield of the target product. Furthermore, the reaction typically relies on stoichiometry or even excess oxidants, resulting in low atom economy. Many oxidants are expensive and highly toxic, increasing costs and creating waste disposal problems, which contradicts the efficient and environmentally friendly principles advocated by green chemistry.

[0128] For the reasons stated above, this invention does not provide a specific comparative example of the oxidative coupling method.

[0129] Although embodiments of the present invention have been shown and described above, it is understood that the above embodiments are exemplary and should not be construed as limiting the present invention. Those skilled in the art can make changes, modifications, substitutions and variations to the above embodiments within the scope of the present invention.

Claims

1. A method for preparing spirocycloxanthone compounds, characterized in that, The spirocycloxanthone compound is 2'-bromo-6'-(dihexylamino)-3'-methyl-3H-spiro[isobenzofuran-1,9'-xanthon]-3-one; The preparation method involves reacting 2-[4-(dihexylamino)-2-hydroxybenzoyl]benzoic acid with 4-bromo-3-methylphenol under concentrated sulfuric acid catalysis, post-treating the reaction product to obtain a crude product, and separating and purifying the crude product to obtain 2'-bromo-6'-(dihexylamino)-3'-methyl-3H-spiro[isobenzofuran-1,9'-xanthon]-3-one.

2. The method for preparing a spirocycloxanthone compound according to claim 1, characterized in that, The concentrated sulfuric acid is an aqueous solution of sulfuric acid, with a mass percentage of 98%.

3. The method for preparing a spirocycloxanthone compound according to claim 1, characterized in that, The reaction is carried out at a temperature of 10-40°C for 8-14 hours.

4. The method for preparing a spirocycloxanthone compound according to claim 1, characterized in that, The molar ratio of 2-[4-(dihexylamino)-2-hydroxybenzoyl]benzoic acid to 4-bromo-3-methylphenol is 1:1 to 1:1.

5.

5. The method for preparing a spirocycloxanthone compound according to claim 1, characterized in that, Before carrying out the reaction, 2-[4-(dihexylamino)-2-hydroxybenzoyl]benzoic acid is mixed with concentrated sulfuric acid, and then 4-bromo-3-methylphenol is added.

6. The method for preparing a spirocycloxanthone compound according to claim 1, characterized in that, The reaction is carried out in an inert gas environment.

7. A method for preparing a spirocycloxanthone compound according to any one of claims 1-6, characterized in that, The post-processing involves quenching the reaction with an ice-water mixture, filtering to obtain a precipitate, washing the precipitate with alkali, and drying to obtain the crude product.

8. The method for preparing a spirocycloxanthone compound according to claim 7, characterized in that, First, the precipitate obtained by vacuum filtration is mixed with dichloromethane, washed with water to obtain a mixture, and then subjected to alkaline washing. The alkaline washing method is to add a 10% sodium hydroxide aqueous solution to make the pH of the aqueous layer of the mixture 10, and stir for 0.5-1.5 hours. After the alkaline washing is completed, the dichloromethane layer of the mixture is washed with water, dehydrated and filtered to obtain the crude product.

9. A method for preparing a spirocycloxanthone compound according to any one of claims 1-6, characterized in that, The separation and purification were carried out by column chromatography using an eluent, wherein the eluent was a mixture of petroleum ether and ethyl acetate, and the volume ratio of petroleum ether to ethyl acetate was 2-4:

1.

10. A method for preparing a spirocycloxanthone compound according to any one of claims 1-6, characterized in that, It also includes monitoring during the reaction process, wherein the monitoring method is TLC tracking.

11. A spirocycloxanthone compound, characterized in that, The spirocycloxanthone compound is 2'-bromo-6'-(dihexylamino)-3'-methyl-3H-spiro[isobenzofuran-1,9'-xanthon]-3-one prepared by the method according to any one of claims 1-10.

12. The use of the spirocyclooxanthone compound as described in claim 11 in the preparation of high color density fluorane dyes.

13. A high color density fluorane dye, characterized in that, It was prepared using the spirocyclooxanthone compound as described in claim 11.

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