Preparation method of substituted diphenyl porphyrin-2-formaldehyde

Abstract

The invention discloses a preparation method of substituted diphenyl porphyrin-2-formaldehyde, belongs to the technical field of preparation of porphyrin derivatives, and solves the problem of excessive operation steps in the existing preparation of formyl porphyrin. The method comprises the following steps: reacting 5-substituted phenyl dipyrromethane and trialkyl orthoformate in an organic solvent system in an oxygen-free environment until the system is in a transparent state; dropwise adding organic acid, and reacting at room temperature under a dark condition until the 5-substituted phenyl dipyrromethene is completely reacted; and adding a pH regulator to regulate the reaction system to be alkaline, mixing until the reaction is quenched, and introducing oxygen for oxidation reaction to obtain the substituted diphenyl porphyrin-2-formaldehyde. According to the method provided by the invention, the preparation method of the substituted diphenyl porphyrin-2-formaldehyde is reduced from four steps to one step, the dosage of reagents is remarkably reduced, the operation is simple and convenient, and the product is easy to separate.

Description

Technical Field

[0001] The invention relates to the technical field of preparation of porphyrin derivatives, and more specifically to a preparation method of substituted diphenylporphyrin-2-carboxaldehyde. Background Art

[0002] Porphyrin is a highly conjugated macrocyclic compound with excellent photophysical properties such as good photothermal stability, large Stokes shift and long emission wavelength. It has a wide range of applications in photodynamic therapy, optoelectronic devices, fluorescence analysis, photoelectrocatalysis and supramolecular chemistry. Therefore, the synthesis of porphyrin and its derivatives has always attracted extensive attention from researchers.

[0003] Traditional porphyrin synthesis includes Adler-Longo method, Lindsey method, 2-substituted pyrrole ring-closure reaction method, [2+2] method, [3+1] method and modification of porphyrin peripheral substituents and other methods. Through these synthetic methods, different types of porphyrin derivatives can be obtained, such as symmetrical and asymmetrical porphyrins, porphyrin derivatives containing one or more functional groups (such as aldehyde group, sulfonic acid group, carboxyl group, halogen, hydroxyl group, nitro group, amino group, alkyl group and aryl group, etc.). At present, the types and quantities of porphyrins have increased significantly, and their performance and application range have also been further improved. Introducing active functional groups in the porphyrin molecular structure is a basic operating method for synthesizing porphyrin intermediates or improving the application performance of porphyrins, such as introducing sulfonic acid group or carboxyl group to improve its water solubility, introducing halogen to carry out intermolecular CC bond coupling, and using the introduced active amino group and aldehyde group to make further modifications and so on. The formylation of porphyrin (introduction of aldehyde groups on the porphyrin ring) has attracted widespread attention from researchers.

[0004] At present, the formylation reaction of porphyrin needs to go through the following four steps: the first step is to synthesize the porphyrin matrix, the second step is to complex the porphyrin matrix with metals such as copper and nickel to obtain metal porphyrin, the third step is to introduce a formyl group at the meso or β (2) position of the metal porphyrin through the Vilsmeier formylation reaction to obtain a formyl metal porphyrin, and the fourth step is to remove the metal from the formyl metal porphyrin under strong acidic conditions to finally obtain a formyl free porphyrin. Because the synthesis steps are many, there are disadvantages such as complex operation, large amount of reagents, and difficulty in separation, which greatly limits the subsequent application of formyl porphyrin. Therefore, how to reduce the synthesis steps of formyl porphyrin as much as possible to reduce the amount of reagents, reduce the difficulty of operation and separation has important practical significance.

[0005] In view of this, the present invention is proposed. Summary of the invention

[0006] The invention provides a method for preparing substituted diphenylporphyrin-2-carboxaldehyde, which is used to solve the problem of too many operation steps in the existing preparation of formylporphyrin.

[0007] In a first aspect, the present invention provides a method for preparing a substituted diphenylporphyrin-2-carboxaldehyde. Exemplarily, the substituted diphenylporphyrin-2-carboxaldehyde is 5,15-diphenylporphyrin-2-carboxaldehyde, 5,15-bis(4-acetoxyphenyl)porphyrin-2-carboxaldehyde, 5,15-bis(4-methoxyphenyl)porphyrin-2-carboxaldehyde, 5,15-bis(4-nitrophenyl)porphyrin-2-carboxaldehyde, 5,15-bis(4-dimethylaminophenyl)porphyrin-2-carboxaldehyde and 5,15-bis(4-diphenylaminophenyl)porphyrin-2-carboxaldehyde. The preparation method comprises the following steps: reacting 5-substituted phenyl dipyrromethane and trialkyl orthoformate in an organic solvent system and an oxygen-free environment until the system is transparent; dropping an organic acid, reacting at room temperature and in the dark until the 5-substituted phenyl dipyrromethane reacts completely; adding a pH regulator to adjust the reaction system to alkalinity, mixing until the reaction is quenched, and introducing oxygen for oxidation reaction to obtain the target product. The oxygen-free environment prevents the 5-substituted phenyl dipyrromethane from being oxidized.

[0008] For example, the synthesis route of the substituted diphenylporphyrin-2-carboxaldehyde is as shown in Formula I.

[0009]

[0010] In formula I, R is any one of -H, -OCOCH3, -OCH3, -NO2, -N(CH3)2 and -N(C6H5)2.

[0011] As a possible implementation, the 5-substituted phenyl dipyrromethane is any one of 5-phenyl dipyrromethane, 5-(4-acetoxyphenyl) dipyrromethane, 5-(4-methoxyphenyl) dipyrromethane, 5-(4-nitrophenyl) dipyrromethane, 5-(4-N,N-dimethylaminophenyl) dipyrromethane and 5-(4-N,N-diphenylaminophenyl) dipyrromethane; and / or the trialkyl orthoformate is one of triethyl orthoformate and trimethyl orthoformate; and / or the organic acid is one of trifluoroacetic acid and trichloroacetic acid. Among them, based on the consideration of electronic effect, 5-substituted phenyldipyrromethane selected the above-mentioned ones, methoxy, 4-N,N-dimethylaminophenyl, 4-N,N-diphenylaminophenyl are electron-donating groups, nitro is an electron-withdrawing group, and 5-phenyldipyrromethane is hydrogen, that is, it does not contain electron-donating and electron-withdrawing groups. It can be seen that the selectivity of substituents on the benzene ring of 5-phenyldipyrromethane is wide. Trialkyl orthoformate has two functions, one is as a reaction reagent (i.e., cyclization agent) for the synthesis of diphenylporphyrin, and the other is as a formylation reagent for diphenylporphyrin (i.e., introducing aldehyde groups).

[0012] As a possible implementation method, 5-substituted phenyl dipyrromethane and trialkyl orthoformate are reacted in an organic solvent system and an oxygen-free environment until the system becomes transparent, wherein the molar ratio of the 5-substituted phenyl dipyrromethane to the trialkyl orthoformate is 1:40 to 80; and / or, the ratio of the 5-substituted phenyl dipyrromethane to the organic solvent is 1 mmol:230 to 300 mL; and / or, an organic acid is added dropwise, wherein the molar ratio of the 5-substituted phenyl dipyrromethane to the organic acid is 1:23 to 26.

[0013] As a possible implementation manner, in the organic solvent system, the organic solvent is one of dichloromethane and chloroform; and / or the oxygen-free environment is a sealed, light-proof, nitrogen environment.

[0014] As a possible implementation manner, the organic acid is an organic acid solution, and the solvent thereof is one of dichloromethane and chloroform; in the organic acid solution, the concentration of the organic acid is 0.17 to 0.25 mol / L.

[0015] As a possible implementation manner, the pH adjuster is any one of triethylamine, pyridine and ammonia water; and / or, adjusting the reaction system to alkalinity means adjusting the pH value of the reaction system to 8-10.

[0016] As a possible implementation method, the method further includes: evaporating and drying the product of the oxidation reaction in sequence to obtain a crude product; separating and purifying the crude product by silica gel column chromatography, collecting a second color band, and obtaining the substituted diphenylporphyrin-2-carboxaldehyde; and performing reduced pressure rotary evaporation to remove dichloromethane and triethylamine.

[0017] As a possible implementation manner, the evaporation is reduced-pressure rotary evaporation; and / or, the drying is vacuum drying; and / or, in the silica gel column chromatography, a mixture of dichloromethane and petroleum ether is used as an eluent; and / or, in the mixture of dichloromethane and petroleum ether, the volume ratio of dichloromethane to the petroleum ether is 1:1 to 3.

[0018] In a second aspect, the present invention provides a substituted diphenylporphyrin-2-carboxaldehyde prepared by the preparation method described in any possible implementation of the first aspect.

[0019] In a third aspect, the present invention provides a use of the substituted diphenylporphyrin-2-carboxaldehyde described in the second aspect in the preparation of a drug.

[0020] The preparation method provided by the present invention uses 5-substituted phenyldipyrromethane as a precursor and trialkyl orthoformate as a cyclization and formylation agent, and under acid catalysis, cyclization, formylation, quenching and oxidation are carried out in one pot to prepare substituted diphenylporphyrin-2-carboxaldehyde. The preparation method of the present invention reduces the four steps of the prior art to one step, significantly reduces the operation steps in the preparation process, significantly reduces the amount of reagents used, is simpler to operate, and the product is easy to separate and purify.

[0021] The preparation method provided by the present invention uses trialkyl orthoformate as a cyclization and formylation agent, and the reagent cost is low and the dosage is small; an organic acid is used as a catalyst, and the reagent source is wide, the cost is low, and the dosage is small; the reagent dosage and preparation cost of substituted diphenylporphyrin-2-carboxaldehyde are significantly reduced. The preparation method provided by the present invention uses a reduced pressure rotary evaporation method to remove impurities dichloromethane and triethylamine, and a vacuum drying method is used to obtain a crude product; the purification method is simple and easy to operate. The present invention uses a silica gel column chromatography method to separate the crude product to obtain a target product with higher purity, and the separation method is simple and easy to operate.

[0022] The preparation method provided by the present invention has potential application value in the further functional modification of porphyrin because multiple functional groups are introduced at the same time. Aldehyde group is a functional group with high chemical activity. Aldehyde group can be reduced to carboxyl group to obtain diphenylporphyrin containing carboxyl group, which enhances water solubility; amino compounds are bonded by Schiff base reaction to form Schiff base porphyrin with amines. Schiff base has antibacterial activity, and porphyrin can produce singlet state, thereby enhancing the application of porphyrin in biomedicine. BRIEF DESCRIPTION OF THE DRAWINGS

[0023] In order to more clearly illustrate the embodiments of the present invention or the technical solutions in the prior art, the drawings required for use in the embodiments or the description of the prior art will be briefly introduced below. Obviously, the drawings described below are only some embodiments of the present invention. For ordinary technicians in this field, other drawings can be obtained based on these drawings without paying creative work.

[0024] Figure 1 Mass spectrum [M+H] of 5,15-diphenylporphyrin-2-carboxaldehyde provided in the embodiment of the present invention + picture.

[0025] Figure 2 The hydrogen nuclear magnetic resonance spectrum of 5,15-diphenylporphyrin-2-carboxaldehyde provided in an embodiment of the present invention.

[0026] Figure 3 Mass spectrum [M+H] of 5,15-bis(4-acetoxyphenyl)porphyrin-2-carboxaldehyde provided in the embodiment of the present invention + picture.

[0027] Figure 4This is a hydrogen nuclear magnetic resonance spectrum of 5,15-bis(4-acetoxyphenyl)porphyrin-2-carboxaldehyde provided in an embodiment of the present invention.

[0028] Figure 5 Mass spectrum [M+H] of 5,15-bis(4-methoxyphenyl)porphyrin-2-carboxaldehyde provided in the embodiment of the present invention + picture.

[0029] Figure 6 This is a hydrogen nuclear magnetic resonance spectrum of 5,15-bis(4-methoxyphenyl)porphyrin-2-carbaldehyde provided in an embodiment of the present invention. DETAILED DESCRIPTION

[0030] The following will be combined with the drawings in the embodiments of the present invention to clearly and completely describe the technical solutions in the embodiments of the present invention. Obviously, the described embodiments are only part of the embodiments of the present invention, not all of the embodiments. Based on the embodiments of the present invention, all other embodiments obtained by ordinary technicians in this field without creative work are within the scope of protection of the present invention.

[0031] In order to solve the problem that the existing preparation of formylporphyrin has too many operation steps, the present invention provides a preparation method of substituted diphenylporphyrin-2-carboxaldehyde.

[0032] The preparation method of substituted diphenylporphyrin-2-carboxaldehyde provided in an embodiment of the present invention comprises the following steps: reacting 5-substituted phenyl dipyrromethane and trialkyl orthoformate in an organic solvent system and an oxygen-free environment until the system is transparent; dropping an organic acid, reacting at room temperature and in the dark until the 5-substituted phenyl dipyrromethane is completely reacted; adding a pH regulator to adjust the reaction system to alkalinity, mixing until the reaction is quenched, and introducing oxygen for oxidation reaction to obtain substituted diphenylporphyrin-2-carboxaldehyde.

[0033] Furthermore, the embodiments of the present invention apply the preparation method provided by the present invention to prepare 5,15-diphenylporphyrin-2-carboxaldehyde, 5,15-bis(4-acetoxyphenyl)porphyrin-2-carboxaldehyde, 5,15-bis(4-methoxyphenyl)porphyrin-2-carboxaldehyde, 5,15-bis(4-nitrophenyl)porphyrin-2-carboxaldehyde, 5,15-bis(4-dimethylaminophenyl)porphyrin-2-carboxaldehyde and 5,15-bis(4-diphenylaminophenyl)porphyrin-2-carboxaldehyde.

[0034] The method provided by the invention reduces the preparation method of substituted diphenylporphyrin-2-carboxaldehyde from 4 steps to 1 step, significantly reduces the amount of reagents used, is more convenient to operate, and is easy to separate and purify the product.

[0035] The technical solution of the present invention will be further described below in conjunction with specific embodiments.

[0036] Example 1

[0037] This embodiment provides a method for preparing 5,15-diphenylporphyrin-2-carboxaldehyde.

[0038]

[0039] According to the synthetic route shown in Formula II, 252 mg of 5-phenyldipyrromethane (compound 1, 1.0 mmol), 6.7 mL of triethyl orthoformate (CH(EtO)3, 40 mmol) and dichloromethane (230 mL) were added to a three-necked flask, and a mixed solution of dichloromethane (92 mL) and 2.3 mL of trichloroacetic acid (TCA, 23 mmol) was added to a constant pressure dropping funnel and shaken well; the reaction apparatus was sealed, protected from light, nitrogen was passed through, and a magnetic stirrer was turned on. After passing nitrogen for 30 minutes, the system was transparent, and the mixed solution in the dropping funnel was added dropwise. After the addition was completed, the mixture was stirred at room temperature and protected from light for 5 hours until the system showed a dark green color, triethylamine (TEA) was added, the pH value of the reaction system was adjusted to 8, and the mixture was stirred for 2 hours to quench the reaction. Finally, air was passed through for oxidation and stirred for 12 hours until the system emitted strong red fluorescence under 365 nm ultraviolet light. The reaction solution was subjected to reduced pressure rotary evaporation to remove dichloromethane and triethylamine, and vacuum dried to obtain a solid crude product. The crude product was separated and purified by silica gel column chromatography, and the eluent was a mixed solvent of dichloromethane and petroleum ether, and the volume ratio of dichloromethane: petroleum ether was 1:1. The second color band was collected to obtain a purple pure product of 5,15-diphenylporphyrin-2-carboxaldehyde (Compound 2); its mass spectrum was as follows Figure 1 , H NMR spectrum (solvent: CD2Cl2) Figure 2 ,Depend on Figure 1 and Figure 2 It can be seen that 5,15-diphenylporphyrin-2-carboxaldehyde was prepared in this example.

[0040] Example 2

[0041] This embodiment provides a method for preparing 5,15-diphenylporphyrin-2-carboxaldehyde.

[0042]

[0043] According to the synthetic route shown in Formula III, 252 mg of 5-phenyldipyrrolmethane (compound 1, 1.0 mmol), 8.8 mL of trimethyl orthoformate (CH(MeO)3, 80 mmol) and dichloromethane (300 mL) were added to a three-necked flask, and a mixed solution of dichloromethane (156 mL) and 1.9 mL of trifluoroacetic acid (TFA, 26 mmol) was added to a constant pressure dropping funnel and shaken well; the reaction apparatus was sealed, protected from light, nitrogen was passed through, and a magnetic stirrer was turned on. After passing nitrogen for 30 minutes, the mixed solution in the dropping funnel was added dropwise. After the addition was completed, the mixture was stirred at room temperature in the dark for 10 hours, pyridine was added, the pH value of the reaction system was adjusted to 10, stirred for 4 hours, the reaction was quenched, and finally air was passed through for oxidation and stirred for 24 hours. The reaction solution was subjected to reduced pressure rotary evaporation to remove dichloromethane and pyridine, and vacuum dried to obtain a solid crude product. The crude product was separated and purified by silica gel column chromatography, and the eluent was a mixed solvent of dichloromethane and petroleum ether, and the volume ratio of dichloromethane: petroleum ether was 1:3. The second color band was collected, and finally the purple pure product of 5,15-diphenylporphyrin-2-carboxaldehyde (Compound 2) was obtained; its mass spectrum was as follows Figure 1 , H NMR spectrum (solvent: CD2Cl2) Figure 2 ,Depend on Figure 1 and Figure 2 It can be seen that 5,15-diphenylporphyrin-2-carboxaldehyde was prepared in this example.

[0044] Example 3

[0045] This embodiment provides a method for preparing 5,15-bis(4-acetoxyphenyl)porphyrin-2-carboxaldehyde.

[0046]

[0047] According to the synthetic route shown in Formula IV, 280 mg of 5-(4-acetoxyphenyl)dipyrromethane (compound 3, 1.0 mmol), 6.7 mL of triethyl orthoformate (CH(EtO)3, 40 mmol) and dichloromethane (230 mL) were added to a three-necked flask, and a mixed solution of dichloromethane (92 mL) and 2.3 mL of trichloroacetic acid (TCA, 23 mmol) was added to a constant pressure dropping funnel and shaken well; the reaction apparatus was sealed, protected from light, nitrogen was passed through, and a magnetic stirrer was turned on. After passing nitrogen for 30 minutes, the mixed solution in the dropping funnel was added dropwise. After the addition was completed, the mixture was stirred at room temperature in the dark for 5 hours, triethylamine (TEA) was added, the pH value of the reaction system was adjusted to 8, stirred for 2 hours, the reaction was quenched, and finally air was passed through for oxidation and stirring for 12 hours. The reaction solution was subjected to reduced pressure rotary evaporation to remove dichloromethane and triethylamine, and vacuum dried to obtain a solid crude product. The crude product was separated and purified by silica gel column chromatography, and the eluent was a mixed solvent of dichloromethane and petroleum ether, and the volume ratio of dichloromethane: petroleum ether was 1:1. The second color band was collected, and finally the purple pure product of 5,15-bis(4-acetoxyphenyl)porphyrin-2-carboxaldehyde (compound 4) was obtained; its mass spectrum was as follows Figure 3 , H NMR spectrum (solvent: CD2Cl2) Figure 4 ,Depend on Figure 3 and Figure 4 It can be seen that 5,15-bis(4-acetoxyphenyl)porphyrin-2-carboxaldehyde was prepared in this example.

[0048] Example 4

[0049] This embodiment provides a method for preparing 5,15-bis(4-methoxyphenyl)porphyrin-2-carbaldehyde.

[0050]

[0051] According to the synthetic route shown in Formula V, 252 mg of 5-(4-methoxyphenyl)dipyrromethane (compound 5, 1.0 mmol), 6.7 mL of triethyl orthoformate (CH(EtO)3, 40 mmol) and dichloromethane (230 mL) were added to a three-necked flask, and a mixed solution of dichloromethane (92 mL) and 2.3 mL of trichloroacetic acid (TCA, 23 mmol) was added to a constant pressure dropping funnel and shaken well; the reaction apparatus was sealed, protected from light, nitrogen was passed through, and a magnetic stirrer was turned on. After passing nitrogen for 30 minutes, the mixed solution in the dropping funnel was added dropwise. After the addition was completed, the mixture was stirred at room temperature in the dark for 10 hours, and then triethylamine (TEA) was added, the pH value of the reaction system was adjusted to 8, stirred for 2 hours, and the reaction was quenched. Finally, air was passed through to oxidize and stir for 12 hours. The reaction solution was subjected to reduced pressure rotary evaporation to remove dichloromethane and triethylamine, and vacuum dried to obtain a solid crude product. The crude product was separated and purified by silica gel column chromatography, and the eluent was a mixed solvent of dichloromethane and petroleum ether, and the volume ratio of dichloromethane: petroleum ether was 1:1. The second color band was collected, and finally the purple pure product of 5,15-di(4-methoxyphenyl)porphyrin-2-carboxaldehyde (Compound 6) was obtained; its mass spectrum was as follows Figure 5 , H NMR spectrum (solvent: CD2Cl2) Figure 6 ,Depend on Figure 5 and Figure 6 It can be seen that 5,15-bis(4-methoxyphenyl)porphyrin-2-carbaldehyde was prepared in this example.

[0052] Example 5

[0053] This embodiment provides a method for preparing 5,15-di(4-nitrophenyl)porphyrin-2-carboxaldehyde.

[0054]

[0055] According to the synthetic route shown in Formula VI, 267 mg of 5-(4-nitrophenyl)dipyrromethane (compound 7, 1.0 mmol), 6.7 mL of triethyl orthoformate (CH(EtO)3, 40 mmol) and dichloromethane (230 mL) were added to a three-necked flask, and a mixed solution of dichloromethane (92 mL) and 2.3 mL of trichloroacetic acid (TCA, 23 mmol) was added to a constant pressure dropping funnel and shaken well; the reaction apparatus was sealed, protected from light, nitrogen was passed through, and a magnetic stirrer was turned on. After passing nitrogen for 30 minutes, the mixed solution in the dropping funnel was added dropwise. After the addition was completed, the mixture was stirred at room temperature in the dark for 5 hours, triethylamine (TEA) was added, the pH value of the reaction system was adjusted to 8, stirred for 2 hours, the reaction was quenched, and finally air was passed through for oxidation and stirring for 12 hours. The reaction solution was subjected to reduced pressure rotary evaporation to remove dichloromethane and triethylamine, and vacuum dried to obtain a solid crude product. The crude product was separated and purified by silica gel column chromatography, and the eluent was a mixed solvent of dichloromethane and petroleum ether, and the volume ratio of dichloromethane: petroleum ether was 1: 1. The second color band was collected, and finally the purple pure product of 5,15-di(4-nitrophenyl)porphyrin-2-carboxaldehyde (Compound 8) was obtained.

[0056] Example 6

[0057] This embodiment provides a method for preparing 5,15-bis(4-dimethylaminophenyl)porphyrin-2-carbaldehyde.

[0058]

[0059] According to the synthetic route shown in Formula VII, 265 mg of 5-(4-N,N-dimethylaminophenyl)dipyrromethane (compound 9, 1.0 mmol), 6.7 mL of triethyl orthoformate (CH(EtO)3, 40 mmol) and dichloromethane (230 mL) were added to a three-necked flask, and a mixed solution of dichloromethane (92 mL) and 2.3 mL of trichloroacetic acid (TCA, 23 mmol) was added to a constant pressure dropping funnel and shaken well; the reaction apparatus was sealed, protected from light, nitrogen was passed through, and a magnetic stirrer was turned on. After passing nitrogen for 30 minutes, the mixed solution in the dropping funnel was added dropwise. After the addition was completed, the mixture was stirred at room temperature in the dark for 5 hours, triethylamine (TEA) was added, the pH value of the reaction system was adjusted to 8, stirred for 2 hours, the reaction was quenched, and finally air was passed through for oxidation and stirred for 12 hours. The reaction solution was subjected to reduced pressure rotary evaporation to remove dichloromethane and triethylamine, and vacuum dried to obtain a solid crude product. The crude product was separated and purified by silica gel column chromatography, and the eluent was a mixed solvent of dichloromethane and petroleum ether, and the volume ratio of dichloromethane: petroleum ether was 1:1. The second color band was collected, and finally the purple pure product of 5,15-bis(4-dimethylaminophenyl)porphyrin-2-carboxaldehyde (Compound 10) was obtained.

[0060] Example 7

[0061] This embodiment provides a method for preparing 5,15-bis(4-diphenylaminophenyl)porphyrin-2-carboxaldehyde.

[0062]

[0063] According to the synthetic route shown in Formula VIII, 389 mg of 5-(4-N,N-diphenylaminophenyl)dipyrromethane (compound 11, 1.0 mmol), 6.7 mL of triethyl orthoformate (CH(EtO)3, 40 mmol) and dichloromethane (230 mL) were added to a three-necked flask, and a mixed solution of dichloromethane (92 mL) and 2.3 mL of trichloroacetic acid (TCA, 23 mmol) was added to a constant pressure dropping funnel and shaken well; the reaction apparatus was sealed, protected from light, nitrogen was passed through, and a magnetic stirrer was turned on. After passing nitrogen for 30 minutes, the mixed solution in the dropping funnel was added dropwise. After the addition was completed, the mixture was stirred at room temperature in the dark for 5 hours, triethylamine (TEA) was added, the pH value of the reaction system was adjusted to 8, stirred for 2 hours, the reaction was quenched, and finally air was passed through for oxidation and stirred for 12 hours. The reaction solution was subjected to reduced pressure rotary evaporation to remove dichloromethane and triethylamine, and vacuum dried to obtain a solid crude product. The crude product was separated and purified by silica gel column chromatography, and the eluent was a mixed solvent of dichloromethane and petroleum ether, and the volume ratio of dichloromethane: petroleum ether was 1:1. The second color band was collected, and finally the purple pure product of 5,15-bis(4-diphenylaminophenyl)porphyrin-2-carboxaldehyde (Compound 12) was obtained.

[0064] Although the preferred embodiments of the present invention have been described, those skilled in the art may make other changes and modifications to these embodiments once they have learned the basic creative concept. Therefore, the appended claims are intended to be interpreted as including the preferred embodiments and all changes and modifications that fall within the scope of the present invention.

[0065] Obviously, those skilled in the art can make various changes and modifications to the present invention without departing from the spirit and scope of the present invention. Thus, if these modifications and variations of the present invention fall within the scope of the claims of the present invention and their equivalents, the present invention is also intended to include these modifications and variations.

Claims

1. A method for preparing substituted diphenylporphyrin-2-carboxaldehyde, characterized in that: The following steps are involved: Reacting 5-substituted phenyldipyrromethane and trialkyl orthoformate in an organic solvent system under an oxygen-free environment until the system becomes transparent; Add an organic acid dropwise and react at room temperature in the dark until the 5-substituted phenyl dipyrromethane reacts completely; A pH regulator is added to adjust the reaction system to alkalinity, the mixture is mixed until the reaction is quenched, and oxygen is introduced for oxidation reaction to obtain the substituted diphenylporphyrin-2-carboxaldehyde.

2. The method according to claim 1, characterized in that The 5-substituted phenyl dipyrromethane is one of 5-phenyl dipyrromethane, 5-(4-acetoxyphenyl) dipyrromethane, 5-(4-methoxyphenyl) dipyrromethane, 5-(4-nitrophenyl) dipyrromethane, 5-(4-N,N-dimethylaminophenyl) dipyrromethane and 5-(4-N,N-diphenylaminophenyl) dipyrromethane; And / or, the trialkyl orthoformate is one of triethyl orthoformate and trimethyl orthoformate; And / or, the organic acid is one of trifluoroacetic acid and trichloroacetic acid.

3. The method according to claim 1, characterized in that The step of reacting 5-substituted phenyl dipyrromethane and trialkyl orthoformate in an organic solvent system and an oxygen-free environment until the system becomes transparent, wherein the molar ratio of the 5-substituted phenyl dipyrromethane to the trialkyl orthoformate is 1:40 to 80; and / or, the ratio of the 5-substituted phenyl dipyrromethane to the organic solvent is 1 mmol: 230-300 mL; And / or, the organic acid is added dropwise, wherein the molar ratio of the 5-substituted phenyldipyrromethane to the organic acid is 1:23-26.

4. The method according to claim 1, characterized in that: In the organic solvent system, the organic solvent is one of dichloromethane and chloroform; And / or, the oxygen-free environment is a sealed, light-proof, nitrogen environment.

5. The method according to claim 1, characterized in that The organic acid is a solution of an organic acid, and the solvent thereof is one of dichloromethane and chloroform; And / or, in the organic acid solution, the concentration of the organic acid is 0.17-0.25 mol / L.

6. The method according to claim 1, characterized in that The pH regulator is any one of triethylamine, pyridine and ammonia water; And / or, adjusting the reaction system to alkalinity means adjusting the pH value of the reaction system to 8-10.

7. The method according to claim 1, characterized in that Also includes: The product of the oxidation reaction is evaporated and dried in sequence to obtain a crude product; The crude product is separated and purified by silica gel column chromatography, and the second color band is collected to obtain the substituted diphenylporphyrin-2-carboxaldehyde.

8. The method according to claim 7, characterized in that The evaporation is reduced pressure rotary evaporation; And / or, the drying is vacuum drying; And / or, in the silica gel column chromatography, a mixture of dichloromethane and petroleum ether is used as an eluent; And / or, in the mixed solution of dichloromethane and petroleum ether, the volume ratio of the dichloromethane to the petroleum ether is 1:1-3.

9. A substituted diphenylporphyrin-2-carboxaldehyde prepared by the preparation method according to any one of claims 1 to 8.

10. Use of the substituted diphenylporphyrin-2-carboxaldehyde according to claim 9 in the preparation of medicines.

Images