Preparation method of anti-aromatic fused ring pentaporphyrin and derivative thereof

Abstract

The invention discloses a preparation method of antiaromatic fused ring pentaporphyrin and derivatives thereof, antiaromatic fused ring pentaporphyrin with a fused ring unit is synthesized by changing a pyrrole connection mode, changing the number of pyrrole units and introducing the fused ring unit, the dislocation pyrrole unit has higher reaction activity, and the derivative of the antiaromatic fused ring pentaporphyrin can be used for preparing the antiaromatic fused ring pentaporphyrin with the fused ring unit. According to the method, the anti-aromatic fused ring pentaporphyrin is further subjected to oxidation reaction under mild conditions, a novel isoporphyrin conversion product is constructed, and regulation and control on properties such as anti-aromaticity, controllable conversion and spectrum of the anti-aromatic fused ring pentaporphyrin are realized.

Description

Technical Field

[0001] The invention relates to the technical field of dislocated porphyrin and extended porphyrin chemistry, and in particular to a method for preparing an antiaromatic condensed-ring pentaporphyrin and derivatives thereof. Background Art

[0002] Porphyrin is a class of tetrapyrrole macrocyclic compounds that are widely present in nature. It has unique properties and can be used in photodynamic therapy, biomimetic catalysis and solar cells. Isoporphyrins developed by changing the porphyrin macrocyclic structure have attracted widespread attention. For example, dislocated porphyrins that change the connection mode of pyrrole units or extended porphyrins that increase the number of pyrrole units often have properties that conventional porphyrins do not have. Compared with aromatic molecules, antiaromatic molecules have smaller energy band gaps, and thus have unique chemical reactivity, near-infrared absorption, single-molecule conductivity, reversible electronic conversion and other unique properties.

[0003] Deficiencies of existing technology: At present, antiaromatic molecules often have poor stability and lack effective construction strategies. Studies in recent years have shown that isoporphyrins represented by extended porphyrins have a large conjugated electronic structure and have become one of the effective platforms for stabilizing antiaromatic molecules. By introducing heterocyclic units such as phenyl on the basis of the pyrrole molecule and developing a unique condensed ring strategy, the spatial configuration and electronic properties of the molecule can often be changed, and specific antiaromatic molecular structures can be developed. Previous studies have shown that by introducing staggered pyrrole units with a unique α-β connection method, the macrocyclic conjugation path can be changed and specific antiaromatic macrocyclic structures can be developed. However, the introduction of staggered pyrrole units often makes the porphyrin macrocycle more distorted, and even obtains a non-fully conjugated macrocyclic structure. Summary of the invention

[0004] The object of the present invention is to provide a method for preparing an antiaromatic fused-ring pentaporphyrin and its derivatives, so as to solve the problems raised in the above background technology.

[0005] To achieve the above object, the present invention provides the following technical solution: an antiaromatic condensed ring pentaporphyrin, wherein the antiaromatic condensed ring pentaporphyrin I has the structural formula: .

[0006] Preferably, the structural formula of the isoporphyrin conversion product II of the antiaromatic fused-ring pentaporphyrin is: .

[0007] The present invention also provides a method for preparing an antiaromatic condensed-ring pentaporphyrin, the method comprising the following steps: S1. Stir Tips-indole-3-methanol and pentafluorophenyltripyrrolidine in DCM at room temperature, then add trifluoroacetic acid, add triethylamine to quench after the reaction, extract, wash, dry and purify in sequence to obtain the intermediate compound I-1; S2. In an inert gas environment, I-1 is dissolved in tetrahydrofuran, and then a tetrahydrofuran solution of tetrabutylammonium fluoride is added dropwise, followed by extraction, washing, drying and purification to obtain an intermediate compound I-2; S3. At room temperature, I-2 was dissolved in DCM, and DDQ was added for oxidation. After the reaction, extraction, washing, drying and purification were performed in sequence to obtain a red solid anti-aromatic condensed ring pentaporphyrin I.

[0008] Preferably, the structural formula of the intermediate compound I-1 is: .

[0009] Preferably, the structural formula of the intermediate compound I-2 is: .

[0010] Preferably, the DDQ is 2,3-dichloro-5,6-dicyano-1,4-benzoquinone.

[0011] The present invention also provides a method for preparing an antiaromatic fused-ring pentaporphyrin and its derivatives, the preparation method comprising: S4, dissolving the antiaromatic fused-ring pentaporphyrin obtained in step S3 in dichloromethane, adding DDQ, and purifying after the reaction to obtain a brown solid as the isoporphyrin product II.

[0012] Preferably, in step S1, the mass ratio of Tips-indole-3-methanol, pentafluorophenyltripyrrolidine and trifluoroacetic acid is 1:0.2:0.16, the reaction time is 2 to 4 hours, and the specific steps of extraction, washing, drying and purification are adding an aqueous solution to quench after the reaction is completed, then extracting the solution three times with dichloromethane, washing the organic phase with an aqueous solution, drying with anhydrous sodium sulfate, and purifying by silica gel column chromatography.

[0013] Preferably, in the step S2, the mass ratio of the intermediate I-1 to tetrabutylammonium fluoride is 1:2-2.4, and the reaction time is 1 hour; in the step S3, the mass ratio of the intermediate I-2 to DDQ is 1:3, and the reaction time is 4-6 hours.

[0014] Preferably, in step S4, the mass ratio of I to DDQ is 1:2, and the reaction time is 4 to 6 hours.

[0015] Compared with the prior art, the present invention has the following beneficial effects: In the present invention, an antiaromatic pentaporphyrin with fused ring units is synthesized by changing the pyrrole connection mode, changing the number of pyrrole units and introducing fused ring units, wherein the misplaced pyrrole unit has a higher reaction activity, so that the antiaromatic fused ring pentaporphyrin can further undergo an oxidation reaction under mild conditions, a new isoporphyrin conversion product is constructed, and the regulation of the antiaromatic properties, controllable conversion and spectrum of the antiaromatic fused ring pentaporphyrin is achieved. BRIEF DESCRIPTION OF THE DRAWINGS

[0016] Figure 1 The synthetic route of the antiaromatic condensed ring pentaporphyrin and its conversion products of the present invention; Figure 2 The absorption spectrum of the antiaromatic condensed ring pentaporphyrin and its conversion product of the present invention; Figure 3 is the H NMR spectrum (298K) of the antiaromatic fused-ring pentaporphyrin I in Example 2 of the present invention; Figure 4 is the H NMR spectrum (298K) of the porphyrin product II in Example 3 of the present invention; Figure 5 Schematic diagram of the single crystal structure of the antiaromatic fused-ring pentaporphyrin I in Example 2 of the present invention; Figure 6 Schematic diagram of the single crystal structure of porphyrin product II in Example 3 of the present invention. DETAILED DESCRIPTION

[0017] 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.

[0018] In the description of the present invention, it is necessary to understand that the terms "center", "longitudinal", "lateral", "length", "width", "thickness", "up", "down", "top", "bottom", "inside", "outside", "clockwise", "counterclockwise" and the like indicating orientations or positional relationships are based on the orientations or positional relationships shown in the accompanying drawings, and are only for the convenience of describing the present invention and simplifying the description, and do not indicate or imply that the device or element referred to must have a specific orientation, be constructed and operated in a specific orientation, and therefore cannot be understood as a limitation on the present invention.

[0019] In the description of this patent, it should be noted that, unless otherwise clearly specified and limited, the terms "installation", "connection" and "setting" should be understood in a broad sense, for example, it can be fixed connection, setting, or detachable connection, setting, or integrated connection, setting. For ordinary technicians in this field, the specific meanings of the above terms in this patent can be understood according to specific circumstances.

[0020] In addition, the terms "first" and "second" are used for descriptive purposes only and should not be understood as indicating or implying relative importance or implicitly indicating the number of the indicated technical features. Thus, a feature defined as "first" or "second" may explicitly or implicitly include one or more of the features. In the description of the present invention, the meaning of "several" is two or more, unless otherwise clearly and specifically defined.

[0021] Example 1 The present invention provides a technical solution for an antiaromatic condensed ring pentaporphyrin: the structural formula of the antiaromatic condensed ring pentaporphyrin I is: ; The structural formula of the isoporphyrin transformation product II of the antiaromatic fused-ring pentaporphyrin is: .

[0022] Example 2 See also Figure 1-3 As shown in Figure 5, the present invention provides a method for preparing an antiaromatic condensed ring pentaporphyrin, which comprises the following steps: S1. In a 100 mL round-bottom flask, add tripyrrolidine (500 mg, 0.898 mmol), Tips-indole-3-methanol (1.35 g, 4.48 mmol, 5 eq) and dissolve in DCM (20 mL), add TFA (53.0 μL, 0.718 mmol, 0.8 eq), stir for 4 h in dark, add triethylamine (100 μL, 0.718 mmol) to quench the reaction, extract with dichloromethane, wash with water, dry, spin-dry at low temperature, and then silica gel column chromatography PE / DCM = 5 / 1 to obtain a green solid intermediate I-1 (1.17 g, 89.2%), and obtain the product's hydrogen nuclear magnetic resonance spectrum and mass spectrum data: 1 H NMR (400 MHz, CDCl3) δ (ppm) 8.02 – 7.59 (m, 3H), 7.28 (dd, J =8.0, 2.5 Hz, 2H), 7.09 (d, J = 6.8 Hz, 1H), 7.02 (d, J = 8.2 Hz, 1H), 6.94 (ddd,J = 8.3, 5.5, 2.7 Hz, 2H), 6.79 (d, J = 12.0 Hz, 3H), 5.83 (s, 2H), 5.78 – 5.66(m, 4H), 5.55 (d, J = 2.6 Hz, 1H), 5.47 (dd, J = 20.0, 9.9 Hz, 3H), 1.48 – 1.36(m, 6H), 0.88 (dd, J = 7.5, 1.2 Hz, 36H). HR-ESI-MS: [MH] - :calcd for C 74 H 65 F 20 N5Si2: 1458.439; found: 1458.361. The structural formula of the intermediate compound I-1 is: ; S2. Add intermediate I-1 (60 mg, 0.041 mmol) and ultra-dry THF (2 mL) to a 25 mL Schlenk tube, replace nitrogen three times at room temperature, inject TBAF (82 μL, 0.082 mmol) and dilute to 100 μL THF solution, stir at room temperature for 90 min, add water to quench the reaction, extract with dichloromethane three times, wash with water, dry with anhydrous sodium sulfate, remove the solvent with a rotary evaporator, and separate the residue by silica gel column chromatography (petroleum ether / dichloromethane = 1 / 1 (v / v)) to obtain a green solid intermediate I-2 (25.0 mg, 53.2%), and obtain the product's hydrogen nuclear magnetic resonance spectrum and mass spectrum data: 1 H NMR (400 MHz, CDCl3) δ (ppm) 8.20 –7.80 (m, 5H), 7.31 (d, J = 8.4 Hz, 2H), 7.21 (dd, J = 11.9, 4.6 Hz, 4H), 7.11 –6.96 (m, 2H), 6.83 (ddd, J = 9.5, 8.7, 1.5 Hz, 2H), 6.08 – 5.85 (m, 6H), 5.79(dd, J = 11.4, 2.7 Hz, 2H), 5.67 (dd, J= 19.5, 11.9 Hz, 2H). HR-ESI-MS: [MH] - :calcd for C 56 H 25 F 20 N5: 1146.172; found: 1146.186. The structural formula of the intermediate compound I-2 is: ; S3. Add intermediate I-2 (300 mg, 0.261 mmol) and 200 mL DCM into a 500 mL round-bottom flask, slowly dropwise add DDQ (178 mg, 0.784 mmol) dissolved in 100 mL DCM, oxidize at room temperature for 24 h, wash with water, extract with dichloromethane three times, dry with anhydrous sodium sulfate, remove the solvent with a rotary evaporator, separate by silica gel column chromatography with PE / DCM=2 / 1, and obtain red antiaromatic fused ring pentaporphyrin I (31 mg, 10%). The H NMR spectrum and mass spectrum data of the product are as follows: 1 H NMR (400 MHz, DMSO- d 6 ) δ (ppm)17.48 (s, 1H, NH), 9.91 (s, 1H, NH), 9.34 (dd, J = 4.1, 2.0 Hz, 1H), 9.26 (d, J =8.0 Hz, 1H), 8.13 (d, J = 8.3 Hz, 1H), 8.04 (dd, J = 4.1, 2.2 Hz, 1H), 7.89 (t, J =7.5 Hz, 1H), 7.62 (t, J = 7.7 Hz, 1H), 7.24 (d, J = 7.7 Hz, 2H), 7.13 (t, J = 7.4Hz, 1H), 6.94 (s, 1H), 6.88 (t, J = 8.1 Hz, 2H), 6.67 (d, J = 7.7 Hz, 1H), 6.56 –6.47 (m, 2H). HR-ESI-MS: [M+H] + : calcd for C 56 H 17 F 20N5: 1140.124; found:1140.125. This indicates that the structure of the compound is correct.

[0023] Example 3 See also Figure 1-2 As shown in , 3, and 6, the present invention provides a method for preparing an antiaromatic fused-ring pentaporphyrin and its derivatives, and the preparation method comprises: S4. Add I (15.0 mg, 0.0132 mmol) and 3 mL DCM into a 50 mL round-bottom flask, add DDQ (6.0 mg, 0.0264 mmol) dissolved in 2 mL DCM, oxidize at room temperature for 6 h, wash with water, wash with dichloromethane three times, dry with anhydrous sodium sulfate, remove the solvent on a rotary evaporator, separate on a PE / DCM=1 / 1 preparative plate, and obtain the isoporphyrin conversion product II (10 mg, 67 %). The H NMR spectrum and mass spectrum data of the product are as follows: 1 H NMR (400 MHz, CDCl3) δ (ppm) 13.70 (s, 1H, NH), 7.71(d, J = 7.6 Hz, 1H), 7.46 – 7.41 (m, 2H), 7.15 (td, J = 7.7, 1.1 Hz, 1H), 6.94(d, J = 4.6 Hz, 1H), 6.89 – 6.86 (m, 2H), 6.78 – 6.73 (m, 2H), 6.64 – 6.60 (m,2H), 6.56 – 6.50 (m, 2H), 6.35 (d, J = 4.7 Hz, 1H). HR-ESI-MS: [M+H]+: calcdfor C 56 H 15 F 20 N5O: 1154.103; found: 1154.105. This indicates that the structure of the compound is correct.

[0024] Furthermore, the Soret-like band of the antiaromatic condensed-ring pentaporphyrin absorbs at 499 nm, has a weak Q-like band absorption peak in the near-infrared region greater than 700 nm, and the absorption sideband extends to 1250 nm, which is consistent with the absorption characteristics of antiaromatic porphyrin compounds. The absorption spectrum of the isoporphyrin product II is overall blue-shifted compared to the antiaromatic condensed-ring pentaporphyrin, the S-like band is red-shifted to 330 nm, has an absorption sideband at 448 nm, and the Q-like band absorption intensity increases, indicating non-aromatic characteristics.

[0025] The above shows and describes the basic principles, main features and advantages of the present invention. Those skilled in the art should understand that the present invention is not limited by the above embodiments. The above embodiments and descriptions are only preferred examples of the present invention and are not intended to limit the present invention. Without departing from the spirit and scope of the present invention, the present invention may have various changes and improvements, which fall within the scope of the present invention. The scope of protection of the present invention is defined by the attached claims and their equivalents.

Claims

1. An antiaromatic fused-ring pentaporphyrin, characterized in that: The structural formula of the antiaromatic fused-ring pentaporphyrin I is: 。 2. An antiaromatic fused-ring pentaporphyrin according to claim 1, characterized in that: The structural formula of the isoporphyrin conversion product II of the antiaromatic fused-ring pentaporphyrin is: 。 3. The method for preparing an antiaromatic fused-ring pentaporphyrin according to claim 1, characterized in that: The preparation method comprises the following steps: S1. Stir Tips-indole-3-methanol and pentafluorophenyltripyrrolidine in DCM at room temperature, then add trifluoroacetic acid, add triethylamine to quench after the reaction, extract, wash, dry and purify in sequence to obtain the intermediate compound I-1; S2. In an inert gas environment, I-1 is dissolved in tetrahydrofuran, and then a tetrahydrofuran solution of tetrabutylammonium fluoride is added dropwise, followed by extraction, washing, drying and purification to obtain an intermediate compound I-2; S3. At room temperature, I-2 was dissolved in DCM, and DDQ was added for oxidation. After the reaction, extraction, washing, drying and purification were performed in sequence to obtain a red solid anti-aromatic condensed ring pentaporphyrin I.

4. The method for preparing an antiaromatic condensed-ring pentaporphyrin according to claim 3, characterized in that: The structural formula of the intermediate compound I-1 is: 。 5. The method for preparing an antiaromatic fused-ring pentaporphyrin according to claim 3, characterized in that: The structural formula of the intermediate compound I-2 is: 。 6. The method for preparing an antiaromatic condensed-ring pentaporphyrin according to claim 3, characterized in that: The DDQ is 2,3-dichloro-5,6-dicyano-1,4-benzoquinone.

7. A method for preparing an antiaromatic fused-ring pentaporphyrin and its derivatives according to any one of claims 1 to 6, characterized in that: This preparation method comprises: S4, dissolving the antiaromatic fused-ring pentaporphyrin obtained in step S3 in dichloromethane, adding DDQ, and purifying after the reaction to obtain a brown solid as isoporphyrin product II.

8. The method for preparing an antiaromatic condensed-ring pentaporphyrin according to claim 3, characterized in that: In step S1, the mass ratio of Tips-indole-3-methanol, pentafluorophenyltripyrrolidine and trifluoroacetic acid is 1:0.2:0.16, and the reaction time is 2-4 hours. The specific steps of extraction, washing, drying and purification are adding aqueous solution to quench after the reaction is completed, then extracting the solution three times with dichloromethane, washing the organic phase with aqueous solution, drying with anhydrous sodium sulfate, and purifying by silica gel column chromatography.

9. The method for preparing an antiaromatic condensed-ring pentaporphyrin according to claim 3, characterized in that: In the step S2, the mass ratio of the intermediate I-1 to tetrabutylammonium fluoride is 1:2-2.4, and the reaction time is 1 hour; in the step S3, the mass ratio of the intermediate I-2 to DDQ is 1:3, and the reaction time is 4-6 hours.

10. The method for preparing an antiaromatic fused-ring pentaporphyrin and its derivatives according to claim 7, characterized in that: In step S4, the mass ratio of I to DDQ is 1:2, and the reaction time is 4 to 6 hours.

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