CN115057873A - 5,10,15,20-tetrakis(pentafluorophenyl)-2,3-benzothiazole fused chlorophyll compound and preparation method thereof - Google Patents

Abstract

The invention discloses a 5,10,15,20-tetrakis(pentafluorophenyl)-2,3-benzothiazole condensed chlorophyll compound and a preparation method. The compound of the present invention is 5,10,15,20-tetrakis(pentafluorophenyl)-2,3-benzothiazole fused chlorophyll compound, and its structural formula is shown in formula (1). The preparation method of the present invention is mainly to weigh a certain amount of 2-nitro-5, 10, 15, 20-tetrakis (pentafluorophenyl) porphyrin, 2-aroyl benzothiazole bromide and triethylamine Placed in the reactor; then add dichloromethane solvent to the reactor, stir at room temperature for 1-3 hours, follow the reaction by chromatography; after the reaction is complete, cool to room temperature, directly use a chromatography column to separate, wash The removal agent is dichloromethane and n-hexane, and the first red band is collected to obtain the crude product. The crude product is concentrated and dried to obtain the target compound. The synthesis route of the invention is simple, and a brand-new synthesis route is provided for the synthesis of 5, 10, 15, 20-tetraaryl chlorophyll.

Description

5,10,15,20-Tetrakis(pentafluorophenyl)-2,3-benzothiazole fused chlorophyll compound and preparation method

technical field

The invention belongs to the technical field of organic synthesis, in particular to a 5,10,15,20-tetrakis(pentafluorophenyl)-2,3-benzothiazole fused chlorophyll compound and a preparation method thereof.

Background technique

5,10,15,20-Tetraarylporphyrins have broad application prospects in the fields of chemical catalysis, molecular switches, anion sensors, biologically relevant metal chemistry, photodynamic therapy, supramolecular self-assembly chemistry and coordination chemistry. And the derivatization of 5,10,15,20-tetraaryl porphyrin to convert it into 5,10,15,20-tetraarylchlorophyll, which can provide functional molecules for scientific research, has become a domestic and foreign One of the research hotspots.

At present, there is no literature report on the synthesis method of 5,10,15,20-tetrakis(pentafluorophenyl)-2,3-benzothiazole fused chlorophyll compounds. After the applicant's research and many attempts, a new way has been developed, and a simple synthetic route has been obtained through a large number of experimental explorations. 5,10,15,20-tetrakis(pentafluorophenyl) -2,3-benzothiazole fused chlorophyll compounds provide a new synthetic route for the synthesis of 5,10,15,20-tetraarylchlorophyll.

SUMMARY OF THE INVENTION

One of the objects of the present invention is to provide a new compound 5,10,15,20-tetrakis(pentafluorophenyl)-2,3-benzothiazole fused chlorophyll compound synthesized by one-step method, and its structural formula is as follows Formula (1) shows:

In formula (1), Ar is one of the structural formulas shown in formula (2) to formula (8):

The second object of the present invention is to provide a method for preparing the above-mentioned 5,10,15,20-tetrakis(pentafluorophenyl)-2,3-benzothiazole fused chlorophyll compound, which comprises the following steps:

(1) Weigh a certain amount of 2-nitro-5,10,15,20-tetrakis (pentafluorophenyl) porphyrin, 2-aroyl benzothiazole bromide and triethylamine and place them in the reactor ; Wherein, the structural formula of 2-aroyl benzothiazole bromide is shown in formula (9):

In formula (9), Ar is one of the structural formulas shown in formula (2) to formula (8):

(2) adding dichloromethane solvent to the reactor of step (1) again, stirring at room temperature for 1-3 hours, and tracking the reaction by chromatographic method;

(3) after the reaction is completed, it is cooled to room temperature, directly separated by a chromatographic column, the eluent is dichloromethane and n-hexane, and the first red band is collected to be the thick product, and the thick product is concentrated and dried to obtain target compound.

Preferably, in step (1), the three types of 2-nitro-5,10,15,20-tetrakis(pentafluorophenyl)porphyrin, 2-aroyl benzothiazole bromide and triethylamine The ratio of the amount of reactants is 1:2:3.

Specifically, in step (2), the chromatographic method for tracking the reaction is any one of thin layer chromatography, gas chromatography and high performance liquid chromatography.

Preferably, in step (3), the eluent is a mixed solvent of dichloromethane and n-hexane with a volume ratio of 1:3.

Compared with the prior art, the present invention has the following characteristics and beneficial effects:

(1) The synthesis method of 5,10,15,20-tetrakis(pentafluorophenyl)-2,3-benzothiazole fused chlorophyll compound has not been reported in literature, and has the characteristics of mild reaction conditions, simple and safe operation, etc. is a brand new technology.

(2) The method of the present invention can prepare 5,10,15,20-tetrakis(pentafluorophenyl)-2,3-benzothiazole fused chlorophyll compounds with different substituents by changing different substituents on the benzene ring .

(3) The 5,10,15,20-tetrakis(pentafluorophenyl)-2,3-benzothiazole fused chlorophyll compound prepared by the method of the present invention is potentially important in the research and application of photodynamic therapy of cancer significance.

Description of drawings

Fig. 1 and Fig. 2 are respectively the calculated value of high-resolution mass spectrometry and high-resolution mass spectrometry of the target product 5,10,15,20-tetrakis(pentafluorophenyl)-2,3-benzothiazole-fused chlorophyll in Example 1 of the present invention mass spectrum.

Detailed ways

The present invention will be described in further detail below with reference to the accompanying drawings and specific experimental examples, which do not limit the present invention in any way.

Example 1:

Weigh out 2-nitro-5,10,15,20-tetrakis(pentafluorophenyl)porphyrin (0.05mmol), 2-benzoylbenzothiazole bromide (0.10mmol) and triethylamine (0.15mmol) ) in a 25mL round-bottomed flask, add dichloromethane (4ml) to the above-mentioned reactor, stir the reaction at room temperature for 1 hour, use thin layer chromatography (TLC) to track the reaction, and after the reaction is complete, use 200-300 mesh silica gel to carry out the column. Chromatography, using a mixed solvent of dichloromethane and n-hexane with a volume ratio of 1:3 as the eluent, collect the solution in the first elution zone, and the collected solution is concentrated and dried to obtain a dark brown product, namely The product 5,10,15,20-tetrakis(pentafluorophenyl)-2,3-benzothiazole condensed chlorophyll compound was obtained, and the yield was 57%.

Spectral characterization data of the products are as follows: ¹ H NMR (400MHz, CDCl ₃ , 298K)δ:-2.19(br,1H),-2.17(br,1H), 5.12-5.14(m,1H), 6.27-6.31(m, 1H), 6.53-6.55(m, 1H), 6.68-6.70(m, 1H), 6.77-6.82(m, 1H), 6.98-7.00(m, 1H), 7.04(s, 1H), 7.37-7.40( m,2H),7.48-7.52(m,2H),7.62-7.66(m,1H),8.34-8.41(m,2H),8.54-8.59(m,2H),8.73-8.80(m,2H). UV-vis(CH ₂ Cl ₂ ) _λmax /nm(logε): 407(4.96), 503(3.91), 531(3.52), 594(3.38), 647(4.26).API-HRMS calc.forC ₅₉ H _21F20N6O3S ⁺ _{[ M} +H] ⁺ : _1273.1071 ,Found:1273.1071.

Spectral data indicated that the above preparation method yielded 5,10,15,20-tetrakis(pentafluorophenyl)-2,3-(benzoyl)benzothiazole fused chlorophyll.

Example 2:

The present embodiment adopts the substantially same synthesis technique as in Example 1, except that the raw material is changed to 2-(4-bromo)benzoylbenzothiazole bromide to obtain a dark brown product, namely, products 5,10, 15,20-Tetrakis(pentafluorophenyl)-2,3-(4-bromobenzoyl)benzothiazole fused chlorophyll in 61% yield.

The spectral characterization data of the products are as follows: ¹ H NMR (400MHz, CDCl ₃ , 298K)δ:-2.18(br,1H),-2.16(br,1H), 5.06-5.07(m,1H), 6.31-6.33(m, 1H), 6.58-6.62(m, 1H), 6.70-6.72(m, 1H), 6.82-6.85(m, 1H), 6.95-6.96(m, 1H), 7.04(s, 1H), 7.34-7.36( m,2H),7.53-7.55(m,2H),8.37-8.42(m,2H),8.56-8.60(m,2H),8.76-8.82(m,2H).UV-vis(CH ₂ Cl ₂ ) λ _max /nm(logε): UV-vis(CH ₂ Cl ₂ )λ _max /nm(logε): 407(5.07), 503(4.04), 531(3.65), 594(3.52), 647(4.39). API-HRMS calc. for C ₅₉ H ₂₀ BrF ₂₀ N ₆ O ₃ S ⁺ [M+H] ⁺ : 1351.0176, Found: 1351.0176.

The spectral data indicated that the above preparation method yielded 5,10,15,20-tetrakis(pentafluorophenyl)-2,3-(4-bromobenzoyl)benzothiazole fused chlorophyll compounds.

Example 3:

The present embodiment adopts the substantially same synthesis technique as in Example 1, except that the raw material is changed to 2-(4-chloro)benzoylbenzothiazole bromide to obtain a dark brown product, namely products 5,10, 15,20-Tetrakis(pentafluorophenyl)-2,3-(4-chlorobenzoyl)benzothiazole fused chlorophyll in 63% yield.

The spectral characterization data of the products are as follows: ¹ H NMR (400MHz, CDCl ₃ , 298K)δ:-2.18(br,1H),-2.15(br,1H), 5.06-5.08(m,1H), 6.31-6.33(m, 1H), 6.57-6.61(m, 1H), 6.70-6.72(m, 1H), 6.81-6.85(m, 1H), 6.95-6.97(m, 1H), 7.05(s, 1H), 7.35-7.38( m,2H),7.42-7.44(m,2H),8.37-8.42(m,2H),8.57-8.59(m,2H),8.76-8.82(m,2H).UV-vis(CH ₂ Cl ₂ ) λ _max /nm(logε): 407(5.01), 503(3.98), 531(3.58), 594(3.44), 647(4.32). API-HRMS calc.for C ₅₉ H ₂₀ ClF ₂₀ N ₆ O ₃ S ⁺ [M+H] ⁺ :1307.0681,Found:1307.0688.

The spectral data indicated that the above preparation method yielded 5,10,15,20-tetrakis(pentafluorophenyl)-2,3-(4-chlorobenzoyl)benzothiazole fused chlorophyll compounds.

Example 4:

The present embodiment adopts the substantially same synthesis technique as in Example 1, except that the raw material is changed to 2-(4-fluoro)benzoylbenzothiazole bromide to obtain a dark brown product, namely products 5,10, 15,20-Tetrakis(pentafluorophenyl)-2,3-(4-fluorobenzoyl)benzothiazole fused chlorophyll compound in 79% yield.

The spectral characterization data of the product are as follows: ¹ H NMR (400MHz, CDCl ₃ , 298K)δ:-2.19(br,1H),-2.17(br,1H), 5.07-5.08(m,1H), 6.29-6.31(m, 1H), 6.56-6.59(m, 1H), 6.70-6.71(m, 1H), 6.80-6.84(m, 1H), 6.96-6.97(m, 1H), 7.04(s, 1H), 7.06-7.08( m,2H),7.51-7.53(m,2H),8.36-8.41(m,2H),8.56-8.59(m,2H),8.75-8.81(m,2H).UV-vis(CH ₂ Cl ₂ ) λ _max /nm(logε): 407(5.02), 503(3.97), 531(3.56), 594(3.41), 647(4.33). API-HRMS calc.for C ₅₉ H ₂₀ F ₂₁ N ₆ O ₃ S ⁺ [M+H] ⁺ :1291.0977,Found:1291.0974.

The spectral data indicated that the above preparation method yielded 5,10,15,20-tetrakis(pentafluorophenyl)-2,3-(4-fluorobenzoyl)benzothiazole fused chlorophyll compounds.

Example 5:

The present embodiment adopts the substantially same synthesis technique as in Example 1, except that the raw material is changed to 2-(3-chloro)benzoylbenzothiazole bromide to obtain a dark brown product, namely products 5,10, 15,20-Tetrakis(pentafluorophenyl)-2,3-(3-chlorobenzoyl)benzothiazole fused chlorophyll compound in 66% yield.

The spectral characterization data of the products are as follows: ¹ H NMR (400MHz, CDCl ₃ , 298K)δ:-2.18(br,1H),-2.16(br,1H), 5.07-5.08(m,1H), 6.32-6.33(m, 1H), 6.58-6.59(m, 1H), 6.72-6.74(m, 1H), 6.84-6.85(m, 1H), 6.95-6.96(m, 1H), 7.05-7.06(m, 1H), 7.33- 7.63(m,4H),8.38-8.43(m,2H),8.58-8.60(m,2H),8.78-8.83(m,2H).UV-vis(CH ₂ Cl ₂ )λ _max /nm(logε) :407(5.08),503(4.02),531(3.59),594(3.42),647(4.36).API-HRMS calc.for C ₅₉ H ₂₀ ClF ₂₀ N ₆ O ₃ S ⁺ [M+H] ⁺ :1307.0681,Found:1307.0684.

The spectral data indicated that the above preparation method yielded 5,10,15,20-tetrakis(pentafluorophenyl)-2,3-(3-chlorobenzoyl)benzothiazole fused chlorophyll compounds.

Claims (5)

1. A 5,10,15,20-tetrakis(pentafluorophenyl)-2,3-benzothiazole condensed chlorophyll compound, the structural formula of which is shown in formula (1):

In formula (1), Ar is one of the structural formulas shown in formula (2) to formula (8):

2. a preparation method of 5,10,15,20-tetrakis (pentafluorophenyl)-2,3-benzothiazole condensed chlorophyll compound as claimed in claim 1, is characterized in that comprising the steps of following order: (1) Weigh a certain amount of 2-nitro-5,10,15,20-tetrakis (pentafluorophenyl) porphyrin, 2-aroyl benzothiazole bromide and triethylamine and place them in the reactor ; Wherein, the structural formula of 2-aroyl benzothiazole bromide is shown in formula (9):

In formula (9), Ar is one of the structural formulas shown in formula (2) to formula (8):

(2) adding dichloromethane solvent to the reactor of step (1) again, stirring at room temperature for 1-3 hours, and tracking the reaction by chromatographic method; (3) after the reaction is completed, it is cooled to room temperature, directly separated by a chromatographic column, the eluent is dichloromethane and n-hexane, and the first red band is collected to be the thick product, and the thick product is concentrated and dried to obtain target compound. 3. The preparation method of 5,10,15,20-tetrakis (pentafluorophenyl)-2,3-benzothiazole condensed chlorophyll compound according to claim 2, wherein: in step (1), the The ratio of the amount of the three reactants of 2-nitro-5,10,15,20-tetrakis(pentafluorophenyl)porphyrin, 2-aroyl benzothiazole bromide and triethylamine is 1 :2:3. 4. The preparation method of 5,10,15,20-tetrakis (pentafluorophenyl)-2,3-benzothiazole condensed chlorophyll compound according to claim 2, characterized in that: in step (2), the The chromatographic method for tracking the reaction is any one of thin layer chromatography, gas chromatography and high performance liquid chromatography. 5. The preparation method of 5,10,15,20-tetrakis (pentafluorophenyl)-2,3-benzothiazole condensed chlorophyll compound according to claim 2, characterized in that: in step (3), the The eluent is a mixed solvent of dichloromethane and n-hexane with a volume ratio of 1:3.

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