Metal-Dependent Halogenation and/or Coupling Reactions of Porphyrins with PhIX₂ (X = Cl, F)

Abstract

Treatment of zinc(II)-5,10,15-trisubstituted porphyrins with PhICl₂ afforded the corresponding meso-chlorinated porphyrins and meso,meso-linked bisporphyrins in almost 50% yield. The reaction of copper(II), nickel(II), or free-base 5,10,15-trisubstituted porphyrins with PhICl₂ gave only meso-chlorinated products without any coupling bisporphyrins. Similarly, the reaction of nickel(II) or free-base 5,15-diphenylporphyrins solely yielded meso-chlorinated products, whereas that of the zinc(II)-5,15-diphenylporphyrin with PhICl₂, produced only coupling products. Interestingly, β-chloroporphyrins were exclusively formed not only for copper(II) or free-base 5,10,15,20-tetraarylporphyrins, but also for the zinc complexes. In contrast to the reaction of PhICl₂, the reaction of PhIF₂ with 5,10,15-trisubstituted metalloporphyrins gave the coupling bisporphyrins in high yields, without any fluorinated product. However, in the presence of I₂, the meso-iodination of free-base 5,10,15-trisubstituted porphyrins proceeded smoothly.

chlorination - iodination - coupling reaction - porphyrinoids - synthetic methods

References

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8

Reaction of Zinc(II)-5,10,15-trisubstituted Porphyrin with PhICl ₂ . A mixture of zinc(II)-5-(4-trifluoromethyl-phenyl)-10,20-diphenylporphyrin (Zn1b, 100 mg, 0.15 mmol) and PhICl₂ (41 mg, 0.15 mmol) was stirred in CH₂Cl₂ (50 mL) at r.t. for 1 h and filtered through a short column of silica gel. The filtrate was treated with 36% HCl (1 mL) at r.t. for 10 min, washed with H₂O, dried over Na₂SO₄, and evaporated in vacuo to give a purple solid. The residue was purified by flash chromatography (silica gel, 300-400 mesh, CH₂Cl₂-hexanes, 1:5) to afford 2b (48 mg, 50%) as the first fraction and 3b (45 mg, 50%) as the second fraction. 2b: ¹H NMR (CDCl₃): δ = 9.65 (d, J = 4.7 Hz, 2 H), 8.91 (d, J = 4.6 Hz, 2 H), 8.82 (d, J = 4.6 Hz, 2 H), 8.70 (d, J = 5.1 Hz, 2 H), 8.29 (d, J = 7.8 Hz, 2 H), 8.20-8.17 (m, 4 H), 8.01 (d, J = 8.2 Hz, 2 H), 7.80-7.73 (m, 6 H), -2.74 (s, 2 H). MS (ESI): m/z = 641.35 (MH⁺). UV-vis (log ε, CH₂Cl₂): λ_max = 414 (5.67), 513 (4.37), 548 (4.05), 591 (3.81), 648 (3.74). Anal. calcd for C₃₉H₂₄ClF₃N₄·0.5H₂O: C, 72.05; H, 3.88; N, 8.62. Found: C, 71.71; H, 3.97; N, 8.14. 3b: ¹H NMR (CDCl₃): δ = 8.97 (d, J = 4.9 Hz, 4 H), 8.88 (d, J = 5.0 Hz, 4 H), 8.63 (d, J = 4.8 Hz, 4 H), 8.45 (d, J = 8.0 Hz, 4 H), 8.26-8.23 (m, 8 H), 8.13-8.09 (m, 8 H), 7.72-7.70 (m, 12 H), -2.18 (s, 4 H). ¹⁹F NMR (CDCl₃): δ = -61.99 (s, 6 F). MS (MALDI): m/z = 1211.4 (MH⁺). UV-vis (relative intensity, CH₂Cl₂): λ_max = 415 (1), 450 (1.1), 523 (0.24), 560 (0.06), 594 (0.07), 651 (0.03). Anal. calcd for C₇₈H₄₈F₆N₈₃·CH₃OH: C, 74.41; H, 4.63; N, 8.57. Found: C, 74.52; H, 5.14; N, 8.15. HRMS (MALDI): m/z calcd for C₇₈H₄₈N₈F₆·H⁺, 1211.3979; found, 1211.3981.

9

Chlorination of 5,10,15-Trisubstituted Porphyrins with PhICl ₂ . A sample of nickel(II)-5,10,15-triphenylporphyrin (Ni1a, 50 mg, 0.08 mmol) and PhICl₂ (23 mg, 0.08 mmol) was stirred in CH₂Cl₂ (50 mL) at r.t. for 2 h. Then the mixture was purified by flash chromatography (silica gel, CH₂Cl₂-hexanes, 1:3) to give Ni2a (47 mg, 90%). ¹H NMR (300 MHz, CDCl₃): δ = 9.48 (d, J = 4.8 Hz, 2 H), 8.79 (d, J = 4.8 Hz, 2 H), 8.68 (s, 4 H), 7.97 (m, 6 H), 7.67 (m, 9 H). UV-vis (relative intensity, CH₂Cl₂): λ_max = 529 (1), 414 (14). MS (MALDI): m/z = 628.1. Anal. calcd for C₃₈H₂₃N₄ClNi·0.5H₂O: C, 71.58; H, 3.72; N, 8.48; Cl, 5.57. Found: C, 71.49; H, 3.76; N, 8.64; Cl, 5.87.

10

Crystallographic data for Zn3b·2CHCl₃: C₈₀H₄₆F₆N₈Cl₆Zn₂, MW = 1576.69, crystal system monoclinic, space group P2 (1)/n, a = 11.755 (3), b = 19.839 (4), c = 32.115 (8) Å, V = 7484 ų, Z = 4, d_c = 1.415 mgm^-3, µ(M_o - K_α) = 0.921 mm^-1, crystal size 0.516 × 0.275 × 0.221 mm, R1 = 0.0981, wR2 = 0.2829, GOF = 0.963 [I > 2σ(I)]. Crystallographic data have been deposited with the Cambridge Crystallo-graphic Data Centre (CCDC 281147). These data can be obtained free of charge at www.ccdc.cam.ac.uk/Data_request/cif or from the Cambridge Crystallographic Data Centre, 12 Union Road, Cambridge CB2 1EZ, UK; Fax: [phone]; E-mail: [e-mail].

11 DiMagno SG. Lin VS.-Y. Therien MJ. J. Org. Chem.  1993,  58:  5983 

12

Chlorination of 5,15-Diphenylporphyrins; General Procedure. A sample of 5,15-diphenylporphyrin (4, 50 mg, 0.11 mmol) and PhICl₂ (30 mg, 0.11 mmol) was stirred in CH₂Cl₂ (50 mL) at r.t. for 2 h. Then the mixture was purified by flash chromatography (silica gel, CH₂Cl₂-hexanes, 1:3) mainly to give 8a (43 mg, 80%). Treating 4 with PhICl₂ (60 mg, 0.22 mmol, 2 equiv) under similar conditions, yielded 9a (52 mg) in 90% yield. 8a: ¹H NMR (CDCl₃): δ = 10.16 (s, 1 H), 9.73 (d, J = 5.1 Hz, 2 H), 9.29 (d, J = 4.9 Hz, 2 H), 8.98 (d, J = 4.8 Hz, 2 H), 8.97 (d, J = 4.8 Hz, 2 H), 8.24-8.21 (m, 4 H), 7.82-7.80 (m, 6 H), -2.94 (s, 2 H). MS (MALDI): m/z = 496 (M⁺). UV-vis (relative intensity, CH₂Cl₂): λ_max = 413 (1), 510 (0.05), 545 (0.015), 587 (0.013), 642 (0.007). Anal. calcd for C₃₂H₂₁ClN₄·H₂O: C, 74.63; H, 4.5; N, 10.88. Found: C, 74.70; H, 4.39; N, 10.65. 9a: ¹H NMR (CDCl₃): δ = 9.60 (d, J = 4.5 Hz, 4 H), 8.87 (d, J = 4.3 Hz, 4 H), 8.19-8.17 (m, 4 H), 7.81-7.78 (m, 6 H), -2.68 (s, 2 H). MS (MALDI): m/z = 531.1 (MH⁺). UV-vis (relative intensity, CH₂Cl₂): λ_max = 418 (1), 520 (0.05), 554 (0.03), 599 (0.015), 658 (0.017). HRMS (MALDI): m/z calcd for C₃₂H₂₀N₄Cl₂·H⁺, 531.1138; found, 531.1136.

13

Reaction of Zinc(II)-5,15-diphenylporphyrin with PhICl ₂ . To a solution of zinc(II)-5,15-diphenylporphin (Zn4, 0.25 mmol, 130 mg) in CH₂Cl₂ (100 mL) was added PhICl₂ (68 mg, 0.25 mmol) at r.t., and the mixture was stirred for 6 h. Then the mixture was concentrated to dryness, purified by dry powder chromatography (silica gel, THF-hexanes, 1:5), and the second brown band was collected (the first red-purple band was the starting porphyrin). The crude product was treated with 36% HCl (1 mL) in CH₂Cl₂ for 10 min, washed with H₂O, and purified by flash chromatography (silica gel, CH₂Cl₂-hexanes, 1:3) to afford 7 (18 mg, 15%), 6 (24 mg, 20%), and 5 (11 mg, 10%). 7: ¹H NMR (CDCl₃): δ = 9.73 (d, J = 4.5 Hz, 4 H), 8.95 (d, J = 4.4 Hz, 4 H), 8.53 (d, J = 4.5 Hz, 4 H), 8.19-8.16 (m, 8 H), 8.01 (d, J = 4.7 Hz, 4 H), 7.68-7.64 (m, 12 H), -2.16 (s, 4 H). MS (MALDI): m/z = 991.3 (MH⁺). UV-vis (relative intensity, CH₂Cl₂): λ_max = 417 (1), 449 (1), 525 (0.2), 561 (0.07), 599 (0.06), 658 (0.03). HRMS (MALDI): m/z calcd for C₆₄H₄₀N₈Cl₂·H⁺, 991.2816; found, 991.2811. 6: ¹H NMR (CDCl₃): δ = 10.33 (s, 1 H), 9.73 (d, J = 4.5 Hz, 2 H), 9.41 (d, J = 4.2 Hz, 2 H), 9.06 (d, J = 4.8 Hz, 2 H), 8.95 (d, J = 5.0 Hz, 2 H), 8.63 (d, J = 4.9 Hz, 2 H), 8.51 (d, J = 5.0 Hz, 2 H), 8.24-8.16 (m, 8 H), 8.09 (d, J = 4.8 Hz, 2 H), 7.98 (d, J = 5.0 Hz, 2 H), 7.70-7.65 (m, 12 H), -2.12 (s, 2 H), -2.44 (s, 2 H). MS (MALDI): m/z = 957.3 (MH⁺). UV-vis (relative intensity, CH₂Cl₂): λ_max = 415 (1), 446 (1), 521 (0.21), 559 (0.06), 596 (0.06), 656 (0.02). HRMS (MALDI): m/z calcd for C₆₄H₄₁N₈Cl·H⁺, 957.3216; found, 957.3238. 5: ¹H NMR (CDCl₃): δ = 10.35 (s, 2 H), 9.42 (d, J = 4.3 Hz, 4 H), 9.07 (d, J = 4.2 Hz, 4 H), 8.61 (d, J = 4.4 Hz, 4 H), 8.23-8.21 (m, 8 H), 8.06 (d, J = 4.8 Hz, 4 H), 7.68-7.67 (m, 12 H), -2.41 (s, 4 H). MS (MALDI): m/z = 923.4 (MH⁺). UV-vis (relative intensity, CH₂Cl₂): λ_max = 409 (1), 443 (0.9), 518 (0.2), 588 (0.06), 643 (0.01). HRMS (MALDI): m/z calcd for C₆₄H₄₂N₈·H⁺, 923.3605; found, 923.3614.

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14b Bhyrappa P. Krishnan V. Inorg. Chem.  1991,  30:  239 

15

Chlorination of 5,10,15,20-Tetraarylporphyrins. A sample of copper(II)-5,10,15,20-tetra(4-methoxy-phenyl)porphyrin (Cu10c, 50 mg, 0.06 mmol) and PhICl₂ (17 mg, 0.06 mmol) was stirred in CH₂Cl₂ (50 mL) at r.t. for 1 h. H₂SO₄ (1 mL) was added, and the reaction was stirred for another 10 min. Then the mixture was washed with H₂O, dried over Na₂SO₄, and purified by flash chromatography (silica gel, CH₂Cl₂-hexanes, 1:2) to give 11c (43 mg, 90%). ¹H NMR (CDCl₃): δ = 8.92-8.92 (m, 7 H), 8.13-7.95 (m, 8 H), 7.30-7.24 (m, 8 H), 4.10 (m, 12 H), 2.84 (s, 2 H). MS (MALDI): m/z = 769.3 (MH⁺). UV-vis (relative intensity, CH₂Cl₂): λ_max = 424 (1), 521 (0.05), 556 (0.025), 595 (0.015), 653 (0.017). HRMS (MALDI): m/z calcd for C₄₈H₃₇N₄O₄Cl·H⁺, 769.2576; found, 769.2585.

16

The one-electron oxidation potentials of the porphyrins were detected in CH₂Cl₂-MeCN (4:1) using 0.1 M TBAPF₆ as supporting electrolyte at r.t. [Glass-carbon working electrode, Pt disk (2 mm diameter) reference electrode, Pt wire counter electrode.]

17a Carpenter W. J. Org. Chem.  1966,  31:  2688 

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18

Coupling Procedure Using PhIF ₂ A sample of nickel(II)-5-chloro-10,20-diphenylporphyrin (Ni1d, 30 mg, 0.054 mmol) and PhIF₂ (13 mg, 0.054 mmol) in CH₂Cl₂ (30 mL) was stirred at r.t. for 30 min. Then the resulting yellow-brown mixture was washed with H₂O several times, the organic layer was dried over anhydrous Na₂SO₄, filtered, and concentrated in vacuo. The residue was purified by flash column chromatography (silica gel, CH₂Cl₂-hexanes, 1:1) to give Ni13d (28 mg, 93%).¹H NMR (CDCl₃): δ = 9.56 (d, J = 5.1 Hz, 4 H), 8.84 (d, J = 4.7 Hz, 4 H), 8.47 (d, J = 4.8 Hz, 4 H), 8.00-7.96 (m, 12 H), 7.64-7.61 (m, 12 H). MS (MALDI): m/z = 1102.1 (M⁺). UV-vis (CH₂Cl₂): λ_max 420-450 (br), 537. HRMS (MALDI): m/z calcd for C₆₄H₃₆N₈Cl₂Ni₂, 1102.1142; found, 1102.1187.

19

meso -Iodination of Free Base 1 A sample of 5-(4-trifluoromethylphenyl)-10,20-diphenylporphyrin (1b, 50 mg, 0.08 mmol), I₂ (20 mg, 0.08 mmol), and PhIF₂ (20 mg, 0.08 mmol) in CH₂Cl₂ (30 mL) was stirred at r.t. for 1 h. Then the resulting mixture was washed with H₂O several times, the organic layer was dried over anhydrous Na₂SO₄, filtered, and concentrated in vacuo. The residue was purified by flash column chromatography (silica gel, CH₂Cl₂-hexanes, 1:3) to give 12b (46 mg, 80%). ¹H NMR (CDCl₃): δ = 9.69 (d, J = 5.0 Hz, 2 H), 8.89 (d, J = 4.8 Hz, 2 H), 8.83 (d, J = 4.8 Hz, 2 H), 8.74 (d, J = 4.8 Hz, 2 H), 8.32 (d, J = 7.7 Hz, 2 H), 8.18 (m, 4 H), 8.03 (d, J = 9.0 Hz, 2 H), 7.80 (m, 6 H), -2.73 (s, 2 H). MS (MALDI): m/z = 732.1 (M⁺). HRMS (MALDI): m/z calcd for C₃₉H₂₄N₄F₃I·H⁺, 733.10705; found, 733.1091.

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