A Mild, Facile, One-Pot Synthesis of Zinc Azido Porphyrins as Substrates for Use in Click Chemistry

Abstract

The conversion of porphyrins bearing primary amines into zinc-protected azido porphyrins utilising a diazo-transfer reagent is reported. This method allows the mild, facile, and one-pot synthesis of zinc azido porphyrins bearing a range of meso functionalities, producing the required porphyrin in high yield. Reactivity of the azide functionality is demonstrated by subsequent model click reactions to produce triazole derivatives.

Key words

porphyrins - azides - zinc - click chemistry - diazotransfer reagent

• References and Notes

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• 16 General Synthesis of Porphyrins 1–14 In a typical experiment, zinc(II) acetate (50 mg) in MeOH (2 mL) was added to a solution of the porphyrin (0.040 mmol) and Et₃N (50 mg) dissolved in a suitable solvent (CH₂Cl₂–THF for lipophilic porphyrins, MeOH for hydrophilic porphyrins). Imidazole-1-sulfonyl azide hydrogen sulfate (0.045 mmol) was added to the stirred suspension, and the mixture stirred at r.t. until completion of the reaction (TLC). The solvent was removed under reduced pressure, and the product was purified by column chromatography (normal-phase silica for lipophilic porphyrins, reverse-phase silica for hydrophilic porphyrins).
• 17 General Synthesis of Porphyrins 15–19 In a typical experiment, in a 10 mL microwave tube the porphyrin (0.037 mmol) was dissolved in THF (7 mL) and phenylacetylene (0.070 mmol) added. A solution of copper(II) sulfate and sodium ascorbate (1 mg) in H₂O (1 mL) was added to the mixture and the mixture heated to 90 °C (MW) until complete consumption of the starting material was observed on TLC. The solvent was removed under reduced pressure, and the product purified by column chromatography (normal phase).
• 18 General Zinc-Removal Procedure for Porphyrins 15–19 In a typical experiment, to a solution the porphyrin (10.0 mg) in CH₂Cl₂ (3 mL) was added HCl in dioxane (4 M, 0.5 mL) and the mixture stirred at r.t. for 5 min. The mixture was neutralised with sat. NaHCO₃ solution, dried (MgSO₄), and the solvent removed under reduced pressure.
• 19 Spectroscopic Data UV-Vis, HRMS, and ¹³C NMR data were obtained as expected for all compounds. Compound 1: ¹H NMR (400 MHz, CDCl₃): δ = 7.25 (d, 2 H, 5-m-Ar), 7.77 (m, 9 H, 10,15,20-m,p-Ar), 8.22 (m, 8 H, 5,10,15,20-o-Ar), 8.87 (m, 8 H, β-H). Compound 2: ¹H NMR (400 MHz, DMSO-d ₆): δ = 4.77 (s, 9 H, CH₃), 8.27 (m, 4 H, 5-Ar), 9.09 (m, 14 H, 10,15,20-o-Ar, β-H), 9.60 (m, 6 H, 10,15,20-m-Ar). Compound 3: ¹H NMR (400 MHz, CDCl₃): δ = 4.11 (s, 9 H, OCH₃), 7.42 (m, 2 H, 5-m-Ar), 8.19 (m, 2 H, 5-o-Ar), 8.30 (m, 6 H, 10,15,20-m-Ar), 8.42 (m, 6 H, 10,15,20-o-Ar), 8.87 (m, 8 H, β-H). Compound 4: ¹H NMR (400 MHz, CDCl₃): δ = 3.80 (s, 9 H, OCH₃), 7.19 (m, 7 H, 10,15,20-p-Ar, 5-m-Ar), 7.55 (m, 3 H, 10,15,20-m-Ar), 7.66 (s, 3 H, 5-2-Ar), 7.80 (m, 3 H, 5-5-Ar), 8.88–9.03 (m, 8 H, β-H). Compound 5: ¹H NMR (400 MHz, CDCl₃): δ = 1.61 (m, 9 H, CH₂CH ₃), 4.31 (m, 6 H, CH ₂CH₃), 7.23 (m, 6 H, 10,15,20-m-Ar), 7.35 (d, 2 H, J = 8.36 Hz, 5-m-Ar), 8.08 (m, 6 H, 10,15,20-o-Ar), 8.17 (d, 2 H, J = 8.36 Hz, 5-o-Ar), 8.89–8.98 (m, 8 H, β-H). Compound 6: ¹H NMR (400 MHz, CDCl₃): δ = 7.44 (d, 2 H, J = 8.36 Hz, 5-m-Ar), 7.75 (m, 6 H, 10,15,20-m-Ar), 8.14 (m, 6 H, 10,15,20-o-Ar),8.19 (d, 2 H, J = 8.16 Hz, 5-m-Ar), 8.96 (m, 8 H, β-H). Compound 7: ¹H NMR (400 MHz, CDCl₃): δ = 7.41 (d, 2 H, J = 7.96 Hz, 5-m-Ar), 7.94 (m, 6 H, 10,15,20-m-Ar), 8.08 (m, 6 H, 10,15,20-o-Ar), 8.18 (d, 2 H, J = 7.92 Hz, 5-o-Ar), 8.87 (m, 8 H, β-H). Compound 8: ¹H NMR (400 MHz, CDCl₃): δ = 7.42 (d, 2 H, J = 8.6 Hz, 5-m-Ar), 7.87 (m, 6 H, 10,15,20-m-Ar), 8.07 (m, 6 H, 10,15,20-o-Ar), 8.19 (d, 2 H, J = 8.36 Hz, 5-m-Ar), 8.84 (m, 8 H, β-H). Compound 9: ¹H NMR (400 MHz, CDCl₃): δ = 7.23 (m, 1 H, 5-o-Ar), 7.52 (m, 1 H, 5-m-Ar), 7.75 (m, 10 H, 10,15,20-m,p-Ar, 5-p-Ar), 7.96 (m, 1 H, 5-o-Ar), 8.21 (m, 6 H, 10,15,20-o-Ar), 8.87 (m, 8 H, β-H). Compound 10: ¹H NMR (400 MHz, CDCl₃): δ = 7.93 (m, 2 H, 5-4,5-Ar),7.75 (m, 10 H, 10,15,20-m,p-Ar, 5-3-Ar), 8.09 (m, 1 H, 5-o-Ar), 8.23 (m, 6 H, 10,15,20-o-Ar), 8.80–8.96 (m, 8 H, β-H). Compound 11: ¹H NMR (400 MHz, CDCl₃): δ = 4.14 (s, 2 H, CH₂),7.35 (d, 2 H, J = 7.76 Hz, 5-m-Ar) 7.74 (m, 9 H, 10,15,20-m,p-Ar), 8.15 (d, 2 H, J =7.72 Hz, 5-o-H), 8.23 (m, 6 H, 10,15,20-o-Ar), 8.85–8.98 (m, 8 H, β-H). Compound 12: ¹H NMR (400 MHz, CDCl₃): δ = 1.61 (m, 9 H, CH₂CH ₃), 4.31 (m, 6 H, CH ₂CH₃),4.67 (s, 2 H, NH₂), 7.25 (m, 6 H, 10,15,20-m-Ar), 7.65 (d, 2 H, J = 6.12 Hz, 5-m-Ar), 8.10 (m, 6 H, 10,15,20-o-Ar), 8.22 (d, 2 H, J = 6.32 Hz, 5-o-Ar), 8.85–8.92 (m, 8 H, β-H). Compound 13: ¹H NMR (400 MHz, MeOH-d ₄): δ = 7.47 (d, 2 H, 5-m-Ar, J = 8.40 Hz), 8.26 (m, 18 H, 5-o-Ar, 10,15,20-o,m-Ar), 8.85 (m, 8 H β-H). Compound 14: ¹H NMR (400 MHz, CDCl₃): δ = 7.04 (d, 2 H, J = 8.36 Hz, 5-m-Ar), 8.09 (d, 2 H, J = 8.36 Hz, 5-m-Ar), 9.00 (m, 8 H, β-H). Compound 15: ¹H NMR (400 MHz, CDCl₃): δ = 4.11 (s, 9 H, OCH₃), 7.45 (m, 1 H, p-Ph), 7.55 (m, 2 H, m-Ph), 8.02 (m, 2 H, o-Ph), 8.20 (m, 2 H, 5-m-Ar), 8.32 (m, 6 H, 10,15,20-m-Ar), 8.43 (m, 8 H, 5,10,15,20-o-Ar), 8.52 (s, 1 H, triazole), 8.86–8.93 (m, 8 H, β-H). Compound 16: ¹H NMR (400 MHz, CDCl₃): δ = 3.96 (s, 9 H, OCH₃), 7.31 (m, 3 H, 10,15,20-p-Ar), 7.43 (m, 1 H, p-Ph), 7.52 (m, 2 H, m-Ph), 7.66 (m, 3 H, 10,15,20-m-Ar), 7.81 (m, 6 H, 10,15,20-o-Ar), 8.01 (m, 2 H, o-Ph), 8.18 (d, 2 H, 5-m-Ar, J = 8.6 Hz), 8.40 (d, 2 H, 5-o-Ar, J = 8.4 Hz), 8.49 (s, 1 H, triazole), 8.84–9.03 (m, 8 H, β-H). Compound 17: ¹H NMR (400 MHz, THF-d ₈): δ = 6.41 (m, 1 H, p-Ph), 6.53 (m, 2 H, m-Ph), 7.01 (m, 6 H, 10,15,20-m-Ar), 7.13 (m, 2 H, o-Ph), 7.17 (m, 6 H, 10,15,20-o-Ar), 7.42 (m, 4 H, 5-o,m-Ar), 7.90–8.00 (m, 8 H, β-H), 8.16 (s, 1 H, triazole H). Compound 18: ¹H NMR (400 MHz, CDCl₃): δ = 5.90 (s, 2 H, CH₂), 7.35 (m, 1 H, p-Ph), 7.44 (m, 2 H, m-Ph), 7.63 (m, 2 H, o-Ph), 7.70 (m, 9 H, 10,15,20-m,p-Ar), 7.87 (d, 2 H, J = 7.76 Hz, 5-m-Ar), 8.03 (s, 1 H, triazole), 8.18 (m, 8 H, 5,10,15,20-o-Ar), 8.76–8.89 (m, 8 H, β-H). Compound 19: ¹H NMR (400 MHz, CDCl₃): δ = 7.42 (m, 1 H, p-Ph), 7.55 (m, 2 H, m-Ph), 8.01 (m, 2 H, o-Ph), 8.18 (d, 2 H, J = 8.96 Hz, 5-m-Ar), 8.37 (d, 2 H, J = 8.98 Hz, 5-m-Ar), 8.59 (s, 1 H, triazole H), 8.89–9.02 (m, 8 H, β-H).