A Facile Synthesis of 2-Diazo-3-oxochlorins by Lewis Acid Activation: Selective Modification of π-Electron Conjugated Macrocycles

Abstract

We report a new and direct synthesis of 2-diazo-3-oxochlorins [M = 2 H, Ni(II), Cu(II), Zn(II)]. Reaction of the corresponding 2,3-dioxochlorin with p-toluenesulfonylhydrazine yields the desired 2-diazo-3-oxochlorins in 59-74% yield after a reaction time of three to nine hours. Addition of a stoichiometric amount of Zn(II) acetate leads to coordination of the dione and increases the electrophilicity of the carbonyl groups. This promotes nucleophilic attack by the hydrazine derivative, leading to a six-fold enhancement of the reaction rate and product formation in very good yields.

Key words

diazo-chlorin - Lewis acid activation - porphyrinoids

References and Notes

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19

Crystallographic data (excluding structure factors) for the structures reported in this paper have been deposited with the Cambridge Crystallographic Data Centre as supplementary publication data CCDC-297852 (2H) and CCDC-297853 (2Ni). Copies of the data can be obtained free of charge on application to CCDC, 12 Union Road, Cambridge CB2 1EZ, UK [fax: [phone]; e-mail: [e-mail]].
Crystal data for 2H: red, 0.20 × 0.13 × 0.11 mm, C₄₄H₂₈N₆O, M = 656.72, triclinic, a = 13.470 (3) Å, b = 14.148 (2) Å, c = 18.597 (4) Å, α = 93.281 (6)°, β = 110.715 (5)°, γ = 90.571 (6)°, V = 3307.7 (10) ų, T = 120 (2) K, space group P-1, Z = 4, ρ_calcd = 1.319 Mgm^-3, µ = 0.081 mm^-1, 2θ_max = 50°, Mo Kα (λ = 0.71073). A total of 28291 reflections were measured, of which 11564 (R _int = 0.055) were unique. Final residuals were R1 = 0.0552 and wR2 = 0.1285 [for 7181 observed reflections with I>2σ (I), 975 parameters] with GOF 1.045 and largest residual peak 0.198 eÅ^-3 and hole -0.217 eÅ^-3.
Crystal data for 2Ni: brown, 0.15 × 0.15 × 0.13 mm, C₄₄H₂₆N₆NiO, M = 713.42, tetragonal, a = b = 15.368 (2) Å, c = 13.614 (2) Å, V = 3215.4 (9) ų, T = 120 (2) K, space group I-42d, Z = 4, ρ_calcd = 1.461 Mgm^-3, µ = 0.652 mm^-1, 2θ_max = 50°, Mo Kα (λ = 0.71073). A total of 13759 reflections were measured, of which 1432 (R _int = 0.044) were unique. Final residuals were R1 = 0.0364 and wR2 = 0.0870 [for 1309 observed reflections with I>2σ (I), 138 parameters] with GOF 1.107 and largest residual peak 0.228 eÅ^-3 and hole -0.174 eÅ^-3, Flack parameter 0.02 (2).

21

2Ni, 2Cu, and 2ZnGeneral Method A Substrate 1M was dissolved in CH₂Cl₂ (50 mL) and p-tolu-enesulfonylhydrazine (20 equiv) was added. The reaction mixture was stirred under reflux. The resulting mixture was cooled to r.t. and the solvent evaporated under reduced pressure. The residue was purified by silica gel (2Ni, 2Cu) or alumina column chromatography (2Zn) (CH₂Cl₂-hexanes, 2:1).
General Method B Substrate 1M was dissolved in CH₂Cl₂ (50 mL), p-toluene-sulfonylhydrazine (20 equiv) and a solution of Zn(OAc)₂·2H₂O (1 equiv) in MeOH (3 mL) was added. The reaction mixture was stirred under reflux. The resulting solution was cooled to r.t. and the solvent was evaporated under reduced pressure. The residue was purified as described above.
2Ni [10]
IR: 2103, 1669, 1594, 1553, 1528, 1448, 1390, 1363, 1338, 1175, 1139, 1069, 1010, 1003, 831, 792, 745, 697 cm^-1. ¹H NMR (CDCl₃): δ = 8.61-8.59 (d, 1 H, β-pyrrolic-H), 8.52-8.47 (m, 4 H, β-pyrrolic-H), 8.43-8.41 (d, 1 H, β-pyrrolic-H), 7.93-7.88 (m, 6 H, meso-Ar), 7.68-7.63 (m, 14 H, meso-Ar). ESI: m/z = 713.2 (M⁺). HRMS-EI: m/z calcd for C₄₄H₂₆N₄ONi (M - N₂): 684.1455; found: 684.1426.
2Cu [10]
IR: 2098, 1735, 1669, 1598, 1576, 1510, 1432, 1388, 1342, 1273, 1175, 1133, 1071, 1007, 991, 844, 795, 795, 750, 702 cm^-1. ESI: m/z = 718.2 (M⁺). HRMS-EI: m/z calcd for C₄₄H₂₆N₄OCu (M - N₂): 689.1397; found: 689.1397.
2Zn IR: 3053, 2130, 2095, 1668, 1485, 1441, 1417, 1363, 1321, 1237, 1175, 1130, 1071, 1007, 987, 797, 756, 740, 702 cm^-1. ¹H NMR (DMSO-d ₆): δ = 8.65-8.64 (d, 1 H, β-pyrrolic-H), 8.57-8.50 (m, 3 H, β-pyrrolic-H), 8.46-8.45 (d, 1 H, β-pyrrolic-H), 8.31-8.30 (d, 1 H, β-pyrrolic-H), 8.13-8.11 (m, 6 H, meso-ArH), 7.84-7.70 (m, 11 H, meso-ArH), 7.65-7.61 (m, 3 H, meso-ArH). ¹³C NMR (DMSO-d ₆): δ = 186.76, 151.23, 149.55, 148.41, 147.60, 146.71, 142.10, 141.39, 139.50, 133.72, 133.56, 132.79, 132.18, 131.56, 130.15, 129.81, 129.50, 129.30, 127.60, 127.28, 126.62, 124.97, 121.99, 116.61, 111.14, 71.56. ESI: m/z = 720 (M + H⁺). HRMS-EI: m/z calcd for C₄₄H₂₆N₄OZn (M - N₂): 690.1393; found: 690.1390. UV-Vis (CH₂Cl₂): λ_max (log ε) = 616 (4.11), 567 (3.66), 433 (4.94). Anal. Calcd for C₄₄H₂₆N₆OZn·0.5H₂O: C, 72.61; H, 3.58; N, 11.55. Found: C, 72.87; H, 3.70; N, 11.35.
2H
Substrate 2Cu (250 mg, 0.355 mmol) was dissolved in CH₂Cl₂, cooled with an ice bath, and concd H₂SO₄ (2 mL) was added. The resulting mixture was neutralized with NaOH (1 M), diluted with H₂O (30 mL), and the brown compound was extracted with CH₂Cl₂ (3 × 20 mL). The combined organic layers were washed with H₂O (3 × 10 mL), dried over Na₂SO₄, and the solvent was evaporated under reduced pressure. The purple residue obtained was filtered, washed with hexanes (3 × 5 mL), and dried in air overnight. The purple compound was purified by silica gel column chromatography (CH₂Cl₂-hexanes, 2:1); yield: 90%.
IR: 2092, 1668, 1596, 1558, 1477, 1441, 1398, 1363, 1334, 1230, 1153, 1115, 1772, 1044, 1001, 965, 797, 750, 701 cm^-1.¹H NMR (CDCl₃): δ = 8.85-8.83 (d, 1 H, β-pyrrolic-H), 8.78-8.77 (d, 1 H, β-pyrrolic-H), 8.68-8.59 (m, 4 H, β-pyrrolic-H), 8.18-8.12 (m, 6 H, meso-ArH), 7.96-7.94 (m, 2 H, meso-ArH), 7.86-7.73 (m, 12 H, meso-ArH), -2.26 (s, 1 H, pyrrolic-H), -2.40 (s, 1 H, pyrrolic-H). ¹³C NMR (CDCl₃): δ = 189.37, 155.99, 154.23, 146.27, 144.91, 142.12, 141.92, 141.21, 140.78, 140.09, 139.35, 138.54, 137.29, 134.75, 134.64, 134.15, 133.78, 130.18, 129.30, 128.40, 128.37, 128.16, 127.81, 127.35, 127.23, 127.10, 124.32, 121.76, 117.32, 112.01, 73.61. ESI: m/z = 657 (M + H⁺). HRMS-EI: m/z calcd for C₄₄H₂₈N₆O (M): 656.2317; found: 656.2314. UV-Vis (CH₂Cl₂): λ_max (log ε) = 652 (3.69), 697 (3.74), 559 (3.83), 524 (4.11), 428 (5.24). Anal. Calcd for C₄₄H₂₈N₆O: C, 80.46; H, 4.30; N, 12.80. Found: C, 79.91; H, 4.44; N, 12.60.
Crystals suitable for X-ray diffraction studies were obtained from slow diffusion of methanol into a CH₂Cl₂ solution of 2H and slow vapor diffusion of Et₂O into CH₂Cl₂ for 2Ni.