Microwave-Enhanced Synthesis of Novel Pyridinone-Fused Porphyrins

Abstract

Condensation adducts of the Ni(II) and Cu(II) complexes of β-amino-meso-tetraphenylporphyrin with dimethyl acetylenedicarboxylate (DMAD) and diethyl ethoxymethylenemalonate were converted into the corresponding esters of pyridinone-fused porphyrins by using three different cyclization protocols: conventional heating, microwave irradiation, and Eaton’s reagent. High yields in a short period of time were obtained by using the microwave-irradiation protocol under closed-vessel conditions. The structure of the copper(II) complex of pyridinone-fused porphyrin was confirmed by X-ray crystallography.

Key words

porphyrins - cyclizations - microwave irradiations

References and Notes

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• Cyclization Reaction
• 21a

  Using a Multimode Reactor
  A solution of porphyrin 3 (21 mg, 0.025 mmol) in nitrobenzene (3.5 mL) under argon atmosphere was irradiated at atmospheric pressure in a Milestone MicroSynth microwave reactor (5 min ramp up to 180 ˚C and 35 min hold at 180 ˚C, using 400 W maximum power). The reaction mixture was then purified by flash chromatography using a 1:2 mixture of hexane-CH₂Cl₂ as eluent to give porphyrin 4a (19 mg, 93% yield).
  

• 21b

  Using a Monomode Reactor
  A solution of porphyrin 3 (28 mg, 0.034 mmol) in nitrobenzene (1.5 mL) was placed in a 10 mL reaction vial, which was then sealed under argon atmosphere and placed in the cavity of a CEM microwave reactor. The reaction vial was irradiated at 220 ˚C (1 min ramp to 220 ˚C and 3 min hold at 220 ˚C, using 200 W maximum power). The reaction mixture was then purified by flash chromatography using a 1:2 mixture of hexane-CH₂Cl₂ as eluent to give porphyrin 4a (24 mg, 88% yield).

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• 27 Sheldrick GM. SHELX-97   University of Göttingen; Germany: 1997. 

15

Condensation Reaction
To a solution of (β-amino-meso-tetraphenylporphyrinato)-nickel(II) (50 mg, 0.073 mmol) in toluene (5 mL), DMAD (0.02 mL, 0.15 mmol) was added, and the resulting mixture was heated at 85 ˚C under argon atmosphere for 150 min. The reaction mixture was cooled to r.t. and purified by flash chromatography using a 1:2 mixture of hexane-CH₂Cl₂ as eluent. The first fraction to be collected was a small amount of starting porphyrin, followed by porphyrin 3, which was collected and crystallized from CHCl₃-MeOH to give 47 mg (78% yield) of red crystals.

16

Spectroscopic Data for [2-(2,3-Dimethoxycarbonyl-2-en-1-yl)amino-5,10,15,20-tetraphenylporphyrinato]nickel(II) (3) ^¹H NMR (500.13 MHz, CDCl₃): δ = 3.57 (s, 3 H, 2′-OCH₃), 3.66 (s, 3 H, 3′-OCH₃), 5.24 (s, 1 H, 3′-H), 7.63-7.69 (m, 12 H, PhH _meta+para ), 7.90-7.91 (m, 3 H, 3-H and PhH _ortho ), 7.96-8.00 (m, 6 H, PhH _ortho ), 8.57 (d, J = 4.9 Hz, 1 H, β-H), 8.66 (d, J = 4.9 Hz, 1 H, β-H), 8.69-8.71 (m, 4 H, β-H), 9.01 (s, 1 H, 1′-NH) ppm. ^¹³C NMR (125.77 MHz, CDCl₃): δ = 51.1 (2′-OCH₃), 52.7 (3′-OCH₃), 94.1 (C-3′), 117.3, 117.7, 118.8, 119.7, 120.5 (C-3), 126.81, 126.84, 126.90, 126.91, 127.5, 127.6, 127.66, 127.74, 127.8, 127.9, 128.12, 128.18, 131.71, 131.84, 132.04, 132.08, 132.13, 132.17, 132.6, 132.7, 133.0, 133.41, 133.45, 133.54, 133.6, 133.7, 139.1, 140.6, 140.7, 142.0, 142.28, 142.33, 142.6, 142.8, 143.4, 143.5, 146.9, 165.0 (2′ -C=O), 168.4 (3′ -C=O) ppm. UV/vis (CHCl₃): λ_max (log ε) 422 (5.07), 537 (4.14), 567 (3.89) nm.
MS-FAB⁺: m/z = 828 [M + H], 827 [M] ⁺. Anal. Calcd for C₅₀H₃₅N₅O₄Ni: C, 72.48; H, 4.26; N, 8.45. Found: C, 72.66; H, 4.06; N, 8.37.

17

Cyclization Reaction Using an Oil Bath
A solution of porphyrin 3 (29 mg, 0.035 mmol) in nitrobenzene (1.5 mL) was heated at 200 ˚C under argon atmosphere for 6 h. The reaction mixture was then purified by flash chromatography [CH₂Cl₂, then CH₂Cl₂-acetone (95:5)] to remove the nitrobenzene and the product pyridinone-fused porphyrin 4a. Porphyrin 4a was further crystallized from CH₂Cl₂-MeOH to give the pure compound (20 mg, 74% yield).

19

Spectroscopic Data for (2-Methoxycarbonyl-6,11,16,21-tetraphenyl-1 H -pyrido-4-one[2,3- b ]porphyrinato)-nickel (4a) ^¹H NMR (300.13 MHz, CDCl₃): δ = 3.94 (s, 3 H, OCH₃), 7.01 (d, J = 1.6 Hz, 1 H, 3-H), 7.63-7.71 and 7.88-8.08 (2 m, 20 H, PhH), 8.51 (d, J = 5.0 Hz, 1 H, β-H), 8.59-8.70 (m, 5 H, β-H), 9.10 (br s, 1 H, 1-NH) ppm. ^¹³C NMR (75.47 MHz, CDCl₃): δ = 53.4 (OCH₃), 114.9, 117.7 (C-3), 119.3, 120.1, 120.5, 126.6, 127.1, 127.5, 128.0, 128.3, 128.6, 129.3, 129.8, 131.2, 131.8, 132.3, 132.5, 132.7, 133.3, 133.65, 133.73, 133.83, 133.92, 137.9, 138.2, 140.04, 140.06, 142.29, 142.31, 142.49, 142.54, 142.7, 143.6, 146.1, 146.8, 162.8 (2 -C=O), 173.7 (4 -C=O) ppm. UV/vis (CHCl₃): λ_max (log ε) = 433 (5.25), 546 (4.17) nm.
MS-FAB⁺: m/z = 796 [M + H]⁺, 795 [M] ⁺. HRMS-FAB: m/z calcd for C₄₉H₃₁N₅O₃Ni [M + H]⁺: 796.1859; found: 796.1855. Anal. Calcd for C₄₉H₃₁N₅O₃Ni˙3/2H₂O: C, 71.46; N, 8.50; H, 4.16. Found: C, 71.66; N, 8.40; H, 3.61.

22

Cyclization Reaction Using Eaton’s Reagent
A mixture of porphyrin 3 (50 mg, 0.060 mmol) and Eaton’s reagent (0.4 mL) was heated at 50 ˚C for 150 min. The reaction mixture was neutralized with an aq sat. soln of Na₂CO₃. The aqueous layer was extracted three times with CH₂Cl₂, and the organic layer was dried (anhyd Na₂SO₄) and evaporated under vacuum to dryness. The resulting residue was purified by flash chromatography using CHCl₃ as eluent and crystallized from CH₂Cl₂-n-hexane to give porphyrin 4c (37 mg, 84% yield) as purple crystals.

23

Spectroscopic Data for 2-Methoxycarbonyl-6,11,16,21-tetraphenyl-1 H -pyrido-4-one[2,3- b ]porphyrin (4c)
^¹H NMR (300.13 MHz, CDCl₃): δ = -2.71 and -2.57 (2 s, 2 H, NH), 3.95 (s, 3 H, OCH₃), 7.09 (d, J = 1.4 Hz, 1 H, 3-H), 7.74-7.79, 7.98-8.11, and 8.19-8.34 (3 m, 20 H, PhH), 8.69-8.74 (m, 3 H, β-H), 8.83, 8.87, and 9.01 (3 d, J = 5.0 Hz, 3 H, β-H), 9.24 (br s, 1 H, 1-NH) ppm. UV/vis (CHCl₃): λ_max (log ε) = 425 (5.16), 523 (4.28), 556 (3.76), 596 (3.76), 651 (3.44) nm. MS-FAB⁺: m/z = 740 [M + H]⁺, 839 [M] ⁺. Anal. Calcd for C₅₁H₃₉N₅O₄˙EtOH: C, 77.94; N, 8.91; H, 5.00. Found: C, 77.62; N, 8.70; H, 5.41.

24

X-ray Single-Crystal Determination
The X-ray data of porphyrin 4c-Cu(II) complex was collected on a CCD Bruker APEX II using graphite monochromatized Mo Kα radiation (λ = 0.71073 Å) with the crystal positioned at 35 mm from the CCD, and the spots were measured using a counting time of 80 s. Data reduction and empirical absorption were carried out using SAINT-NT from Bruker aXS. The structure was solved by direct methods and by subsequent difference Fourier syntheses and refined by full matrix least squares on F ^² using the SHELX-97 system programs.^²7 The CH₂Cl₂ solvent molecule was found disordered over three tetrahedral positions with occupation factors of 0.333. In addition, the chlorine atoms of one disorder component are also disordered occupying two alternative positions with occupation factors of 0.166. Anisotropic thermal parameters were used for all nonhy-drogen atoms excluding the atoms of CH₂Cl₂, which were refined with group isotropic temperature factors. The hydrogen atoms of this molecule was not inserted in the structure refinement while the hydrogen atoms of the copper porphyrin derivative complex were included in refinement in calculated positions with isotropic parameters equivalent 1.2 times those of the atom to which they are attached. Crystal structure has been deposited with the Cambridge Crystallographic Data Center and allocated with the deposit number CCDC 710189.