Synthesis and Structural Characterization of Corrole and Sapphyrin Analogs of Imidazolium-Pyridine Cyclophanes

Abstract

Dissociation of metals from medicinal agents and deposition in healthy tissue is a major problem with many metal-based pharmaceuticals. N-heterocyclic carbenes have been shown to complex more strongly than do phosphines to a variety of metals. By incorporating N-heterocyclic carbenes into the structure of a multi-donor ligand, we envision the resulting moiety to be able to retain the metals better than other ligands. We report the synthesis of three novel mixed donor imidazolium salts. The two imidazolium cyclophanes have the potential to coordinate and stabilize metals of ­various sizes into their inner cavity.

condensation - heterocycles - imidazolium - ligand design - macrocyclic ligands

References

1 Öfele K. J. Organomet. Chem.  1968,  12:  42 

2 Wanzlick H.-W. Schönherr H.-J. Angew. Chem., Int. Ed. Engl.  1968,  7:  141 

3 Cardin DJ. Doyle MJ. Lappert MF. J. Chem. Soc., Chem. Commun.  1972,  927 

4 Herrmann WA. Köcher C. Angew. Chem., Int. Ed. Engl.  1997,  36:  2162 

5 Bourissou D. Guerret O. Gabbaï FP. Bertrand G. Chem. Rev.  2000,  100:  39 

6 Herrmann WA. Angew. Chem. Int. Ed.  2002,  41:  1290 

7 Sessler JL. Mody TA. Hemmi GW. Lynch V. Inorg. Chem.  1993,  32:  3175 

8 Simons RS. Garrison JC. Kofron WG. Tessier CA. Youngs WJ. Tetrahedron Lett.  2002,  43:  3423 

9 Alcalde E. Mesquida N. Perez-Garcia L. Ramos S. Alemany M. Rodriguez ML. Chem.-Eur. J.  2002,  474 

10 Garrison JC. Simons RS. Talley JM. Wesdemiotis C. Tessier CA. Youngs WJ. Organometallics  2001,  20:  1276 

11 Barnard PJ. Baker MV. Berners-Price SJ. Skelton BW. White AH. J. Chem. Soc., Dalton Trans.  2004,  1038 

12 Garrison JC. Simons RS. Tessier CA. Youngs WJ. J. Organomet. Chem.  2003,  673:  1 

13 Baker MV. Skelton BW. White AH. Williams CC. Organometallics  2002,  21:  2674 

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General Procedure and Analytical Data for C ₃₈ H ₃₆ N ₁₂ P ₂ F ₁₂ :
6,6′-Bis(bromomethyl)-2,2′-bipyridyl (2.0 mmol, 1.90 mg) and 2,6-bis(imidazolemethyl)pyridine (2.2 mmol, 0.53 g) were dissolved in 200 mL of CH₂Cl₂. The solution was stirred for 2 d at r.t. The solid was collected and then dissolved with H₂O. The material underwent anion exchange upon addition of an excess amount of NH₄PF₆. The crude solid was collected and found to be a mixture of at least three compounds. The solid was dissolved in MeCN and allowed to slowly evaporate. Crystals slowly formed and were collected. Yield: 0.25 g, 0.26 mmol, 13%. ¹H NMR (750 MHz, DMSO-d ₆): δ = 5.37 (s, 4 H, CH₂), 5.62 (s, 4 H, CH₂), 5.71 (s, 4 H, CH₂), 7.31 (br s, 2 H), 7.35 (d, 2 H, J = 7.5 Hz), 7.37 (br s, 2 H), 7.43 (d, 2 H, J = 7.5 Hz), 7.55 (d, 2 H, J = 7.5 Hz), 7.77 (s, 2 H), 7.87 (s, 2 H), 7.92 (t, 2 H, J = 7.5 Hz), 7.97 (t, 2 H, J = 7.5 Hz), 8.15 (d, 2 H, J = 7.5 Hz), 8.42 (br s, 2 H), 9.39 (s, 2 H, NCHN). ¹³C{¹H} NMR (75 MHz, DMSO-d ₆): δ = 51.70, 52.80 and 53.03 [CH₂], 120.05, 121.33, 121.54, 121.68, 122.87, 123.23, 123.25, 136.77, 137.72, 138.72, 138.77, 153.28, 153.47, 154.40 and 154.99 [aromatics]. MS-ES: m/z calcd for C₃₈H₃₆N₁₂: 660.3; found: 659.6.

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General Procedure and Analytical Data for C ₂₇ H ₂₃ N ₇ P ₂ F ₁₂ :
2,9-Bis(bromomethyl)-1,10-phenanthroline (5.0 mmol, 1.83 g) was placed in a 500 mL Erlenmeyer flask and dissolved in 400 mL of CH₂Cl₂. 2,6-Bis(imidizolemethyl)pyridine (5.1 mmol, 1.22 g) was added to solution and then the flask was capped with a serum cap. The solution was stirred for 2 d at r.t. over which time a solid precipitate had formed. The solution was filtered and solid was readily dissolved in H₂O and anion exchange was performed using NH₄PF₆. The solution was filtered and a white precepitate was obtained. Yield: 1.84 g, 2.50 mmol, 50%. ¹H NMR (750 MHz, DMSO-d ₆): δ = 5.54 (s, 4 H, CH₂), 5.84 (s, 4 H, CH₂), 7.62 (d, 2 H, J = 7.5 Hz), 7.94 (m, 5 H), 7.99 (d, 2 H, J = 8.1 Hz), 8.05 (s, 2 H), 8.62 (d, 2 H, J = 8.1 Hz), 9.20 (s, 2 H, NCHN). ¹³C{¹H} NMR (75 MHz, DMSO-d ₆): δ = 52.68 and 53.47 [CH₂], 123.06, 123.24, 123.37, 123.96, 126.89, 128.31, 136.40 (NCHN), 137.81, 139.04, 144.63, 153.19 and 153.28 [aromatics]. MS-FAB: m/z calcd for C₂₇H₂₃N₇PF₆: 591; found: 591.

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General Procedure and Analytical Data for C ₂₁ H ₁₈ N ₆ P ₂ F ₁₂ :
A mixture of 2,9-bis(bromomethyl)-1,10-phenanthroline (0.1 mmol, 0.0384 g) and 1,1′-methylene bis(imidazole) (0.2 mmol, 0.0296 g) was stirred at reflux in MeCN-H₂O (50:50) for 12 h. Solvent was removed and water and excess NH₄PF₆ was added. The crude product was collected as a yellowish orange solid 0.0322 g (50%). The crude was purified by column chromatography on alumina using MeCN as the eluting solvent. The clean product was collected as a pale yellow solid. Yield: 0.0110 g, 0.017 mmol, 17%. Crystals were obtained from MeCN as colorless plates. ¹H NMR (300 MHz, CH₃CN-d ₃): δ = 5.89 (s, 4 H), 6.75 (s, 4 H), 7.55 (s, 2 H), 7.78 (d, 2 H), 7.88 (s, 2 H), 7.99 (s, 2 H), 4.48 (d, 2 H), 9.68 (s, 2 H). ¹³C NMR (75 MHz, CD₃CN-d ₃): δ = 54.95 and 60.84 [CH₂], 122.87, 123.26, 125.67, 128.33, 130.35, 139.34, 140.14, 153.18 [aromatic]. MS-FAB: m/z calcd for C₂₁H₁₈N₆PF₆: 499.12; found: 499.

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Crystal Data for C ₃₈ H ₃₇ F ₁₈ N ₁₂ P ₃ [8][PF ₆ ] ₂ : M _w = 1096.72, monoclinic, space group P2/n, a = 14.067 (1), b = 8.1197 (7), c = 19.900(2) Å, β = 107.073 (2)°, V = 2172.8 (3) ų, Z = 4, D _calcd = 1.678 mg/m³, µ = 0.263 mm^-1, T = 100 (2) K, refinement for data with I>2σ(I) (3840 reflections, R _int = 0.0259) gave R ₁ (F) = 0.0877 and wR ₂ (F ²) = 0.2341 for all data.

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Crystal Data for C ₂₇ H ₂₄ F ₁₂ N ₇ OP ₂ [10][PF ₆ ] ₂ : M _w = 752.47, triclinic, space group P-1, a = 8.8384 (9), b = 12.467 (1), c = 14.134 (1) Å, α = 107.558 (2)°, β = 97.807 (2)°, γ = 92.270 (2)°, V = 1465.7 (3) ų, Z = 2, D _calcd = 1.705 mg/m³, µ = 0.264 mm^-1, T = 100 (2) K, refinement for data with I>2σ(I) (6462 reflections, R _int = 0.0259) gave R ₁ (F) = 0.0523 and wR ₂ (F ²) = 0.1172 for all data.

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CCDC 221345-221347 contains the supplementary crystallographic data for this paper. These data can be obtained online free of charge [or from the Cambridge Crystallographic Data Centre, 12, Union Road, Cambridge CB2 1EZ, UK; fax: [phone]; or [e-mail]].

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Crystal Data for C ₂₉ H ₄₂ N ₆ O ₄ S ₄ P ₂ F ₁₂ [12][PF ₆ ] ₂ : M _w = 752.47, monoclinic, space group P2(1)/n, a = 14.956 (3), b = 15.366 (4), c = 18.869 (4) Å, β = 112.274 (4)°, V = 4012.9 (16) ų, Z = 4, D _calcd = 1.584 mg/m³, µ = 0.416 mm^-1, T = 100 (2) K, refinement for data with I>2σ(I) (9498 reflections, R _int = 0.0436) gave R ₁ (F) = 0.0495 and wR ₂ (F ²) = 0.1026 for all data.