Efficient One-Pot Regioselective Synthesis of 2,3-Dibromo-5,10,15,20-tetra­arylporphyrins from 5,10,15,20-Tetraarylchlorins

Abstract

2,3-Dibromo-5,10,15,20-tetraarylporphyrins were prepared from easily available 5,10,15,20-tetraarylchlorins in one flask and two steps, namely regioselective dibromination and subsequent oxidation. An improvement in the synthesis of 2,3,12,13-tetrabromo-5,10,15,20-tetraarylporphyrins has also been achieved.

Key words

bromination - porphyrin - chlorin - regioselective - synthesis

References and Notes

• 1a Senge MO. In The Porphyrin Handbook   Vol. 1:  Kadish KM. Smith KM. Guilard R. Academic Press; San Diego: 2000.  p.273-281  ; and references cited therein
• 1b Spyroulias GA. Despotopoulos AP. Ratopoulou CP. Terzis A. Montauzon D. Poilblanc R. Coutsolelos AG. Inorg. Chem.  2002,  41:  2648 
• 1c Baciocchi E. Boschi T. Cassioli L. Galli C. Jaquinod L. Lapi A. Paolesse R. Smith KM. Tagliatesta P. Eur. J. Org. Chem.  1999,  3281 
• For recent and selective reports, see:
• 2a Shen DM. Liu C. Chen XG. Chen QY. J. Org. Chem.  2009,  74:  206 
• 2b Liu C. Shen DM. Chen QY. J. Org. Chem.  2007,  72:  2732 
• 2c Maeda C. Shinokubo H. Osuka A. Org. Lett.  2007,  9:  2493 
• 2d Shen DM. Liu C. Chen QY. J. Org. Chem.  2006,  71:  6508 
• 2e Hao E. Fronczek FR. Vicente MGH. Chem. Commun.  2006,  4900 
• 2f Sahoo AK. Mori S. Shinokubo H. Osuka A. Angew. Chem. Int. Ed.  2006,  45:  7972 
• 2g Shen DM. Liu C. Chen QY. Chem. Commun.  2005,  4982 
• 2h Smith MJ. Clegg W. Nguyen KA. Rogers JE. Pachter R. Fleitz PA. Anderson HL. Chem. Commun.  2005,  2433 
• 2i McEwan KJ. Fleitz PA. Rogers JE. Slagle JE. McLean DG. Akdas H. Katterle M. Blake IM. Anderson HL. Adv. Mater.  2004,  16:  1933 
• 2j Aratani N. Cho HS. Ahn TK. Cho S. Kim D. Sumi H. Osuka A. J. Am. Chem. Soc.  2003,  125:  9668 
• 2k Blake IM. Rees LH. Claridge TDW. Anderson HL. Angew. Chem. Int. Ed.  2000,  39:  1818 
• For reviews, see:
• 3a Setsune J. J. Porphyrins Phthalocyanines  2004,  8:  93 
• 3b For leading reports, see: Sharman WM. van Lier JE. J. Porphyrins Phthalocyanines  2000,  4:  441 
• 3c Locos OB. Dahms K. Senge MO. Tetrahedron Lett.  2009,  50:  2566 
• 3d Gao GY. Chen Y. Zhang XP. Org. Lett.  2004,  6:  1837 
• 3e Chen Y. Zhang XP. J. Org. Chem.  2003,  68:  4432 
• 3f Tse MK. Zhou ZY. Mak TCW. Chan KS. Tetrahedron  2000,  56:  7779 
• 3g Chan KS. Zhou X. Au MT. Tam CY. Tetrahedron  1995,  51:  3129 
• 3h Ali H. van Lier JE. Tetrahedron  1994,  50:  11933 
• 3i Chan KS. Zhou X. Luo BS. Mak TCW. J. Chem. Soc., Chem. Commun.  1994,  271 
• 3j Dimagno SG. Therien MJ. Science  1994,  264:  1105 
• 3k Dimagno SG. Lin VSY. Therien MJ. J. Org. Chem.  1993,  58:  5983 
• 3l Dimagno SG. Lin VSY. Therien MJ. J. Am. Chem. Soc.  1993,  115:  2513 
• 4a Liu C. Chen QY. Eur. J. Org. Chem.  2005,  3680 
• 4b Terazono Y. Dolphin D. J. Org. Chem.  2003,  68:  1892 
• 5a Callot HJ. Bull. Chim. Soc. Fr.  1974,  1492 
• 5b Callot HJ. Tetrahedron Lett.  1973,  14:  4987 
• For reviews, see:
• 6a Jaquinod L. In The Porphyrin Handbook   Vol. 1:  Kadish KM. Smith KM. Guilard R. Academic Press; San Diego: 2000.  p.201-237  
• 6b Vicente MGH. In The Porphyrin Handbook   Vol. 1:  Kadish KM. Smith KM. Guilard R. Academic Press; San Diego: 2000.  p.149-199  
• 6c For leading reports, see: Ou Z. Shao J. D’Souza F. Tagliatesta P. Kadish KM. J. Porphyrins Phthalocyanines  2004,  8:  201 
• 6d Gao GY. Ruppel JV. Allen DB. Chen Y. Zhang XP. J. Org. Chem.  2007,  72:  9060 
• 6e Liu C. Shen DM. Chen QY. Chem. Commun.  2006,  770 
• 6f Kumar DK. Bhyrappa P. Varghese B. Tetrahedron Lett.  2003,  40:  4849 
• 6g Jaquinod L. Khoury RG. Shea KM. Smith KM. Tetrahedron  1999,  55:  13151 
• 6h Arnold DP. Bott RC. Eldridge H. Elms FM. Smith G. Zojaji M. Aust. J. Chem.  1997,  50:  495 
• 6i Tagliatesta P. Li J. Autret M. Caemelbecke EV. Villard A. D’Souza F. Kadish KM. Inorg. Chem.  1996,  35:  5570 
• 6j Zou JZ. Li M. Xu Z. You XZ. Wang HQ. Acta Chim. Sinica  1994,  52:  683 
• 6k D’Souza F. Villard A. Caemelbecke EV. Franzen M. Boschi T. Tagliatesta P. Kadish KM. Inorg. Chem.  1993,  32:  4042 
• 6l DiMagno SG. Lin VSY. Therien MJ. J. Org. Chem.  1993,  58:  5983 
• 6m Bhyrappa P. Krishnan V. Inorg. Chem.  1991,  30:  239 
• 6n Crossley MJ. Burn PL. Chew SS. Cuttance FB. Newsom IA. J. Chem. Soc., Chem. Commun.  1991,  1564 
• 7a Jiao L. Hao E. Fronczek FR. Vicente MGH. Smith KM. Chem. Commun.  2006,  3900 
• 7b Nath M. Pink M. Zaleski JM. J. Am. Chem. Soc.  2005,  127:  478 
• 7c Nath M. Huffman JC. Zaleski JM. Chem. Commun.  2003,  858 
• 7d Aihara H. Jaquinod L. Nurco DJ. Smith KM. Angew. Chem. Int. Ed.  2001,  40:  3439 
• 8a Medforth CJ. In The Porphyrin Handbook   Vol. 5:  Kadish KM. Smith KM. Guilard R. Academic Press; San Diego: 2000.  p.1-80  
• 8b Boronat M. Orti E. Viruela PM. Tomas F. J. Mol. Struct. (Theochem)  1997,  390:  149 
• 8c Reimers JR. Lu TX. Crossley MJ. Hush NS. J. Am. Chem. Soc.  1995,  117:  2855 
• 8d Crossley MJ. Harding MM. Sternhell S. J. Am. Chem. Soc.  1992,  114:  3266 
• 8e Crossley MJ. Harding MM. Sternhell S. J. Org. Chem.  1988,  53:  1132 
• 8f Crossley MJ. Field LD. Harding MM. Sternhell S. J. Am. Chem. Soc.  1987,  109:  2335 
• 8g Crossley MJ. Harding MM. Sternhell S. J. Am. Chem. Soc.  1986,  108:  3608 
• For leading reports, see:
• 9a Silva AMG. Tome AC. Neves MG. Silva AMS. Cavaleiro JAS. J. Org. Chem.  2002,  67:  726 
• 9b Chen Y. Medforth CJ. Smith KM. Alderfer J. Dougherty TJ. Pandey RK. J. Org. Chem.  2001,  66:  3930 
• 9c Silva AMG. Tome AC. Neves MGPM. Silva AMS. Cavaleiro JAS. Chem. Commun.  1999,  1767 
• 9d Shea KM. Jaquinod L. Khoury RG. Smith KM. Chem. Commun.  1998,  759 
• 9e Tome AC. Lacerda PSS. Neves MGPMS. Cavalcivo JAS. Chem. Commun.  1997,  1199 
• 9f Brückner C. Dolphin D. Tetrahedron Lett.  1995,  36:  9425 
• 9g Catalano MM. Crossley MJ. Harding MM. King LG. Chem. Commun.  1984,  1535 
• 9h Callot HJ. Johnson AW. Sweoney A. J. Chem. Soc., Perkin Trans. 1  1973,  1424 
• 9i Whitlock HW. Hanauer R. Oester MY. Bower BK. J. Am. Chem. Soc.  1969,  91:  7485 
• 18 Whitlock HW. Oester MY. J. Am. Chem. Soc.  1973,  95:  5738 

10

Typical Procedure for the Synthesis of 2,3-Dibromo-5,10,15,20-tetraarylporphyrins 4
5,10,15,20-Tetraarylchlorin 2 (0.2 mmol) and NBS (80 mg, 0.44 mmol) were added to a Schlenk flask (50 mL). The flask was then evacuated and backfilled with nitrogen (three cycles). Then dry CHCl₃ (EtOH free, 20 mL) was charged with a syringe. The reaction mixture was stirred and heated under reflux for 4 h. After being slightly cooled, a solution of DDQ (184 mg, 0.8 mmol) in toluene (2 mL) was added, and the mixture was refluxed for further 1 h. After being cooled to r.t., Et₃N (1 mL) was added to neutralize the acids produced in the reaction. Then the reaction mixture was filtered through a short silica plug (300-400 mesh, eluting with CH₂Cl₂). The filtrate was evaporated to dryness, and the resulting solid was purified by flash chromatography (silica gel, 300-400 mesh, PE-CH₂Cl₂ as eluent) to yield the products 4.

11

Synthesis of 12,13-Dibromo-2,3-dihydro-5,10,15,20-tetraphenylchlorin 3a
5,10,15,20-Tetraphenylchlorin (2a, 124 mg, 0.2 mmol) and NBS (80 mg, 0.44 mmol) were added to a Schlenk flask (50 mL). The flask was then evacuated and backfilled with nitrogen (three cycles). Then dry CHCl₃ (EtOH free, 20 mL) was charged with a syringe. The reaction mixture was stirred and heated under reflux for 4 h. After being cooled to r.t., Et₃N (1 mL) was added to neutralize the acids produced in the reaction. Then the reaction mixture was quickly filtered through a short silica plug (300-400 mesh, eluting with CH₂Cl₂). The filtrate was concentrated and recrystallized from CH₂Cl₂-MeOH to give pure products 3a.
12,13-Dibromo-2,3-dihydro-5,10,15,20-tetraphenylchlorin (3a)
Purple crystals, 151 mg, yield 98%. ^¹H NMR (300 MHz, CDCl₃): δ = 8.51 (d, J = 2.7 Hz, 2 H, β-H), 8.08 (d, J = 2.7 Hz, 2 H, β-H), 8.02 (d, J = 6.0 Hz, 4 H, o-PhH), 7.82 (d, J = 6.0 Hz, 4 H, o-PhH), 7.67-7.70 (m, 12 H, m-PhH and p-PhH), 4.07 (s, 4 H, CH₂), -1.40 (s, 2 H, NH). UV/vis (CH₂Cl₂): λ_max (rel. int.) = 428 (1.00), 529 (0.08), 598 (0.05), 650 (0.10) nm. MS (MALDI): m/z = 774.1 [M⁺]. Anal. Calcd for C₄₄H₃₀Br₂N₄×2H₂O (from CH₂Cl₂-wet MeOH): C, 65.20; H, 4.23; N, 6.91. Found: C, 65.00; H, 4.01; N, 6.90.

12

Synthesis of Zinc 12,13-Dibromo-2,3-dihydro-5,10,15,20-tetraphenylchlorin Zn3a
Zn3a was synthesized according to the literature method. [¹8] 12,13-Dibromo-2,3-dihydro-5,10,15,20-tetraphenylchlorin (3a, 77 mg, 0.1 mmol) and zinc acetate dihydrate (66 mg, 0.3 mmol) were added to a Schlenk flask (20 mL). The flask was then evacuated and backfilled with nitrogen (three cycles). Then pyridine (10 mL) was charged with a syringe. The reaction mixture was stirred and heated at 100 ˚C under nitrogen for 1 h. To the cooled reaction mixture, benzene (20 mL) and distilled H₂O (20 mL) were added. The organic layer was quickly washed with distilled H₂O and brine and then filtered through a short silica plug (300-400 mesh, eluting with CH₂Cl₂). The filtrate was concentrated and recrystallized from CH₂Cl₂-MeOH to give monopyridinate complex of Zn3a.
Zinc 12,13-Dibromo-2,3-dihydro-5,10,15,20-tetraphenylchlorin (Zn3a)
Purple crystals, 66 mg, yield 72%. ^¹H NMR (300 MHz, CDCl₃): δ = 8.36 (d, J = 4.2 Hz, 2 H, β-H), 7.96 (d, J = 4.2 Hz, 2 H, β-H), 7.86 (d, J = 7.2 Hz, 4 H, o-PhH), 7.77 (d, J = 7.2 Hz, 4 H, o-PhH), 7.59-7.61 (m, 12 H, m-PhH and p-PhH), 3.97 (s, 4 H, CH₂). UV/vis (CH₂Cl₂): λ_max (rel. int.) = 424 (1.00), 553 (0.05), 619 (0.08) nm. MS (MALDI): m/z = 836.0 [M⁺]. Anal. Calcd for C₄₄H₂₈Br₂N₄Zn˙C₅C₅N×4H₂O (from CH₂Cl₂-wet MeOH-pyridine): C, 59.50; H, 4.18; N, 7.08. Found: C, 59.68; H, 3.86; N, 7.08.

13

C₄₄H₂₈Br₂N₄Zn˙C₅H₅N×0.5CHCl₃ (Zn3a) crystallized by diffusion of MeOH into a CHCl₃-pyridine (100:1) solution.
Crystal Data
M = 976.68, monoclinic, space group P2(1)/c, a = 13.330 (4), b = 19.918 (6), c = 17.843 (6) Å, α = 90.00, β = 109.285 (4), γ = 90.00˚, V = 4472 (2) Å^³, T = 293 (2) K, Z = 4, D _c = 1.451 g cm^-³, µ (Mo Kα) = 2.466 mm^-¹, 21287 reflections measured, 9543 unique which were used in all calculations. R1 (all data) = 0.1106. R1 = 0.0551. CCDC 689519.

14

5,10,15,20-Tetraarylchlorins were synthesized according to the literature method. [9i]
5,10,15,20-Tetra( p -chlorophenyl)chlorin (2b)
Purple crystals, 736 mg, yield 60%. ^¹H NMR (300 MHz, CDCl₃): δ = 8.56 (d, J = 4.5 Hz, 2 H, β-H), 8.40 (s, 2 H, β-H), 8.18 (d, J = 4.5 Hz, 2 H, β-H), 8.02 (d, J = 7.8 Hz, 4 H, o-PhH), 7.80 (d, J = 7.8 Hz, 4 H, o-PhH), 7.67 (d, J = 7.5 Hz, 8 H, m-PhH), 4.15 (s, 4 H, CH₂), -1.52 (s, 2 H, NH). UV/vis (CH₂Cl₂): λ_max (rel. int.) = 419 (1.00), 519 (0.09), 545 (0.06), 599 (0.04), 652 (0.19) nm. MS (MALDI): m/z = 754.1 [M⁺]. Anal. Calcd for C₄₄H₂₈Cl₄N₄×0.5H₂O (from CH₂Cl₂-wet MeOH): C, 69.21; H, 3.83; N, 7.34. Found: C, 69.35; H, 3.68; N, 7.34.

15

For the details of the synthesis of 4b and 4c, see ref. 10.
2,3-Dibromo-5,10,15,20-tetrakis( p -chlorophenyl)-porphyrin (4b)
Purple crystals, 172 mg, yield 95%. ^¹H NMR (300 MHz, CDCl₃): δ = 8.85 (s, 4 H, β-H), 8.68 (s, 2 H, β-H), 8.11 (d, J = 6.0 Hz, 4 H, o-PhH), 8.05 (d, J = 6.6 Hz, 4 H, o-PhH), 7.74-7.76 (m, 8 H, m-PhH), -2.93 (s, 2 H, NH). UV/vis (CH₂Cl₂): λ_max (rel. int.) = 425 (1.00), 522 (0.06), 599 (0.02), 687 (0.05) nm. MS (MALDI): m/z = 909.9 [M⁺]. Anal. Calcd for C₄₄H₂₄Br₂Cl₄N₄×0.5H₂O (from CH₂Cl₂-wet MeOH): C, 57.49; H, 2.74; N, 6.09. Found: C, 57.39; H, 2.60; N, 6.16.

16

H₂(2,3,12,13-Br₄TPP) was first synthesized by Callot [5a] in 1974, but its structure was misassigned as 2,7,12,17-tetrabromo-5,10,15,20-tetraphenylporphyrin. In 1991, work by Crossley et al. [6n] revealed the antipodal nature of the bromination reaction of metal-free tetraarylporphyrins, and H₂(2,3,12,13-Br₄TPP) was prepared by refluxing H₂(TPP) with NBS in 80% yield, but no detail operation was reported. In 1994, Xu et al. [6i] obtained H₂(2,3,12,13-Br₄TPP) using the same method by directly recrystallized from CH₂Cl₂-MeOH after the reaction mixture was concentrated, but no yield was reported. In 2003, Bhyrappa et al. [6f] reported the synthetic procedure of H₂(2,3,12,13-Br₄TPP) in detail, in which the crude product was purified by chromatography and the yield was 65%.

17

Typical Procedure for the Synthesis of 2,3,12,13-Tetrabromo-5,10,15,20-tetraarylporphyrins 5
5,10,15,20-Tetraarylporphyrin 1 (0.5 mmol) and NBS (580 mg, 3.25 mmol) were dissolved in CHCl₃ (EtOH free, 60 mL). The reaction mixture was stirred and heated under reflux for 4 h. After being cooled to r.t., Et₃N (3 mL) was added to neutralize the acids produced in the reaction. Then the reaction mixture was filtered through a short silica plug (300-400 mesh, eluting with CH₂Cl₂). The filtrate was evaporated to dryness, and the resulting solid was purified by flash chromatography (silica gel, 300-400 mesh, CH₂Cl₂ as eluent) to yield the products 5. The spectroscopic data were in agreement with literature values. [²g] [6f]