Simple Methodology for the Synthesis of meso-Unsubstituted β-Substituted Alkyl Porphyrins

Abstract

The MacDonald [2+2]-type condensation of meso-free β-alkyldipyrromethane with different meso-free-1,9-bis(for­myl)dipyrromethanes yields new asymmetric sterically unencumbered porphyrins.

β-alkylporphyrins - MacDonald condensation - disymmetric β-alkyldipyrromethane - pyrroles

References and Notes

1a The Porphyrin Handbook   Vol. 1-10:  Kadish K. Smith KM. Guilard R. Academic Press; Boston: 2000. 

1b The Porphyrin Handbook   Vol. 11-20:  Kadish K. Smith KM. Guilard R. Academic Press; San Diego: 2003. 

2 Ryppa C. Senge MO. Hatscher SS. Kleinpeter E. Wacker P. Schilde U. Wiehe A. Chem. Eur. J.  2005,  11:  3427 

3 Neya S. Funasaki N. Tetrahedron Lett.  2002,  43:  1057 

4 Neya S. Quan J. Hoshino T. Hata M. Funasaki N. Tetrahedron Lett.  2004,  45:  8629 

5 Nguyen LT. Senge MO. Smith KM. J. Org. Chem.  1996,  61:  998 

6 Arsenault GP. Bullock E. MacDonald SF. J. Am. Chem. Soc.  1960,  82:  4384 

7 Chong R. Clezy PS. Liepa AJ. Nichol AW. Aust. J. Chem.  1969,  22:  229 

8 Helms A. Heiler D. McLendon G. J. Am. Chem. Soc.  1992,  114:  6227 

9 Young R. Chang CK. J. Am. Chem. Soc.  1985,  107:  898 

10 Porphyrins and Metalloporphyrins   Smith KM. Elsevier; Amsterdam: 1975. 

11 Taniguchi S. Hasegawa H. Nishimura M. Takahashi H. Synlett  1999,  73 

12

Selected Data Compound 1: ¹H NMR (500 MHz, CDCl₃): δ = -3.94 (br s, 2 H, NH), 1.93 (t, 3 H, CH₂CH ₃), 3.71 (s, 3 H, CH₃), 4.18 (q, 2 H, CH ₂CH₃), 9.46 (m, 4 H, 7,8,17,18-H_pyrrolic), 9.54 (s, 2 H, 12,13-H_pyrrolic), 10.24 (s, 1 H, α- or δ-H_meso), 10.25 (s, 1 H, α- or δ-H_meso), 10.33 (s, 1 H, β- or γ-H_meso), 10.34 (s, 1 H, β- or γ-H_meso) ppm. ¹³C NMR (125 MHz, CDCl₃): δ = 11.45 (CH₃), 17.53 (CH₂ CH₃), 19.78 (CH₂CH₃), 99.89 (Cα,δ), 104.37 (Cβ,γ), 129.00 (C12,13), 132.96 (C7,8,17,18), 142.07 (C3), 153,03 (C2) ppm. UV/vis (CH₂Cl₂): λ_max (ε mM^-1cm^-1): 394 (158.9), 490 (8.1), 526 (2.8), 560 (3.7), 615 (0.5) nm. HRMS: m/z calcd for C₂₃H₂₁N₄ [M + H]⁺: 353.1766; found: 353.1766.
Compound 2: ¹H NMR (500 MHz, CDCl₃): δ = -3.81 (br s, 2 H, NH), 1.92 (t, 6 H, CH₂CH ₃), 3.65 (s, 6 H, CH₃), 4.12 (q, 4 H, CH ₂CH₃), 9.45 (dd, 4 H, H_pyrrolic), 10.11 (s, 1 H, α-H_meso), 10.19 (s, 2 H, β,δ-H_meso), 10.27 (s, 1 H, γ-H_meso) ppm. ¹³C NMR (125 MHz, CDCl₃): δ = 11.52 (CH₃), 17.71 (CH₂ CH₃), 19.90 (CH₂CH₃), 95.57 (Cα), 100.19 (Cβ,δ), 104.71 (Cγ), 130.21 (C11,19), 130.50 (C12,13,17,18), 136.15 (C2,8), 142.74 (C3,7) ppm. UV/vis (CH₂Cl₂): λ_max (ε mM^-1cm^-1): 393 (216.9), 491 (19.1), 523 (7.4), 560 (7.8), 613 (2.7) nm. HRMS: m/z calcd for C₂₆H₂₇N₄ [M + H]⁺: 395.2236; found: 395.2243.
Compound 3: ¹H NMR (500 MHz, CDCl₃): δ = -3.50 (br s, 2 H, NH), 1.91 (m, 9 H, CH₂CH ₃), 3.64 (s, 3 H, 8-CH₃), 3.69 (s, 6 H, 2,12-CH₃), 4.10 (q, 2 H, 7-CH ₂CH₃), 4.16 (m, 4 H, 3,13-CH ₂CH₃), 9.43 (s, 2 H, H_pyrrolic), 10.14 (s, 1 H, α- or β-H_meso), 10.15 (s, 1 H, α- or β-H_meso), 10.20 (s, 1 H, δ- or γ-H_meso), 10.21 (s, 1 H, δ- or γ-H_meso) ppm. ¹³C NMR (125 MHz, CDCl₃): δ = 11.51 (CH₃), 17.65 (CH₂ CH₃), 19.85 (CH₂CH₃), 96.02 (Cα,β), 100.64 (Cδ,γ), 131.73 (C17,18), 133.86 (C12), 134.69 (C2), 136.73 (C8), 141.00 (C3), 141.70 (C13), 143.81 (C7) ppm. UV/vis (CH₂Cl₂): λ_max (ε mM^-1cm^-1): 395 (180.7), 496 (10.5), 532 (6.7), 563 (5.5), 617 (1.9) nm. HRMS: m/z calcd for C₂₉H₃₃N₄ [M + H]⁺: 437.2705; found: 437.2694.
Compound 4: ¹H NMR (500 MHz, CDCl₃): δ = -3.72 (br s, 2 H, NH), 1.91 (t, 12 H, CH₂CH ₃), 3.67 (s, 12 H, CH₃), 4.13 (q, 8 H, CH ₂CH₃), 10.12 (s, 2 H, H_meso), 10.13 (s, 2 H, H_meso) ppm. ¹³C NMR (125 MHz, CDCl₃): δ = 11.59 (CH₃), 17.75 (CH₂ CH₃), 19.92 (CH ₂ CH₃), 96.29 (C_meso), 135.03 (C2), 142.12 (C3) ppm. UV/vis (CH₂Cl₂): λ_max (ε mM^-1cm^-1): 396 (162.9), 497 (12.3), 530 (8.9), 565 (6.0), 619 (4.3) nm. HRMS: m/z calcd for C₃₉H₃₉N₄ [M + H]⁺: 479.3175; found: 479.3174.
Compound 6a: ¹H NMR (500 MHz, CDCl₃): δ = 1.06 and 1.33 (all t, 9 H, 3 CH₂CH ₃), 2.32 (s, 3 H, CH₃), 2.45 and 4.29 (two q, 6 H, 3 CH ₂CH₃), 3.98 (s, 2 H, CH₂), 6.04 and 7.29 (two s, 2 H, 2 H_pyrrolic), 9.60 and 10.00 (two br s, 2 H, 2 NH) ppm. ¹³C NMR (125 MHz, CDCl₃): δ 10.55, 14.42, 15.53, 17.22, 24.67, 59.86, 60.53, 108.87, 116.26, 117.28, 122.01, 124.20, 127.02, 129.62, 134.87, 161.65, 162.50 ppm. HRMS: m/z calcd for C₁₈H₂₄N₂O₄ [M^{+ ·}]: 332.1736; found: 332.1704.
Compound 6b: ¹H NMR (500 MHz, CDCl₃): δ = 1.13 (t, 3 H, CH₂CH ₃), 2.08 (s, 3 H, CH₃), 2.48 (q, 2 H, CH ₂CH₃), 3.94 (s, 2 H, 5-CH₂), 6.04, 6.17, 6.41, 6.68 (all m, 4 H, 4 H_pyrrolic), 7.49, 7.87 (two br s, 2 H, 2 NH) ppm. ¹³C NMR (125 MHz, CDCl₃): δ = 10.31, 16.00, 17.40, 24.51, 106.26, 108.50, 113.90, 116.99, 117.90, 121.22, 124.32, 129.21. HRMS:
m/z calcd for C₁₂H₁₆N₂ [M^+· ]: 188.1313; found: 188.1313.
Compound 6c: ¹H NMR (500 MHz, CDCl₃): δ = 0.91 (t, 3 H, CH₂CH ₃), 2.32 (s, 3 H, CH₃), 2.50 (q, 2 H, CH ₂CH₃), 4.06 (s, 2 H, 5-CH₂), 6.19, 6.91, 9.42, 9.55 (all m, 4 H, 4 H_pyrrolic), 10.99, 11.36 (two br s, 2 H, 2 NH). ¹³C NMR (125 MHz, CDCl₃): δ = 8.86, 15.32, 16.98, 24.79, 110.37, 122.83, 125.31, 128.74, 133.23, 135.51, 138.18, 177.04, 179.04. HRMS: m/z calcd for C₁₄H₁₆N₂O₂ [M^+· ]: 244.1212; found: 244.1198.