Synthesis of Functionalized Unsymmetrical Thiophene Diols and Their Use in the Synthesis of cis-21-Monothia- and cis-21,23-Dithiaporphyrin Building Blocks with Two Different Functional Groups

Abstract

A series of functionalized unsymmetrical thiophene ­diols were synthesized and used for the synthesis of cis-21-monothia and cis-21,23-dithiaporphyrin building blocks having two ­different functional groups at meso-positions. To show the use of the cis-thiaporphyrin building blocks with two different functional groups, a porphyrin trimer comprised of N₄, N₃S and N₂S₂ por­phyrin sub-units was synthesized by using both covalent and non-covalent interactions.

functionalized unsymmetrical diols - cis-thiaporphyrin - porphyrin trimer - covalent - non-covalent interactions

References

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5

Experimental Procedure and Spectroscopic Data for Selected Compounds. Diol 9: the thiophene mono-ol 3 (1.00 g, 3.67 mmol), tetramethylethylenediamine (1.39 mL, 9.18 mmol) and n-BuLi (5.74 mL of ca. 15% solution in hexane) were added successively to freshly distilled dry Et₂O (30 mL) in a 250-mL three-necked round-bottomed flask and stirred for 15 min under nitrogen atmosphere at 0 °C. An ice-cold solution of 4-pyridine carboxaldehyde (0.87 mL, 9.18 mmol) in dry THF (30 mL) was added to it. The mixture was stirred for 15 min and ice-cold NH₄Cl (50 mL, ca. 1 M) was added to quench the reaction. After standard work up, the crude compound was purified by silica gel column chromatography using CH₂Cl₂-MeOH (95:5) and diol 4 obtained as a yellow oily liquid (0.40 g, 29%). ¹H NMR (400 MHz, CDCl₃): δ = 0.92 (6 H, s, CH₃), 4.00 (3 H, br s, OH), 5.99-6.15 (2 H, m, CHOH), 6.82-6.86 (2 H, m, thiophene), 7.42-7.44 (2 H, m, aryl), 7.70 (2 H, d, J = 7.8 Hz, pyridyl), 8.03-8.06 (2 H, m, aryl), 8.30 (2 H, br s, pyridyl) ppm. ES-MS: m/z calcd for C₂₂H₂₁NO₃S: 379.48; found: 378.09 (100%) [M⁺ - H]. Anal. Calcd: C, 69.63; H, 5.58; N, 3.69. Found: C, 69.74; H, 5.51; N, 3.74.
Porphyrin 15: condensation of diol 9 (0.45 g, 1.19 mmol) with 10 (0.50 g, 1.19 mmol) in propionic acid (125 mL) at refluxing temperature for 2 h followed by standard work up and chromatography on silica using CH₂Cl₂-MeOH (96:4) gave the desired porphyrin 15 as a purple solid (0.07 g, 8%). ¹H NMR (400 MHz, CDCl₃): δ = 0.94 (6 H, s, CH₃), 2.69 (6 H, s, CH₃), 7.52 (2 H, d, J = 7.8 Hz, aryl), 7.62 (4 H, d, J = 8.0 Hz, aryl), 7.98 (2 H, d, J = 7.8 Hz, aryl), 8.11 (4 H, d, J = 8.0 Hz, aryl), 8.20 (2 H, d, J = 7.8 Hz, 3,5-pyridyl), 8.54 (1 H, m, β-pyrrole), 8.64 (1 H, d, J = 4.6 Hz, β-pyrrole), 8.72 (1 H, d, J = 4.6 Hz, β-pyrrole), 8.78-8.81 (1 H, m, β-pyrrole), 9.14 (2 H, br s, 2,6-pyridyl), 9.54 (1 H, d, J = 4.4 Hz, β-thiophene), 9.72 (1 H, d, J = 4.4 Hz, β-thiophene), 9.76 (2 H, s, β-thiophene) ppm. ¹³C NMR (100 MHz, CDCl₃): δ = 22.56, 22.68, 31.06, 31.49, 128.03, 129.49, 133.61, 134.71, 134.93, 135.14, 135.73, 136.13, 138.02, 146.90, 147.61, 148.53, 148.68, 149.75, 150.87, 155.11, 156.63, 157.01 ppm. ES-MS: m/z calcd for C₅₀H₃₇N₃OS₂: 759.96; found: 760.31 (100%) [M⁺]. UV/Vis (in toluene, λ_max/nm, ε/mol^-1 dm³ cm^-1): 437 (292652), 515 (26193), 549 (9062), 634 (2073), 697 (5030).
Porphyrin 16: sample of porphyrin 15 (0.05 g, 0.07 mmol) was dissolved in benzene-MeOH (3:1, 40 mL) taken in a 100-mL round-bottomed flask and excess KOH (0.20 g) was added to it. The reaction mixture was refluxed at 80 °C using a Dean-Stark apparatus. The excess solvent was removed under vacuum and the crude compound was subjected to silica gel column chromatography using PE-CH₂Cl₂ (5:95) to afford the pure desired porphyrin 16 as a purple solid (0.04 g, 88%). ¹H NMR (400 MHz, CDCl₃): δ = 2.70 (6 H, s, CH₃), 3.32 (1 H, s, CH), 7.50 (2 H, d, J = 7.8 Hz, aryl), 7.62 (4 H, d, J = 8.0 Hz, aryl), 7.96 (2 H, d, J = 7.8 Hz, aryl), 8.14 (4 H, d, J = 8.0 Hz, aryl), 8.20 (2 H, d, J = 7.8 Hz, 3,5-pyridyl), 8.56 (1 H, d, J = 4.5 Hz, β-pyrrole), 8.64 (1 H, d, J = 4.6 Hz, β-pyrrole), 8.72 (1 H, d, J = 4.6 Hz, β-pyrrole), 8.80 (1 H, d, J = 4.5 Hz, β-pyrrole), 9.11 (2 H, br s, 2,6-pyridyl), 9.58 (1 H, d, J = 4.4 Hz, β-thiophene), 9.68 (1 H, d, J = 4.4 Hz, β-thiophene), 9.76 (2 H, s, β-thiophene) ppm. ¹³C NMR (100 MHz, CDCl₃) δ = 21.61, 31.07, 31.49, 121.95, 128.31, 131.29, 132.54, 134.18, 134.55, 134.92, 135.75, 135.93, 138.32, 141.98, 147.52, 147.80, 148.92, 150.98, 155.95, 156.54, 156.60, 160.02 ppm. ES-MS: m/z calcd for C₄₇H₃₁N₃S₂: 701.90; found: 702.22 (100%) [M⁺]. UV/Vis (in toluene, λ_max/nm, ε/mol^-1 dm³ cm^-1): 436 (262893), 515 (24005), 549 (8393), 634 (1845), 697 (4601).
Dimer 18: A solution of 16 (0.02 g, 0.03 mmol) and 17 (0.02 g, 0.03 mmol) in dry toluene-Et₃N (3:1, 30 mL) was purged with nitrogen for 10 min. The coupling was initiated by adding AsPh₃ (0.01 g, 0.03 mmol) followed by Pd₂(dba)₃ (0.01 g, 0.01 mmol) and the reaction mixture was then stirred at 40 °C for 12 h. After work-up, the crude compound was subjected to silica gel column chromatography and the desired dimer 18 was collected with PE-CH₂Cl₂ (15:85) mixture as a violet solid (0.02 g, 64%). ¹H NMR (400 MHz, CDCl₃): δ = -2.71 (1 H, br s, NH), 2.70 (9 H, s, CH₃), 2.73 (6 H, s, CH₃), 7.53 (4 H, d, J = 7.6 Hz, aryl), 7.61 (8 H, d, J = 7.6 Hz, aryl), 7.96 (2 H, d, J = 8.0 Hz, aryl), 8.06 (4 H, d, J = 7.6 Hz, aryl), 8.12 (10 H, m, aryl), 8.17 (2 H, m, 3,5-pyridyl), 8.62 (4 H, m, β-pyrrole), 8.68 (3 H, m, β-pyrrole), 8.73 (1 H, d, J = 5.6 Hz, β-pyrrole), 8.94 (2 H, m, β-pyrrole), 9.03 (2 H, br m, 2,6-pyridyl), 9.58 (1 H, d, J = 5.2 Hz, β-thiophene), 9.67 (1 H, d, J = 5.2 Hz, β-thiophene), 9.72 (3 H, m, β-thiophene), 9.76 (1 H, d, J = 5.2 Hz, β-thiophene) ppm. ES-MS: m/z calcd for C₉₄H₆₃N₆S₃: 1373.76; found: 1373.57 (52%) [M⁺]. UV/Vis (in toluene, λ_max/nm, ε/mol^-1 dm³ cm^-1): 433 (484803), 515 (41725), 549 (13604), 624 (3694), 680 (5357), 696 (4918).
Trimer 20: The dimer 18 (0.02 g, 0.02 mmol) was dissolved in 30 mL of toluene in a two-necked 100-mL round-bottomed flask and was purged with N₂ for 10 min. RuTPP(CO)(EtOH) (19; 0.019 g, 0.02 mmol) was then added and the solution was refluxed with stirring for 4 h. The crude compound was purified by silica gel column chromatography using PE-CH₂Cl₂ (50:50) mixture as an eluent and afforded trimer 20 as a purple solid (0.01 g, 35%). ¹H NMR (400 MHz, CDCl₃): δ = -2.61 (1 H, br s, NH), 1.64 (2 H, d, J = 3.2 Hz, 2,6-pyridyl), 2.68 (6 H, s, CH₃), 2.70 (9 H, s, CH₃), 6.08 (2 H, d, J = 3.2 Hz, 3,5-pyridyl), 7.10 (1 H, d, J = 4.4 Hz, β-pyrrole), 7.56 (18 H, m, aryl), 7.63 (4 H, d, J = 7.8 Hz, aryl), 7.71 (10 H, m, aryl), 7.91 (4 H, t, J = 7.4 Hz, aryl), 8.04 (8 H, m, aryl), 8.14 (4 H, d, J = 7.8 Hz, aryl), 8.19 (1 H, m, β-pyrrole), 8.33 (1 H, m, β-thiophene), 8.57 (2 H, m, β-pyrrole), 8.63 (2 H, m, β-pyrrole), 8.74 (8 H, s, β-pyrrole of TPP), 8.90 (4 H, m, β-pyrrole), 9.29 (2 H, m, β-thiophene), 9.57 (1 H, dd, J = 5.2 Hz, β-thiophene), 9.83 (2 H, m, β-thiophene) ppm. ES-MS: m/z calcd for C₁₃₉H₉₂N₁₀OS₃Ru: 2115.57; found: 2115.79 (23%). UV/Vis (in toluene, λ_max/nm, ε/mol^-1 dm³ cm^-1): 412 (302417), 432 (527038), 516 (35230), 549 (17975), 626 (bs), 683 (6228), 698 (5204).

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