Synthesis of Chlorins Extended by Highly Substituted Double Bonds

Abstract

Chlorins with highly substituted exocyclic double bonds extending the chromophoric system were synthesized starting from the readily accessible oxochlorin. After sulfurization of the keto function of oxochlorin 7 the formed thioketo chlorin 8 underwent Barton olefination with diazo compounds.

Key words

chlorins - Barton olefination - diazo compounds - extended chromophore

References and Notes

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10

Procedure for the Preparation of the Chlorin Thioketone 8
Diethylenglycol dimethyl ether (5 mL) was added by a syringe to a mixture of 7 (76.9 mg, 0.155 mmol) and Lawesson’s reagent (96.6 mg, 0.239 mmol) placed in a flask equipped with a reflux condenser and a septum. The mixture was stirred for 2.5 h at 150 ˚C under argon. After cooling to r.t. the mixture was transferred by a small volume of CH₂Cl₂ into a 50 mL round-bottom flask, and the solvent was removed at 80 ˚C in high vacuum by Kugelrohr distillation. The residue was chromatographed on silica gel with a slice of 2 cm alumina on top with CH₂Cl₂-PE (8:2). The light-green main fraction was collected and the solvent was removed in vacuo. After isothermic crystallization from CH₂Cl₂-n-pentane 8 (73.9 mg, 0.145 mmol, 93.5%) was obtained.

11

Typical Procedure for the Preparation of Chlorin Derivatives 9-11
Compound 8 (96.3 mg, 0.188 mmol) and 9-diazofluorene (72.3 mg, 0.376 mmol, 2 equiv) were dissolved under argon in 13 mL of anhyd THF. After stirring for 30 min at r.t. the reaction mixture was refluxed for 60 min. Then, tris(2-cyanoethyl)phosphine (72.6 mg, 0.376 mmol) was added and refluxing was continued for further 3 h. The reaction mixture was diluted with CH₂Cl₂ and the organic layer was washed with H₂O (50 mL). The organic extract was dried by filtration over cotton wool and evaporated in vacuo. The residue was chromatographed over alumina (activity II-III) first with PE and then with CH₂Cl₂-PE (1:1) giving a crude product which was again chromatographed on silica gel with CH₂Cl₂-PE (1:1) to yield after evaporation of the solvent the light-green product. Isothermic crystallization from chloroform-n-pentane yielded chlorin 11 (71.8 mg, 0.112 mmol, 60%).

12

All compounds show correct spectroscopic and analytic data.

Selected Spectroscopic and Analytic Data for Compounds 8-11
Compound 8: mp >350 ˚C. TLC: silica gel, CH₂Cl₂-PE (8:2): R _f  = 0.74. ^¹H NMR (360 MHz, CDCl₃): d = 1.93 (s, 6 H, 3-CH₃), 3.16, 3.17, 3.19, 3.21, 3.22 (5 s, 18 H, 7-, 8-, 12-, 13-, 17-, 18-CH₃), 8.57, 9.13, 9.19, 9.81 (4 s, 4 H, 5-, 10-, 15-, 20-H). UV/Vis (CHCl₃): l_max (lg e) = 354 mm (4.586), 400 (4.665), 454 (4.652), 551 (4.040), 591 (4.044), 690 (4.605). IR (KBr): 1222 cm^-¹ (s, n, C=S). MS (EI, 70 eV, 286 ˚C): m/z (%) = 514 (10), 513 (17), 512 (47), 511 (33), 510 (100) [M(⁵⁸Ni)⁺], 497 (25), 496 (19), 495 (51) [M⁺ - CH₃], 480 (38) [M⁺ - 2 CH₃], 465 (11) [M⁺ - 3 CH₃]. HRMS: m/z calcd for C₂₈H₂₈N₄S⁵⁸Ni: 510.13882; found: 510.13907. Anal. calcd for C₂₈H₂₈N₄SNi + 0.1 CH₂Cl₂: C, 64.93; H, 5.45; N, 10.78; S, 6.17. Found: C, 64.97; H, 5.41; N, 10.5; S, 6.26.
Compound 9: mp >350 ˚C. TLC: silica gel, CH₂Cl₂-PE (1:2): R _f  = 0.63. ^¹H NMR (360 MHz, CDCl₃/20 mL pyridine-d ₅): d = 1.89 (s, 6 H, 3-CH₃), 3.13, 3.14, 3.19, 3.21, 3.22 (5 s, 18 H, 7-, 8-, 12-, 13-, 17-, 18-CH₃), 5.75 (s, 1 H, 2-CH), 6.46 (s, 1 H, 2-CH), 8.00, 8.53, 8.61, 8.96 (4 s, 4 H, 5-, 10-, 15-, 20-H). UV/Vis (CHCl₃): l_max (lg e) = 401 nm (4.980), 577 (4.102), 624 (4.638). MS (EI, 70 eV, 255 ˚C): m/z (%) = 495 (13), 494 (39), 493 (26), 492 [84, M(⁵⁸Ni)⁺], 479 (44), 478 (40), 477 (100) [M⁺ - CH₃], 476 (14), 475 (12), 461 (12), 246 (11), 238 (11), and fragment ions of lower mass. HRMS: m/z calcd for C₂₉H₃₀N₄ ⁵⁸Ni: 492.18220; found: 491.18240.
Compound 10: mp >350 ˚C. TLC: silica gel, PE-EtOAc (9:1): R _f  = 0.41. ^¹H NMR (360 MHz, CDCl₃/20 mL pyridine-d ₅): d = 1.74 (s, 6 H, 3-CH₃), 2.54, 3.03, 3.07, 3.15, 3.16 (5 s, 18 H, 7-, 8-, 12-, 13-, 17-, 18-CH₃), 7.04-7.17 (m, 4 H, aryl H), 7.41-7.55 (m, 4 H, aryl H), 7.88, 8.01, 9.01, 9.05 (4 s, 4 H, 5-, 10-, 15-, 20-H). UV/Vis (CHCl₃): l_max (lg e) = 415 nm (4.959) 556 (4.203), 645 (4.647). MS (DCI, positive, NH₃): m/z (%) = 649 (10), 648 (24) 647 (54), 646 (55), 645 (100) [MH⁺]. MS (DCI, negative, NH₃): m/z (%) = 648 (10), 647 (20), 646 (47), 645 (43), 644 (99) [M^-], and fragments of lower mass, 96 (100). HRMS: m/z calcd for C₄₁H₃₈N₄ ⁵⁸Ni: 644.24480; found: 644.24500.
Compound 11: mp >350 ˚C, TLC: silica gel, CH₂Cl₂-PE (1:1): R _f  = 0.58. ^¹H NMR (360 MHz, C₆D₆): d = 1.97, 2.46 (2 s, 6 H, 3-CH₃), 2.66, 2.82, 2.87, 2.95, 2.98, 2.99 (6 s, 18 H, 7-, 8-, 12-, 13-, 17-, 18-CH₃), 6.48 (ddd, ^³ J = 8.1 Hz, ^³ J = 7.0 Hz, ⁴ J = 1.1 Hz, 1 H, aryl H), 7.03 (ddd, ^³ J = 7.6 Hz, ^³ J = 7.0 Hz, ⁴ J = 1.1 Hz, 1 H, aryl H), 7.25-7.32 (m, 2 H, aryl H), 7.59 (d, ^³ J = 7.0 Hz, 1 H, aryl H), 7.68-7.70 (m, 1 H, aryl H), 7.79 (d, ^³ J = 8.6 Hz, 1 H, aryl H), 8.45-8.47 (m, 1 H, aryl H), 8.02, 9.12, 9.16, 9.68 (4 s, 4 H, 5-, 10-, 15-, 20-H). UV/Vis (CHCl₃): l_max (lg e) = 344 nm (4.618), 444 (4.680), 590 (4.123), 687 (4.683). MS (DCI, negative, NH₃): m/z (%) = 646 (12), 645 (28), 644 (46), 643 (51), 642 (100) [M^-]. HRMS: m/z calcd for C₄₁H₃₆N₄ ⁵⁸Ni: 642.22937; found; 642.22907.