Dipyrromethane + Dipyrromethanedicarbinol Routes to an Electron Deficient meso-Substituted Phlorin with Enhanced Stability

Abstract

Two dipyrromethane + dipyrromethanedicarbinol routes to a meso-substituted phlorin bearing electron-withdrawing pentafluorophenyl substituents (TpFPPhl) were investigated in an attempt to obtain a phlorin with enhanced stability toward light and air and to explore the application of dipyrromethanecarbinol chemistry to the preparation of phlorins. For each route, a systematic survey of reaction parameters for the two-step, one-flask reaction leading to TpFPPhl was performed. The analytical-scale reactions were monitored for yield of TpFPPhl by HPLC. Sharp differences were observed in the yield of TpFPPhl afforded by the two synthetic routes. The most promising reaction condition (TFA catalysis, 100 mM) was performed on a preparative scale providing TpFPPhl in a yield of 45% (189 mg). The stability of the electron-deficient phlorin in dilute solution upon exposure to light and air was probed in a number of solvents, and decomposition was monitored by UV-vis spectroscopy and HPLC. Many of the solutions of TpFPPhl were found to be quite stable for periods of approximately 8 h, with decomposition requiring exposure periods of several days. Taken together, this work contributes an efficient synthesis of a meso-substituted phlorin of practical stability and provides further insights toward the adaptation of dipyrromethanecarbinol chemistry to the preparation of diverse porphyrinoids.

A Tetrapyrrole Macrocycle Displaying a Multielectron Redox Chemistry and Tunable Absorbance Profile

“…23 The synthesis and isolation of this porphyrinoid has also been carried out using typical acid catalysis, 24 and Geier and coworkers have described a pioneering general phlorin synthesis. 25 However, the electrochemical, photophysical and other basic properties of the phlorin have escaped characterization. We began our studies by preparing a 5,5-dimethyl phlorin architecture containing ancillary pentafluorophenyl groups (3H(Phl F )), 25 the solid-state structure of which is shown in Figure 1.…”

Evaluating Nanoshells and a Potent Biladiene Photosensitizer for Dual Photothermal and Photodynamic Therapy of Triple Negative Breast Cancer Cells

“…Pd[DMBil1]-PEG 750 was synthesized using methods described previously [ 28 , 38 , 39 , 40 , 41 ]. Reactions requiring an inert atmosphere were carried out in oven-dried round bottomed flasks fitted with Suba-seal rubber septa purchased from Chemglass and maintained under positive nitrogen pressure using standard schlenk techniques.…”

“…Reagents and solvents were purchased from Strem (Newburyport, MA, USA), VWR (Radnor, PA, USA), Sigma-Aldrich (St. Louis, MO, USA), Fisher (Hampton, NH, USA), Matrix Scientific (Columbia, SC, USA), Acros (NJ, USA), Decon Laboratories Inc. (King of Prussia, PA, USA), Cambridge Isotopes Laboratories (Tewksbury, MA, USA), or Alfa Aesar (Haverville, MA, USA). All solvents used for synthesis were of reagent grade or better, and anhydrous solvents were dried via passage through activated alumina [ 41 ]. Column chromatography was carried out with 40–63 μm silica gel purchased from Silicycle, or C 2 -silica prepared as detailed in a published procedure [ 28 ].…”

Factors Controlling the Spectroscopic Properties and Supramolecular Chemistry of an Electron Deficient 5,5-Dimethylphlorin Architecture

“…34,49 Reduction of the diacylated dipyrromethane ( 1 ) with NaBH 4 in THF/MeOH (3:1) generated the corresponding dicarbinol, which was condensed with 5-(3,5- bis -trifluoromethylphenyl)-dipyrromethane ( 2 ) in the presence of trifluoroacetic acid (TFA). Subsequent oxidation with DDQ delivered the desired phlorin ( 3H(Phl CF 3 ) ) in 41% yield.…”