O'Brien Anna Y, McGann John P, Geier G Richard
Department of Chemistry, Colgate University, 13 Oak Drive, Hamilton, New York 13346, USA.
J Org Chem. 2007 May 25;72(11):4084-92. doi: 10.1021/jo070216k. Epub 2007 Apr 27.
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.
研究了两条由二吡咯甲烷和二吡咯甲烷二甲醇合成带有吸电子五氟苯基取代基的中位取代卟吩（TpFPPhl）的路线，旨在获得一种对光和空气具有更高稳定性的卟吩，并探索二吡咯甲烷二甲醇化学在卟吩制备中的应用。对于每条路线，对两步一锅法反应生成TpFPPhl的反应参数进行了系统研究。通过高效液相色谱法监测分析规模反应中TpFPPhl的产率。观察到两条合成路线得到的TpFPPhl产率存在显著差异。最有前景的反应条件（三氟乙酸催化，100 mM）在制备规模上进行，得到TpFPPhl的产率为45%（189 mg）。在多种溶剂中研究了缺电子卟吩在稀溶液中暴露于光和空气时的稳定性，并通过紫外可见光谱和高效液相色谱法监测分解情况。发现许多TpFPPhl溶液在约8小时内相当稳定，分解需要暴露数天。综上所述，这项工作有助于高效合成具有实际稳定性的中位取代卟吩，并为将二吡咯甲烷二甲醇化学应用于制备各种卟啉类化合物提供了进一步的见解。
