Rao P D, Dhanalekshmi S, Littler B J, Lindsey J S
Department of Chemistry, North Carolina State University, Raleigh, North Carolina 27695-8204, USA.
J Org Chem. 2000 Nov 3;65(22):7323-44. doi: 10.1021/jo000882k.
Porphyrins bearing specific patterns of substituents are crucial building blocks in biomimetic and materials chemistry. We have developed methodology that avoids statistical reactions, employs minimal chromatography, and affords up to gram quantities of regioisomerically pure porphyrins bearing predesignated patterns of up to four different meso substituents. The methodology is based upon the availability of multigram quantities of dipyrromethanes. A procedure for the diacylation of dipyrromethanes using EtMgBr and an acid chloride has been refined. A new procedure for the preparation of unsymmetrical diacyl dipyrromethanes has been developed that involves (1) monoacylation with EtMgBr and a pyridyl benzothioate followed by (2) introduction of the second acyl unit upon reaction with EtMgBr and an acid chloride. The scope of these acylation methods has been examined by preparing multigram quantities of diacyl dipyrromethanes bearing a variety of substituents. Reduction of the diacyl dipyrromethane to the corresponding dipyrromethane-dicarbinol is achieved with NaBH(4) in methanolic THF. Porphyrin formation involves the acid-catalyzed condensation of a dipyrromethane-dicarbinol and a dipyrromethane followed by oxidation with DDQ. Optimal conditions for the condensation were identified after examining various reaction parameters (solvent, temperature, acid, concentration, time). The conditions identified (2.5 mM reactants in acetonitrile containing 30 mM TFA at room temperature for <7 min) provided reaction without detectable scrambling (LD-MS) for aryl-substituted dipyrromethanes, and trace scrambling for alkyl-substituted dipyrromethanes. The desired porphyrins were obtained in 14-40% yield. The synthesis is compatible with diverse functionalities: amide, aldehyde, carboxylic acid, ester, nitrile, ether, bromo, iodo, ethyne, TMS-ethyne, TIPS-ethyne, perfluoroarene. In total 30 porphyrins of the types A(3)B, trans-A(2)B(2), trans-AB(2)C, cis-A(2)B(2), cis-A(2)BC, and ABCD were prepared, including >1-g quantities of three porphyrins.
带有特定取代基模式的卟啉是仿生化学和材料化学中的关键构建单元。我们已开发出一种方法，该方法可避免统计反应，使用最少的色谱法，并能提供高达克级量的区域异构体纯的卟啉，这些卟啉带有多达四种不同中取代基的预定模式。该方法基于可得的多克量的二吡咯甲烷。使用乙基溴化镁和酰氯对二吡咯甲烷进行二酰化的程序已得到改进。已开发出一种制备不对称二酰基二吡咯甲烷的新程序，该程序包括（1）用乙基溴化镁和吡啶基苯硫酯进行单酰化，然后（2）在与乙基溴化镁和酰氯反应时引入第二个酰基单元。通过制备多克量的带有各种取代基的二酰基二吡咯甲烷，研究了这些酰化方法的适用范围。在甲醇四氢呋喃中用硼氢化钠将二酰基二吡咯甲烷还原为相应的二吡咯甲烷 - 二甲醇。卟啉的形成涉及二吡咯甲烷 - 二甲醇与二吡咯甲烷的酸催化缩合，然后用2,3 - 二氯 - 5,6 - 二氰基对苯醌氧化。在研究了各种反应参数（溶剂、温度、酸、浓度、时间）后，确定了缩合的最佳条件。所确定的条件（在室温下于含30 mM三氟乙酸的乙腈中2.5 mM反应物，反应时间<7分钟）对于芳基取代的二吡咯甲烷提供了无可检测重排的反应（液相色谱 - 质谱），对于烷基取代的二吡咯甲烷有微量重排。所需的卟啉以14 - 40%的产率获得。该合成与多种官能团兼容：酰胺、醛、羧酸、酯、腈、醚、溴、碘、乙炔、三甲基硅乙炔、三异丙基硅乙炔、全氟芳烃。总共制备了30种类型为A₃B、反式 - A₂B₂、反式 - AB₂C、顺式 - A₂B₂、顺式 - A₂BC和ABCD的卟啉，包括三种卟啉的克级以上量。
