Dogutan Dilek Kiper, Ptaszek Marcin, Lindsey Jonathan S
Department of Chemistry, North Carolina State University, Raleigh, North Carolina 27695-8204, USA.
J Org Chem. 2008 Aug 15;73(16):6187-201. doi: 10.1021/jo800588n. Epub 2008 Jul 19.
New methodology is described for the synthesis of porphyrins bearing four (A 4, cis-A 2B 2, cis-ABC 2, trans-A 2B 2) or fewer (A, cis-AB, cis-A 2, trans-A 2) meso substituents. The method entails condensation of two 1-acyldipyrromethanes in the presence of a metal salt (MgBr 2, 3 mol equiv) and a noncoordinating base (DBU, 10 mol equiv) in a noncoordinating solvent (toluene) with heating (conventional or microwave irradiation) and exposure to air. The rational synthesis of trans-A 2B 2- or trans-A 2-porphyrins was achieved via condensation of two identical 1-acyldipyrromethanes. The statistical synthesis of various meso-substituted porphyrins was achieved via condensation of two nonidentical 1-acyldipyrromethanes. Both routes possess attractive features including (1) no scrambling, (2) good yield (up to 60%) at high concentration (100 mM) for the macrocycle-forming step, (3) reasonable scope (aryl, heteroaryl, alkyl, or no substituent), (4) short reaction time ( approximately 2 h) via microwave irradiation, (5) magnesium porphyrins as the products, which easily undergo demetalation, and (6) facile chromatographic purification. A key advantage of the statistical route is to obtain a cis-substituted porphyrin without the corresponding trans isomer. For example, reaction of an A/B-substituted 1-acyldipyrromethane and the fully unsubstituted 1-formyldipyrromethane gave the magnesium chelates of three porphyrins: the trans-A 2B 2-porphyrin, the "hybrid" cis-AB-porphyrin, and porphine (no trans-AB-porphyrin can form), which were readily demetalated and separated as the free base species. Altogether 26 1-acyldipyrromethanes and 26 target porphyrins have been prepared, including many with two different pyridyl substituents. One set of amphipathic porphyrins includes cis-A 2B 2- or cis-A 2BC-porphyrins wherein A = pentyl and B/C = pyridyl ( o-, m-, p-). Taken together, the rational and statistical routes enable facile conversion of readily available 1-acyldipyrromethanes to diverse porphyrins bearing 1-4 meso substituents for which access is limited via other methods.
本文描述了一种合成具有四个（A₄、顺式-A₂B₂、顺式-ABC₂、反式-A₂B₂）或更少（A、顺式-AB、顺式-A₂、反式-A₂）中位取代基的卟啉的新方法。该方法是在金属盐（MgBr₂，3摩尔当量）和非配位碱（DBU，10摩尔当量）存在下，于非配位溶剂（甲苯）中，将两种1-酰基二吡咯甲烷进行缩合反应，同时加热（常规加热或微波辐射）并暴露于空气中。通过两种相同的1-酰基二吡咯甲烷缩合可实现反式-A₂B₂-或反式-A₂-卟啉的合理合成。通过两种不同的1-酰基二吡咯甲烷缩合可实现各种中位取代卟啉的统计合成。这两种路线都具有吸引人的特点，包括：（1）无取代基重排；（2）在大环形成步骤中，高浓度（100 mM）下产率良好（高达60%）；（3）适用范围合理（芳基、杂芳基、烷基或无取代基）；（4）通过微波辐射反应时间短（约2小时）；（5）产物为镁卟啉，易于脱金属；（6）易于通过色谱法纯化。统计路线的一个关键优势是能够获得无相应反式异构体的顺式取代卟啉。例如，A/B-取代的1-酰基二吡咯甲烷与完全未取代的1-甲酰基二吡咯甲烷反应，得到三种卟啉的镁螯合物：反式-A₂B₂-卟啉、“杂化”顺式-AB-卟啉和卟吩（不会形成反式-AB-卟啉），它们很容易脱金属并以游离碱形式分离。总共制备了26种1-酰基二吡咯甲烷和26种目标卟啉，包括许多带有两种不同吡啶基取代基的卟啉。一组两亲性卟啉包括顺式-A₂B₂-或顺式-A₂BC-卟啉，其中A = 戊基，B/C = 吡啶基（邻、间、对）。总体而言，合理合成路线和统计合成路线能够轻松地将易于获得的1-酰基二吡咯甲烷转化为带有1 - 4个中位取代基的各种卟啉，而通过其他方法获得这些卟啉则受到限制。
