New route to ABCD-porphyrins via bilanes
New route to ABCD-porphyrins via bilanes
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DOI：
10.1021/jo701294d
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发表时间：
2007-09-28
影响因子：
3.6
通讯作者：
Lindsey, Jonathan S.
中科院分区：
文献类型：
--
作者：
Dogutan, Dilek Kiper;Zaidi, Syeda Huma H.;Lindsey, Jonathan S.
[图解]一种新的制备含四种不同中间取代基的卟啉(ABCD-卟啉)的策略依赖于两个关键反应。一个关键反应是通过在高浓度(0.5M)下酸催化缩合1-酰基二吡咯甲烷和9-保护的二吡咯甲烷-1-甲醇(由9-保护的1-酰基二吡咯甲烷衍生而来)，直接合成1-保护的19-酰基双环丁烷。考察了三个保护基团(X)，包括硫氰酸盐、乙硫基和溴，其中溴被证明是最有效的。以72-80%的产率获得了双烷类化合物，对其进行了充分的表征，并用N-15核磁共振波谱进行了鉴定。第二个关键反应需要在碱性金属模板条件下对I保护的19-酰基双环丙烷进行一瓶转化，得到相应的金属卟啉。考察了溶剂、金属盐、碱、浓度、温度、气氛和时间等因素对环化反应的影响。最佳反应条件为：1-溴-19-酰基双环丙烷100 mm，在含有DBU(10mol当量)和MgBr2(3mol当量)的甲苯中，在115℃、空气中反应2 h，以65%的产率合成了卟啉镁。镁卟啉很容易脱金属，得到游离碱的卟啉。开发了一种分步过程(包括将1-(乙硫基)-19-酰基双环丁烷处理成氧化、金属络合、脱硫、羰基还原和酸催化缩合)，但效率远低于一瓶法。新的合成路线保留了现有的“2+2”方法(二吡咯甲烷+二吡咯甲烷-1，9-二醇)的优点，如没有杂乱，但具有显著的优点。本发明的优点包括：在形成卟啉的步骤中不需要酸，使用金属模板进行环化，能够在高浓度下进行反应，不使用苯醌氧化剂，避免使用二氯甲烷，以及增加大环形成的产率，以得到目标ABCD-金属卟啉。
[GRAPHICS]A new strategy for preparing porphyrins that bear up to four different meso-substituents (ABCD-porphyrins) relies on two key reactions. One key reaction entails a directed synthesis of a 1-protected 19-acylbilane by acid-catalyzed condensation at high concentration (0.5 M) of a 1-acyldipyrromethane and a 9-protected dipyrromethane-1-carbinol (derived from a 9-protected 1-acyldipyrromethane). Three protecting groups (X) were examined, including thiocyanato, ethylthio, and bromo, of which bromo proved most effective. The bilanes were obtained in 72-80% yield, fully characterized, and examined by N-15 NMR spectroscopy. The second key reaction entails a one-flask transformation of the I-protected 19-acylbilane under basic, metal-templating conditions to give the corresponding metalloporphyrin. The reaction parameters investigated for cyclization of the bilane include solvent, metal salt, base, concentration, temperature, atmosphere, and time. The best conditions entailed the 1-bromo-19-acylbilane at 100 mM in toluene containing DBU (10 mol equiv) and MgBr2 (3 mol equiv) at 115 degrees C exposed to air for 2 h, which afforded the magnesium porphyrin in 65% yield. The magnesium porphyrin is readily demetalated to give the free base porphyrin. A stepwise procedure (which entailed treatment of the 1-(ethylthio)-19-acylbilane to oxidation, metal complexation, desulfurization, carbonyl reduction, and acid-catalyzed condensation) was developed but was much less efficient than the one-flask process. The new route to ABCD-porphyrins retains the desirable features of the existing "2 + 2" (dipyrromethane + dipyrromethane-1,9-dicarbinol) method, such as absence of scrambling, yet has significant advantages. The advantages include the absence of acid in the porphyrin-forming step, the use of a metal template for cyclization, the ability to carry out the reaction at high concentration, the lack of a quinone oxidant, avoidance of use of dichloromethane, and the increased yield of macrocycle formation to give the target ABCD-metalloporphyrin.