5-[[3-[(5-carboxy-3-ethyl-4-methyl-1H-pyrrol-2-yl)methyl]-4,5,6,7-tetrahydro-2H-isoindol-1-yl]methyl]-4-ethyl-3-methyl-1H-pyrrole-2-carboxylic acid | 202798-24-1

• 分子结构分类: 有机化合物 - 有机杂环化合物 - 异吲哚及其衍生物
• 英文名称: 5-[[3-[(5-carboxy-3-ethyl-4-methyl-1H-pyrrol-2-yl)methyl]-4,5,6,7-tetrahydro-2H-isoindol-1-yl]methyl]-4-ethyl-3-methyl-1H-pyrrole-2-carboxylic acid
• CAS: 202798-24-1
• 化学式: C₂₆H₃₃N₃O₄
• 分子量: 451.566
• InChiKey: YHHGUBLWNYQDJP-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  5.7
• 重原子数：
  33
• 可旋转键数：
  8
• 环数：
  4.0
• sp3杂化的碳原子比例：
  0.46
• 拓扑面积：
  122
• 氢给体数：
  5
• 氢受体数：
  4

反应信息

• 作为反应物：
  描述：

  5-[[3-[(5-carboxy-3-ethyl-4-methyl-1H-pyrrol-2-yl)methyl]-4,5,6,7-tetrahydro-2H-isoindol-1-yl]methyl]-4-ethyl-3-methyl-1H-pyrrole-2-carboxylic acid 在 三氟乙酸 、 2,3-二氯-5,6-二氰基-1,4-苯醌 作用下， 以 甲苯 为溶剂， 反应 19.0h， 生成 9,18-diethyl-8,19-dimethylbenzo-2-oxyptriporphyrin
  参考文献：
  名称：

  Conjugated Macrocycles Related to the Porphyrins. 12.¹ Oxybenzi- and Oxypyriporphyrins:  Aromaticity and Conjugation in Highly Modified Porphyrinoid Structures

  摘要：

  The "3 + 1" route for porphyrinoid synthesis is an excellent methodology for preparing aromatic porphyrin analogues with six-membered ring subunits. Condensation of 5-formylsalicylaldehyde with tripyrranes 15, 24, and 25 in the presence of 5% TFA-dichloromethane, followed by neutralization and oxidation with DDQ, afforded a series of semiquinone-containing porphyrinoids 12, 26, and 27 in 35-52% yield. In these novel systems, the macrocycle achieves aromatization by undergoing a keto-enol tautomerization whereby the phenolic subunit is transformed so that the inner three carbon atoms become part of the 18 pi-electron aromatic core, whereas the outer carbons generate an enone unit. The aromatic nature of these "oxybenziporphyrins" is evident from their porphyrin-like electronic spectra and the presence of powerful diamagnetic ring currents in their proton NMR spectra, where the inner CH is shifted upfield to delta = -7 ppm, whereas the external meso-protons appear downfield between 8.8 and 10.3 ppm. The presence of a carbonyl unit is confirmed by IR and proton NMR spectroscopy. Addition of trace amounts of TFA give an aromatic monocation, but further protonation to the dication leads to the loss of macrocyclic aromaticity. Modified tripyrranes 15b, 26, and 27 were used to prepare oxybenziporphyrins with fused benzene, phenanthrene, and acenaphthylene ring systems, the former via a tetrahydrobenzo intermediate; and these compounds showed many of the same characteristics, including aromatic free bases and nonaromatic dications. The ring fusion gave rise to gradual bathochromic shifts from benzo- (23) to phenanthro- (26) to acenaphtho- (27) oxybenziporphyrins, which qualitatively followed the same trends observed for true porphyrins, although the influence of the acenaphthylene ring system was somewhat muted in this series. Condensation of isophthalaldehyde with tripyrrane 15a gave the nonaromatic analogue "benziporphyrin" in 28% yield, and this species was thoroughly characterized and contrasted to oxybenziporphyrin 12a. Reaction of 3-hydroxypyridine-2,6-dicarboxaldehyde with tripyrranes under the "3 + 1" conditions afforded exceptionally high yields of the corresponding azaoxybenziporphyrins (named "oxypyriporphyrins''; 35, 47-49), and these structures also exhibited porphyrinoid aromaticity. For this series, the dications retained their aromatic character as did the related nickel(II), copper(II), and zinc chelates. Ring fusion effects were investigated for the oxypyriporphyrins and their metal complexes, and again the major absorptions shifted to higher wavelength from benzo- to phenanthro- to acenaphthooxypyriporphyrins. However the effect of metalation on the oxypyriporphyrin chromophore differed considerably from the trends seen for metalloporphyrins. These results show that novel aromatic porphyrinoids are easily accessible via the "3 + 1" approach, and this work will facilitate in-depth studies on the chemical and physical properties of these exciting new bridged annulene structures.

  DOI：

  10.1021/jo981872a
• 作为产物：
  描述：

  4,5,6,7-四氢异吲哚 在 palladium on activated charcoal 氢气 、 对甲苯磺酸 、 三乙胺 作用下， 以 四氢呋喃 、 甲醇 为溶剂， 反应 22.0h， 生成 5-[[3-[(5-carboxy-3-ethyl-4-methyl-1H-pyrrol-2-yl)methyl]-4,5,6,7-tetrahydro-2H-isoindol-1-yl]methyl]-4-ethyl-3-methyl-1H-pyrrole-2-carboxylic acid
  参考文献：
  名称：

  Simple Methodology for Syntheses of Porphyrins Possessing Multiple Peripheral Substituents with an Element of Symmetry

  摘要：

  New methodology was developed for synthesis of regiochemically pure porphyrins with D-2h symmetry (e.g. 9) via tetramerization reactions involving two different pyrroles. The two pyrrole components were a 2,5-diunsubstituted pyrrole (e.g. 11) and a 2,5-bis[(N,N-dimethylamino)methyl]pyrrole (e.g, 10), the latter being formed from a 2,5-di-unsubstituted pyrrole by treatment with excess Eschenmoser's reagent (N,N-dimethylmethyleneammonium iodide). A bis-butanoporphyrin 16 was transformed into the corresponding opp-bis-benzoporphyrin 17 by treatment with DDQ. The synthetic method was further extended to allow the synthesis of more unsymmetrical porphyrins, with C-2v symmetry (e.g. 32), by reacting a tripyrrane (e.g. 27) with a 2,5-bis[(N,N-dimethylamino)methyl]pyrrole (e.g. 18). The structures and substituent arrays in both type of porphyrins were confirmed by single-crystal X-ray crystallography.

  DOI：

  10.1021/jo951870f

文献信息

• Conjugated Macrocycles Related to the Porphyrins. 21. Synthesis, Spectroscopy, Electrochemistry, and Structural Characterization of Carbaporphyrins
  作者：Timothy D. Lash、Michael J. Hayes、John D. Spence、Melanie A. Muckey、Gregory M. Ferrence、Lisa F. Szczepura

  DOI：10.1021/jo020267b

  日期：2002.7.1

  albeit in low yields ranging from 5 to 8%. These hybrid bridged annulene structures have porphyrin-like electronic absorption spectra with strong Soret bands near 420 nm and a series of Q-bands through the visible region. The proton NMR spectrum confirms the presence of a strong diamagnetic ring current, and the meso-protons show up at 10 ppm, while the internal CH is shielded to approximately -7 ppm

  麦当劳缩合反应的“ 3 +1”变体已被证明是合成碳卟啉的极佳方法。特别地，在TFA存在下，1，3-二烯二甲醛与三吡喃缩合，在用DDQ氧化后，以优异的产率得到一系列苯并羰基卟啉。三甲酰基环戊二烯也可提供碳卟啉产物，尽管收率低，从5％到8％。这些杂化的桥接环结构具有类似卟啉的电子吸收光谱，在420 nm附近具有很强的Soret带，并且在可见光区有一系列Q带。质子NMR光谱证实存在强反磁性环电流，中质子出现在10 ppm处，而内部CH被屏蔽到大约-7 ppm。碳卟啉用TFA进行可逆的质子化。尽管在中等浓度的TFA存在下观察到质子化物质的混合物，酸的初始添加提供了单阳离子。但是，在存在50％TFA的情况下，会生成C质子化的指示。这些指示剂通过苯并咔唑卟啉的苯并部分重新定位pi脱位途径，因此尽管它们仍然保留了强大的大环电流，但仍代表了桥接的苯并[18]环烯。已经制备了带有稠合和菲环的碳卟啉，前者在紫
• Synthesis, Spectroscopy, and Reactivity of <i>m</i><i>eso</i>-Unsubstituted Azuliporphyrins and Their Heteroanalogues. Oxidative Ring Contractions to Carba-, Oxacarba-, Thiacarba-, and Selenacarbaporphyrins
  作者：Timothy D. Lash、Denise A. Colby、Shelley R. Graham、Sun T. Chaney

  DOI：10.1021/jo0402531

  日期：2004.12.1

  favored due to the associated charge delocalization. Two different “3 + 1” syntheses of meso-unsubstituted azuliporphyrins have been developed. Acid-catalyzed reaction of readily available tripyrrane dicarboxylic acids with 1,3-azulenedicarbaldehyde, followed by oxidation with DDQ or FeCl3, affords good yields of azuliporphyrins. Alternatively, azulene reacted with acetoxymethylpyrroles (2 equiv) in refluxing

  本文报道了首次详细研究内消旋取代的天青卟啉，这是一种重要的卟啉样分子家族，其中一个常见的吡咯环已被天青石亚基取代。尽管a唑部分引入了交叉共轭的元素，但具有对苯二酚和碳卟啉亚结构的两性离子共振贡献子却使氮杂卟啉的亲液性介于真碳卟啉和非芳族苯甲醛之间。质子化提供了芳族指示，其中由于相关的电荷离域，这种类型的共振相互作用是有利的。中观的两种不同的“ 3 +1”合成-未取代的天青卟啉已被开发。易得的三吡喃二羧酸与1,3-氮杂二甲醛的酸催化反应，然后用DDQ或FeCl 3氧化，可得到良好的氮杂卟啉收率。或者，a在回流的乙酸/ 2-丙醇中与乙酰氧基甲基吡咯（2当量）反应生成三吡喃类似物，并在脱保护步骤后，与吡咯二醛在TFA-CH 2 Cl 2中缩合。产生了天青卟啉系统。后一种方法也用于制备23-硫杂和23-硒杂卟啉。但是，金刚烷吡喃与2,5-呋喃二甲醛的反应以中等收率产生了三种草酰氨基卟啉的混合物。硫
• Conjugated Macrocycles Related to the Porphyrins. 12.¹ Oxybenzi- and Oxypyriporphyrins:  Aromaticity and Conjugation in Highly Modified Porphyrinoid Structures
  作者：Timothy D. Lash、Sun T. Chaney、Daniel T. Richter

  DOI：10.1021/jo981872a

  日期：1998.11.1

  The "3 + 1" route for porphyrinoid synthesis is an excellent methodology for preparing aromatic porphyrin analogues with six-membered ring subunits. Condensation of 5-formylsalicylaldehyde with tripyrranes 15, 24, and 25 in the presence of 5% TFA-dichloromethane, followed by neutralization and oxidation with DDQ, afforded a series of semiquinone-containing porphyrinoids 12, 26, and 27 in 35-52% yield. In these novel systems, the macrocycle achieves aromatization by undergoing a keto-enol tautomerization whereby the phenolic subunit is transformed so that the inner three carbon atoms become part of the 18 pi-electron aromatic core, whereas the outer carbons generate an enone unit. The aromatic nature of these "oxybenziporphyrins" is evident from their porphyrin-like electronic spectra and the presence of powerful diamagnetic ring currents in their proton NMR spectra, where the inner CH is shifted upfield to delta = -7 ppm, whereas the external meso-protons appear downfield between 8.8 and 10.3 ppm. The presence of a carbonyl unit is confirmed by IR and proton NMR spectroscopy. Addition of trace amounts of TFA give an aromatic monocation, but further protonation to the dication leads to the loss of macrocyclic aromaticity. Modified tripyrranes 15b, 26, and 27 were used to prepare oxybenziporphyrins with fused benzene, phenanthrene, and acenaphthylene ring systems, the former via a tetrahydrobenzo intermediate; and these compounds showed many of the same characteristics, including aromatic free bases and nonaromatic dications. The ring fusion gave rise to gradual bathochromic shifts from benzo- (23) to phenanthro- (26) to acenaphtho- (27) oxybenziporphyrins, which qualitatively followed the same trends observed for true porphyrins, although the influence of the acenaphthylene ring system was somewhat muted in this series. Condensation of isophthalaldehyde with tripyrrane 15a gave the nonaromatic analogue "benziporphyrin" in 28% yield, and this species was thoroughly characterized and contrasted to oxybenziporphyrin 12a. Reaction of 3-hydroxypyridine-2,6-dicarboxaldehyde with tripyrranes under the "3 + 1" conditions afforded exceptionally high yields of the corresponding azaoxybenziporphyrins (named "oxypyriporphyrins''; 35, 47-49), and these structures also exhibited porphyrinoid aromaticity. For this series, the dications retained their aromatic character as did the related nickel(II), copper(II), and zinc chelates. Ring fusion effects were investigated for the oxypyriporphyrins and their metal complexes, and again the major absorptions shifted to higher wavelength from benzo- to phenanthro- to acenaphthooxypyriporphyrins. However the effect of metalation on the oxypyriporphyrin chromophore differed considerably from the trends seen for metalloporphyrins. These results show that novel aromatic porphyrinoids are easily accessible via the "3 + 1" approach, and this work will facilitate in-depth studies on the chemical and physical properties of these exciting new bridged annulene structures.
• Simple Methodology for Syntheses of Porphyrins Possessing Multiple Peripheral Substituents with an Element of Symmetry
  作者：Liem T. Nguyen、Mathias O. Senge、Kevin M. Smith

  DOI：10.1021/jo951870f

  日期：1996.1.1

  New methodology was developed for synthesis of regiochemically pure porphyrins with D-2h symmetry (e.g. 9) via tetramerization reactions involving two different pyrroles. The two pyrrole components were a 2,5-diunsubstituted pyrrole (e.g. 11) and a 2,5-bis[(N,N-dimethylamino)methyl]pyrrole (e.g, 10), the latter being formed from a 2,5-di-unsubstituted pyrrole by treatment with excess Eschenmoser's reagent (N,N-dimethylmethyleneammonium iodide). A bis-butanoporphyrin 16 was transformed into the corresponding opp-bis-benzoporphyrin 17 by treatment with DDQ. The synthetic method was further extended to allow the synthesis of more unsymmetrical porphyrins, with C-2v symmetry (e.g. 32), by reacting a tripyrrane (e.g. 27) with a 2,5-bis[(N,N-dimethylamino)methyl]pyrrole (e.g. 18). The structures and substituent arrays in both type of porphyrins were confirmed by single-crystal X-ray crystallography.