A survey of acid catalysts in dipyrromethanecarbinol condensations leading to meso-substituted porphyrins

Abstract

ABSTRACT:The successful use of dipyrromethanecarbinols in rational routes to porphyrinic macrocycles requires catalysis conditions that enable irreversible condensation, thereby avoiding substituent scrambling and formation of undesired porphyrin products. Previously, successful conditions of trifluoroacetic acid (TFA) (30 mM) in acetonitrile were identified following a lengthy survey of TFA and BF 3 -etherate catalysis in diverse solvents. In this study, focus was placed on the acid catalyst by examining 17 acids in CH 2 Cl 2 , the traditional solvent for two-step, one-flask porphyrin syntheses. In the self-condensation of the carbinol derived from 1-(4-methylbenzoyl)-5-phenyldipyrromethane, porphyrin yields of 9-55% were obtained from the various acids, compared to 20% under TFA catalysis in acetonitrile. A number of catalytic conditions that produce little to no porphyrin in reactions of pyrrole benzaldehyde afforded good yields of porphyrin and the suppression of scrambling in reactions of dipyrromethanecarbinols. The four best acid catalysts (InCl 3 , Sc(OTf) 3 , Yb(OTf) 3 , and Dy(OTf) 3 ) initially identified were then examined with dipyrromethanecarbinols bearing challenging substituents (alkyl, pyridyl, or no substituent). The greatest improvement was obtained with the pyridyl substrates. Selected reactions performed on a preparative scale (115 to 460 mg of isolated porphyrin) verified the results of the analytical-scale experiments and revealed the more facile isolation of the porphyrin from reactions performed in CH 2 Cl 2 rather than acetonitrile. This study provides alternatives to the use of TFA/acetonitrile that offer advantages in terms of yield and isolation of the porphyrin without sacrificing suppression of scrambling. Furthermore, the finding that poor catalysts for the benzaldehyde pyrrole reaction can be excellent catalysts for dipyrromethanecarbinols provides guidance for the identification of other catalysts for use with reactive precursors in porphyrin-forming reactions.

Multistate molecular information storage using S-acetylthio-derivatized dyads of triple-decker sandwich coordination compounds

“…The synthesis of A 3 B-porphyrin 3 [15] and trans-A 2 BC-porphyrin 6 [27] has been described previously, where the critical dipyrromethane + dipyrromethane-dicarbinol condensation was performed using TFA in acetonitrile. Herein, we performed the condensation under new acidic conditions (InCl 3 or Yb(OTf) 3 in CH 2 Cl 2 ) [30]. The requisite dipyrromethanes (2, 5) [31] and diacyldipyrromethanes (1, 4) [32] were readily available.…”

Effects of diverse acid catalysts on the reaction course in the two-step one-flask synthesis of meso-tetraphenylporphyrin

“…Preliminary accounts of this study have reported the optimal yields of TPP and NC-TPP for each acid [38], and the discovery of reaction conditions for the synthesis of NC-TPP in yields of ~40% [39]. In addition, we have recently found that a subset of the acids examined in this study is applicable to condensations with dipyrromethanecarbinol species [40]. This broad examination of acid catalysis provides a greater understanding of porphyrin-forming reactions and opens a wider set of options for addressing synthetic challenges.…”

“…One such example is the efficient synthesis of NC-TPP using methanesulfonic acid [39], a feat not possible with TFA or BF 3 -etherate catalysis [7]. Another example is our recent application of acids [Yb(OTf) 3 , Dy(OTf) 3 , Sc(OTf) 3 , and InCl 3 ] in condensations involving dipyrromethane-carbinols; these acids are poorly suited for the preparation of porphyrins by pyrrole-aldehyde condensations but are very effective with the more reactive dipyrromethane-carbinols, affording porphyrins bearing specific patterns of meso-substituents with minimal or no detectable scrambled products [40].…”

Synthesis and Reactivity of Allenylporphyrins

“…IR spectra were recorded on a Perkin-Elmer Spectrum 100 FT-IR spectrometer. Starting Materials: Formylporphyrins 1a, [29] 1b; [30] bromoporphyrins 4a, [31] 4j, [32] 4l; [31] dipyrromethane [15] , 5,15-disubstituted porphyrins: 8a, [33] 8b, [14b] 8c, [34] 8d, [14b] 8e, [35] 8f, [36] 10a, [37] 5,10,15-triphenylporphyrin 9a and the nickel(II) complex 11a, [39] and 5,15-bis(4-methylphenyl)-10-phenylporphyrin (9b) [40] were prepared using standard methodologies and had analytical data consistent with that in the literature. General Procedure A.…”