Two-Step, One-Flask Synthesis of a Meso-Substituted Phlorin

Abstract

A two-step, one-flask reaction of pyrrole with pentafluorobenzaldehyde and acetone was investigated to determine the potential for a streamlined synthesis of a phlorin and/or 5-isocorrole as an alternative to stepwise, dipyrromethanecarbinol routes. Analytical-scale reactions were performed examining the effect of reactant concentration, reactant ratio, acid catalyst (TFA or BF3·OEt2), concentration of acid catalyst, oxidant quantity, and reaction time on the distribution of phlorin and 5-isocorrole as well as three additional porphyrinoids (porphodimethene, porphyrin, and corrole). Phlorin was observed ubiquitously in yields up to 20-26%, whereas 5-isocorrole was not detected. Promising reaction conditions for the one-flask synthesis of the phlorin were performed on a preparative scale. The best reaction condition afforded the phlorin in an isolated yield of 20-21% (249-268 mg). Preliminary attempts to extend the methodology to the preparation of phlorins derived from other ketones resulted in a low yield of phlorin from acetophenone (5%) and no detectable phlorin from benzophenone. The discovery of reaction conditions for the two-step, one-flask synthesis of a phlorin provides easier access to this interesting compound, and provides encouragement for the further study of reactions of pyrrole with an aldehyde and a ketone.

Mechanical Trapping of the Phlorin Intermediate

“…In principle, phlorins can be prepared by two major strategies: (1) starting from porphyrin, which can be attacked by nucleophiles-for example, alkyl lithium reagents or hydride-at its meso-position [13][14][15][16] and (2) starting from acyclic (oligo)pyrrole building blocks and aldehydes or ketones employing an acid-catalyzed condensation followed by the oxidative dehydrogenation of intermediates. 1,[17][18][19][20][21] However, native phlorins with unmodified core-structures are highly unstable and readily oxidized, 9,19,22,23 making it difficult to isolate them. To stabilize phlorins during their synthesis, chemists have proposed five methods: (1) introducing bulky substituents, for example, mesityl and phenyl, at the meso-sp 3 -carbon atom to hinder oxidation 1,13,18,19,22,[24][25][26][27] and electron-withdrawing substituents, for example, pentafluorophenyl, 1,19,24,27 to enhance the oxidation potential of the phlorin; (2) N-substitution 16,28,29 so as to distort its conformation; (3) metalation with metal ions in the core of the phlorin 30 ; (4) replacing pyrrole with thiophene 31 ; and (5) introducing electron-withdrawing groups at the β-position of these pyrroles.…”

Acid Activation and Chemical Oxidation in the Synthesis of meso‐Tetraphenylporphyrin using a Mixed‐Solvent System

“…In 1987, p ‐chloranil and 2,3‐dichloro‐5,6‐dicyano‐1,4‐benzoquinone (DDQ) were utilized as chemical oxidants in a porphyrin preparation reaction by Lindsey et al, in which the yield of TPP product was markedly improved. Then DDQ was widely used as an oxidant in the synthesis of porphyrin and its analogs ,. In addition, SeO 2 was also proposed as a heterogeneous oxidant in the TPP synthesis .…”

An Easily Prepared Monomeric Cobalt(II) Tetrapyrrole Complex that Efficiently Promotes the 4e–/4H+ Peractivation of O2 to Water

“…[18][19][20]24,48 Recent work has been aimed at development of nonaromatic tetrapyrrole scaffolds (e.g. phlorins, [49][50][51][52][53][54][55][56] biladienes, [57][58][59][60] and isocorroles [61][62][63][64][65][66][67] ) that include an sp 3 -hybridized meso-carbon and which support unique photophysical and multielectron redox properties. These nontraditional tetrapyrroles provide alternate platforms to consider for ORR and other small molecule activation processes and may offer distinct reactivity profiles and catalytic activities.…”