Synthetic porphyrins. I. Synthesis and spectra of some para‐substituted meso ‐ Tetraphenylporphines

Abstract

A series of derivatives of meso-tetraphenylporphine, with neutral, acidic and basic functional groups, has been prepared. Several of these compounds were synthesized directly via the Rothemund reaction, under a variety of conditions to obtain optimal yields; others were prepared by interconversions of various functional groups. Drastic reaction conditions employed for hydrolysis, alcoholysis, o r lithium aluminum hydride reduction did not affect the porphine ring system. The two amino derivatives showed anomalous spectra in the visible range.Synthetic porphyrins are of potential interest in medicinal chemistry for a variety of reasons: (1) they a r e structurally related to important biological substances (heme, vitamin Biz); ( 2 ) they a r e powerful metal chelating agents; (3) they absorb radiation energy a t certain wavelengths, including the visible spectral range, and may act either a s radiation sensitizers o r protecting agents against radiation; (4) they show selective tissue distribution properties. Hematoporphyrin reportedly accumulates in tumors and other rapidly growing tissues (3-5) and was used a s a fluorescent indicator for the delineation of neoplastic tissue in cancer patients (6). A sulfonated derivative of meso-tetraphenylporphine was recently reported to be even more selective and to attain a 50-100 times greater tumor concentration than hematoporphyrin (7-9). It would seem, therefore, that such compounds may be used a s tumor-selective radiation sensitizers, and in the form of their chelates either with a toxic metal ( e . g . , Hg) (10) o r , with a gamma-ray emitting radioistope ( e . g . , Co5?) (9), a s potential chemotherapeutic agents.In order to establish the effects of various functional groups in the porphyrin molecule on the solubility, tissue distribution and specificity of binding to certain cell-constituents, a series of new meso-tetraphenylporphine derivatives, substituted in the para positions with acidic, basic or neutral groups (11-VIII), were synthesized and studied. The previously known meso-tetra-p-tolylporphine (I) was prepared in serial experiments designed to study the optimal methods and conditions for the synthesis of these compounds.Compounds I to V were prepared directly by various applications of the Rothemund reaction, i. e . , by condensation of the appropriately substituted benzaldehyde with pyrrole. Compounds VI to VIII were prepared by chemical conversion from I1 and 111 .Two major variations of the Rothemund reaction a s applied to the synthesis of mesotetraphenylporphine and some of i t s derivatives were found in the literature:(A) Heating a mixture of pyrrole with the appropriate aldehyde in a sealed bomb at high pressure and temperature, usually with pyridine as a solvent. This method originally used by Rothemund (11,12) gave extremely low yields (~1%). When the reaction was conducted in the presence of metal salts (Calvin, I, R CH3 3 --' 111, R = CN VII. R = COOH Vlll. R CH20H

Synthesis and characterization of a novel series of meso (nitrophenyl) and meso (carboxyphenyl) substituted porphyrins

“…These bands appear in the spectrum of 4 as very intense and large bands centred at 1402 and 1268 cm -1 , which agree with data reported by Datta-Gupta and Bardos for this free-base porphyrin 16 . The intensity of these bands decreases in the order: 4 > 1 > 2 > 3, as expected, due to the decrease in the number of carboxylic acid groups in these porphyrins (Figure 2).…”

“…The others bands, not assigned here, are atributed to the vibration of the ring porphyrinic and phenyls group meso-substituents, and are well established in the literature 16,26 .…”

“…In this way, the synthesis of porphyrins bearing carboxy groups often requires the acid groups to be masked as esters. This consequently involves an extra step of group deprotection after the porphyrin has been formed 16 . We decided to use the method of Gonsalves et al 11 , which employs propionic acid and nitrobenzene medium, in the synthesis of the orthonitrophenyl and para-carboxyphenyl substituted porphyrin series.…”

Modifications of Porphyrins and Hydroporphyrins for their Solubilization in Aqueous Media

“…meso-Tetrakis(4-carboxyphenyl)porphyrin, and its ester, are well known, and readily synthesized by condensation of the corresponding aldehydes with pyrrole [98][99][100]. They are also commercially available [58].…”

Molecular Interactions of Some Free Base Porphyrins with σ- and π-Acceptor Molecules

“…Simultaneously, the intensities of the vibrational bands (II and IV) are diminished. [3] The ethio type of the spectrum of tetraphenylporphyrin is distorted because the band I becomes more intense than the band II.…”