Synthesis of highly substituted meso-tetraarylporphyrins

meso-Tetraphenylporphyrin (and its derivatives), in the reaction with fuming yellow nitric acid (d=1.53), form either 5-(4-nitroaryl)-10,15,20-triarylporphyrin, 5,10-bis(4-nitroaryl)-15,20-diarylporphyrin, or 5,10,15-tris(4-nitroaryl)-20-arylporphyrin, depending on the reaction temperature (0-20 °C), amounts of the acid used, and reaction time. The above nitroporphyrins react, in the presence of a base (t-BuOK) at 0 °C, with carbanions (which bear nucleophugal groups at the carbanionic center: ⁻CH(Cl)SO₂Tol, ⁻CH(Br)SO₂Tol, and ⁻CH(Cl)SO₂NMe₂), leading to the nucleophilic substitution of hydrogen in one or more of the meso-nitroaryl rings. By this route, the preparation of the highly substituted ‘synthetic’ porphyrins (bearing up to ten O-, N-, Cl-, or C-substituents) was demonstrated.     

Reaction of meso-tetraarylporphyrins with pyrazine ortho-quinodimethanes

Novel π-extended porphyrins were obtained from the Diels-Alder reaction of meso-tetraarylporphyrins with a pyrazine o-quinodimethane derivative.     

Novel synthesis of meso-tetraarylporphyrins using CF3SO2Cl under aerobic oxidation

meso-Tetraarylporphyrins are synthesized from pyrrole and aryl aldehydes cleanly and efficiently in one pot at room temperature using equimolar amount of CF₃SO₂Cl in the presence of air as oxidant. By this novel method 5,10,15,20-tetraarylporphyrins can be prepared in excellent yields.     

Synthesis of meso-tetraarylporphyrins using SeO2 as oxidant

The oxidative step of the two-step, one-flask synthesis of meso-tetraarylporphyrins is herein conducted with heterogeneous oxidant SeO₂ instead of the usual quinones DDQ or p-chloranil. Evaluation of BF₃O(Et)₂ or I₂ amount for the condensation of the first step combined with the excess of SeO₂ defined porphyrin synthesis conditions employing benzaldehydes and pyrrole (or 5-phenyldipyrromethane) as starting materials. The simplicity of the workup, allied with reaction mild conditions, makes this method a good option for the synthesis of this kind of compound.     

Synthesis and characterization of phenanthrene derivatives with anticancer property against human colon and epithelial cancer cell lines

A variety of polycyclic aromatic hydrocarbons have been synthesized and structurally characterized in our laboratory. Phenanthrene derivatives were efficiently prepared in excellent yields and high purity via a two-step sequence. Heck coupling yielded the corresponding diarylethenes, followed by classical oxidative photocyclization to achieve the expected phenanthrenes. First, we envisioned to synthesize a variety of substituted phenanthrenequinones. Second, we investigated the possibility of a dibenz[a,c]phenazine formation by addition of o-phenylenediamine after completion of the oxidation process. Moreover, because phenanthrenequinones are available so simply, it is likely that other uses will be found for these compounds. For example, 9,10-phenanthrenequinone can be sequentially reduced, alkylated, acetylated, and sulfonated. All the synthesized derivatives were evaluated for cytotoxic activity in vitro against the human epidermoid carcinoma epithelial cells Hep-2 and human colon carcinoma cells Caco-2 using the 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide (MTT) assay. From the structure–activity point of view, position and nature of the electron donating and electron withdrawing functional groups attached to the phenanthrene skeleton may contribute to the anticancer action. Interestingly, the analysis of the IC₅₀ values suggests that most compounds exerted cytotoxic effects with selectivity against both cancer cells. Among them, methyl 8-methyl-9,10-phenanthrenequinone-3-carboxylate 11d showed the highest potency with IC₅₀ values of 2.81 and 0.97 μg/mL.     

Synthesis of mono meso-pyridyl 21,23-dithiaporphyrins and unsymmetrical non-covalent porphyrin dimers

A new method has been developed to synthesize 21,23-dithiaporphyrins having one pyridyl group at the meso position. The method required easily available unknown precursors and the condensation resulted in mono meso-pyridyl 21,23-dithiaporphyrins as single products in 8-11% yield. Two of the three mono meso-pyridyl N₂S₂ porphyrins were used to synthesize non-covalent unsymmetrical porphyrin dimers containing one N₂S₂ and one N₄ porphyrin cores.     

meso-Tetraaryl-7,8-diol-21,23-dithiachlorins and their pyrrole-modified derivatives: a spectroscopic comparison to their aza-analogues

Osmium tetraoxide-mediated dihydroxylation of meso-tetraaryl-21,23-dithiaporphyrins generates the corresponding meso-tetraaryl-7,8-dihydroxy-21,23-dithiachlorins and meso-tetraaryl-7,8,17,18-tetrahydroxy-21,23-dithiabacteriochlorins. Oxidative diol cleavage reactions of the meso-tetraaryldithia-7,8-dihydroxychlorin generate, depending on the conditions chosen, the corresponding meso-tetraaryldithia-7-oxa-8-oxo-21,23-dithiaporphyrin (dithiaporpholactone) or meso-tetraaryl-7,8-ethoxy-7a-oxa-7a-homo-21,23-dithiaporphyrin (morpholinodithiachlorin), respectively. The UV-vis spectra of the heterochlorins and pyrrole-modified dithiaporphyrins are compared to those of the corresponding all-aza homologues. In general, the trends which distinguish the spectra of dithiaporphyrins from those of all-azaporphyrins are preserved. Thus, the spectra of the dioldithiachlorins tetraoldithiabacteriochlorins are chlorin- and bacteriochlorin-like and bathochromically shifted as compared to the all-azaanalogues, respectively. Also, the dithiaporpholactone spectrum is porphyrin-like. However, the UV-vis spectrum of the morpholinodithiachlorin is uncharacteristic for a morpholinochlorin spectrum. The derivatives described are the first examples of heterochlorins and pyrrole-modified dithiaporphyrins.     

Synthesis and characterization of intermediate sitting-atop (i-SAT) complexes of free base meso-tetraarylporphyrins and tin(IV) chloride

The reaction of meso-tetraarylporphyrins (H₂T(X)PP) with SnCl₄ affords green intermediate sitting-atop (i-SAT) complexes, [(H₂T(X)PP)SnCl₄]. UV–Vis, ¹H NMR and ¹³C NMR spectral data show that the porphyrin core of the complexes is distorted, thus two nitrogen atoms of the pyrrolenine groups on one side of the porphyrin plane act as electron donors to the tin center of SnCl₄. The intermediate sitting-atop (i-SAT) complex is formed each time during the incorporation of the metal center, where in the intermediate state the pyrrolic protons still remain on the porphyrin.     

Sitting-atop complex formation of free base meso-tetraarylporphyrins with zirconium(IV) chloride

We have succeeded in the preparation and spectroscopic characterization of sitting-atop (SAT) complexes of meso-tetraarylporphyrins (H₂t(X)pp) with zirconium(IV) chloride under mild conditions and at room temperature, where two pyrrolenine nitrogens in the SAT complexes, [(H₂t(X)pp)ZrCl₄], coordinate to a zirconium atom and two protons still remain on the pyrrole nitrogens. UV–Vis and NMR (¹H and ¹³C) spectral data show that the porphyrin core of the SAT complexes is distorted and two pyrrolenine nitrogen atoms of the porphyrin act as electron donors to the zirconium atom of ZrCl₄.     

Synthesis and characterization of meso-ferrocenylethynyl 5,15-diphenylporphyrins

A series of four meso-ferrocenylethynyl (5,15-diphenylporphyrinato)nickel(II) derivatives have been synthesized by Sonogashira coupling reactions. Three of these compounds contain the electron-withdrawing groups including -CHO, -CHC(CN)₂, and -CCC₆H₄NO₂ at the remaining meso position, with a view to preparing push-pull chromophores, in which ferrocene serves as the electron donor. All the new compounds have been characterized spectroscopically and the molecular structure of one of these porphyrins (compound 11) has also been determined. The studies show that although the ferrocenylethynyl group can extend the π system of the central porphyrin core, the cyclopentadienyl rings of ferrocene are almost orthogonal to the porphyrin ring. This hinders ferrocene serving as a good electron donor in these systems.     

Porphyrins with exocyclic rings. Part 20: Synthesis and spectroscopic characterization of porphyrins with fused 2,1,3-benzoxadiazole and 2,1,3-benzoselenadiazole moieties

Porphyrins with fused 2,1,3-benzoxadiazole and 2,1,3-benzoselenadiazole units were prepared by the ‘3+1’ MacDonald-type methodology. 4-Nitro-2,1,3-benzoxadiazole, 6-chloro-4-nitro-2,1,3-benzoxadiazole and 4-nitro-2,1,3-benzoselenadiazole condensed with isocyanoacetates in the presence of the non-nucleophilic base DBU to give tricyclic pyrrole derivatives in excellent yields. Further cleavage of the ester moieties and decarboxylation afforded α-unsubstituted pyrroles and these were further condensed with 2 equiv of an acetoxymethylpyrrole tert-butyl ester to give crude preparations of tripyrranes. The tert-butyl ester protective groups were cleaved with TFA and following dilution with dichloromethane, ‘3+1’ condensation with a pyrrole dialdehyde, and oxidation with ferric chloride, the heterocyclic ring fused porphyrins were obtained in moderate yields. The yields were lower than expected because of difficulties in preparing required tripyrranes due to the reduced reactivity of the pyrrolic intermediates. The UV-vis spectra of these new porphyrin systems were highly modified showing broadened split Soret bands. In addition, the nickel(II), copper(II) and zinc complexes gave unusual UV-vis spectra with weakened split Soret bands and strong Q-type absorptions above 600 nm. These modified structures show some potential for applications as photosensitizers in photodynamic therapy.     

Synthesis,spectroscopic/electrochemical characterization and DNA interaction study of novel ferrocenyl‐substituted porphyrins

We report the synthesis and characterization of two new meso‐ferrocenylporphyrins, with the ferrocenyl unit attached at the para position of a C₆F₄ group by a C? N bond with ? NH(CH₂)₂NH? ( 2a ) and ? NH(CH₂)₄NH? ( 2b ) spacers. Compounds 2a and 2b were characterized through elemental analyses, electrospray ionization high‐resolution mass spectrometry, ¹H NMR, UV–visible and fluorescence spectroscopies, electrochemistry and spectroelectrochemistry. The free base porphyrin 2 was included for comparison purposes. The binding ability of 2 and the porphyrin derivatives 2a and 2b with calf thymus DNA was determined using UV–visible and fluorescence spectroscopies. The results suggest that the interaction of these systems most probably occurs through π‐stacking by non‐classical modes involving the partial insertion of the C₆F₅ ring between adjacent base pairs on DNA and possible hydrogen interaction with the aliphatic ? NH(CH₂)_nNH? (n = 2 or 4) groups with calf thymus DNA. Moreover, we also demonstrate that porphyrins generate singlet oxygen species and show good photostability after irradiation.     

Facile synthesis of meso-substituted dipyrromethanes and porphyrins using cation exchange resins

The macroporosity and acidity of cation exchange resins play a crucial role in the synthesis of dipyrromethanes and porphyrins; for the first time, cation exchange resins have been used as heterogeneous solid acid catalysts to produce dipyrromethanes and porphyrins in good yields. The reaction, at room temperature, of substituted aromatic aldehydes with pyrrole catalysed by cation exchange resin afforded the corresponding meso-substituted dipyrromethane in yields ranging from 70 to 80%, indicating the broad scope of the reaction. Further, the condensation of meso-substituted dipyrromethane with similar or different substituted aromatic aldehydes, using cation exchange resins furnished meso-tetrakis-symmetrical and mixed porphyrins, respectively. One-pot synthesis of porphyrins can also be carried out directly from the aldehydes and pyrrole under the above conditions. Acidolysis of the dipyrromethane is negligible under the conditions of the porphyrin-forming reaction.     

Heptaphyrins: Expanded porphyrins with seven heterocyclic rings

Expanded porphyrins containing seven pyrrole/heterocyclic rings linked in a cyclic fashion are termed heptaphyrins. The number ofπ-electrons in heptaphyrins depends on the number ofmeso carbon bridges used to link the heterocyclic rings, accordingly heptaphyrins with 28π-electrons and 30π-electrons are reported to date. Both condensation reactions of the appropriate precursors and acid-catalysed oxidative coupling reactions have been utilized to synthesise the heptaphyrins. The 30π heptaphyrins exhibit rich structural diversity where some of the heterocyclic rings in the macrocycle undergo a 180° ring flipping. An overview of the synthetic methods employed for the synthesis of heptaphyrins, their spectroscopic properties, structural behaviour and aromatic properties are highlighted in this paper. Dedicated to Professor C N R Rao on his 70th birthday     

Synthesis of meso-furyl porphyrins with N4, N3S, N2S2 and N3O porphyrin cores

A series of meso-furyl porphyrins with four different porphyrin cores (N₄, N₃S, N₂S₂ and N₃O) were synthesized and characterized. The comparison of NMR, optical and fluorescence properties of meso-furyl porphyrins with porphyrins with six-membered aryl groups indicates that electronic properties of porphyrins were changed drastically on the introduction of furyl groups at meso positions. The maximum shifts in spectral bands were observed for meso-furyl porphyrins with N₂S₂ core. On protonation, the absorption bands of meso-furyl porphyrins were further red shifted. All these changes were ascribed to the possibility of more planarity of the meso-furyl porphyrins due to the small size of the furyl groups which results in extending the π-delocalisation of the porphyrin ring in to the furyl groups.     

Synthesis of Thalicthuberine

The structure previously assigned to the phenanthrene alkaloid thalicthuberine has been confirmed by a total synthesis in which the key step involved the formation of ring C of the aporphine alkaloid (±)‐nantenine by a radical‐initiated cyclisation. Opening of ring B of (±)‐nantenine with methyl chloroformate and subsequent reduction of the N‐carbomethoxy group afforded thalicthuberine.     

Synthesis of meso-fluorotetrabenzoporphyrins

Fluorination of quadruply bicyclo[2.2.2]octadiene-fused porphyrin (CP) with 1-chloromethyl-4-fluoro-1,4-diazoniabicyclo[2.2.2]octane bis(tetrafluoroborate) (Selectfluor) occurred at the meso positions to give a mixture of various meso-fluorinated CPs, which were separated and then quantitatively transformed to the corresponding meso-fluorinated tetrafluorobenzoporphyrins (BPs) at 240 °C for 30 min. X-ray analysis of the mono-fluoro BPs revealed that the BP skeleton remained flat, which is crucial for retaining aggregation behavior similar to that of the parent BP, thus producing highly crystalline BP derivatives.     

Molecular complexation of free base meso-tetraarylporphyrins with antimony(III) chloride in free solvent media

The reaction of meso-tetraarylporphyrins (H₂t(Xp)p) with SbCl₃ under free solvent conditions affords green complexes with a 1:1 H₂t(X)pp:SbCl₃ ratio. These complexes have dimeric structures with a (μ-Cl)₂bridge. UV–VIS, ¹H NMR and ¹³C NMR spectra data show that the porphyrin core of [(H₂t(Xp)p)₂Sb₂Cl₆], similar to 1:2 (donor:acceptor) molecular complexes of meso-tetraarylporphyrins and porphyrin diacid, is distorted, thus two nitrogen atoms of pyrrolenine in a side of the porphyrin plane act as electron donors to an antimony atom of SbCl₃. Molecular complexation of meso-tetraarylporphyrins with SbCl₃ produces a large downfield shift for the NH signal, although there is no hydrogen bonding present.     

Synthesis and characterization of aromatic polyamides containing S-triazine rings in the main chain

Ten new aromatic polyamides containing s-triazine rings in the main chain were synthesized by the low temperature interfacial polycondensation technique involving the reactions of each of the two s-triazine containing diacylchlorides, viz., 2,4-bis (4-chlorocarbonylphenoxy)-6-methoxy-s-triazine and 2,4-bis(3-chlorocarbonylphenoxy)-6-methoxy-s-triazine, with five aromatic diamines namely, 4,4′-bis(4-aminophenoxy)diphenyl sulfone, 4,4′-bis(3-aminophenoxy)diphenyl sulfone, 2,2-bis[4(4-aminophenoxy) phenyl] propane, 1,4 bis (4-amino-phenoxy) benzene, and 1,3-bis (4-aminophenoxy)benzene. The resulting polyamides were characterized by viscosity measurements, IR and ¹H-NMR spectroscopy, solubility tests, x-ray diffraction, and thermogravimetry. The polyamides had inherent viscosities in the range of 0.16–1.06 dL/g in N,N-dimethylacetamide at 30°C. Most of the s-triazine containing polyamides dissolved readily at room temperature in polar solvents. Except for the polyamide PA-2, the polyamides did not lose weight below 350°C under a nitrogen atmosphere. © 1997 John Wiley & Sons, Inc. J Polym Sci A: Polym Chem 35: 1077–1085, 1997