Porphyrinogens and porphodimethenes,intermediates in the synthesis of meso-tetraphenylporphins from pyrroles and benzaldehyde

The reaction between pyrroles and benzaldehyde in refluxing acetic acid gives meso-tetraphenylporphins and chlorins. The initial condensations give a porphyrinogen which undergoes an acid catalyzed autoxidation to porphyrin via a porphodimethene. The chlorin is shown to be derived from the reduction of porphyrin.     

meso-Tetraaryl-7,8-dihydroxydithiachlorins: first examples of heterochlorins

Osmium tetraoxide-mediated dihydroxylation of meso-tetraaryldithiaporphyrins generates the corresponding meso-tetraaryldithia-7,8-dihydroxychlorins and meso-tetraaryldithia-7,8,17,18-tetrahydroxybacteriochlorins. The products are spectroscopically characterized and the substitution positions were unequivocally determined. The UV-vis of the heterochlorins and heterobacteriochlorins are chlorin- and bacteriochlorin-like, respectively. However, the chlorin spectra are surprisingly hypsochromically shifted as compared to the corresponding all-aza chlorins, whereas the bacteriochlorin is bathochromically shifted. meso-Tetraaryldithia-7,8-dihydroxychlorins are susceptible to oxidative ring-opening reactions to form the corresponding meso-tetraaryldithia-7-oxo-8-oxa-dithiaporphyrin (dithiaporpholactone). These derivatives are the first examples of heterochlorins and β-modified dithiaporphyrins.     

Facile iodination of the vinyl groups in protoporphyrin IX dimethyl ester and subsequent transformation of the iodinated moieties

Iodination of protoporphyrin IX dimethyl ester using phenyliodine bis(trifluoroacetate) (PIFA) and I₂ was studied. Iodine added to both the C3- and C8-vinyl groups equally to afford the iodohydrin or iodoether in the presence of water or alcohol, respectively. Any meso-hydrogen atom was not substituted by an iodine atom under these conditions, although both the vinyl group and one of the meso positions of methyl pyropheophorbide-a bearing a chlorin π-system, a chlorophyll-a derivative, was modified with PIFA and I₂. The reaction intermediates derived from the porphyrin were more reactive than those from the chlorin and liable to form intermolecular linkages. The obtained 2-iodo-1-hydroxyethyl group was transformed into a formyl group by a mild treatment. The corresponding iodoether moiety was readily converted into the acetyl group under basic conditions. These transformations were also applicable to smaller olefins such as styrene.     

Novel fullerene receptors based on calixarene-porphyrin conjugates

Several different synthetic approaches enabling a direct covalent connection between the meso-position of porphyrin and the upper rim of calix[4]arene have been studied. The best results were obtained via condensation of an excess of pyrrole and p-methylbenzaldehyde with calix[4]arene-5,17-dialdehyde under BF₃·Et₂O catalysis in CHCl₃. Subsequent oxidation of the intermediate porphyrinogen gave the corresponding bis-porphyrin-calixarene conjugate in 15% overall yield. The ¹H NMR complexation study revealed the pronounced selectivity of the bis-porphyrin derivative towards C₇₀ fullerene.     

Synthesis of meso-tetraphenyl porphyrins via condensation of dipyrromethanes with N-tosyl imines

A new synthetic route for the synthesis of 5,10,15,20-tetraphenyl porphyrins has been developed based on the reaction of 5-substituted dipyrromethanes with N-tosyl imines in the presence of a metal triflate catalyst. meso-Substituted tetraphenyl porphyrins were synthesized in a two-step process. The first step of the method is the metal triflate-catalyzed condensation of 5-substituted dipyrromethanes with N-tosyl imines to form a porphyrinogen intermediate and the second step is the oxidation of the porphyrinogen to porphyrin. The method was applied to the synthesis of trans-A₂B₂-tetraarylporphyrins and the products were obtained with only a trace amount of one scrambling product. The synthesis of two important building blocks for porphyrin synthesis, mono and di-sulfonamide alkylated 5-substituted dipyrromethanes, was achieved by the addition of 5-substituted dipyrromethane to N-tosyl imine. The application of mono and di-sulfonamide alkylated 5-substituted dipyrromethanes in ‘2+2’ porphyrin formation reactions is presented.     

The π Complexation of Calcium inside the meso-Octaethylporphyrinogen Tetraanion Cavity

A possible binding cavity for alkali and alkaline earth metal ions: The synthesis and structural characterization of the complex shown, which was obtained from meso-octaethylporphyrinogen and calcium metal, shows that the porphyrinogen functions as a binucleating ligand with four η³-azaallyl binding sites for two calcium cations.     

[2-Methylazeteochlorinato]Ni(II): a pyrrole ring-contracted chlorin analogue

The formal replacement of one of the pyrrole rings in [meso-tetraphenylporphyrinato]Ni(II) (5Ni) by an azete moiety is reported. Thus, reaction of known chlorophin monoaldehyde 7Ni (made in three steps from 5Ni) with methyl-Grignard, followed by an acid-catalyzed ring-closure reaction, generates the title compound [meso-tetraphenyl-2-methylazeteochlorinato]Ni(II) (10Ni) in a rational and scalable process in good yields. The UV-vis spectroscopic properties of this chromophore are, as expected for this chlorin analogue, red-shifted when compared to the corresponding [porphyrinato]Ni(II) (5Ni) complex. A much improved synthesis of the starting material 7Ni by Vilsmeier-Haack formylation of [meso-tetraphenylchlorophinato]Ni(II) (8Ni) is also reported.     

Convenient peripheral aroyloxylation reactions of porphyrins and chlorophyll-a-based chlorins with benzoyl peroxide

A practical and efficient methodology for the formation of C–O bonds on the porphyrin/chlorin periphery was developed. The aroyloxy-substituted porphyrins and chlorins related to chlorophyll-a at the β- and meso-positions, respectively, were conveniently synthesized by the free radical substitution reaction with benzoyl peroxide and its homologs.     

Axial Imidazole Binding Strengths in Porphyrinoid Cobalt(III) Complexes as Studied by Tandem Mass Spectrometry

The Co(II) complexes of twelve meso-tetraaryl-porphyrins, -chlorins, and chlorin analogues containing non-pyrrolic heterocycles were synthesized and converted in situ to the corresponding Co(III) complexes coordinated to one or two imidazoles. Electrospray ionization tandem mass spectrometry (ESI-MS/MS) in conjunction with the energy-variable collision-induced dissociation (CID) technique was used to compare the relative gas-phase binding strength of the axially coordinated imidazoles to the octahedral and square planar Co(III) porphyrinoid complex ions. The observed binding energies of these ligands were rationalized in terms of the effects of porphyrinoid core structure and meso-substitution on the electron density on the central Co(III) centers. Some of these trends were supported by DFT-based computational studies. The study highlights to which extend porphyrins vary from chlorins and chlorin analogues in their coordination abilities and to which extraordinary degree meso-thienyl-substituents influence the electronic structure of porphyrins. The study also defines further the scope and limits CID experiments can be used to interrogate the electronic structures of metalloporphyrin complexes.     

Orientation of nucleophilic substitution in π-cation radicals or π-dications from meso-substituted metalloporphyrins

Treatment of meso-substituted metalloporphyrins [meso -substituent = OCOCF₃, OCOCH₃, OMe, CHO, CN, Cl; metal = Zn(II) or Cd(II)] with thallium(III) trifluoroacetate, followed by an acidic work-up, gives the corresponding β-substituted α-oxophlorins which were either characterised as such or else further derivatised. In all cases the major (or only) disubstitution product has the αβ orientation at the meso positions, indicating that the existing meso substituent directs the incoming one (trifluoroacetate) into the flanking, rather than opposite, meso position of the intermediate π-cation radical or π-dication. In contradistinction, meso substituted zinc(II) porphyrins which are able to lose protons (e.g. α-oxophlorins or α-aminoporphyrins) react with thallium(III) trifluoroacetate, and after a work-up with HCl the corresponding γ-chloro-α-oxophlorin or γ-chloro-α-aminoporphyrin is obtained.     

Sparsely substituted chlorins as core constructs in chlorophyll analogue chemistry. III. Spectral and structural properties

The availability of stable chlorins bearing few or no substituents has enabled a variety of fundamental studies. The studies described herein report absorption spectra of diverse chlorins, comparative NMR features of chlorins bearing 0-3 meso-aryl substituents, and X-ray structures of the fully unsubstituted chlorin and the oxochlorin.     

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.     

Mechanistic insights on the site selectivity in successive 1,3-dipolar cycloadditions to meso-tetraarylporphyrins

A DFT study on site selectivity in successive 1,3-dipolar cycloadditions of meso-tetraarylporphyrins with azomethine ylide and N-methylnitrone has been carried out. The calculation of the thermodynamic stability of both ylide and nitrone-derived adducts reveals that bacteriochlorins are more stable and have stronger aromatic character than isobacteriochlorins. Calculations of whole reaction pathways show that cycloadditions of azomethine ylide on porphyrin and its derived chlorin are irreversible and hence kinetically controlled. Solvent influence on the site selectivity of this reaction has also been considered, and appears to be decisive in controlling the site selectivity. In contrast, cycloadditions of nitrone over porphyrin and chlorin are clearly reversible, pointing to a thermodynamic control of these reactions.     

Synthesis of non-aggregating chlorins and isobacteriochlorins from meso-tetrakis(pentafluorophenyl)porphyrin: a study using 1,3-dipolar cycloadditions under mild conditions

The 1,3-dipolar cycloaddition of meso-tetrakis(pentafluorophenyl)porphyrin and its nickel complex, with the bulky azomethine ylide dipole was studied under mild conditions, and yielded chlorin and isobacteriochlorin derivatives self-prevented from aggregation. The reactions were performed at room temperature or 0 °C, and we were able to establish a set of reaction conditions to obtain only the chlorin or the isobacteriochlorin. These compounds were evaluated in solution, and no aggregation was observed at less than 25 mM (∼30 mg mL⁻¹) using ¹H NMR experiments.     

Spectroscopic properties of meso-thienylporphyrins with different porphyrin cores

The absorption and fluorescence properties of a series of meso-thienylporphyrins with different porphyrin cores (N₄, N₃O, N₃S and N₂S₂ cores) were studied and compared with the corresponding meso-tetraarylporphyrins. The replacement of six-membered phenyl groups with five-membered thienyl groups at meso-positions resulted in red shifts and broadening of absorption and emission bands, low quantum yields and decreased S₁ state lifetimes and the maximum effects were observed for meso-tetrathienylporphyrin with N₂S₂ porphyrin core. Similar observations were noted for the dications of meso-thienylporphyrins compared to the dications of the corresponding meso-tetraarylporphyrins. These results suggest that the replacement of six-membered aryl group with five-membered thienyl groups at meso-positions, the electronic properties of the porphyrin were altered significantly.     

焦脱镁叶绿酸-a甲酯20-meso-1-位的亲电取代反应

利用焦脱镁叶绿酸-a甲酯与亲电试剂发生的取代反应, 在焦脱镁叶绿酸-a甲酯的20-meso-位上分别引进硝基和卤原子, 得到了20-meso位取代的焦脱镁叶绿酸衍生物. 所合成的新叶绿素-a衍生物均经UV, IR, ¹H NMR及元素分析证明其结构. 另外, 对叶绿素-a卟吩环上的芳香性和相应的化学反应活性也进行了讨论, 提出了可能的亲电取代反应机理.     

meso-Dithiole and tetrathiafulvalene dipyrromethanes a route to metal dithiole-dipyrrin complexes and to fluorescent tetrathiafulvalene-BODIPY

A series of meso-dithiole and tetrathiafulvalene (TTF) dipyrromethanes have been prepared via the reaction of the appropriate aldehyde with either pyrrole or 3-ethyl-2,4-dimethyl-pyrrole under acid catalysis. Oxidation to the corresponding meso-dithiole dipyrrins is reported together with the formation of the metal chelate complexes (M=Zn, Cu, Ni) as well as the meso-dithiole boron-dipyrromethene (BODIPY). The molecular structures of these metal (Cu, Ni) and boron complexes are presented and discussed. According to a similar strategy the meso-TTF BODIPY is prepared and its photophysical properties are presented and compared with those of the meso-dithiole BODIPY.     

Porphyrin derivatives: Synthesis and potential applications

Porphyrin‐porphyrin and porphyrin‐chlorin dimers have been synthesized and evaluated for their photo‐physical and in vivo photodynamic therapy properties. Two of them can become potential new photosensitizers. Study of the reactivity of meso‐tetraaryl porphyrins, as dienophiles, in Diels‐Alder transformations and as dipolarophiles in 1,3‐dipolar cycloadditions, has been undertaken. New synthetic methodologies for certain chlorin, bacteriochlorin and isobacteriochlorin type macrocycles, with potential biological significance, have been established.     

Chiral bidiaziridines by a two-step domino aziridination of meso-α-diimines

Chiral racemic α-diimines, tested in aziridination reactions with NsONHCO₂Et, for the first time led to the synthesis of (±)-bidiaziridines, stereoselectively derived from the corresponding meso (E-s-trans-E)-α-diimines. Moreover, a minor bidiaziridine isomer, probably a meso form that was lost under classical work-up conditions, can be obtained by adding water to the crude mixtures at the end of amination reactions. The results definitively prove that the imine aziridination by carbamates is a two-step domino process. The structures of the compounds were determined using 2D NMR on purified bidiaziridines.     

Organocatalytic desymmetrization of cyclic meso-anhydrides through enantioselective alcoholysis with functionalized primary nitroallylic alcohols

The direct organocatalytic desymmetrization of cyclic meso-anhydrides was achieved by alcoholysis with nitroallylic alcohols. The reaction between primary nitroallylic alcohols and cyclic meso-anhydrides catalyzed by cinchonidine derived thiourea organocatalyst II (10 mol %) proceeded smoothly. The corresponding hemiesters were obtained in high chemical yields with high to excellent levels of stereoselectivity (up to 90% yield and 99% ee). On the other hand, the reversal of enantioselectivity was observed when an amino cinchonidine derivative (III) was used as the organocatalyst under the similar reaction conditions. This demonstrated an example of activation of the nucelophilic component in the desymmetrization of cyclic meso-anhydrides.