Design, Synthesis And Properties Of N-Confused Porphyrin Derivatives

N-confused porphyrin(NCP) has attracted great attention because of its unique structures, novel properties and wide potential applications in chemistry, medicine and material science. In this paper, a novel series of N-confused porphyrin derivatives were synthesized, separated, characterized and some meaningful results were achieved.1). Reaction of paraformaldehyde with NCP in the presence of a basic catalyst afforded fused lactam derivatives comprising a C=O bridge linking the internal carbon C21 with one of the internal nitrogens. For meso-tetrakis-(3’,5’-dimethoxy)- and meso-tetrakis-(3’,4’,5’-trimethoxy)-21,24-carbonyl-NCP, an efficient external ring fusion by linking C3 with an ortho carbon of the adjacent aryl was observed, yielding derivatives comprising a linear system of five fused rings. The chirality and configurational stability of these carbonylated systems were established by a chiral stationary phase HPLC and circular dichroism. The interaction of the product with chiral acids and alcohols leading to the formation of diastereomers was observed by 1H NMR. Slow racemization of the product under acidic conditions was established by HPLC and 1H NMR and a mechanism for this process was proposed.2). A 3-phosphonated N-confused phlorin was synthesized by the reaction of N-confused porphyrin and trimethyl or triethyl phosphite in the presence of acetic acid in good yield. The presence of hydrogen and aryl substituents in one of the meso positions(C5) generates a stereogenic center, resulting in configurationally stable enantiomers. The enantiomers were separated by HPLC and characterized by the circular dichroism method for the first time in the case of phlorin. Further oxidation by DDQ(2,3-dichloro-5,6-dicyano-1,4-benzoquinone) afforded the achiral 3-phosphonated N-confused porphyrin. Chiral chlorozinc complexes and chlorocadmium complexes, as well as achiral nickel(II) complexes were also characterized. For chlorocadmium complexes in the solid state, formation of a dimer consisting of heterochiral subunits joined by two H-bonds was established by a single crystal X-ray analysis. For chlorocadmium complexes, separation of enantiomers was achieved. The relationship between circular dichroism and absolute configuration of 3-phosphonated N-confused phlorin and chlorocadmium complexes was established on the basis of TD-DFT calculations.3). An oxidative addition of primary alkoxyls into two sites of NCP has been accomplished by means of alcohols in the presence of a stoichiometric amount of DDQ. The resulting aromatic monocationic species were characterized by the NMR and, in the case of triethoxy-NCP, by monocrystal X-ray diffraction analysis. One alkoxy group is located in position C3, on the macrocycle’s perimeter, while two-OR moieties are attached to the internal carbon(position 21) of the confused pyrrole. The 3-EtO-C21l-NCP, which is formed as a byproduct, was also structurally characterized by means of X-ray diffraction. Reduction of 3-RO-21-(RO)2NCP with hydrazine hydrate gave selectively a neutral and intrinsically chiral 3,21-bis(alkoxy)NCP. Dealkylation of the externally bonded 3-OR fragment under basic conditions leading to a zwitterionic aromatic 3-oxo-species, which still possesses the internal ketal functionality, was established by the NMR and X-ray diffraction methods. An unprecedented transetherification for the internal alkoxyl of 3,21-bis(alkoxy)NCP can be achieved under very mild conditions and without catalyst. The alkoxyl-exchange products of 3-ethoxy-21-methoxy-NCP was characterized by the X-ray diffraction method. The substitution proceeds via an associative(SN2) mechanism resulting in an inversion of the chirality of 3-RR’, which was shown by means of the NMR and chirooptical methods.4). Active methylene compounds such as acetone, butanone, cyclopentanone, nitromethane, malononitrile, ethyl 2-cyanoacetate, diethyl malonate, and ethyl acetylacetate react with the C3 position of N-confused porphyrin in the presence of L-proline in refluxing THF-EtOH affording a variety of N-confused porphyrin derivatives in moderate yield. L-Proline catalyzes the reaction facilitating the formation of the carbanion derived from an active methylene compound simultaneously delivering protons to the N-confused porphyrin. Both processes are key factors of this reaction.5). The reaction of azo-intermediate generated in situ from 2-aminobenzoic acid and isopentyl nitrite to N-confused porphyrins afforded novel 21-azo-N-confused porphyrin derivatives in the presence of triethylamine. The reaction was found to be general with respect to various substituted arylamine.6). The 21-(dimethylamino)methyl N-confused porphyrin derivatives were synthesised by Mannich reaction of dimethylmethyleneimmonium chloride and N-confused porphyrin. The reaction took placed regioselectively in inner carbon of inverted pyrrole of N-confused porphyrins.