New Route to ABCD-Porphyrins via Bilanes

Abstract

A new strategy for preparing porphyrins that bear up to four different meso-substituents (ABCD-porphyrins) relies on two key reactions. One key reaction entails a directed synthesis of a 1-protected 19-acylbilane by acid-catalyzed condensation at high concentration (0.5 M) of a 1-acyldipyrromethane and a 9-protected dipyrromethane-1-carbinol (derived from a 9-protected 1-acyldipyrromethane). Three protecting groups (X) were examined, including thiocyanato, ethylthio, and bromo, of which bromo proved most effective. The bilanes were obtained in 72-80% yield, fully characterized, and examined by 15N NMR spectroscopy. The second key reaction entails a one-flask transformation of the 1-protected 19-acylbilane under basic, metal-templating conditions to give the corresponding metalloporphyrin. The reaction parameters investigated for cyclization of the bilane include solvent, metal salt, base, concentration, temperature, atmosphere, and time. The best conditions entailed the 1-bromo-19-acylbilane at 100 mM in toluene containing DBU (10 mol equiv) and MgBr2 (3 mol equiv) at 115 degrees C exposed to air for 2 h, which afforded the magnesium porphyrin in 65% yield. The magnesium porphyrin is readily demetalated to give the free base porphyrin. A stepwise procedure (which entailed treatment of the 1-(ethylthio)-19-acylbilane to oxidation, metal complexation, desulfurization, carbonyl reduction, and acid-catalyzed condensation) was developed but was much less efficient than the one-flask process. The new route to ABCD-porphyrins retains the desirable features of the existing "2 + 2" (dipyrromethane + dipyrromethane-1,9-dicarbinol) method, such as absence of scrambling, yet has significant advantages. The advantages include the absence of acid in the porphyrin-forming step, the use of a metal template for cyclization, the ability to carry out the reaction at high concentration, the lack of a quinone oxidant, avoidance of use of dichloromethane, and the increased yield of macrocycle formation to give the target ABCD-metalloporphyrin.

The first series of alkali dipyrrinato complexes

“…[41][42][43] With our current work, the published 15 N dipyrrinato chemical-shift ranges 23 can now be expanded to include alkali dipyrrinato complexes. As indicated in Fig.…”

Trends in Interdisciplinary Studies Revealing Porphyrinic Compounds Multivalency Towards Biomedical Application

“…8): the condensation process involving pyrrole and various aldehydes, reaction mixture involved also in MW assisted procedures, the combination of substituted pyrroles carrying the desired future porphyrin substituents or via bilane structure; this last option was successfully applied on ABCD substituted porphyrins via synthesis of a protected acylbilane (by acid-catalyzed condensation of a acyldipyrromethane and protected dipyrromethane-n-carbinol) (Dogutan et al, 2007) and insertion of the substituents in meso positions in the already formed porphyrin core. The unsymmetrical porphyrins were chosen as our main synthetic target (Boscencu, 2008(Boscencu, , 2010) because a. they are easy to prepare either via the Adler route (Adler et al, 1976) or by microvawe (MW) irradiation b. the phenolic hydroxy group is a suitable site on which to build a different substituent (Milgrom LR, 1983) c. the 4-methoxycarbonyl side-chains of the other meso-substituents may be de-esterified to convert a hydrophobic porphyrin into a hydrophilic one.…”

Rapid access to C 3- and C s-symmetric AAT organogelators via ring opening of a common benzotrifuranone precursor

“…Traditionally, access to molecules of lower symmetry is realised via a statistical approach from symmetrical precursors (often plagued by low yields and difficult separations), sequential couplings followed by cyclisation (popular in peptides and porphryins) (27)(28)(29)(30) or selective protection/deprotection (generally plagued by low yields and poor atom economy) (31,32). In rare cases, best characterised by triazine derivatives, (33) the chemical properties of the core allow for desymmetrisation with careful control of reaction conditions.…”