title: Rational or statistical routes from 1-acyldipyrromethanes to meso-substituted porphyrins. Distinct patterns, multiple pyridyl substituents, and amphipathic architectures.
abstract: New methodology is described for the synthesis of porphyrins bearing four (A 4, cis-A 2B 2, cis-ABC 2, trans-A 2B 2) or fewer (A, cis-AB, cis-A 2, trans-A 2) meso substituents. The method entails condensation of two 1-acyldipyrromethanes in the presence of a metal salt (MgBr 2, 3 mol equiv) and a noncoordinating base (DBU, 10 mol equiv) in a noncoordinating solvent (toluene) with heating (conventional or microwave irradiation) and exposure to air. The rational synthesis of trans-A 2B 2- or trans-A 2-porphyrins was achieved via condensation of two identical 1-acyldipyrromethanes. The statistical synthesis of various meso-substituted porphyrins was achieved via condensation of two nonidentical 1-acyldipyrromethanes. Both routes possess attractive features including (1) no scrambling, (2) good yield (up to 60%) at high concentration (100 mM) for the macrocycle-forming step, (3) reasonable scope (aryl, heteroaryl, alkyl, or no substituent), (4) short reaction time ( approximately 2 h) via microwave irradiation, (5) magnesium porphyrins as the products, which easily undergo demetalation, and (6) facile chromatographic purification. A key advantage of the statistical route is to obtain a cis-substituted porphyrin without the corresponding trans isomer. For example, reaction of an A/B-substituted 1-acyldipyrromethane and the fully unsubstituted 1-formyldipyrromethane gave the magnesium chelates of three porphyrins: the trans-A 2B 2-porphyrin, the "hybrid" cis-AB-porphyrin, and porphine (no trans-AB-porphyrin can form), which were readily demetalated and separated as the free base species. Altogether 26 1-acyldipyrromethanes and 26 target porphyrins have been prepared, including many with two different pyridyl substituents. One set of amphipathic porphyrins includes cis-A 2B 2- or cis-A 2BC-porphyrins wherein A = pentyl and B/C = pyridyl ( o-, m-, p-). Taken together, the rational and statistical routes enable facile conversion of readily available 1-acyldipyrromethanes to diverse porphyrins bearing 1-4 meso substituents for which access is limited via other methods.
authors.affiliation: Department of Chemistry, North Carolina State University, Raleigh, North Carolina 27695-8204, USA.
authors.forename: Dilek Kiper
authors.initials: DK
authors.lastname: Dogutan
authors.forename: Marcin
authors.initials: M
authors.lastname: Ptaszek
authors.forename: Jonathan S
authors.initials: JS
authors.lastname: Lindsey
mesh_terms: D008274:Magnesium / Q000737:chemistry; D008697:Methane / Q000031:analogs & derivatives* / Q000138:chemical synthesis / Q000737:chemistry; D008872:Microwaves; D011166:Porphyrins / Q000138:chemical synthesis*; D011758:Pyrroles / Q000138:chemical synthesis / Q000737:chemistry*
chemical_list: D011166:Porphyrins; D011758:Pyrroles; D008274:Magnesium; D008697:Methane