Rational Syntheses of Porphyrins Bearing up to Four Different Meso Substituents

• Published in: Journal of organic chemistry 2000-11, Vol.65 (22), p.7323-7344
• Main Authors: Rao, Polisetti Dharma, Dhanalekshmi, Savithri, Littler, Benjamin J, Lindsey, Jonathan S
• Format: Article
• Language: English
• Subjects: Acylation; Catalysis; Indicators and Reagents; Molecular Mimicry; Porphyrins - chemical synthesis; Porphyrins - chemistry; Solvents; Temperature
• ISSN: 0022-3263; 1520-6904
• DOI: 10.1021/jo000882k

Porphyrins bearing specific patterns of substituents are crucial building blocks in biomimetic and materials chemistry. We have developed methodology that avoids statistical reactions, employs minimal chromatography, and affords up to gram quantities of regioisomerically pure porphyrins bearing predesignated patterns of up to four different meso substituents. The methodology is based upon the availability of multigram quantities of dipyrromethanes. A procedure for the diacylation of dipyrromethanes using EtMgBr and an acid chloride has been refined. A new procedure for the preparation of unsymmetrical diacyl dipyrromethanes has been developed that involves (1) monoacylation with EtMgBr and a pyridyl benzothioate followed by (2) introduction of the second acyl unit upon reaction with EtMgBr and an acid chloride. The scope of these acylation methods has been examined by preparing multigram quantities of diacyl dipyrromethanes bearing a variety of substituents. Reduction of the diacyl dipyrromethane to the corresponding dipyrromethane-dicarbinol is achieved with NaBH4 in methanolic THF. Porphyrin formation involves the acid-catalyzed condensation of a dipyrromethane-dicarbinol and a dipyrromethane followed by oxidation with DDQ. Optimal conditions for the condensation were identified after examining various reaction parameters (solvent, temperature, acid, concentration, time). The conditions identified (2.5 mM reactants in acetonitrile containing 30 mM TFA at room temperature for 1-g quantities of three porphyrins.