Synthesis of meso-substituted porphyrins Mariusz Tasior

Rothemund, P., J. Am. Chem. Soc. 1935, 57, 2010. Rothemund method – in 1935... Rothemund, P., J. Am. Chem. Soc. 1935, 57, 2010.

Rothemund method – in 1935... First report about effects of metals in pyrrole-aldehyde condensation: Ball, R. H. et al. J. Am. Chem. Soc. 1946, 68, 2278.

Some general considerations...

Some general considerations...

Adler method Adler, A.D.; Longo, F. R.; Shergalis, W., J. Am. Chem. Soc. 1964, 86, 3145.

Scope of Adler method

Scope of Adler method

Mixed-aldehyde condensation

Mixed-aldehyde condensation Leznoff, C. C.; Svirskaya, P.I, Angew. Chem. In. Ed. 1978, 12, 947.

Acid cocatalysis, salt effect: Lindsey et al. JPP, 2001, 5, 681 Lindsey method 1979-... Lindsey, J. S., Hsu, H. C., Schreiman, I. C. Tetrahedron Lett. 1986, 27, 4969. Lindsey, J. S., Schreiman, I. C., Hsu, H. C., Kearney, P. C., Marguerettaz, A. M. Tetrahedron Lett. 1986, 27, 4969. Acid cocatalysis, salt effect: Lindsey et al. JPP, 2001, 5, 681

Scope of Lindsey method

Comparison of synthetic methods Rothemund Adler Lindsey Solvent Pyridine Propionic acid Acetic acid RCOOH+benzene DCM Chloroform Temperature 140-220ºC 141ºC 25ºC Catalyst - Same as solvent TFA BF3-etherate Clays, other acids Concentration 0.4-3.6M 0.3-0.1M 0.1-0.001M Reaction time 24-48hr 1hr Workup Separate crystals Filter crystals Chromatography Yield <10% ~20% ~ 40% Scope very narrow modest broad

Routes to specific classes of meso-substituted porphyrins

Trans-A2B2-porphyrins For dipyrromethane synthesis: Lindsey, J. S. et al. Org. Process Res. Dev. 2003, 7, 799. For condensation conidtions and scrambling: Lindsey, J. S. et al. J. Org. Chem. 1999, 8, 2864

Scrambling

Porphyrins bearing up to 4 different meso substituents

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