Transcript Synthesis of meso-substituted porphyrins

Synthesis of meso-substituted
porphyrins
Mariusz Tasior
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.
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
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
Thank you...