1. Synthesis of meso-substituted porphyrins
Mariusz Tasior

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

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

4. Some general considerations...

5. Some general considerations...

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

7. Scope of Adler method

8. Scope of Adler method

9. Mixed-aldehyde condensation

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

11. Acid cocatalysis, salt effect: Lindsey et al. JPP, 2001, 5, 681
Lindsey method
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

12. Scope of Lindsey method

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

14. Routes to specific classes of meso-substituted porphyrins

16. 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

17. Scrambling

18. Porphyrins bearing up to 4 different meso substituents

20. Thank you...