Route to formyl-porphyrins
A method of making a 5-formylporphyrin, comprises the steps of: condensing a 5-acetaldipyrromethane with a dipyrromethane-1,9-dicarbinol to produce a porphyrin having an acetal group substituted thereon at the 5 position; and then hydrolyzing said porphyrin to produce said 5-formylporphyrin. Products and intermediates useful in such methods, along with methods of making such intermediates, are also described.
1. A method of making a 5-formylporphyrin, comprising the steps of:
condensing a 5-acetaldipyrromethane with a dipyrromethane-1,9-dicarbinol to produce a porphyrin having an acetal group substituted thereon at the 5 position;
hydrolyzing said porphyrin having an acetal group substituted thereon to produce said 5-formylporphyrin.
2. The method of claim 1 , wherein said condensing step is carried out in a polar or nonpolar solvent in the presence of a Lewis acid followed by oxidation with 2,3-dichloro-5,6-dicyano-1,4-benzoquinone (DDQ).
3. The method of claim 1 , wherein said hydrolyzing step is carried out with a biphasic mixture of CH 2 Cl 2 , trifluoroacetic acid (TFA) and water at room temperature.
4. The method of claim 1 , wherein said dipyrromethane-1,9-dicarbinol is produced by reducing a 1,9-diacyldipyrromethane to form said dipyrromethane-1,9-dicarbinol.
5. The method of claim 1 , wherein said 5-acetaldipyrromethane is produced by the steps of:
reacting glyoxal with neopentyl glycol to provide a mixture of monoacetal and bis-acetal; and then
reacting said mixture with excess pyrrole to produce said 5-acetaldipyrromethane.
6. The method of claim 1 , wherein said dipyrromethane-1,9-dicarbinol has a surface attachment group substituted thereon at the 5 position.
7. The method of claim 6 , wherein said surface attachment group is selected from the group consisting of carboxylic acid, alcohol, thiol, selenol, tellurol, phosphono, alkenyl, and alkynyl surface attachment groups.
8. A method of making a 5,15-diformylporphyrin, comprising the steps of:
hydrolyzing a 5,15-diacetalporphyrin to produce said 5,15-diformylporphyrin.
9. The method of claim 8 , wherein said 5,15-diacetalporphyrin is produced by:
reducing a 5-acetal-1-acyldipyrromethane to produce a corresponding carbinol; and then
self-condensing said carbinol to produce said 5,15-diacetalprophyrin.
10. The method of claim 9 , wherein said 5-acetal-1-acyldipyrromethane is produced by:
acylating a 5-acetal-dipyrromethane with a pyridyl thioester to produce said 5-acetal-1-acyldipyrromethane.
11. The method of claim 10 , wherein said acyl group comprises a surface attachment group.
12. A method of making a 5,15-diacetalporphyrin, comprising the steps of:
acylating a dipyrromethane with a pyridyl thioester of the formula:
where R 1 is 2-pyridyl and R 2 is an acetal to produce a 1-(acetalcarbonyl)dipyrromethane;
reducing said 1-(acetalcarbonyl)dipyrromethane to produce a 1-(acetalcarbinol)dipyrromethane; and then
self-condensing said 1-(acetalcarbinol)dipyrromethane to produce a 5,15-diacetalporphyrin.
13. The method of claim 12 , further comprising the step of:
hydrolyzing said 5,15-diacetalporphyrin to produce a 5,15-diformylporphyrin.
14. The method of claim 12 , wherein said pyridyl thioester is produced by reacting an acetal-acid with 2,2′-dipyridyldisulfide and Ph 3 P to produce said pyridyl thioester.
15. A method of making a 5,10-diacetalporphyrin, comprising the steps of:
acylating a 1-(acetalcarbonyl)dipyrromethane to produce a 1-(acetalcarbonyl)-9-acyldipyrromethane;
reducing said a 1-(acetalcarbonyl)-9-acyldipyrromethane to produce a corresponding dicarbinol;
condensing said dicarbinol with a dipyrromethane to produce an intermediate;
oxidizing said intermediate to produce a 5,10-diacetalporphyrin.
16. The method of claim 15 , wherein said acyl group comprises a surface attachment group.
17. The method of claim 16 , wherein said surface attachment group is selected from the group consisting of carboxylic acid, alcohol, thiol, selenol, tellurol, phosphono, alkenyl, and alkynyl surface attachment groups.
18. The method of claim 15 , further comprising the step of:
hydrolyzing said 5,10-diacetalporphyrin to produce a 5,10-diformylporphyrin.
19. A 5-formylporphyrin having a surface attachment group substituted thereon at the 10 or 15 position, wherein said surface attachment group is a tripodal linker selected from the group consisting of:
1,1,1-tris[4-(S-acetylthiomethyl)phenyl]methyl,
4-{1,1,1-tris[4-(S-acetylthiomethyl)phenyl]methyl}phenyl,
1,1,1-tris[4-(dihydroxyphosphoryl)phenyl]methyl,
4-{1,1,1-tris[4-(dihydroxyhosphoryl)phenyl]methyl}phenyl,
1,1,1-tris[4-(dihydroxyphosphorylmethyl)phenyl]methyl, and
4-{1,1,1-tris[4-(dihydroxyphosphoiylmethyl)phenyl]methyl}phenyl.
20. A 5,15-diformylporphyrin having a surface attachment group substituted thereon at either or both of the 10 and 20 positions, wherein said surface attachment group is a tripodal linker selected from the group consisting of:
1,1,1-tris[4-(S-acetylthiomethyl)phenyl]methyl,
4-{1,1,1-tris[4-(S-acetylthiomethyl)phenyl]methyl}phenyl,
1,1,1-tris[4-(dihydroxyphosphoryl)phenyl]methyl,
4-{1,1,1-tris[4-(dihydroxyphosphoryl)phenyl]methyl}phenyl,
1,1,1-tris[4-(dihydroxyphosphorylmethyl)phenyl]methyl, and
4-{1,1,1-tris[4-(dihydroxyphosphorylmethyl)phenyl]methyl}phenyl.
21. A 5,10-diformylporphyrin having a surface attachment group substituted therein at either or both of the 15 and 20 positions wherein said surface attachment group is a tripodal linker selected from the group consisting of:
1,1,1-tris[4-(S-acetylthiomethyl)phenyl]methyl,
4-{1,1,1-tris[4-(S-acetylthiomethyl)phenyl]methyl}phenyl,
1,1,1-tris[4-(dihydroxyphosphoryl)phenyl]methyl,
4-{1,1,1-tris[4-(dihydroxyphosphoryl)phenyl]methyl}phenyl,
1,1,1 -tris[4-(dihydroxyphosphorylmethyl)phenyl]methyl, and
4-{1,1,1-tris[4-(dihydroxyphosphorylmethyl)phenyl]methyl}phenyl.