Methods and intermediates for the synthesis of porphyrins

1. A method of making a porphyrin of Formula I:

wherein:

A is aryl;

B is H, alkyl, alkenyl, alkynyl, cycloalkyl, cycloalkylalkyl, cycloalkylalkenyl, cycloalkylalkynyl, aryl, arylalkyl, arylalkenyl, arylalkynyl, alkoxy, halo, mercapto, azido, cyano, hydroxyl, nitro, acyl, alkoxy, alkylthio, amino, alkylamino, arylalkylamino, disubstituted amino, acylamino, acyloxy, amide, sulfonamide, urea, alkoxylacylamino, aminoacyloxy, hydrophilic groups, surface attachment groups, cross-coupling groups or bioconjugatable groups;

R 1 is selected from the group consisting of H, alkyl and aryl;

R 2 , R 3 , R 4 , R 5 , R 7 , R 8 , R 9 , and R 10 are each independently selected from the group consisting of H, halo, loweralkoxy, and loweralkylthio; and

M is a metal or a pair of hydrogen atoms;

said method comprising:

(a) condensing (i) a bis(imino)dipyrromethane of Formula II:

wherein:

R is alkyl, alkenyl, alkynyl, cycloalkyl, cycloalkylalkyl, cycloalkylalkenyl, cycloalkylalkynyl, aryl, arylalkyl, arylalkenyl, arylalkynyl, alkoxy, or acyl; and

A, R 1 , R 2 , R 3 , R 4 , and R 5 are as given above, with (ii) a dipyrromethane of Formula III:

wherein B, R 7 , R 8 , R 9 and R 10 are as given above in an organic solvent containing a metal salt to produce a reaction product; then

(b) optionally oxidizing said reaction product with an oxidizing agent; and then

(c) optionally demetallating said reaction product to produce the porphyrin of Formula I.

2. The method of claim 1 , wherein said alcohol is selected from the group consisting of methanol, ethanol, propanol, isopropanol, chloroform, tetrahydrofuran, dichloromethane, toluene, and mixtures thereof.

3. The method of claim 1 , wherein said metal salt is a zinc, palladium, copper, nickel or cobalt salt.

4. The method of claim 1 , wherein said oxidizing agent is selected from the group consisting of DDQ, p-chloranil, and o-chloranil.

5. The method of claim 1 , wherein A is an aromatic hydrophilic group, an aromatic surface attachment group, an aromatic cross-coupling group, or an aromatic bioconjugatable group.

6. The method of claim 5 , wherein A is an aromatic alkene, alkyne, alcohol, thiol, selenyl, phosphono, carboxylic acid, formyl, halo or amine containing-group.

7. The method of claim 1 , wherein B is a hydrophilic group, surface attachment group, cross-coupling group, or bioconjugatable group.

8. The method of claim 7 , wherein B is an alkene, alkyne, alcohol, thiol, selenyl, phosphono, carboxylic acid, formyl, halo or amine group.

9. The method of claim 1 , wherein:

A is a bioconjugatable group and B is a hydrophilic group; or

A is a hydrophilic group and B is a biconjugatable group.

10. The method of claim 1 , wherein R 2 , R 3 , R 4 , R 5 , R 7 , R 8 , R 9 , and R 10 are each independently selected from the group consisting of H and halo.

11. The method of claim 1 , wherein R 2 , R 3 , R 4 , R 5 , R 7 , R 8 , R 9 , and R 10 are each H.