Pyrroles and related compounds-XXXV. A stepwise, general synthesis of unsymmetrically substituted porphyrins

Using a new, general approach involving the stepwise progression through pyrrole, dipyrrole, tripyrrole, to tetrapyrrole, followed by cyclisation of the resulting a,c-biladiene by the copper salt method, syntheses of isocoproporphyrin tetramethyl ester (1b), coproporphyrin-III tetramethyl ester (24), protoporphyrin-IX dimethyl ester (26), 2,4,6,7-tetrakis (2-methoxycarbonylethyl)-5-methoxycarbonylmethyl-1,3,8-trimethylporphin (29) (the ester of the pentacarboxylic porphyrin recently associated with haem metabolism), rhodoporphyrin-XV dimethyl ester (27) and 2,4,7-triethyl-6-methoxycarbonyl-1,3,5,8-tetramethylporphin (28), are described. The route employs condensation of unsymmetrically substituted pyrromethanes with 2-formyl-5-methylpyrroles to give crystalline and fully characterised tripyrrene salts in high yield. These are then condensed with a second mole of a different 2-formyl-5-methylpyrrole to give very high yields of a,c-biladiene dihydrobromides; cyclisation with copper(II) chloride indimethylformamide gives copper(II) porphyrins which are demetallated in trifluoroacetic acid containing sulphuric acid to give high overall yields of the corresponding metal free porphyrins. © 1976