The two-step mechanochemical synthesis of porphyrins

Abstract

Porphyrin synthesis under solvent-free conditions represents the “greening” of a traditional synthesis that normally requires large amounts of organic solvent, and has hindered industrial-scale synthesis of this useful class of molecules. We have found that the four-fold acid-catalysed condensation of aldehyde and pyrrole to yield a tetra-substituted porphyrin is possible through mechanochemical techniques, without a solvent present. This represents one of the still-rare examples of carbon-carbon bond formation by mechanochemistry. Specifically, upon grinding equimolar amounts of pyrrole and benzaldehyde in presence of an acid catalyst, cyclization takes place to give reduced porphyrin precursors (reversible), which upon oxidation form tetraphenylporphyrin (TPP). The approach has been found suitable for synthesis of a variety of meso-tetrasubstituted porphyrins. Oxidation can occur either by using an oxidizing agent in solution, to give yields comparable to those published for traditional methods of porphyrin synthesis, or through mechanochemical means resulting in a two-step mechanochemical synthesis to give slightly lower yields that are still being optimized. We are also working on “green” methods of porphyrin isolation, including entrainment sublimation, which would hopefully further reduce the need for large amounts of organic solvent. These results hold promise for the development of mechanochemical synthetic protocols for porphyrins and related classes of compounds.

Systematic studies on mechanochemical synthesis: Schiff bases from solid aromatic primary amines and aldehydes

“…In a recent Faraday discussion‐themed issue on “ Mechanochemistry: From Functional Solids to Single Molecules, ” the mechanochemistry of organic molecules, soft materials and pharmaceuticals, the mechanochemistry of inorganic compounds and coordination‐based materials, sonication and macromolecular mechanochemistry, current theoretical models for mechanochemical reactions, the mechanistic and kinetic understanding, catalysis, and scaling up of mechanochemistry were broadly discussed …”

Organic Synthesis without Conventional Solvents

“…[13] This challenge was addressed by direct sublimation of the product from the solid reaction mixture, e.g. in the synthesis of nitrosobenzenes [44] and porphyrins, [45] avoiding the use of a solvent for product isolation.…”

Mechanochemistry for Organic Chemists: An Update

“…In N , N ‐dimethylformamide solution such transformations typically require hours or days at reflux, but ball milling provided complexes of Zn, Cu, and Ni after 20–90 min, without excessive use of a base or solvent. The clean, efficient synthesis of the actual porphyrin ligands, which is a particularly challenging area of synthesis, was demonstrated by the Hamilton group . Mechanochemistry has been used with great success for the synthesis of covalent crystalline polymers, macrocycles, and cages.…”