Novel Synthetic Methodology for Metalloporphyrins in Ionic Liquid

5,10,15,20-Tetraarylporphyrins undergo metalation with metal salts in the presence of reusable 1-hexyl-3-methylimidazolium bromide ([hmim][Br]) as solvent at room temperature to afford the corresponding metalloporphyrins in 80-98% yields.


Introduction
Heme proteins (which contain iron porphyrins) are ubiquitous in nature and serve many roles, including O 2 storage and transport (myoglobin and hemoglobin), electron transport (cytochromes b and c), and O 2 activation and utilization (cytochrome P450 and cytochrome oxidase). 1The metalloprphyrins with various transition metals have been used as synthetic chemical model systems to mimic heme proteins and other natural oxidation and oxygenation reactions. 2,35][6][7][8] Metalation is usually carried out in a carefully chosen solvent which can offer mutual solubility to both the metal salt and free-base porphyrin.However, these methods suffer from certain disadvantages such as rates of reactions are slow, yields are low and workup of the product for purification is troublesome.5][6] DMF as a solvent is known to decompose during reflux and results in the formation of dimethylamine during metalation which acts as a nucleophile and gives side products during metalation of porphyrins having electron withdrawing groups such as H 2 F 20 TPP. 7 The use of pyridine as solvent in the metalation reaction is discouraged as it forms complexes with metals of high charge and retards the metalation process. 8Hence, the environmental friendly synthesis of iron porphyrins and related metalloporphyrins has its importance in agrochemical, chemical and pharmaceutical industries.

Results and Discussion
The free-base 5,10,15,20-tetraarylporphyrins (1-5) used in this study were prepared according to the reported procedure. 14,15The metalloporphyrins (6-15) have been prepared by simple stirring of the porphyrins with metal salts in [hmim][Br] ionic liquid (Table 1, Scheme 1).The metalation of free base porphyrins 1-5 was studied with different metal salts in [hmim] [Br].The separation of metalloporphyrins from the reaction mixture was easy and the recovered ionic liquid was further used for other reactions.It has been observed that the ionic liquid was found to be active even after eight runs.Hence, this metalation process offers less health and environmental hazards than the traditional used solvents such as chlorinated solvents and DMF.5][6] On the formation of a metallporphyrin, in most of the cases, the four banded spectrum collapses into an essentially two-banded one in visible region, whereas the soret may remain in the usual range or shifted to higher or lower energy depending upon the metal used. 16Interestingly, the bromide ion present in the reaction mixture does not get exchanged with the axial chloride of the metallated porphyrins (6-15) as confirmed by the far IR spectra.The presence of peak at 294 cm -1 in
the far IR of manganese complex of H 2 TPP with MnCl 2 indicated that the axial ligand is chloride.
In conclusion, we have developed a simple, convenient and eco-friendly method for the metallation of porphyrins in reusable ionic liquid in high yields.The method avoids the use of organic solvents, excess of metal salts and refluxing at high temperature.The ionic liquids have been used as alternative of organic solvents.

Experimental
The purities of the compounds were determined on silica-coated Al plates (Merck).The electronic spectra were recorded on a Shimadzu UV-260 UV-visible spectrophotometer and the absorption maxima are expressed in nanometers (nm).

General procedure for the reaction of porphyrin with metal salt
The porphyrin (0.5 mmol) and metal salt (0.6 mmol) were stirred at room temperature in [hmim][Br] ionic liquid (15 mL) for one hour.After completion of the reaction as indicated by the TLC, the mixture was extracted with Et 2 O (5×20 mL).The combined ether layers were washed with water (2×20 mL) and dried (Na 2 SO 4 ), concentrated in vacuum to afford the metallated compound, which was further purified by column chromatography using chloroform as eluting solvent.The rest of the viscous ionic liquid was further washed with Et 2 O and dried under reduced pressure to retain its activity in subsequent runs.

Table 1 .
Yields and UV-Visible spectroscopic data of metalloporphyrins prepared a Isolated yield.