A Novel Method for the Synthesis of Dipyrromethanes Under Solvent-Free Condition

As we know, green chemistry is defined as the design of chemical products and processes that reduce or eliminate the use and generation of hazardous substances. For the purposes of this definition, synthetic chemists have great interest in developing highly efficient transformations for the preparation of organic compounds. One of the main themes of contemporary synthetic organic chemistry is the use of environmentally feasible reagents particularly in solvent-free conditions and environmentally benign catalytic systems, which are also required to be efficient and economic. Solvent-free organic reactions are usually rapid, eco-friendly, high yielding, and economically viable. In this context, organic reactions under solvent-free conditions at room temperature have been achieved.


Introduction
As we know, green chemistry is defined as the design of chemical products and processes that reduce or eliminate the use and generation of hazardous substances.For the purposes of this definition, synthetic chemists have great interest in developing highly efficient transformations for the preparation of organic compounds.One of the main themes of contemporary synthetic organic chemistry is the use of environmentally feasible reagents particularly in solvent-free conditions and environmentally benign catalytic systems, which are also required to be efficient and economic.Solvent-free organic reactions are usually rapid, eco-friendly, high yielding, and economically viable.In this context, organic reactions under solvent-free conditions at room temperature have been achieved.
Dipyrromethanes are compounds known for more than a century and are widely being used as important building blocks for the synthesis of porphyrins 1 , Calixpyrrols 2 and Corroles 3 .Which have recent applications as chiral catalysts, chiral sensors, synthetic receptors for small molecular devices, potential sensitizers for photodynamic cancer therapy [4][5][6] .In the past decades, a variety of conditions have been established for the synthesis of dipyrromethanes in the presence of various catalysts such as p-toluenesulfonic acid 7,8 , TiCl 4 9 , CF 3 COOH [10][11][12] , pyrrolidinium tetrafluoroborate 13 .Recently, several methods have been developed, for the synthesis of dipyrromethanes in various catalysts such as ionic liquid [Hmim] BF 4   14   , HCL/water 15 , cation exchange resin 16 , metal triflate catalysis 17  , InCl 3 20 and methanesulfonic acid 21 .However, all of the synthetic protocols reported so far suffer from disadvantages such as, use of metal 17 and expensive reagent 16 , prolonged reaction time 18 , use of organic solvent 19 , harsh reaction condition 18,21 , use of excess pyrrole 17 and low yield . 14 , because of that the researcher still continuous to have a better methodology for the synthesis of dipyrromethanes in terms of simplicity, ecofriendly, economic viability and high yielding at lowest pyrrole/aldehyde ratio.This is achieved by using iodine under solvent free condition.In recent years I 2 in solvent free conditions was found to be an efficient catalyst in terms of handling, temperature, reaction time and yield for various organic transformations [22][23][24][25] .

Experimental
Purity of the compounds were checked by thin layer chromatography (TLC) on Merck silica gel 60 F254 pre-coated sheets Melting points of the synthesized compounds were determined in open-glass capillaries on a stuart-SMP10 melting point apparatus. 1H-NMRs were recorded on a Bruker spectrometer operating at 200 MHz.The 1 H-NMR chemical shifts are reported as parts per million (ppm) downfield from TMS (Me 4 Si) used as an internal standard.Mass spectra were recorded on LCQ ion trap mass spectrometer.
All compounds were known, and all physical and spectroscopic data were compared with authentic samples.

General Procedure for the synthesis of dipyrromethanes
A mixture of pyrrole (2 mmol), ketone (1 mmol) and I 2 (0.1 mmol) was crushed in a mortar with a pestle at room temperature.Progress of reaction was monitored by TLC.After completion of reaction (< 1 min) the crude product was washed with water, dried and purified by column chromatography using silica gel with petroleum ether/chloroform as the eluent.Pure products were obtained as solids.

Results and Discussion
We began our study by grinding the mixture of pyrrole (2 mmol) ketone (1 mmol) and iodine (0.1 mmol) under solvent free condition (Scheme 1).The result demonstrated that this protocol gives excellent yield of the product.Thus, from this result it was cleared that there is no need of solvent for the synthesis of dipyrromethanes.In this protocol iodine plays excellent role as a Lewis-acid catalyst, because its absence did not conduce to the desired product.
The generality of the reaction was authenticated by taking various ketones with pyrrole under solvent free condition (scheme 2).
The results demonstrated that all products give excellent yield (90-97%).When we compared this result with literature best result (Table 1) then it was cleared that all reported literatures were suffered from disadvantages such as expensive reagent 14 , prolonged reaction time 21 , use of hazardous catalyst 15,21 and use of excess pyrrole/aldehyde ratio 14,21 .Thus, in this article our strength is that we overcome all this disadvantages with excellent yield.The probably mechanism for synthesis of substituted dipyrromethanes has shown in scheme 3.
Scheme 3. The probably mechanism for the synthesis of dipyrromethanes.

Et
Me 94 56 [14] a: Isolated yield of the products.

Conclusion
In conclusion, a simple and efficient procedure for the synthesis of dipyrromethanes has been explored.Mild reaction conditions, absence of solvent, shorter reaction time, easy and quick isolation of the products and excellent yields are main advantages of this procedure, which make this method economically and environmentally attractive.

Table 1 .
Comparison of the yields with best methods found in the literatures.