A Facile Synthesis of Polysubstituted Pyrroles by One-Pot Three-Component Reaction

A new and efficient one-pot synthesis of polysubstituted pyrrole derivatives by three-component reaction between dialkyl acetylenedicarboxylates, triphenylphosphine, 2-aminopyridin derivatives in the presence of arylglyoxals is described. The reactions were performed in dichloromethane at room temperature and neutral conditions and afforded high yields of products.


Introduction
6][7] They are also valuable intermediates in organic synthesis. 2,8Various pyrrole derivatives are widely used as organic conducting materials. 91][12][13] However, many of the methods are associated with various drawbacks such as harsh reaction conditions, tedious experimental procedures, unsatisfactory yields, and long reaction times.Moreover, the number of methods for the synthesis of polysubstituted pyrroles is relatively limited.
Addition reaction between phosphines and activated carbon-carbon triple bonds is well known to produce a reactive zwitterionic intermediate, which may be trapped by various electrophiles.14-18 Reaction of triphenylphosphine with dialkyl acetylenedicarboxylates (DAAD's) has been studied in the presence of a variety of organic acidic compounds, in order to trapp the zwitterionic intermediate.][21][22][23] Keeping in mind the biological importance of pyrrole ring and in continuation of our current studies on the development of new routes in heterocyclic synthesis, [23][24] in this letter we report a simple and efficient synthesis of some functionalized pyrrole.Thus, threecomponent reaction between triphenylphosphine 1, 2-aminopyridin derivative 2, dialkyl acetylenedicarboxylates 3 in the presence of arylglyoxals 4 at ambient temperature in dichloromethane, leads to substituted pyrrole derivatives 5 in good yields (Figure 1).

Experimental
Melting points were determined with an electrothermal 9100 apparatus.Elemental analyses were performed using a Heraeus CHN-O-Rapid analyzer.Mass spectra were recorded on a FINNIGAN-MAT 8430 mass spectrometer operating at an ionization potential of 70 eV.IR spectra were recorded on a Shimadzu IR-470 spectrometer. 1 H and 13 C NMR spectra were recorded on Bruker DRX-500 Avance spectrometer at solution in CDCl 3 using TMS as internal standard.The chemicals used in this work purchased from Fluka (Buchs, Switzerland) and were used without further purification.

General Procedure
To a magnetically stirred solution of triphenylphosphine (1 mmol) and 2-aminopyridin derivatives (1 mmol) in dichloromethane (10 mL) was added dropwise a mixture of dialkyl acetylenedicarboxylate (1 mmol) in dichloromethane (3 mL) at room temperature over 5 min.The reaction mixture was then stirred for 10 minute.Arylglyoxal (1 mmol) was added and the reaction mixture was stirred for more 24 hours.Solvent was evaporated and the residue was purified by column chromatography on silica-gel using ethyl acetate-hexane (1:4) mixture as eluent.
Figure 2 Suggested mechanism for formation of compound 5a.
To explore the scope and limitations of this reaction further, we extended our studies to the reaction of various dialkyl acetylenedicarboxylates and 2-aminopyridin derivative with arylglyoxals (Table 1 The structures of compounds 5a-e were deduced from their elemental analyses and their IR, 1 H NMR, 13 C NMR spectra.The 1 H NMR spectrum 5a exhibited three sharp signals at δ = 3.85, 3.88 and 7.33 ppm for two methoxy groups protons and the proton of pyrrole ring, respectively.The aryl moiety exhibited characteristic signals in the aromatic region of the spectrum.The 13 C NMR spectrum of compound 6a showed 17 distinct resonances in agreement with the proposed structure.

Conclusion
In conclusion here we reported a three-component reaction between dialkyl acetylenedicarboxylates, 2-aminopyridin derivatives and arylglioxals promoted by triphenylphosphine, to produce functionalized pyrrole derivatives in high yields.The present method carries the advantage that, not only is the reaction performed under neutral conditions, but also the substances can be mixed without any activation or modification.The simplicity of the present procedure makes it an interesting alternative to complex multi-step approaches.