One-pot, three component reactions between isocyanides and dialkyl acetylenedicarboxylates in the presence of phenyl isocyanate: synthesis of dialkyl 2-(alkyl/arylimino)-2,5-dihydro-5- oxo-1-phenyl-1H-pyrrole-3,4-dicarboxylate

The reactive 1:1 adduct, generated from the reaction between alkyl/aryl iscyanides and dialkyl acetylenedicarboxylates, was trapped by phenyl isocyanate to yield dialkyl 2-(alkyl/arylimino)2,5-dihydro-5-oxo-1-phenyl-1H-pyrrole-3,4-dicarboxylate in good yields.


Result and Discussion
The structure of compounds 3a-h was deduced from their IR, 1 H NMR, 13 C NMR, mass spectral data, HRMS data and elemental analysis.The mass spectra of these compounds 3a-h displayed molecular ion peaks at appropriate m/e values.The 1 H NMR spectrum of compound 3a exhibited a multiplet for the five CH 2 of cyclohexyl ring (δ 1.49-1.81ppm), a multiplet for the N-CH cyclohexyl proton (δ 3.78 ppm), two singlet for the methoxy groups (δ 3.96 and 3.99 ppm).The aromatic hydrogens gave rise to characteristic multiplet signal in the aromatic region of the spectrum (δ 7.23-7.43ppm).
The 13 C NMR spectrum of 3a showed sixteen distinct resonances in agreement with proposed structure.The characteristic signal due to the amide carbonyl group was discernible at δ 148.0 ppm.Carbons of imino and two ester carbonyls resonated at δ 147.6, 160.3 and 160.6 ppm, respectively.Partial assignment of these resonances is given in the experimental data.Dimethyl 2-(cyclohexylimino)-2,5-dihydro-5-oxo-1-phenyl-1H-pyrrole-3,4-dicarboxylate 3a was obtained as a orange powder.Its molecular formula, C 20 H 22 N 2 O 5 , was determined on the basis of the positive HRESIMS at m⁄z 393.1435 [M+Na] + (calcd 393.1426) and supported by the 1 H , 13 C NMR and IR spectra.
The IR spectra of 3a showed strong absorptions at 1718 and 1750 cm -1 due to the ester carbonyls and also at 1656 cm -1 because of the carbonyl of amide.The 1 H and 13 C NMR spectra of 3b-h are similar to 3a and the results are described in experimental section.
Mechanistically, it is conceivable that the reaction involves the initial formation of a 1:1 zwitterionic intermediate 4 in accord with reaction between alkyl/aryl isocyanide 1 and dialkyl acetylenedicarboxylate 2. Nucleophilic addition of 4 to the carbonyl group of phenyl isocyanate formed a dipolar species 5. Cyclization of the latter leads to the 2,5-dihydro-5-oxo-1-phenyl-1Hpyrrole derivatives 3 (Scheme 2).
In this work, we used two factors to generated pyrrole derivatives, first, temperature factor by refluxing in CH 2 Cl 2 at 38 ºC and the second, time factor between 24-48 hours.Therefore we have developed a one-pot three-component reaction between alkyl/aryl isocyanides 1 and dialkyl acetylenedicarboxylate 2 in the presence of phenyl isocyanate for the preparation of dialkyl 2-(alkyl/arylimino)-2,5-dihydro-5-oxo-1-phenyl-1H-pyrrole derivatives 3a-h.Scheme 2. mechanism for the formation of compound 3.

Conclusions
In summary, we have found that the reaction of alkyl/aryl isocyanides with dialkyl acetylenedicarboxylates in the presence of phenyl isocyanate leads to the one-pot and simple synthesis of highly functionalized 2,5-dihydro-5-oxo-1-phenyl-1H-pyrrole derivatives.The present method carries the advantages that, not only is the reaction performed under neutral conditions, but the substances can be mixed without any activation or modification.

Experimental Section
General.Cyclohexyl isocyanide, t-butyl isocyanide, 2,6-dimethylphenyl isocyanide, dialkyl acetylenedicaboxylates and phenyl isocyanate were purchased from Fluka and Aldrich and used without further purification.Melting points and IR spectra were measured on an Electrothermal 9100 apparatus and a JASCO FT-IR spectrometer, respectively.The 1 H and 13 C NMR spectra were recorded on a BRUKER DRX-400 and 500 AVANCE instrument with CDCl 3 as solvent at 400.1 MHz ( 1 H NMR), 100.6 and 125.7 MHz ( 13 C NMR).Mass spectra were recorded on a Shimadzu GC/MS QP 1100 EX mass spectrometer operating at an ionization potential of 70 eV.Elemental analyses for C, H and N using a Heraeus CHN-O-Rapid analyser were carried out at the Iranian Central Research of Petroleum Company.High resolution mass spectra (HRMS) were recorded on a Waters LCT Premier XW (ESI-TOF MS) spectrometer at Research School of Chemistry, Australian National University, Canberra ACT 0200, Australia.