Meldrum's acid as an excellent catalyst for the facile, efficient and one-pot synthesis of N ,3-diarylimidazo[1,2-a ]pyridin-2-amines

Using the three-component reaction between aryl glyoxals, arylamines

In this regard, and in continuation of our previous work on the development of multicomponent reactions for the synthesis of imidazole compounds, 29 we herein describe a facile and efficient strategy for the synthesis of N,3-diarylimidazo [1,2-a]pyridin-2-amines via the one-pot, three-component reaction of aryl glyoxals, arylamines, and 2-aminopyridine in the presence of Meldrum's acid in ethanol at room temperature.
Table1.Synthesis of N,3-diarylimidazo [1,2-a]pyridin-2-amine 4a-j and 3-aryl-N-(pyridin-2-yl)imidazo [ a Isolated yields To the best of our knowledge, all the synthesized compounds are unknown and were characterized by 1 H and 13 C NMR, IR, CHN analysis, and melting points.The detailed spectroscopic data, presented in the Experimental, are in agreement with the assigned structures.
A proposed mechanism for the formation of compounds 4a-j and 5a-c is shown in Scheme 1.The compounds 4a-j are formed in three steps.Initially, an intermediate A is prepared from the condensation of aryl glyoxal 1 and arylamine 2. Subsequently, compound B is produced through nucleophilic addition of 2aminopyridine 3 to the intermediate A. In continuation, compounds 4a-j result from intramolecular cyclization the pyridine ring nitrogen to the carbonyl group and elimination of water.To explain the formation of 5a-c, it is suggested that firstly, condensation occurs between aryl glyoxal and 2-aminopyridine, and intermediate C is formed.Then, a second molecule of 2-aminopyridine, instead of arylamine, adds to C, leading to the intermediate D.Then, an intramolecular cyclization occurs, as in the formation of compounds 4, and 5a-c are obtained with the elimination of water.

Scheme 1. Proposed mechanism for the preparation of compounds 4a-j and 5a-c
Further studies showed that Meldrum's acid is an excellent catalyst for the formation of only product N,3diarylimidazo[1,2-a]pyridin-2-amines 4 in the above reaction.For this purpose, a mixture of aryl glyoxal (1, 1.0 mmol), arylamine (2, 1.0 mmol), and 2-aminopyridine (3, 1.0 mmol) in the presence of Meldrum's acid (0.3 mmol) in EtOH (5.0 mL) were reacted at room temperature, when only the products 4 were obtained (Table 2).a Isolated yields When Meldrum's acid is used as a catalyst for the above reaction, it is proposed that there are two pathways, shown in Scheme 2, for the formation of N,3-diarylimidazo [1,2-a]pyridin-2-amines 4a-k.Scheme 2. Proposed mechanism of the formation of 4a-k in the presence of Meldrum's acid as catalyst.
In the sequence shown on the right, 4a-k are formed in five steps.Initially, an intermediate A is formed from the Knoevenagel condensation of the aryl glyoxal 1 with Meldrum's acid.Subsequently, nucleophilic addition of arylamine 2 to the intermediate A leads to compound B. In continuation, with the help of nitrogen nonbonding pair, the Meldrum's acid group is removed and an intermediate of C is obtained.Then, compound D is obtained by Michael's addition of 2-aminopyridine to intermediate C, and finally, intramolecular cyclization and elimination of water leads to compounds 4a-k.Alternatively, as shown on the left in Scheme 2, initially intermediate A is formed as before.Subsequently, compound E is formed through nucleophilic addition of 2-aminopyridine 3 to the intermediate A. In continuation, with the help of the nitrogen nonbonding pair, the Meldrum's acid group is removed and intermediate F is obtained.Next, by Michael's addition of arylamine to intermediate F, compound D is obtained.In the final stage, intramolecular cyclization, followed by the removal of a molecule of H2O, leads to compounds (Scheme 2).
A comparison of the data presented in Tables 1 and 2 clearly shows that the use of Meldrum's acid has (i) considerably enhanced the yields of the products (from 53-65% to 72-89%) and (ii) reduced the reaction time from 4-8 h to 1.5-2 h.Also, no by-product (5) was formed in the method using Meldrum's acid.

Conclusions
We have successfully prepared new N,3-diarylimidazo[1,2-a]pyridin-2-amines, which were synthesized by the one-pot, three-component reaction of aryl glyoxals, arylamines, and 2-aminopyridine in the presence of Meldrum's acid as a catalyst.The advantages of the reaction are the simple reaction conditions, using cheap and readily available starting materials, high yields, and short reaction times.Moreover, the participation of Meldrum's acid makes this process highly efficient.

Experimental Section
General.All chemicals were purchased from Aldrich and Merck with high-grade quality and used without any purification.All products were obtained by reaction at room temperature in ethanol as solvent.All melting points were obtained by Barnstead Electro thermal 9200 apparatus and are uncorrected.IR spectra were recorded on a Bruker FT-IR Equinax-55 spectrophotometer in KBr with absorption in cm -1 .The NMR spectra were recorded on a Varian model UNITY Inova 500 MHz spectrometer ( 1 H: 500, 13 C: 125 MHz) in CDCl3 using TMS as an internal standard.Elemental analyses were performed using a Carlo Erba EA 1108 instrument.All products were characterized by their spectral and physical data.