A new procedure to synthesize the N-substituted pyrrole derivatives by Clauson Kaas reaction catalyzed by acidic ionic liquid under microwave irradiation was developed. This procedure provides several advantages such as high yield, clean product formation, and short reaction time.
Pyrrole derivatives have great importance in organic chemistry, because they are present in many compounds which were natural, medicinal, and agricultural products and semiconductor polymers [
Using microwaves for carrying out reactions is advantageous for the synthesis of numerous types of compound. The most important improvements with this technique are reduced reaction time, cleaner reactions due to fewer side reactions, and the use of minimal quantities of solvent [
Ionic liquids (ILs) have been widely used in organic reactions as solvent due to their advantages such as negligible vapor pressure, variable polarity, and good solvating ability [
All reagents were of commercial quality, and reagent quality solvents were used without further purification. IR spectra were determined on a Perkin Elmer, Spectrum One FT-IR spectrometer. NMR spectra were recorded on Mercury VX-400 MHz and Bruker Avance III 500 MHz spectrometer. Chemical shifts
Amine (1 mmol) was added to 2,5-dimethoxytetrahydrofuran (1 mmol or 2 mmol for amine 2b) in [hmim][HSO4] (1 mmol) and mixed thoroughly. The mixture was then exposed to microwave irradiation (90 W) for a period of time enough to complete the reaction. The reaction mixture was dissolved in water, and the product was extracted with diethyl ether (3
Colorless liquid (85% yield). [
Colorless oil (91% yield). IR (neat):
Colorless oil (73% yield). [
Colorless oil (69% yield). [
Colorless oil (89% yield). [
Colorless oil (91% yield). [
Yellow oil (83% yield). [
Yellow oil (81% yield). [
White solid, mp. 44-45°C; Lit. 44.5–46°C [
The acidic ionic liquid [hmim][HSO4] was prepared under microwave irradiation starting from [hmim][Br] according to the literature procedure [
The catalytic activity of [hmim][HSO4] was compared with those of acetic acid, [bmim][BF4], and [hmim][H2PO4], which was prepared by the same procedure with [hmim][HSO4], under the optimum conditions. As one can see from the results shown in the Table
Comparison of the catalytic activity of the catalysts.
Catalyst | Time (min) | Yield (%) |
---|---|---|
CH3CO2H | 80 | 52 |
|
30 | 56 |
|
30 | 61 |
|
60 | 73 |
|
4 | 85 |
aWithout MW.
In a typical reaction procedure, 2,5-dimethoxytetrahydrofuran (1 mmol), equimolar amount of amine, and [hmim][HSO4] were mixed, and the mixture was exposed to microwave irradiation (90 W) for a period of time enough to complete the reaction. The reaction mixture was dissolved in water, and the product was extracted with diethyl ether and purified by column chromatography. To check the reusability of the ionic liquid, water was removed from the aqueous layer under vacuum, and the residue was washed with diethyl ether and dried under vacuum. Decreasing in the yield of pyrrole was seen after recycling of ionic liquid. The main problem with the Clauson Kaas reaction is the decomposition of acid sensitive derivatives, especially derived from amino acids. Using this procedure, various amine compounds such as aliphatic amines, amino acid esters, amino alcohols, and heteroaromatic amine were converted to their pyrrole derivatives without any significant decomposition (Scheme
The synthesized pyrrole derivatives.
Amine ( |
Pyrrole ( |
Reaction time (min) | Yield (%)a |
---|---|---|---|
|
|
4 | 85 |
|
|
4 | 91 |
|
|
3 | 73 |
|
|
3 | 69 |
|
|
5 | 89 |
|
|
5 | 91 |
|
|
5 | 83 |
|
|
5 | 81 |
|
|
25 | 72 |
aIsolated yield.
The synthesis of N-substituted pyrroles catalyzed by [hmim][HSO4].
In conclusion, efficient synthesis of N-substituted pyrrole derivatives has been achieved by Clauson Kaas reaction catalyzed by acidic ionic liquid under microwave irradiation. This new method provides a clean, fast, high yielded, environmentally friendly, and effective way to pyrroles without any significant decomposition of acid sensitive derivatives.