Trifluoroacetic Acid Catalyzed One-Pot Four-Component Domino Reaction for the Synthesis of Substituted Dihydro 2-Oxypyrroles

Abstract

Trifluoroacetic acid was applied as an efficient catalyst for the one-pot four-component synthesis of N-aryl/alkyl-3-aminodihydropyrrol-2-one-4-carboxylates via the domino reaction of amines, formaldehyde and dialkyl acetylenedicarboxylates at ambient temperature in methanol. This methodology includes number of advantages such as: short reaction time, clean work-up, use of inexpensive catalyst, high yields and clean work-up. The work-up of this reaction involves only a filtration and a simple washing step with MeOH, and there is no need for column chromatography.

Synthetic Approaches to Novel Human Carbonic Anhydrase Isoform Inhibitors Based on Pyrrol-2-one Moiety

“…All of the compounds were obtained in good yields (between 47 and 88%) and bidimensional correlation experiments provided the clear proton and carbon signal assignments for all novel compounds that are detailed in the Experimental Section. As support of the Experimental Section, in the Supporting Information (SI) are presented 1 H, 13 C, 19 F, 1 H, 13 C HMBC, 1 H, 15 N-HMBC, IR, and matrix-assisted laser desorption ionization-mass spectrometry (MALDI-MS) spectra of some representative novel compounds.…”

“…For the majority of investigated benzenesulfonamide derivatives, most of the proton and carbon atoms have resonance signals in the low-field regions: above 6 ppm in 1 H NMR and 100 ppm in 13 C NMR spectra. Proton and proton− carbon spin systems information was obtained from homo-and heteronuclear bidimensional correlation experiments like H,H-COSY, H,C-HSQC, and H,C-HMBC.…”

“…Proton and proton− carbon spin systems information was obtained from homo-and heteronuclear bidimensional correlation experiments like H,H-COSY, H,C-HSQC, and H,C-HMBC. Four doublets in the range of 7.40−7.90 ppm in the 1 H NMR spectra (as an example 1 H NMR spectrum of compound 1 in Figure S1 and Experimental Section), exhibiting the roof-effect characteristic of para-substitution, were easily attributed to the two nonequivalent para-benzenesulfonamide rings. Throughout this series, their presence in 1 H NMR spectra was a fast indicator for the formation of derivatives with the pyrrol-2(5H)-one cycle.…”

“…Four doublets in the range of 7.40−7.90 ppm in the 1 H NMR spectra (as an example 1 H NMR spectrum of compound 1 in Figure S1 and Experimental Section), exhibiting the roof-effect characteristic of para-substitution, were easily attributed to the two nonequivalent para-benzenesulfonamide rings. Throughout this series, their presence in 1 H NMR spectra was a fast indicator for the formation of derivatives with the pyrrol-2(5H)-one cycle. For almost all investigated compounds, the two protons from the pyrrol-2(5H)-one cycle appear in the interval 6.20−6.80 ppm as doublets with a 2 or 3 Hz vicinal coupling constant (Figures S1−S6 and Experimental Section).…”

Use of Dialkyl Acetylenedicarboxylates in the Multicomponent Synthesis of Heterocyclic Structures

“… in the presence tartaric acid as a eco‐friendly and di‐functional Brønsted acid catalyst in methanol at room temperature (Table 1 , Entry 1), [22] in the presence of lactic acid as catalyst in ethanol at room temperature (Table 1, Entry 2), [23] using graphene oxide in ethanol at room temperature (Table 1, Entry 3), [24] in the presence of CF 3 CO 2 H (20 mol %) in methanol at room temperature (Table 1, Entry 4), [25] in the presence of citric acid in methanol at room temperature (Table 1, Entry 5), [26] using caffeine in methanol at room temperature (Table 1, Entry 6), [27] using ZnCl 2 (15 mol %) as a Lewis acid catalyst in methanol at room temperature (Table 1, Entry 7), [28] using formic acid as a natural green and bio‐based catalyst in methanol at room temperature (Table Figure 1, Entry 8), [29] in the presence of nano‐Fe 3 O 4 @SiO 2 / SnCl 4 in EtOH at 60 °C (Table 1, Entry 9), [30] and using [TMBSED][OMs] 2 (20 mol %) ethanol at room temperature (Table 1, Entry 10) [31] . using Zn(SO 4 ) 2 ⋅ 7H 2 O as catalyst, in methanol at room temperature (Table 1, Entry 11) [32] .…”