3.2.1. General Procedure for the Synthesis of Pyrroles

The synthesis of pyrrole derivatives 1–3 was accomplished through a one-pot reaction, as shown in Scheme 2, according to our previous study [31]. A mixture of a suitable aldehyde (1.0 mmol), enolizable ketone (1.0 mmol), and lithium hydroxide monohydrate (0.1 mmol) in absolute ethanol (3 mL) was stirred at room temperature. The progress of the reaction was monitored by TLC. After the completion of the reaction, p-tosylmethyl isocyanide (2.4 mmol) and lithium hydroxide monohydrate (2.2 mmol) were added and the reaction mixture was stirred at room temperature for approximately 24 h. The precipitate was filtered, washed with cold water, and recrystallized from appropriate solvents.

(E)-(4-chlorophenyl) (4-(4-(dimethylamino)styryl)-1H-pyrrol-3-yl)methanone (1): The aforementioned general method was followed with minor modifications. In the second step, 2.7 mmol of lithium hydroxide monohydrate and 2.4 mmol of p-tosylmethyl isocyanide were added. The residue was treated with ethyl acetate and recrystallized to give the pure product. Yield: 39%; R_f: 0.47 (n-hexane-ethyl acetate, 2:1, v/v); decomposes at 229–230 °C; IR (KBr, cm⁻¹): 3186 (Ν-H), 1603 (C=O); ¹H-NMR (500 MHz, DMSO-d₆) δ 11.62 (br s, 1H), 7.75–7.71 (m, 2H), 7.58–7.54 (m, 2H), 7.41 (d, J = 16.6 Hz, 1H), 7.30–7.26 (m, 3H), 7.19 (s, 1H), 6.87 (d, J = 16.6 Hz, 1H), 6.70 (d, J = 8.4 Hz, 2H), 2.90 (s, 6H); ¹³C-NMR (126 MHz, DMSO-d₆) δ 189.8, 149.5, 139.4, 136.0, 130.4, 128.4, 128.3, 126.8, 126.7, 126.1, 123.8, 120.1, 117.5, 117.1, 112.5, 40.1; LC-MS (ESI, m/z): [Μ + CH₃OH + Κ]⁺ = 421/423 (3:1), [Μ − N(CH₃)₂]⁺· − ·H = 305/307 (3:1), [Μ − H]¹⁻ = 349/351 (3:1); elemental analysis calculated: C 71.89, H 5.46, N 7.98 Found: C 71.95, H 5.32, N 7.63.

(4-chlorophenyl) (4-(4-(dimethylamino) phenyl)-1H-pyrrol-3-yl) methanone (2): The general method was followed. The residue was treated with ethyl acetate and methanol drops and recrystallized to give the pure product. Yield: 18%; R_f: 0.46 (n-hexane-ethyl acetate, 1:1, v/v); m.p.: 195–197 °C; IR (KBr, cm⁻¹): 3182 (Ν-H), 1611 (C=O); ¹H-NMR (500 MHz, DMSO-d₆) δ 11.53 (br s, 1H), 7.71 (d, J = 8.3 Hz, 2H), 7.50 (d, J = 8.3 Hz, 2H), 7.22–7.18 (m, 3H), 6.94 (s, 1H), 6.63 (d, J = 8.6 Hz, 2H), 2.86 (s, 6H); ¹³C-NMR (126 MHz, DMSO-d₆) δ 189.2, 148.9, 138.9, 136.1, 130.8, 129.1, 128.2, 128.0, 125.8, 123.2, 120.1, 118.5, 112.1, 40.3; LC-MS (ESI, m/z): [Μ + H]⁺ = 325/327 (3:1), [Μ + Na]⁺ = 347/349 (3:1), [Μ + Κ]⁺ = 363/365 (3:1), [Μ + CH₃OH + Na]⁺ = 379/381 (3:1), [Μ − H]¹⁻ = 323/325 (3:1); elemental analysis calculated: C 70.26, H 5.28, N 8.62 found: C 70.0, H 5.35, N 8.78.

(4-(4-(dimethylamino) phenyl)-1H-pyrrol-3-yl) (thiophen-2-yl) methanone (3): The general method was followed with a few modifications. In the first step, 4-(dimethylamino) benzaldehyde, 2-acetylthiophene, and lithium hydroxide monohydrate were added at a molar ratio of 2:2:1. In the second step, 2.5 mmol of lithium hydroxide monohydrate and 2.5 mmol of p-tosylmethyl isocyanide were added. The residue was recrystallized by methanol to give the pure product. Yield: 39%; R_f: 0.71 (n-hexane-ethyl acetate, 1:2, v/v); decomposes at 192–195 °C; IR (KBr, cm⁻¹): 3272 (Ν-H), 1609 (C=O); ¹H-ΝΜR (500 MHz, DMSO-d₆) δ 11.50 (br s, 1H), 7.91 (d, J = 4.9 Hz, 1H), 7.69 (d, J = 3.6 Hz, 1H), 7.46-7.44 (m, 1H), 7.23–7.18 (m, 3H), 6.95–6.94 (m, 1H), 6.66 (d, J = 8.6 Hz, 2H), 2.87 (s, 6H); ¹³C-NMR (126 MHz, DMSO-d₆) δ 181.9, 148.8, 145.9, 133.0, 132.8, 128.8, 128.1, 126.2, 125.4, 123.3, 120.1, 118.2, 112.1, 40.3; LC-MS (ESI, m/z): [Μ + H]⁺ = 297, [Μ + Na]⁺ = 319, [Μ + Κ]⁺ = 335, [Μ + CH₃OH + Na]⁺ = 351, [2Μ + Na]⁺ = 615, [Μ − H]¹⁻ = 295; elemental analysis calculated: C 68.89, H 5.44, N 9.45 found: C 69.02, H 5.37, N 9.81.