Synthesis, Anticonvulsant Activity and <i>In silco</i> Studies of Schiff Bases of 2-Aminothiophenes via Guanidine- Catalyzed Gewald Reaction

Abstract

Purpose: To synthesize Schiff bases of 2-aminothiophenes and evaluate their anticonvulsant activity and in silco propertiesMethods: thiophene-3-carboxamide was synthesized using 1,1,3,3-tetramethylguanidine lactate as a basic catalyst and by microwave irradiation. 2-substitued-o-tolyl-5,6-dihyro-4H-cylcopenta[b]

Expeditious Scalable Catalyst-Free One-Pot Synthesis of 4-Alkoxy-5-amino-3-methylthiophene-2-carbonitriles via Sequential Reactions­ of Lithiated Alkoxyallenes with Isothiocyanates and 2-Bromoacetonitrile

“…IR spectra were recorded neat or as KBr pellets on a Bruker Vertex-70 IR spectrophotometer. 1 H (400.13 MHz), 13 C (100.62 MHz), 15 N (40.55 MHz), and 19 F (376.50 MHz) NMR spectra were recorded on a Bruker DPX-400 and Bruker AV-400 spectrometers in CDCl 3 at r.t. Chemical shifts (δ) are quoted in ppm, to the nearest 0.01 ppm (for 1 H) and 0.1 ppm (for 13 C, 15 N, and 19 F), and are referenced to HMDS (for 1 H), CDCl 3 (for 13 C), MeNO 2 (for 15 N), and CFCl 3 (for 19 F) as internal standards. Coupling constants (J) are reported in hertz (Hz) to the nearest 0.1 Hz.…”

“…IR (neat): 3330, 3116, 3052, 2935IR (neat): 3330, 3116, 3052, , 2877IR (neat): 3330, 3116, 3052, , 2192IR (neat): 3330, 3116, 3052, (C≡N), 1620IR (neat): 3330, 3116, 3052, , 1565IR (neat): 3330, 3116, 3052, , 1498IR (neat): 3330, 3116, 3052, , 1460IR (neat): 3330, 3116, 3052, , 1410IR (neat): 3330, 3116, 3052, , 1348IR (neat): 3330, 3116, 3052, , 1321IR (neat): 3330, 3116, 3052, , 1272IR (neat): 3330, 3116, 3052, , 1243IR (neat): 3330, 3116, 3052, , 1195IR (neat): 3330, 3116, 3052, , 1128IR (neat): 3330, 3116, 3052, , 1106IR (neat): 3330, 3116, 3052, , 1088IR (neat): 3330, 3116, 3052, , 1022 The 1 H-13 C HMBC and 1 H-13 C HSQC 2D experiments provided additional support for the proposed structure. 13), 181 (25), 180 (16), 179 (85), 166 (11), 165 (16), 154 (9), 153 (44), 152 (100), 140 (14, 138 28), 126 (10), 125 (21), 124 (18, 120 (8), 112 (7), 110 (9), 99 (10), 98 (6), 97 (36), 96 (11), 86 (18), 75 (7), 73 (15), 72 (30), 71 (11), 70 (29), 69 (7), 66 (18), 65 (10), 64 (12), 60 (13), 59 (22), 58 (92), 57 (20), 54 (15), 53 (8), 52 (7), 45 (74), 44 (12), 43 (28), 42 (34), 41 (15), 39 (19), 38 (8).…”

“…For instance, a variety of dyes, 11 agrochemicals, 12 and pharmaceuticals 13 often use a 2-aminothiophene motif in its skeletal backbone. In addition, 2-aminothiophene derivatives exhibit a diverse set of therapeutic activities, for example, anti-inflammatory, 14 anticonvulsant, 15 antimicrobial, 16 antifungal, 17 antioxidant, 18 and other activities. 19 Some marketed drugs such as Olanzapine (antipsychotic drug) 20 and Raltitrexed (Tomudex, anticancer drug) 21 were developed onto a 2-aminothiophene scaffold.…”

The Gewald reaction in dye chemistry

“…These catalysts have several advantages over homogeneous organic basic catalysts, such as easy recovery of the catalysts, simple product isolation, and reusability. The use of microwave irradiation has been further extended using a soluble support .…”

Microwave-Assisted Syntheses in Organic Chemistry

“…A guanidine-catalyzed Gewald condensation was reported (Scheme 2.37) [64]. In the course of the reaction, a mixture of cyclopentanone, 2-cyano-N-o-tolylacetamide and elemental sulfur was irradiated continuously in a MW reactor in the presence of a 1,1,3,3-tetramethylguanidine lactate IL.…”