Exploring Isopropyl and Allyl Isothiocyanates to Design 2-Aminobenzothiazoles: Synthesis, Characterization, Single-Crystal XRD, DFT, Hirshfeld Analysis, Antimicrobial Evaluation, Molecular Docking, and ADME Studies

2-Aminobenzothiazoles constitute a significant class of heterocyclic compounds, notable for their extensive pharmacological significance. While their synthesis has typically utilized phenyl isothiocyanate, the potential of alternative isothiocyanates remains largely unexplored. This research presents an alternative synthetic route for the preparation of known substituted 2-aminobenzothiazoles, N-(propan-2-yl)-1,3-benzothiazol-2-amine (SISI) and N-(prop-2-en-1-yl)-1,3-benzothiazol-2-amine (SIAL) using isopropyl isothiocyanate (IPI) and allyl isothiocyanate (AITC) as underutilized precursors under mild copper-catalyzed conditions. Structural elucidation was conducted using FTIR, HRMS, NMR, and single-crystal XRD. DFT results (B3LYP/6-31G(d,p) level) demonstrated a strong correlation with experimental crystallographic data. Hirshfeld surface analysis identified key intermolecular interactions that contribute to crystal packing stability. The antimicrobial assay revealed substantial inhibitory effects against Gram −ve and Gram +ve strains for bacteria along with fungal species, with Escherichia coli exhibiting particular sensitivity. In silico ADME profiling suggested promising pharmacokinetic properties, including high GI and BBB permeability. Molecular docking results indicated strong binding interactions with bacterial DNA gyrase (6F86) and topoisomerase IV (1s14), with SISI and SIAL demonstrating higher binding affinities for topoisomerase IV than streptomycin (binding affinity SISI; −6.0 kcal mol⁻¹, SIAL; −5.8 kcal mol⁻¹, streptomycin; −5.5 kcal mol⁻¹). The enhanced interaction suggests a potential mechanism for their antimicrobial activity, highlighting the synthetic and biological relevance of IPI and AITC as alternative precursors in aminobenzothiazole chemistry, through an efficient and comparative synthetic route for known derivatives.