Application of the intramolecular Diels-Alder vinylarene (IMDAV) reaction for the synthesis of benzo-, carbocyclo-, thienothiopheneisoindolecarboxylic acids and its limitations.

Thienylallylamines, readily accessible from the corresponding thienyl aldehydes, react with maleic and trifluoromethylmaleic anhydrides leading to the formation of acids with a thieno[2,3-f]isoindole core. The reaction sequence involves two successive steps: acylation of the nitrogen atom of the initial allylamine and the intramolecular Diels-Alder vinylarene (IMDAV) reaction. The scope and limitations of the proposed method were thoroughly investigated. It has been revealed with the aid of X-ray analysis and DFT calculations that the key step, the IMDAV reaction, proceeds through an exo-transition state, giving rise to the exclusive formation of a single diastereomer of the target heterocycle. The obtained functionally substituted thieno[2,3-f]isoindole carboxylic acids are potentially useful substrates for further transformations and bioscreening. The antimicrobial evaluation of the obtained compounds revealed that 1-oxo-2-(3-(trifluoromethyl)phenyl)hexahydrobenzo[4,5]thieno[2,3-f]isoindole-10-carboxylic acid is the most active sample in the synthesized library. It exhibits antibacterial activity against sensitive strains of Gram-positive bacteria, including S. aureus, Enterococcus faecium, Bacillus cereus, and Micrococcus luteus, as well as the Gram-negative bacteria E. coli and Pseudomonas fluorescens, with MIC values ranging from 4 to 64 µg mL-1. 9-Oxo-8-phenyloctahydronaphtho[2,1-d]thieno[2,3-f]isoindole-10-carboxylic acid showed antifungal activity against yeast culture C. albicans with a MIC value of 32 µM.

Crystal structure and Hirshfeld surface analysis of 4-cyano-N-[(4-cyano-phen-yl)sulfon-yl]-N-[2-(5-methyl-furan-2-yl)phen-yl]benzene-sulfonamide.

In the title compound, C25H17N3O5S2, intra-molecular π-π inter-actions [centroid-to-centroid distance = 3.5640 (9) Å] are observed between the furan and benzene rings of the 4-cyano-phenyl group. In the crystal, mol-ecules are connected via C-H⋯O and C-H⋯N hydrogen bonds, forming layers parallel to the (100) plane. These layers are inter-connected by C-H⋯π inter-actions and weak van der Waals inter-actions. Hirshfeld surface analysis indicates that H⋯H (30.2%), N⋯H/H⋯N (22.3%), C⋯H/H⋯C (17.9%) and O⋯H/H⋯O (15.4%) inter-actions make the most significant contributions to the crystal packing.

Crystal structure and Hirshfeld surface analysis of 10-hy-droxy-2-(4-meth-oxy-phen-yl)-3-oxo-2,3,3a,4,10,10a-hexa-hydro-1H-9-thia-2-aza-cyclo-penta-[b]fluorene-4-carb-oxy-lic acid dimethyl sulfoxide-d6 monosolvate.

In the title compound, C22H19NO5S·C2D6OS, the central six-membered ring has a slightly distorted boat conformation, while the fused pyrrolidine ring adopts an envelope conformation. These conformations are stabilized by O-H⋯O hydrogen bonds between the main compound and solvent mol-ecules. In addition, intra-molecular C-H⋯O hydrogen bonds in the main mol-ecule form two S(6) rings. Mol-ecules are connected by pairs of inter-molecular C-H⋯O hydrogen bonds, forming dimers with a R 2 2(8) motif. These dimers form a three-dimensional network through O-H⋯O, O-H⋯S and C-H⋯O hydrogen bonds with each other directly and through solvent mol-ecules. In addition, weak π-π stacking inter-actions [centroid-to-centroid distances = 3.9937 (10) and 3.9936 (10) Å, slippages of 2.034 and 1.681 Å] are observed. The inter-molecular contacts were qu-anti-fied using Hirshfeld surface analysis and two-dimensional fingerprint plots, revealing the relative contributions of the contacts to the crystal packing to be H⋯H 41.7%, O⋯H/H⋯O 27.7%, C⋯H/H⋯C 17.0%, and S⋯H/H⋯S 7.5%.