Synthesis, characterization, and crystal structure of a novel spirocyclic 2-indolinone bearing a 5-(trifluoromethyl)benzothiazoline moiety

Abstract

Background and Aims: Spirocyclic 2-indolinones are important and promising compounds because of their various biological activities in drug development studies. The main aim of this study is to determine spirocyclic, molecular and stereoisomeric structure of the new 5’-chloro-1’,7’-dimethyl-5-(trifluoromethyl)-3H-spiro[1,3-benzothiazole-2,3’-indole]-2’-one (4) and to examine the contribution of the trifluoromethyl group. Methods: Compound 4 was synthesized from the reaction of 2-amino-4-(trifluoromethyl)benzenethiol with 5-chloro-1,7-dimethyl1H-indole-2,3-dione in ethanol. The purity and structure determination of compound 4 was carried out by elemental and spectral analyzes. The crystal structure of compound 4 was characterized by X-ray single crystal diffraction analysis method (SC-XRD). Additionally, compliance with Lipinski’s rule of 5 (RO5) and some pharmacokinetic parameters of compound 4 were evaluated using the Qikprop modüle (Schrödinger). Results: The molecular structure of 4 was confirmed by elemental and spectral (IR, 1H NMR, 13C NMR-APT, HSQC-2D, HMBC2D and LCMS-APCI) data. The crystal, spirocyclic and stereoisomeric structure of compound 4 was elucidated by SC-XRD, and it was observed that N-H···O hydrogen bonding interactions take place within the molecular layers aligned parallel to the (010) plane. As a drug candidate, compound 4 exhibited physicochemical parameters consistent with Lipinski’s RO5. Conclusion: In the crystal, both intra- and intermolecular hydrogen bonds are present. The molecular packing is stabilized by intermolecular N— H···O hydrogen bonds.

Keywords

• 2-Indolinone
• Benzothiazoline
• Crystal structure
• Structural characterization
• Synthesis

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