Synthesis, Structure and Stereochemistry of Dispirocompounds Based on Imidazothiazolotriazine and Pyrrolidineoxindole

• Published in: International journal of molecular sciences Vol. 23; no. 22; p. 13820
• Main Authors: Izmest'ev, Alexei N, Karnoukhova, Valentina A, Larin, Alexander A, Kravchenko, Angelina N, Fershtat, Leonid L, Gazieva, Galina A
• Format: Journal Article
• Language: English
• Published: Switzerland MDPI AG 10.11.2022; MDPI
• Subjects: 1,3-dipolar cycloaddition; azomethine ylides; Chromatography; Column chromatography; Cycloaddition; Diastereoisomers; dispirooxindoles; Heterocyclic compounds; Natural products; Nitrogen; oxindolylidene imidazothiazolotriazines; Pyrrolidines - chemistry; rearrangement; Single crystals; Spectrum analysis; Spiro Compounds - chemistry; Stereochemistry; Thiosemicarbazones - chemistry; Triazine; Triazines; azomethine ylides; oxindolylidene imidazothiazolotriazines; dispirooxindoles; rearrangement; 1,3-dipolar cycloaddition
• ISSN: 1422-0067; 1661-6596; 1422-0067
• DOI: 10.3390/ijms232213820

Methods for the synthesis of two types of isomeric dispirocompounds based on imidazothiazolotriazine and pyrrolidineoxindole, differing in the structure of imidazothiazolotriazine fragment, namely, linear dispiro[imidazo[4,5- ]thiazolo[3,2- ][1,2,4]triazine-6,3'-pyrrolidine- 4',3″-indolines] and angular dispiro[imidazo[4,5- ]thiazolo[2,3- ][1,2,4]triazine-7,3'-pyrrolidine-4',3″-indolines] were proposed. The first method relies on a 1,3-dipolar cycloaddition of azomethine ylides generated in situ from paraformaldehyde and N-alkylglycine derivatives to the corresponding oxindolylidene derivatives of imidazothiazolotriazine. The cycloaddition leads to a mixture of two diastereomers resulted from - and -approaches of azomethine ylide in approximately a 1:1 ratio, which were separated by column chromatography. Another method consists in rearrangement of linear dispiro[imidazo[4,5- ]thiazolo[3,2- ][1,2,4]triazine-6,3'-pyrrolidine-4',3″-indolines] into hitherto unavailable angular dispiro[imidazo[4,5- ]thiazolo[2,3- ]-[1,2,4]triazine-7,3'-pyrrolidine-4',3″-indolines] upon treatment with KOH. It was found that the -diastereomer of linear type underwent rearrangement into the isomeric angular -diastereomer, while the rearrangement of the linear -diastereomer gave the angular -diastereomer.