Heteroaromatic Sulfonyl Chlorides and Fluorides Bearing Carbonyl/Carboxylate Moieties: Bifunctional Building Blocks for Drug Discovery
Тип публікації :
Препринт
Дата випуску :
19 серпня 2026 р.
Автор(и) :
Oleksandr I. Shevchuk
Oleksandra V. Shvek
Bohdan V. Vashchenko
Vasyl Y. Hys
Illia O. Doroshenko
Oleksandr Karpenko
Mykhailo O. Redka
Serhii Zhersh
A. O. Tolmachov
Oleksandr O. Grygorenko
eKNUTSHIR URL :
Журнал :
ChemRxiv
Цитування :
[APA 7] Oleksandr, I. S., Oleksandra, V. S., Bohdan, V. V., Vasyl, Y. H., Illia, O. D., Oleksandr, K., Mykhailo, O. R., Serhii, Z., A., O. T., & Oleksandr, O. G. (2026). Heteroaromatic Sulfonyl Chlorides and Fluorides Bearing Carbonyl/Carboxylate Moieties: Bifunctional Building Blocks for Drug Discovery. ChemRxiv,. https://doi.org/10.26434/chemrxiv.15007628/v1
[ДСТУ] Heteroaromatic Sulfonyl Chlorides and Fluorides Bearing Carbonyl/Carboxylate Moieties: Bifunctional Building Blocks for Drug Discovery / I. S. Oleksandr та ін. ChemRxiv. 2026. DOI: 10.26434/chemrxiv.15007628/v1 (дата звернення: 11.09.2026).
Heteroaromatic sulfonyl halides bearing a free carboxylic acid, ester, aldehyde, or methyl ketone group were prepared for a series of heterocycles (pyridine, pyrazine, imidazole, pyrazole, oxazole, and thiazole). The synthetic scheme involved elaboration of the carboxylate/carbonyl handle on a hetaryl thioether intermediate, obtained by S N Ar or Pd-catalyzed thiolation, and the sulfur was oxidized to the corresponding sulfonyl halide only at the final step. The title products were obtained on up to 40 g scale in a single run. The stability of sulfonyl chlorides depended on the position of the sulfonyl group relative to the ring nitrogen and on the electronic nature of the additional functional group, free carboxylic acids being more demanding than the corresponding esters and aldehydes than carboxylic acids. For the labile cases, sulfonyl fluorides were obtained by KHF 2 halogen exchange or by a one-pot sequence bypassing isolation of the chloride; in addition, a set of primary sulfonamide building blocks bearing a free COOH group was prepared. Both organosulfur and carbonyl-containing handles were addressed chemoselectively under conditions compatible with parallel chemistry, and a virtual library enumerated from these transformations showed good compliance with drug- and lead-likeness criteria.
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