Direct Iodination of Sydnones and Their Cycloadditions to Form 5‐Iodopyrazoles

Abstract

Direct iodination of sydnones has been achieved using iodine monochloride, leading to yields in excess of 80%. The products were subjected to 1,3-dipolar cycloaddition reactions affording novel 5-iodopyrazoles, To date, there has been only one report on the direct iodination of the sydnone ring, the reagent used being N-iodosuccinimide and the reported yield rather low (23 %). [l] Previously, two indirect methods had been described, which involved treatment of the GrignardL2] or 4-chloromerc~r y [~I [~l derivatives of the sydnones with iodine. In 1957, Ohta and KatoL21 claimed to have obtained the 4-iodo-3-phenylsydnone (2c) by iodination of the corresponding bromo derivative. However, the procedure was not mentioned in a review article by the same authors[5] published in 1969. The only 4-iodo-substituted sydnones described in literature are those bearing 3-phenyl, L2]L3l 3-(3-pyridyl) ['l and 3-(2-amin0phenyl)[~I groups.We have obtained excellent results in the direct iodination of the sydnone ring by using the mild reagent iodine monochloridelacetic acid. This reagent has been used in the iodination of activated aromatic compounds such as acetanilide, p-nitrophenol, salicylic acid and p-nitroaniline, affording either mono-or diiodo derivatives. c6] More recently, the same method has been used for iodination of 2-and 6-aminopyrimidine derivatives in the 5-position. C7l 8-Hydroxyquinolines were iodinated in the 7-position by using ethanol in place of acetic acid. ['] Sydnones la-j could be readily iodinated with this reagent in the presence of an equivalent amount of sodium acetate added to neutralize the hydrochloric acid formed in the reaction. The products were obtained in a highly pure state and in yields of over 80%. Eight new 4-iodosydnones (2a-b, d-j) were obtained by this method. Yields, melting points, and 'H-and 13C-NMR data are given in Table 1 and elemental analyses in Table 3. 13C-NMR spectra of 4-iodo-and 4-bromosydnones have not previously been measured and there is only one published example of that of a chloro derivative.L9I Upon examination of the 13C-NMR spectra of the 4-iodosydnones a strong negative increment could be observed at C-4 (A6 = 38.5-45.1). A weak influence on the polarization of the carbonyl group could also be observed with bromine and chlorine as substituents. A shielding effect of the 3-phenyl group on C-4 was also apparent, provided that the aromatic

Facile Access to 3,5‐Dihalogenated Pyrazoles by Sydnone Cycloaddition and their Versatile Functionalization by Pd‐Catalyzed Cross‐Coupling Processes

“…Commercially available reagents were used as purchased. Halosydnones 1a – f were prepared in three steps from the corresponding N ‐arylglycines according to published procedures 10b,22. Haloalkynes 2a – c were obtained by silver‐catalyzed halogenation of ethyl or tert ‐butyl propiolates with N ‐bromo‐ or N ‐iodosuccinimide 23…”

Mesoionic Sydnone: A Review in Their Chemical and Biological Properties

“…Chloro, iodo and bromo substituted sydnones were prepared successfully with a satisfactory yield as summarized in Scheme 4 [39][40][41][42]. To date, fluoro-containing derivatives at C4 have not been reported.…”

Synthesis, spectroscopic, and X-ray structural characterization of pharmacologically active substituted pyrazolyl-acetanilides

“…The 13 C NMR spectra of pyrazoles 1-5 show all the expected signals. The chemical shifts of compounds 1-5 were established by two-dimensional H/C experiments, as well as by comparison with data reported for similar structures [21][22][23]. In Table 2 the influence of the substituents on the values of the chemical shifts on the carbon atoms (C-3, C-4, C-5) from the pyrazole ring is shown, as well as the chemical shifts for the attached substituents.…”