1,3‐Dipolar Additions of Sydnones to Alkynes. A New Route into the Pyrazole Series

Abstract

was verified by gas-phase molecular weight determination. The H2S pressure (in mm. Hg) over trithiocarbonic acid between -25 "C. and +15 "C. can be described by the following equation:The evaluation of the measured values gives AHR = +10.6 f0.3 kcal./mole for the heat of reaction, and ASR = +32.0 f 0.7 e.u./mole for the reaction entropy. The heat of formation and normal entropy of liquid trithiocarbonic acid is then AH$9* = +5.6 & 1.4 kcal./mole, and S298 = +53.3 i 1.3 e.u.1 mole.The assumption [I] that 1 mole of trithiocarbonic acid dissolves exactly 1 mole of sulfur with the formation of the brown oily tetrathiocarbonic acid H2CS4 proved to be incorrect. Rather, a clear temperature dependence of the sulfur absorption was found; it is only coincidental that at 22 "C. 1 mole of S is dissolved (at +25 "C., 1.08 moles and at -10 OC., 0.50 mole of S per mole of H2CS3). The IRand UV-spectra also point to the solution of sulfur in H2CS3. On the basis of vapor pressure measurements, the heat of solution of sulfur in H2CS3 was determined to be AHs = -0.4f 0.5 kcal. /mole.

Cu‐Promoted Sydnone Cycloadditions of Alkynes: Scope and Mechanism Studies

“…Even more remarkably, full conversion occurred within the first hour using Cu(OTf) 2 (entry 8). On further investigation of the additive effects of Cu(OTf) 2 , it was discovered that complete conversion actually occurred within 20 min, compared to a 13 % conversion within the same time in the absence of Lewis acid. Accordingly, we decided to explore the scope of the Cu(OTf) 2 -promoted reaction, and to compare this to the reaction conducted in the absence of promoter.…”

“…[1] From a synthesis standpoint, the cycloaddition reaction of these compounds with alkynes offers an effective method to prepare pyrazoles, and this chemistry has attracted a great deal of attention since its initial discovery by Huisgen. [2] A limitation of sydnone cycloadditions is the requirement to conduct these reactions at elevated temperatures over extended time periods. Nonetheless, such processes can provide the corresponding pyrazoles with excellent levels of regiocontrol, especially for terminal alkyne substrates.…”

Bioorthogonal Cycloadditions: Computational Analysis with the Distortion/Interaction Model and Predictions of Reactivities

“…32 Widely used as a powerful tool in the synthesis of heterocyclic compounds, the 1,3-dipolar cycloaddition of sydnone was recently applied to bioorthogonal chemistry. Taran and co-workers reported the highly efficient and selective copper-catalyzed cycloadditions of sydnone with terminal alkynes 33 and demonstrated the satisfying biocompatibility of such reactions.…”

Discovery of Chemoselective and Biocompatible Reactions Using a High‐Throughput Immunoassay Screening

“…Indeed, according to the screening results in Figure 2 D, this particular combination appeared to be the most efficient, chemoselective, and bioorthogonal of the 2816 combinations we tested. In accordance with the optimization data obtained during the screening procedure, the reaction proceeded efficiently under Cu I -phenanthroline catalysis at room temperature or with gentle heating to produce pure 1,4-pyrazole 10 C. The thermal 1,3-dipolar cycloaddition of sydnones with alkynes, known since Huisgens work in 1962, [11] has been of limited success over the years because of harsh conditions and low regioselectivity, which generates a mixture of pyrazoles. In accordance with the optimization data obtained during the screening procedure, the reaction proceeded efficiently under Cu I -phenanthroline catalysis at room temperature or with gentle heating to produce pure 1,4-pyrazole 10 C. The thermal 1,3-dipolar cycloaddition of sydnones with alkynes, known since Huisgens work in 1962, [11] has been of limited success over the years because of harsh conditions and low regioselectivity, which generates a mixture of pyrazoles.…”