Verifying the Predictability of 13C Chemical Shifts for a Series of Substituted-2-(4-Chlorophenyl)-3-Phenyl-1,3-Thiazolidin-4-Ones

Abstract

Previously, an "additivity" equation relating experimental 13 C chemical shift data for two monosubstituted diphenyl-1,3-thiazolidin-4-one series was developed to predict chemical shifts for a similarly substituted bis-disubstituted thiazolidinone series. The sites of interest in the 1,3-thiazolidin-4-one are at the C-2, C-4, and C-5 carbons. The empirically derived equation for predicting the chemical shifts iswhere  XY is the predicted chemical shift for the disubstituted thiazolidinone,  H is the experimental chemical shift for the unsubstituted thiazolidinone,  X is the experimental chemical shift for substituent in the 2-phenyl ring, and  Y is the experimental chemical shift for substituent in the N-(3)-phenyl ring. This article discusses the application of the aforementioned equation with respect to a new series of 2-(p-chlorophenyl)-substituted-3-phenyl-1,3-thiazolidin-4-oneswith a comparison of both experimental and predicted 13 C chemical shifts for the C-2, C4 and C-5 sites in the thiazolidinone ring. Utilization of the equation showed a level of chemical shift predictability with a degree of accuracy in concert with a previously reported series. The degree of predictability again showed a dependency on the particular substituent and the chemical shift for the site being predicted. This was ±0.06 ppm for C-2, ±0.2 ppm for C-4 and ±0.09 ppm for C5. Finally, there was a correlation between Hammett  values and the substituent chemical shifts using13 C values at C-2. The r value was -0.86 indicating that the C-2 carbon preferred a positive charge.

A Study of 13C Chemical Shifts for a Series of 2-(4-methoxyphenyl)-substituted-3-phenyl-1,3-thiazolidin-4-ones

“…Another indicator of the degree of scatter is discernible from a plot of the actual chemical shifts versus the calculated values shown for the series of compounds in Figure 9 (Tierney, et al, 2005). Prior Hammett correlations for disubstituted systems were in concert with plots for predicted chemical shifts (Silverberg, et al, 2013;Tierney, et al, 2005). The first inkling that the para-methoxy group interfered with the transmission of substituent effects was in the instance where the para-methoxy group was fixed in the N-3 phenyl ring and the substituents were varied in the C-2 phenyl ring ( Figure 1) (Tierney, et al, 2008).…”

“…A wide array of thiazolidinones related to those shown in Figures 1-5 have been synthesized and analyzed by 13 C NMR. In all these examples the 13 C substituent chemical shift effects, particularly at C-2 in the thiazolidinone ring, have been documented in the literature (Woolston, et al, 1992;Woolston, et al, 1993;Tierney, et al, 1996;Tierney, et al, 2005;Tierney, et al, 2008;Silverberg, et al, 2013). Figure 1 represents a combination of substituents that potentially leads to a 13 x 13 matrix array of 169 compounds.…”

“…These compounds have been shown to possess anticancer, antiviral, anticonvulsant, antidiabetic, antimicrobial, antituberculosis, antihyperlipidemic, and cardiovascular activities. The importance of studying the spectroscopic and biological properties of substituted 2,3-diphenyl-1,3-thiazolidin-4-one systems ( Figure 1) has been extensively documented (Woolston, Lee, Swinbourne, & Thomas, 1992;Woolston, Lee, & Swinbourne, 1993;Tierney et al, 1996;Tierney et al 2005;Tierney, Koyfmann, Cannon, Mascavage, & Lagalante, 2008;Silverberg, et al, 2013). A wide array of thiazolidinones related to those shown in Figures 1-5 have been synthesized and analyzed by 13 C NMR.…”

Σχεδιασμός, Σύνθεση Και Μελέτη Βιολογικής Δράσης Νέων Θειαζολικών Παραγώγων

“…ηδ θαζιαημζημπζηή ελέηαζδ ηςκ εκχζεςκ ιε13 C-NMR παναηδνήεδηε παναηηδνζζηζηή ημνοθή ζηα 170-171 δ πμο μθείθεηαζ ζημ άημιμ άκεναηα ημο ηαναμκοθίμο 259. ηα 163-165 δ παναηδνήεδηε δ ημνοθή ημο αηυιμο άκεναηα ζηδ εέζδ 2 ημο αεκγμεεζαγμθζημφ ζοζηήιαημξ (N=C-S) ηαζ αημθμφεδζακ μζ ημνοθέξ ηςκ αηυιςκ άκεναηα πμο ζοιιεηέπμοκ ζε ανςιαηζηά ζοζηήιαηα ζηα 140-107 δ. Σμ άημιμ άκεναηα ηδξ εέζδξ 2 ημο δαηηοθίμο ηδξ εεζαγμθζδζκυκδξ (N-CΖ-S) πανμοζζάγεζ ημνοθή ζηα 60-63 δ, εκχ ημ άημιμ άκεναηα ηδξ εέζδξ 5 (CO-CH 2 -S) ζηα 31-34 δ. ηζξ εκχζεζξ ιε ιεεμλο-οπμηαηάζηαζδ ειθακίγεηαζ ημνοθή πενίπμο ζηα 55 δ ημο αηυιμο άκεναηα ηδξ ιεεμλο-μιάδαξ, εκχ ζηδκ πενίπηςζδ αζεμλο-οπμηαηάζηαζδξ ζηα 56 ηαζ ζηα 14 δ. Σα άημια άκεναηα ημο αδαιακηακίμο πανμοζζάγμοκ ημνοθή ζε 41-44, 32-36 ηαζ 27-28.5 δ. Σέθμξ, ημ άημιμ άκεναηα ημο αεκγμθίμο ζοκδεδειέκμ ιε οδνμλφθζμ ειθακίγεζ ημνοθή πενίπμο ζηα 156 δ ηαζ ηα άημια άκεναηα ηδξ -CF 3 οπμηαηάζηαζδξ ζημ αεκγμεεζαγμθζηυ ζφζηδια έπμοκ ημνοθή ζηα 129 δ. Απυ ηδκ ιεθέηδ ηςκ θαζιάηςκ ιάγδξ (ΜS) δ φπανλδ ηςκ εοβαηνζηχκ ζυκηςκ δζηαζμθμβείηαζ ιε ημοξ πνμηεζκυιεκμοξ ιδπακζζιμφξ δζάζπαζδξ μζ μπμίμζ είκαζ ζε ζοιθςκία ιε ηα αζαθζμβναθζηά δεδμιέκα θαζιάηςκ ιάγδξ πμθθχκ εεζαγμθζηχκ παναβχβςκ 242-244 ηαζ πανμοζζάγμκηαζ ζηα παναηάης ζπήιαηα 5-9.…”