An Experimental and Theoretical Conformational Study of a Series of Substituted 3-cyclohexyl-2-phenyl-1,3-thiazolidin-4-ones

Abstract

A series of novel 3-cyclohexyl-2-phenyl-1,3-thiazolidin-4-one derivatives with substituents on the 2-phenyl ring were synthesized, and a study of their solid state and solution conformations was effected. In solution the thiazolidin-4-one ring preferred the C2 phenyl in a pseudo-equatorial orientation and the solid state indicated a preference for the C2 phenyl being in a pseudo-axial orientation. Less robust substituent chemical shift (SCS) correlations utilizing 13 C NMR were observed in this instance than in prior studies. Molecular modeling studies using Møller-Plessett second-order perturbation theory (MP2) indicate that the thiazolidinone ring and cyclohexyl ring conformations exhibit a global minimum consistent with the solution studies.

Selective Synthesis of Ortho-substituted 3-Cyclohexyl-2-phenyl-1,3-thiazolidin-4-one Sulfoxides and Sulfones by S-Oxidation with Oxone

“…The ortho-substituted 3-cyclohexyl-2-phenyl-1,3-thiazolidin-4-ones 1a-j (Table 1) were prepared by the conversion of the respective ortho-substituted benzaldehyde to the cyclohexyl imine, followed by condensation with thioglycolic acid (Scheme 1) (Cannon, et al, 2013;Tierney, et al, 1996). Scheme 1.…”

“…(Cannon, et al, 2013;Tierney, et al, 1996) Isolated yields are based on starting amounts for the imines (amine is the limiting reactant) and it was assumed that 100% of the imine was produced in situ. No attempt was made to maximize the product yields.…”

“…Oxone ® , a mixture of potassium sulfates (2 KHSO 5 /1 K 2 SO 4 /1 KHSO 4 ), is a very desirable material to use because it is a "green" reagent which is inexpensive, safe, and easy to use (Yu, et al, 2012;Hussain, Green & Ahmed, 2013). It has been used as a chemoselective reagent for the oxidation of sulfides to either sulfoxides (Trost & Curran, 1981;Yu, et al, 2012;Webb, 1994;Madesclaire, 1986) or sulfones (Trost & Curran, 1981;Yu, et al, 2012;Webb, 1994;Cannon, et al, 2013;Tierney, et al, 1996). Selectivity toward the sulfoxide or sulfone has been shown to depend on the amount of Oxone ® used, the temperature, and the solvent (Trost & Curran, 1981;Yu, et al, 2012;Webb, 1994).…”

“…We have previously reported the preparation of a series of meta-and para-substituted 3-cyclohexyl-2-phenyl-1,3-thiazolidin-4-ones (Cannon, et al, 2013;Tierney, et al, 1996). In this study, we report the preparation of a series of ortho-substituted 3-cyclohexyl-2-phenyl-1,3-thiazolidin-4-ones and show that Oxone ® is a stronger oxidizer than NaIO 4 as evidenced by the higher yields of sulfone products for the parent and chloro-substituted thiazolidin-4-ones.…”

Crystal structure of a 1:1 adduct of triphenyltin chloride with 3-cyclohexhyl-2-phenyl-1,3-thiazolidin-4-one

“…The ligand of the title compound, (N)-3-xyclohexyl-2-phenyl-1,3thiazolidine-4-one, is easily prepared from N-cyclcohexylidene aniline and thioglycolic acid utilizing a method originally proposed by Surrey (1947). The crystal structure of (N)-3cyclohexyl-2-phenyl-1,3-thiazolidine-4-one has previously been reported (Cannon et al 2013), as have a number of other 2,3-disubstituted-thiazolidin-4-one structures (Yennawar et al, 2017;Vigorita et al, 1979). Furthermore, the X-ray crystal structure of 2,3-diphenyl-1,3-thiazolidin-4-one as a 1:1 adduct with triphenyltin chloride has been described (Smith et al 1995), and along with related complexes has biological activity against Cerotysistis Ulmi, the fungus that causes Dutch Elm Disease (Beraldo & de Lima, 2008).…”