Simple Method for the Preparation of Dialkyl (2,3-Dihydro-1,3-thiazol-2-YL)-phosphonates

Synthesis, X-ray Analysis, Biological Evaluation and Molecular Docking Study of New Thiazoline Derivatives

“…The solid product that formed was filtered and washed with ethanol, and recrystallized to afford the corresponding thiazolines 2a – e . The physical properties and spectroscopic data of compounds 2a – d are in agreement with the literature [45,47,48].…”

“…In addition, their 13 C-NMR spectra confirmed the assigned structures and revealed the presence of the expected signals of carbonyl and thiocarbonyl at δ 177.5–188.17 and δ 190.0–193.18, respectively (see the Materials and Methods section). It is important to note that compounds 2a – d were prepared by another two methods as follows: (i) in 54% and 74% yield, respectively, by using the same reagents as for compounds 2a , b in the presence of NaOH as basic catalyst [47]; (ii) in yields of 74% and 75%, respectively, by the second literature method for synthesis of derivatives 2c , d from α-halo-compounds with ammonium dithiocarbamate [48]. Our method for synthesis of compounds 2a – e features better yields of these compounds.…”

“…Next, the reaction of the thiazoline-2-thione derivative 2a [45,47] with 2-oxo- N ′-phenylpropane hydrazonoyl chloride ( 6 ) [49,50] produced the spiro-compound 7 [51] (Scheme 3). The reaction was assumed to proceed via a 1,3-dipolar cycloaddtion reaction between nitrile imine (formed in situ from hydrazonoyl halide 6 by the action of triethylamine) and C=S of thiazoline-2-thione derivative 2a .…”

“…172–174 °C (EtOH) [lit mp. 171–174 °C [45,47]]; IR v max 1630 (C=O), 1490 (C=S) cm −1 ; 1 H-NMR (CDCl 3 ) δ 2.25 (s, 3H, CH 3 ), 2.35 (s, 3H, CH 3 ), 7.14–7.52 (m, 5H, Ph); 13 C-NMR (CDCl 3 ) δ 16.14, 30.23 (2CH 3 ), 112.50, 147.34, 121.50, 128.05, 130.16, 137.08, 188.17, 190.00. Anal.…”

“…There are many methods for preparing thiazoline-2-thione derivatives from alkyl ammonium dithiocarbamates with the appropriate α-halocompound in the presence of an acid [38,39,40,41,42] or by using primary amines, CS 2 and α-haloketone in DMF [43] or toluene [44] or in water as a solvent [45], or without solvent or catalyst [46]. These findings encouraged us to conduct a slightly modification of the reported reaction condition [45,47,48] to synthesize new thiazoline derivatives and to investigate their synthetic potential in the preparation of new thiazoline based heterocycles in order to assess their biological activities.…”