Bifunctional Derivative of p,p'-Dichlorochalcone. Part II. Synthesis of a Novel Compound 2-[2-Carboxymethylthio-2-(4-chlorophenyl)ethyl]-2-(4chlorophenyl)-4-thiazolidinone

The synthesis of 2-[2-carboxymethylthio-2-(4-chlorophenyl) ethyl]-2-(4-chlorophenyl) - 4-thiazolidinone (1) from p, p'- dichlorochalcone using thioglycollic acid in the presence of ammonium carbonate is described. Structural assignment and stereochemistry are discussed.


Results and Discussion
We report here the synthesis of compound (1) in two ways (Scheme 1): (i) -a mixture of chalcone (2), thioglycollic acid and ammonium carbonate (molar ratio (1:2.5:5) in dry benzene was refluxed for 35 h.Purification of the products by column chromatography over silicagel followed by crystallisation afforded compound (1) as colourless globules in good yield (65%).
(ii-b) -the thioether (3) in dry benzene was then refluxed with thioglycollic acid and ammonium carbonate (molar ratio 1:1.25:5) for 32 h and the products on purification as above furnished compound (1) (64%).The constitution of (1) is confirmed by 1 H-NMR, 13 C-NMR, INEPT, COSY, HETCOR and longrange-HETCOR spectra (Tables 1 and 2).These spectra and an additional NOE-experiment also suggest that the relative configuration of product ( 1) is most probably u (unlike [5]), and the partial conformation of both central bonds C-2-C-1' and C-1'-C-2 ' is antiperiplanar (Figure 1 [6]).  of H-Ar'-2,6 activates H-2', but also H dn -1' and H up -1'', which means that also these protons are very near to each other.Molecular mechanics calculations confirm that the structure as shown in figure 1 is the most stable form of compound (1).

Experimental
Melting points were determined on a Koffler hot-plate apparatus and are uncorrected.IR spectra were recorded on a Perkin Elmer 621 spectrophotometer; 1 H-and 13 C-NMR spectra were recorded on a Varian Unity 400 spectrometer and DCI-mass spectra with a Ribermag R10-10B quadrupole mass spectrometer.Reagents and solvents were of commercial grade and were used without further purification.Column chromatography was performed on Silica Gel 60 (120 mesh) (194013).p,p'-Dichlorochalcone (2) was prepared following a published but slightly modified procedure [9] by condensing p-chloroacetophenone with p-chlorobenzylidene diacetate (both prepared according to reported procedures [10]) in equimolar ratio in the presence of 2.5 equivalents of sodium hydroxide as light yellow crystalline needles in 85% yield, m.p. 156°C, Rf 0.72 (petroleum ether (40-60°): benzene -1:1 v/v).

Table 1 .
[8] spectrum contains stereochemical information.Both the diastereotopic hydrogen atoms as well at C-1'' as at C-5 are well separated from each other, one hydrogen atom of each pair, H up , being above the phenyl ring in the shielding cone and the other one, H dn , outside of it.Also the diastereotopic hydrogen atoms at C-1' are well separated.According to Karplus[8]the coupling constants reveal an antiperiplanar torsion angle for H dn -1' and H-2', and a synclinal torsion angle for H up -1' and H-2'.Further, irradiation of the NH-proton results in a NOE-enhancement of H-Ar- 1H-NMR data of (1).2,6, but also of H-2' which means that the NH-proton and H-2' are very near to each other.Irradiation
a Assignment may be reversed.