Improved approaches in the synthesis of new 2-(1, 3-thiazolidin-2 Z -ylidene)acetophenones

Phenyl isothiocyanate reacts stereoselectively with several acetophenones in basic conditions to give after alkylation with dibromoethane, the corresponding new 2-(1,3-thiazolidin-2Z-yliden ) p - R-acetophenones ( 1b-f ). All compounds were characterized by conventional spectroscopic techniques and in the case of 1a the structure was fully established by X ray diffraction analysis


Introduction
α,β-Unsaturated carbonyl compounds are used as ligands to form either η 2 or η 4 complexes when they react with Fe(CO) 9 . 1 Our interest in the chemistry of iron led us to synthesize new mono and dinuclear Fe(0) complexes, which have been prepared by reaction of α,β-unsaturated ketones analogues containing sulphur (A) 2 or nitrogen (B) 3 in β-position with Fe 2 (CO) 9 .In continuing with our studies, we are interested in exploring the reactivity of α,β-unsaturated ketones having both N and S atoms in β-position such as an α-oxo ketenes N,S-acetals (1).Gompper and co-workers 4 reported the synthesis of α-oxo ketene N,S-acetals from the addition of amines to ketene-dithioacetals with high yields, however this method involves a multi-step synthesis and in several cases the α-oxo ketene N,N-acetal is an important byproduct. 5This procedure was used by other research groups to obtain several heterocyclic compounds. 6Another approach to obtain the α-oxo ketene N,S-acetals is by alkylation of the corresponding thioamide analogue.These exist as two tautomeric forms in solution, and after alkylation yield a mixture of E/Z isomers (Scheme 1).6a

Scheme 1
In this way, alkylation reactions with 1,2-, 1,3-, and 1,4-alkyldihalides have been carried out affording thiazole, thiazine and thiazepine derivatives, respectively.Sometimes a carbonyl group protecting reaction is required as the first step, and to carry out the heterocyclization reaction phase transfer catalysis is involved. 7A general experimental methodology for heterocyclization of α-oxo ketene thioamides is characterized firstly by the synthesis and isolation of the thioamide compound.Thus, this synthon is then treated with a dihalide to form the corresponding heterocyclic compound.Rudorf and co-workers 8 have used this methodology to prepare 1-benzoyl-2-anilino-2-methylthioethene from the reaction of an acetophenone enolate with an isothiocyanate, followed by an S-alkylation reaction (Scheme 2) giving the E/Z mixture.

Results and Discussion
In this paper we report the stereoselective one-pot synthesis of several 2-(1,3-thiazolidin-2Zyliden)acetophenones.The title compounds were prepared as shown in Scheme 3, using a modification to the Rudorf's methodology, 8 which involves carrying out the nucleophilic addition to an acetophenone enolate over phenyl isothiocynanate (without isolating the corresponding N-phenyl thioamide) followed by the addition of The EIMS spectrum for each product showed a molecular ion consistent with the expected molecular formula.As selected data the FTIR spectra showed a narrow band at 1600 cm -1 assigned to the carbonyl group, a strong fine band in 1490 cm -1 corresponding to C=C-N vibration, in addition to the respective bands for each compound.The band intensities for the CO and C=C groups indicate that an S…O interaction through to C-C double bond was present 9 in agreement for a Z geometry of the double bond.
The 1 H NMR spectrum of 1a showed signals corresponding to 10 benzene-ring protons (δ 7.74-7.34,m), one vinylic proton (δ 6.23, s) and four methylene protons (δ 4.03,t; and 3.21, t).The NOESY spectrum (Figure 1) suggested coupling of the vinylic hydrogen with the ortho hydrogens of both phenyl and N-phenyl fragments consistent with the formation of the Z geometric isomer.Similar results were observed for 1b-f.The 13 C NMR spectrum of 1a exhibits two signals at δ 27.9 and 56.0, which are assigned to the C-S and C-N respectively.The C α and C β to the carbonyl group were observed at δ 90.4 and 166.7, and the C CO at δ 186.7.For the other products (1b-f) similar spectroscopic data were observed.
The structural arrangement for 1a was fully established by a single-crystal X-ray diffraction analysis. 9The ORTEP view of this compound appears in the Figure 2  The distances (O1…S9, 2.741Å and O2…S28, 2.700Å) are shorter than the ∑ of van der Walls radii, these features indicate that an interaction between the sulfur and oxygen atoms through the conjugated systems is present, in agreement with the obtained results from IR technique and, with similar systems described in the literature. 2,10,11 Slected bond lengths and bond angles are shown in table 2.

Conclusions
We have found a stereoselective one-pot method for the synthesis of several 2-(1,3-thiazolidin-2Z-yliden)acetophenones.In all cases, a Z geometry according with the 1 H and 13 C NMR data were assigned and the structural arrangement for 1a was fully established by X-Ray diffraction analysis.Reactivity studies of these compounds with Fe 2 (CO) 9 are on development.

Experimental Section
General Procedures.FTIR spectra were recorded in solution (CHCl 3 ) using a Perkin-Elmer 283 spectrophotometer; 1 H, 13 C, NOESY and HETCOR NMR spectra were obtained on Jeol Eclipse 300 MHz instrument, using CDCl 3 as solvent and TMS as internal reference.The EIMS spectra were obtained from a Hewlett Packard 5953 spectrometer.THF was distilled from sodium/benzophenone under argon immediately before used.The reactions required inert atmosphere (nitrogen) and the reagents were used as purchased from Aldrich.Column chromatography was performed on silica gel (70-230 mesh).Melting points were determined using a Melt-Temp II capillary melting apparatus and are uncorrected.

General procedure for the syntheses of title compounds
To a stirred ice-cooled solution of NaH (8.0 mmol) in dry THF (150 mL) under nitrogen atmosphere a mixture of acetophenone (4.0 mmol) and phenyl isothiocyanate (4.0 mmol) previously dissolved in dry THF (10 mL) was added.The cooled mixture was stirred over 3 hours and 1,2-dibromoethane (4.0 mmol) was added and this mixture was cooled and stirred over 18 hours.Then, the reaction mixture was concentrated under vacuum and ethyl acetate (30 mL) was added.The organic layer was washed with water (2 X 30 mL), dried with sodium sulphate and evaporated.Finally, the residue was purified by column chromatography on silica gel and eluting with hexane/ethyl acetate in different ratios.

X-Ray crystal structure determinations of compound 1a
Data collection and refinement parameters are summarized in Table 3.The diffraction data for 1a was collected on a Bruker Smart Apex CCD diffractometer with MoKα radiation, λ = 0.71063 Å.Each data set was corrected for Lorentz and polarization effects and analytical absorption corrections based on face indexed were applied.The structures were solved by direct methods 12 and each structure was refined by full-matrix least squares on F 2 using all data with the all non-hydrogen atoms assigned anisotropic displacement parameters and hydrogen atoms bound to carbon atoms inserted at calculated position with isotropic temperature factor 1.2 times