Reactions of 5-Aroylmethylene-3-benzyl-4-oxo-2-thioxo-1,3-thiazolidines with Nitrile Oxides

E,Z-5-Aroylmethylene-3-benzyl-4-oxo-2-thioxo-1,3-thiazolidines (3a-c) react with 4-methoxy and 4-chlorophenylnitrile oxides (4a and b) in pyridine solution to afford one or more of the following compounds: Z-3, Z-2,4-dioxo analogues 5 and 3,6-diaryl- 1,4,2,5-dioxadiazines (6a-b). The interconversion route is discussed and the structures of all of the synthesised compounds are proven by microanalytical and spectral data.

Our intent was to perform the reactions in pyridine as, on the one hand, it is able to dissolve the starting thiazolidinones which are sparingly soluble in most organic solvents, and, on the other hand, it can be used to liberate the required nitrile oxide in situ from stable α-hydroximinobenzyl chlorides precursors.

Scheme 1
The structures of the isomerized 4-oxo-2-thioxo-1,3-thiazolidines (Z-3b and c) and the respective 2,4-dioxo counterparts (Z-5a-c) were deduced from microanalytical, IR, 1 H-NMR and MS spectral data (cf . Tables 2 and 3). All the IR spectra of compounds 5 show the complex carbonyl pattern extending to 1750 cm -1 consistent with the stretching vibrations of coupled carbonyl groups, whereas those of 3 show the carbonyl absorptions at mostly lower frequency values not exceeding 1715 cm -1 . Their EI-mass spectra exhibit parent peaks at m/e 91, molecular ion peaks and M .+ -CS(CO) [A] and M .+ -PhCH 2 NCS(O) [B] fragments. The structures of 6a and 6b, which were believed to be the head to the tail dimerised products, was confirmed by comparison (m.p and IR) with authentic samples [11]. incremented values [12]; the olefinic protons of the Z-isomers are relatively deshielded by the 4-oxogroups compared with the E-counterparts. The Z-configuration was assigned to 3b and 3c by comparing with the starting E-counterparts and to 5a by comparing with a sample previously prepared [1] upon treating a solution of 2a in glacial acetic acid with bromine. A role for pyridine alone in the isomerisation process can be ruled out as compounds E,Z-3a-c are recovered without detectable configurational change upon refluxing in this solvent. The larger proportions of Z-isomers observed in the compounds prepared as compared to the starting materials indicates that isomerisation has occured during the reactions. The great stability of the Z-isomers as compared with the E-counterparts is probably due to steric considerations Although isomerisation may be explained according to the hypothesis of formation of zwitterionic or biradical intermediates [13], it is better explained in terms of successive addition and elimination of nitrile oxide at the β-terminus of the exocyclic α,β-unsatured carbonyl system of compounds 3 as outlined in Scheme 3. The instability of the hypothetically formed adducts may be attributed to a sterically hindered transition state. The negative results reported for the reaction of tri-and tetra-alkyl ethylenes with nitrile oxides [14] seem to be in accordance with our results.
The formation of the 2,4-dioxo compounds 5 rather than the spiranes 7; which could be produced by the attack of nitrile oxides at the thiono group of compounds 3 could be rationalised in terms of decomposition of the 1,4,2-oxathiazole ring of the spirane ring system by expelling 4-chlorophenyl-or 4methoxyphenylisothiocyanates. The decomposition has occured most likely via a radical reaction as it has been reported by Husigen et al [15] that all the 1,4,2-oxathiazoles which are formed via cycloaddition of nitrile oxides to thiocarbonyl compounds decompose exothermically at 90-150°C to form isothiocyanates and the oxygen analogues of the thiocarbonyl compounds. The molecular rearrangement leading to the isothiocyanate probably proceeds concurrently with the ring opening [15] (Scheme 2). The preference for the nitrile oxides to react with C=S rather than the C=O groups may be attributed to the polarizability of the sulfur function which is manifested by the great readiness with which several thiono containing compounds react with dipolar species [16]. Formation of stable spiranes is reported upon reacting 2-thioxo-1,3,4-thiadiazole with nitrile imines [16].

General
All melting points are uncorrected. IR spectra were measured on a Unicam SP1200 spectrometer as KBr discs. 1

Reactions of Compounds E,Z-3a-c with Arylnitrile Oxides 4a and b: General Procedure
Powdered α-hydroximino-4-chlorobenzyl chloride (4a) [19] or the 4-methoxybenzyl counterpart (4b) [20] (25 mmol) was added to a suspension of each of E,Z-3a-c (10 mmol) in anhydrous pyridine (10 mL) and the whole mixture was refluxed for 10 hrs. during which it acquired a violet colouration. The solid which precipitated after allowing the reaction mixture to stand at room temperature overnight was filtered off, washed with small portion of ether and chromatographed or recrystallised from an appropriate solvent to give Z-3 and/or Z-5 along with starting materials slightly enriched with the Zconfigured isomers E,Z-3.
The crude product (2.98 g, 80%) which was obtained upon reacting E,Z-3c with 4b was crystallised from dioxane to give E,Z-3c (0.75 g, 20%) containing 90% of the Z-isomer as orange crystals m.p. 248-250°C. On leaving the dioxane mother liquor to stand at room temperature for 24 hrs., it precipitated a yellow solid (1.96 g, 55%) which was recrystallised from benzene-methanol to give Z-5c as yellow crystals m.p. 226-228°C.

Action of pyridine on E,Z-3a-c
A suspension of each of E,Z-3a-c (3 mmol) in pyridine (10 mL) was refluxed for 15 hrs. while the solution acquired a violet colouration. The crude product which precipitated upon leaving the reaction mixture to stand at room temperature overnight (90-95%) was recrystallised from dioxane to give 90% of each E,Z-3a-c with similar E/Z ratios as the starting materials.  (20)[90] ---5c(55) 6b(10) * configurational assignment is based on 1 H-NMR spectroscopy. ** yield of actually isolated compounds *** % of the Z-isomer in the E,Z-mixture.