Synthesis and Characterization of some New Mesoionic 1,3-Thiazolium-5-thiolates via Cyclodehydration and in situ 1,3-Dipolar Cycloaddition/Cycloreversion

The title compounds were synthesized from C-aryl-N-methylglycines by N-aroylation followed by a cyclodehydration to form the corresponding 1,3-oxazolium-5-olates. These were not isolated but converted to the title compounds by an in situ 1,3-dipolar cycloaddition/cycloreversion sequence using carbon disulphide. We have studied the cyclodehydration step using acetic anhydride, trifluoroacetic anhydride and 1,3-dicyclohexyl-carbodiimide (DCC) at temperatures not exceding 60oC. Trifluroacetic anhydride proved to be the best reagent, giving a better yield and more easily purified products, although yields were also acceptable with the other two reagents.


Introduction
Compounds now classified as mesoionic have been known for more than a century [1]. Since that time both the concept of mesoionic compounds and methods for synthesizing them have undergone extensive changes and modifications. Following an important paper by Schönberg [2], Baker and Ollis [3], Ollis and Ramsden [4] and Potts [5] put forward broadly similar definitions of mesoionic compounds. In particular, they stated or implied that they are aromatic. Structure (1) corresponds to these definitions.
However Miller, Simas [6] et al. indicated that mesoionic compounds are not aromatic although strongly stabilized by π-electron and charge delocalization. They proposed the following definition: "Mesoionic compounds are planar five-membered heterocyclic betaines with at least one side-chain whose α-atom is also in the ring plane and with dipole moments of the order of 5D. The electrons are delocalized over two regions separated by what are essentially single bonds. One region which includes the α-atom of the side-chain is associated with the HOMO and negative π-charge, while the other is associated with the LUMO and positive π-charge". Structure (2) corresponds to this definition, where it should be noted that a, b, c, d, e and f are commonly C, N, O, S or Se.
Mesoionic 1,3-oxazolium-5-olates [7] and 1,3-thiazolium-5-thiolates [8] are well-known, and there are extensive more recent references and reviews [9]. The munchnones have been conveniently prepared by cyclodehydration of α-acylaminoacids at about 55°C. They are however relatively unstable, especially when they possess a 3-H atom. Their lability is evident if , for example, the cyclodehydration reaction temperature is allowed to reach 100°C -ring opening then occurs (see Scheme 1, in which our representation (3) of mesoionic compounds is used).

Scheme 2
(3) Our principal interest in the title compounds relates to their potential for non-linear optics applications and as a source of useful biologically active compounds.
The overall reaction sequence is as follows: Stage 1 (Scheme 3): A Strecker reaction of aromatic aldehydes with sodium cyanide and methylammonium chloride and posterior hydrolysis gave C-aryl-N-methylglycines (5) [10].

Aknowlegements
We are indebted to the Conselho Nacional de Desenvolvimento Científico e Tecnológico (CNPq) and the Coordenação de Aperfeiçoamento de Pessoal de Nível Superior (CAPES) for financial support.

General
Solvents and reagents were purified and dried when necessary. The course of reactions forming mesoionic compounds was monitored by TLC using silica gel G. Hexane/chloroform mixtures were used as eluents. The final products were purified by column chromatograpy using neutral alumina (Merck) and the same eluents used for TLC. Mass spectra were obtained on a Finnigan GCQ Mat quadrupole Ion-Trap Spectrometer. IR spectra were obtained on a Bomen-Michelson IFS 66 spectrometer, using KBr discs. 1 H-and 13 C-NMR spectra were obtained on a Varian Unity Plus spectrometer (300 MHz for 1 H and 75 MHz for 13 C), using TMS as internal reference and DMSO-d 6 or CDCl 3 as solvents. Elemental analyses were determined on a Perkin Elmer 240 instrument. Melting points were determined on a platinum plate in a Koffler apparatus coupled with a Carl-Zeiss microscope and are uncorrected.
Method 3: C-p-tolyl-N-p-chlorobenzoyl-N-methylglycine (6a) (0.5g, 1.57 mmol) and 1,3-dicyclohexylcarbodiimide (DCC, 0.32g, 1.57 mmol) [14] were refluxed in chloroform (20 mL) for one hour. Carbon disulphide (5 mL) was then added forming a red solution which was refluxed for another hour. The solvent was then removed in the rotary evaporator at reduced pressure leaving a red solid. This was washed several times with ethanol in order to remove N,N'-dicyclohexylurea. The residue was chromatographed on neutral alumina and the product eluted with chloroform/hexane was allowed to evaporate slowly. The product was obtained as red crystals in 48% yield and had m.p. 188-190°C.