5-Methyl-4-(5-Bromo-2-hydroxyphenyl)-1,3-Dithiolium Derivatives


Novel 4-(5-bromo-2-hydroxyphenyl)-5-methyl-2-(N,N-dialkylamino)-1,3-dithiol-2-ylium hydrogen sulphates have been synthesized by the heterocyclisation of the 1-(5-bromo-2-hydroxyphenyl)-1-oxapropan-2-yl dithiocarbamates. The latter compounds have been obtained from the reaction of the corresponding substituted a-bromopropiophenone with various salts of dithiocarbamic acids. These derivatives were characterized by NMR and MS spectrometry, UV-Vis and IR spectroscopy.



Analysis methods
Melting points were obtained on a KSPI melting point apparatus. IR spectra were recorded on a Bruker Tensor 27 instrument. NMR spectra were recorded on a Bruker 500 MHz spectrometer. Chemical shifts are reported in ppm downfield from TMS. UV-Vis spectra were recorded on a Varian BioChem 100 spectrophotometer. Mass spectra were recorded on a Thermo Scientific ISQ LT instrument. Elemental analyses (C, H, N and S) were conducted using a CE440 Elemental Analyser; the results were found to be in good agreement (±0.28%) with the calculated values.

Synthesis
The synthetic pathway for the synthesis of dithiocarbamates 2a-c and 1,3-dithiolium hydrogen sulphates 3a-c is described in scheme 1.
To a saturated sodium hydrogen carbonate solution (20mL), hydrogen sulphate 3a (1g, 2.3 mmol) was added. Carbon dioxide evolved and the reaction mixture became yellow. After 2 h under vigorous stirring at room temperature, the yellow solid was filtered off, washed with water, and dried. Recrystallization from N,N-dimethylformamide gave yellow crystals; yield 0.77g (100%). Analytical and spectral data of 1,3-dithiolium phenolates 4a-c are presented in table 3.
The structure of dithiocarbamates 2 has been proved by analytical and spectral data (table 1). The 1 H NMR spectra indicate a shift for the signal of α-CH to the carbonyl group up to 5.7ppm. Also, new signals are recorded in the aliphatic area corresponding to the N,N-dialkylamino moieties. 13  Under heterogeneous conditions the treatment of hydrogen sulphates 3a-c with saturated aqueous sodium hydrogen carbonate solution has provided 4-bromo-2-[5methyl-2-(N,N-dialkylamino)-1,3-dithiol-2-ylium-4yl]phenolates 4a-c, in quantitative yields as yellow compounds (scheme 2). The molecular structure of the new compounds was proved by analytical and spectral data (table 3) and by the following chemical transformation: treatment of an acetone suspension of the mesoionic phenolates 4 with sulfuric acid regenerates the 1,3-dithiolium perchlorates 3 in quantitative yields (scheme 2).
It was previously reported that the presence of a hydroxy substituent in the orthoor para-positions of the aromatic ring induce an extended delocalization of the negative charge up to the C4-C5 bond of the dithiolium ring [27,30]. Thus, the comparative study of UV-Vis absorption spectra of 2-, 3-, and 4-[2-(pyrrolidin-1-yl)-1,3-dithiol-2-ylium-4yl]phenolates has shown that the yellow color of these zwitterionic compounds is due to a charge transfer between electron-rich and electron-deficient regions of the molecules and not to the contribution of quinoid structures in the ground states. As mentioned above, phenolates 4 have been isolated as yellow products that present the features of mesoionic compounds [27]. The yellow color of mesoionic phenolates 4a-c is also provided by an intramolecular charge transfer that was proved by measurement of UV-Vis absorption spectra at different concentrations.

Conclusions
The synthesis of several of 4-(5-bromo-2-hydroxyphenyl)-5-methyl-2-(N,N-dialkylamino)-1,3-dithiol-2-ylium derivatives has been accomplished by the heterocyclization of the corresponding phenacyl carbodithioates  [20,23,65]. After 10 min at 80°C the homogeneous reaction mixture was cooled to room temperature and water was added. Filtration and recrystallization of the precipitate gives hydrogen sulphates 3a-c as colorless crystals, in good yields (table 2). The cyclization of dithiocarbamates 2 was accompanied by important spectral changes. The IR spectra revealed the disappearance of the absorption band corresponding to the carbonyl group (ca. 1640cm -1 ) and the presence of new, strong and broad absorption bands at 1000-1100cm -1 , corresponding to the hydrogen sulphate anion. The 1 H NMR spectra of 1,3-dithiol-2-ylium hydrogen sulphates indicate the absence of the quartet signal of a-carbonyl hydrogens from compounds 2 (ca. 5.7ppm). 13 C NMR spectra also support the synthesis of 1,3-dithiolium salts 3 by the disappearance of the signals of carbonyl and thiocarbonyl carbon atoms present in the dithiocarbamates spectra and the appearance of a new signal at a very low field (ca. 183ppm) which correspond to the electron deficient C (2)  derived from propiophenone. The structure of new synthesized compounds has been proved by analytical and spectral (NMR, IR, UV-Vis, MS) data.