Reactivity of Hydrazine, Some Hydrazine derivatives and Diamines toward Ethyl 2,2-Dicyano-1-aryl (or alkyl) vinylcarbamate

2197 | P a g e J u n e 1 4 , 2 0 1 4 Reactivity of Hydrazine, Some Hydrazine derivatives and Diamines toward Ethyl 2,2-Dicyano-1-aryl (or alkyl) vinylcarbamate Fathi Zribi, Mansour Salem and Fakher Chabchoub Laboratoire de Chimie Appliquée : Hétérocycles, Corps gras et Polymères à la Faculté des Sciences de Sfax. Route de Soukra Km 3.5. BP 802. Sfax 3000. Tunisia *Corresponding author: zfnfethi@yahoo.fr ABSTRACT


INTRODUCTION
Over the years pyrimidinones derivatives have emerged as an interesting class of heterocycles with an astonishingly wide range of applications in pharmaceutical chemistry [1][2][3][4]. It is of great interest that specifically functionalized pyrimidinones may possess specific biological properties. Some are endowed with antiviral activity [5][6], antitumor activity [7][8], anti-inflammatory [9], antioxidant [10]. Many synthetic procedures exist for the synthesis of pyrimidinones derivatives [11][12][13][14][15]. However, the development of simple, easy and efficient methodologies to get pyrimidinones is one of the major aspects in organic synthesis. In fact, the ethyl 2,2-dicyano-1-aryl (or alkyl)vinylcarbamate derivatives are valuable intermediates in a variety of synthetic transformations. In the present study, we report the synthesis of some new pyrimidinones, dipyrimidinones and triazolones derivatives.

RESULTS AND DISCUSSION
Pyrimidine derivatives 2a-c were synthesized by cyclization, involving the reaction of substrates 1a-c with phenylhydrazine in chlorobenzene under reflux (scheme 1). The prepared compounds were characterized by spectroscopic techniques. The IR spectra showed the presence of two NH groups stretching at 3420-3241cm -1 and CN group stretching at 2220-2210 cm -1 . In 1 H NMR spectra the most significant information was the disappearance of the triplet and the quadruplet of ethoxy groups of the starting reagent 1ac.
Compounds 2a-c can be used for the synthesis of heterocyclic compounds. For example we have condensed 2b with tetraethyl othocarbonate. The result is the formation of 7-benzyl-2-ethoxy-5-oxo-3-phenyl-3,5-dihydro- [1,2,4] Furthermore, the reactivity of 1 towards benzohydrazide and acetohydrazide was also investigated as an alternative route to obtain pyrimidinylbezamide derivatives 4a-b and pyrimidinylacetamide derivatives 4c-e (scheme 3). The reaction was carried out in ethanol under reflux (benzohydrazide and acetohydrazide are not soluble in chlorobenzene). The intracyclization of compounds 4a-e is not observed (scheme 3). J u n e 1 4 , 2 0 1 4  The structures of compounds 4a-e are in accordance with their spectroscopic data. These new products were assigned by IR, NMR and mass spectroscopy. The IR spectra showed bands (NH), (CN), and (2C=O). In the 1 HNMR spectra of compounds 4c-e we have noticed the appearance of the singlet of methyl groups at around 2ppm.

Scheme 4
The reaction products were confirmed on the basis of their spectral data and mass spectroscopy (5a-b). The IR spectra of the isolated products showed the absence of cyano groups. It also showed absorption bands due to (NH) and (C=O). Besides, the mass spectra displayed the respective [M + H] + peaks.
Hydrazine hydrate reacts with its two nucleophilic centers (NH2 groups) but hydrazine derivatives (phenylhydrazine, benzohydrazide and acetohydrazide) react with one of their nucleophilic centers (NH2 and not NH). This may be due to the conjugation of NH with carbonyl or phenyl groups.
The structure of compounds 6a-f was proved on the basis of spectral data and mass spectroscopy. The IR spectra of 6a-f indicated the presence of NH group stretching at 3328-3132 cm -1 , CN group stretching at 2207-2210 cm -1 and C=O group stretching at 1660-1676 cm -1 . The 1 HNMR spectra of compounds 6a-b indicated a singlet at δ 3.74-3.79 due to CH2 group. Also, the mass spectra showed the respective [M + H] + peaks.

EXPERIMENTAL
Melting points are recorded in degrees Celsius on a Kofler apparatus. All reactions were followed by TLC (E. Merck Kieselgel 60 F-254), with UV detection at 254 nm. The IR spectra were recorded in the solid state as KBr discs on a Perkin-Elmer PARAGON 1000 FT-IR spectrometer. 1 H and 13 C NMR were determined in solution in DMSO-d6 with an AC Bruker spectrometer at 300 MHz using TMS as an internal standard. The mass spectra were recorded on an ion trap mass spectrometer (Finnigan LCQ Deca XP Max) using electrospray as an ionization source. The purity of all compounds was determined by LC-PDA-MS methods and was found to be in the range between 96-99%.

GENERAL EXPERIMENTAL PROCEDURE
General procedure for the preparation of 2a-c , 4a-e and 6a-f.
To a magnetically stirred solution of the ethyl 2,2-dicyanolvinylcarbamate derivatives 1a-d (1 mmol) in chlorobenzene or ethanol (10 mL), the appropriate hydrazine derivatives or diamine (1.2 mmol) were added and the reaction mixture stirred under reflux. The progress of the reaction was monitored by TLC (mobile phase, ethyl acetate: dichloromethane; 70/30;v/v). The resulting mixture was allowed to cool at room temperature. The precipitate formed was isolated by filtration and washed with diethyl ether to obtain the pure product.