Synthesis of some Pyrimidine-2-one and Pyrimidine-2-thione Compounds

An efficient synthesis of chalcones (1-7) was achived by condensation of substituted benzaldehyde with substituted acetophenone in ethanolic sodium hydroxide (50%).The chalcones were reacted with urea and thiourea to give the pyrimidinones(8-14) and pyrimidinethiones(15-21) respectively. All the prepared compounds were confirmed by the available physical and spectral methods.


INTRODUCTION
The hetrocyclic molecules are of biological interest due to their potential physical and chemical properties (Brown,1998).Among these the pyrimidine compounds which occupy aunique position in pharmaceutical chemistry.They are components of nucleic acids.The important pyrimidine compounds have diverse applications as anti-bacterial (Pershin et al.,1972), fungicidal (Metolcsy,1971), analgesics (Regnier et al., 1972), anti-inflammatory (Winter et al.,1962) and anti-tumor agents (Suguira et al.,1973).Nowadays the one step method involving three component condensation using different reagents (Dipti et al., 2010) are popular in synthetic organic chemistry for the synthesis of heterocyclic compounds.They are present in nature and are of great significance to life because their structural subunits exist in many natural products such as vitamins, hormones, antibiotics (Yuhong and Varma, 2006).Hence,they have attracted considerable attention in the design of biologically active molecules.(Kawamoto et al., 2003).A practical method for the synthesis of such compounds is of great interest in synthetic organic chemistry.(Junichi et al., 2000).
Chalcones either natural or synthetic are known to exhibit various biological activities.They have been reported to possess anti-oxidant, anti-leishmanial, anti-inflammatory antitumor and anti-bacterial activity.The presence of reactive α,β -unsaturated keto function in chalcone is found to be responsible for their anti microbial activity (Larsen et al., 2005).
Chalcones considered as a precursor of flavonoids and isoflavonoids and they are present in edible plants (stevens et al., 2000) and have also been shown to display a diverse array of pharmacological activities, such as anti-protozoal and antihyperglycemic properties (Liu et al., 2001) (Satyanarayana et al., 2004).In the present research, a series of chalcones was prepared as a synthon to synthesize new pyrimidine and pyrimidine thione compounds.

EXPERIMENTAL
Melting points (M.P) were measured on Electrothermal, Gallenkamp melting point apparatus and are uncorrected.Infrared (FTIR) spectra were recorded as (KBr) disc using a Bruker, FT.IR spectrophotometer tensor 27.Ultraviolet (U.V) spectra were performed on shimadzu UV-visible spectrophotometer UV-1650 PC using chloroform as a solvent.

A. Synthesis of 1,3-diaryl-2-propen-1-one (1-7) (Vogel, 1974):
To a stirred and ice cooledsolution of ( 0.055 mole, 50%) sodium hydroxide in (20 ml) of water and (12.5 ml ) of ethanol, a freshly distilled substituted acetophenone (0.043 mole) was added followed by (0.043 mole) of substituted benzaldehyde.The temperature of the mixture was mentained at (20-25 º C) with vigorous stirring for (2-3 hours), until the mixture became thick.The mixture was left in the refrigerator overnight.The product was filtered off under vacuum and washed with water until the filterates became neutral to litmus paper, washed with (20 ml) ice-cold ethanol, then recrystalized from ethanol.The physical properties and the spectral data were listed in Table (1).To amixture of chalcone(1-7)(0.025mole) and urea (3.0g,0.05mole), an aqueous sodium hydroxide solution (30%,15mℓ) and ethanol (75 mℓ) were added with stirring.The mixture was refluxed for (2 hours).The mixture was poured with stirring on (125ml) of water, then allowed to stand for (15 minutes).The mixture was filtered, and the filtrate was cooled in an ice-bath and acidified with concentrated hydrochloric acid.The precipitate was filtered off under reduce pressure then recrystallized from ethanol.The physical and the spectral data were listed in Table (2).
Table2: The physical properties and the spectral data of compounds (8-14).
Table3:The physical properties and the spectral data for compounds (15-21).

RESULT AND DISCUSSION
The carbonyl compounds are considered as a precursor for synthesis of many important heterocyclic compounds, through their reaction with other different compounds.This work involves preparation of chalcones which reacted consequently with urea and thiourea to form the pyrimidine-2-ones, pyrimidine-2-thiones respectively.The synthetic routes are shown in Scheme (1).The chalcones (1-7) have been prepared by condensation of aromatic aldehyde with substituted acetophenone under basic conditions (ethanolic sodium hydroxide solution).
The structure of compounds (8-14) was established by spectroscopic methods (Table 2).The FT, IR spectra showed a strong absorption bands at (1686-1672 cm -1 ) for the C=O bond stretching and a bands at (1635-1625cm -1 ) for the C=C bond stretching in addition to broad bands at (3450-3400 cm -1 ) for the N-H bond stretching.
The U.V spectra of compounds (8-14) (Jackman, 1978) showed λ max at 320-380 nm, i.e, they showed a blue shift relative to the λ max exhibited by chalcones.This blue shift attributed to the destruction of the conjugation.
On the other hand, the condensation of compounds (1-7) with thiourea under phase transfer catalysis afforded the pyrimidine-2-thione compounds (15-21).The structure of these compounds was established on the bases of spectroscopic methods (Table 3).
According to the theoretical calculations the preferred mechanistic route is the Michael addition (H.F and S.E for compound 15a are -25.089and 24.232 Kcal/mole respectively).This product is more stable than 15b (formed via Claisen addition H.F and S.E are -19.716and 29.158 Kcal/mole respectively).