Synthesis of some substituted pyrimidines via cycloaddition reaction of amidines and chalcones

Substituted amidines (1,2) where prepared from the condensation of benzyl, furfuryl alcohols and ethyl sulphate with thiourea. Chalcone compounds (3,5a and 5b) where also prepared from condensation of 4nitrobenzaldehyde to give compound (3) while acetophenone, 4-hydroxy benzaldehyde and 1,3-dibromopropane gave the diformyl intermediate (4) then it was underwent further reaction with either acetophenone or 4methyl acetophenone to afford compounds (5a,5b) respectively. Condensation of the above amidines with the resulted chalcones or dichalcones afforded the substituted pyrimidines (6-11). Their structures confirmation were studied by IR and were discussed. Synthesis of some substituted pyrimidines via cycloaddition reaction of ... 39 INTRODUCTION Azarifar and Shacbanzadeh (1) prepared a number of chalcones by condensing substituted 1-acetyl naphthalene with naphthaldehyde in ethanolic solution. The Chalcones themselves were prepared in high temperature water without any use for base or acid catalysis (2) ,and treated the later with hydrazine derivatives to obtain the corresponding pyrazolines. Different pyrazolines (3-8) and bis pyrazolenes (9,10) have been synthesized in good to excellent yields from the precursor chalcones and bis-chalcones with suitable reagents. Pyrimidine derivatives have been prepared from the reaction of chalcones and amidines (11,12) . On the other hand 2-amino-4-(2,4-dichalcon-5-flurophenyl)-6-aryl pyrimidines were also prepared from substituted chalcones and quanidine (13) . Transchalcones represent an important class of compounds employed as such for their luteratiy antineoplastic, spasmolytic, antibiotic, bacterostatic and bactericidal properties (14) or due to their chemical flexibility, as synthons for the production of five and six-membered ring systems (15) . Some researchers studied the biochemical characterization and mutational of a chalcone synthesized from yellow snapdragou (Antirrhinum majus). According to the abover importance of chalcones, we investigate the reaction of new series of amidates and some new synthesized chalcones to afford new derivatives of pyrimidines. EXPERIMENTAL Melting points were determined using Electrothermal 9300 melting point apparatus (uncorrected). I.R. spectra was recorded by infrared spectrophotometer model Tensor 27 Bruker Co. using KBr discs. Synthesis of 5-benzyl isothioronium chloride (1a) (16) A mixture of (0.24 mole) of benzyl chloride and (0.24 mole) of thiourea in 20 ml of ethanol was refluxed carefully for 30 minutes, during which time a vigorous reaction takes place the resulting homogeneous solution was cooled and the precipitated solid was recrystallized from ethanol. The product is melts at (172-174) C with yield of 95% (Lit. m.p. = 172-174 o C). Synthesis of 5-ethyl thioronium sulfate (1b) (17) A mixture of (1.0 mole) thiourea and (0.55 mole) of diethyl sulfate was heated in an oil bath at a temperature of about (130-140 C) a vigorous exothermic reaction starts and the temperature of the mixture was held below 180 C heating was continued at temperature of 170-180 C for 2 hours and the cooled product was titurated with a mixture of ethanol and ether to remove excess diethyl sulfate yield (80%), m.p. = 9799 C (Lit. = 95-97 o C). M. S. Al-Ajely & G. T. Sedeek & H. M. Al-Ajely 40 Synthesis of S-2-furfuryl isothiouream chloride (1c) (18) In round bottomed flask was placed (0.5 mole)of thiourea and (5 ml) of water and (4 ml) of concentrated hydrochloric acid, the solid was dissolved by gentle heating and the solution was cooled to 30 C. (0.5 mole) furfuryl alcohol was added to the reaction mixture. The reaction which usually commences spontaneously within a few minutes was strongly exothermic and should be controlled by suitable cooling with tap water so as to hold the temperature near 60 C when the reaction subsides cooling was discontinued and the clear dark green solution was allowed to stand at room temperature for 12 hours to obtain solid product with yield of (93%), m.p. > 300 C. Synthesis of pyridino amidine hydrochloride (2) (19) A flask containing (0.058 mole) of 3-cyanopyridine dissolved in 50 ml of dry chloroform and (0.065 mole) of absolute ethyl alcohol was cooled to 0 C while dry hydrogen chloride saturates the reaction mixture the contents were allowed to stand at (0 C) for 16 hrs., and then poured into a separatory funnel containing enough of ice-cold 50% sodium hydroxide solution to give an alkaline solution. The mixture was shaken vigorously and the chloroform layer separated, washed with water until neutral, dried over potassium carbonate and concentrated to give the crude imidate. The later was dissolved 75% aqueous ethanol containing (0.0224 mole) of ammonium chloride and heated at 70 C for 4 hrs., charcoal filtered and diluted with 2-3 volume of acetone. The unreacted ammonium chloride that separated was filtered and the filtrate was again diluted with acetone until the cloud point. After standing for several hours at 0 C, the product was separated as colourless needles with melting point of 190 C and 78% yield. Synthesis of 4-nitrobenzal acetophenone (3) (20) Acetophenone (1.2 gm, 0.01 mole) dissolved in (3 ml) ethanol. The mixture was added to a solution of (1.5 gm, 0.01 mole) of pnitrobenzaldehyde in (3 ml) ethanol, (5 ml) of 10% NaOH. The final mixture was stirred for 24 hours at room temperature. Then it was filtered off, washed with water till neutralization, dried and purified by recrystallization from ethanol, yield (89%), m.p. = 159-161 C. Synthesis of 1,3-bis (4-formyl phenoxy) propane (4) (21) A mixture of 4-hydroxy benzaldehyde (24.4 gm, 0.2 mole). 1,3Dibromopropane (18.7 gm, 0.1 mole) and anhydrous potassium carbonate (60 gm) in absolute ethanol (150 ml) was refluxed with stirring for six hours. The cold mixture was poured onto water, solid materials Synthesis of some substituted pyrimidines via cycloaddition reaction of ... 41 immediately was obtained. The desired product was filtered off, washed several times with water and cold ethanol, dried and recrystallized from ethanol to afford a white crystals yield (88%), m.p. = 118-120 C (Lit. = 119-120 o C). Synthesis of 1,3-bis (phenoxy propyl)-4,4`-bis chlacone (5a,b) (22) 1,3-Bis (4-formyl phenoxy) propane (0.134 gm, 0.001 mole) was dissolved in ethanol (5 ml) and added to the solution of (0.002 mole) of an appropriate acetophenones in ethanol (5 ml) and (2 ml) of (4% ethanolic NaOH). The mixture was stirred for 24 hours (at room temperature). Then the mixture was solidified and the pale yellow chalcones were separated by suction filtration, washed with ethanol and water to neutralize, dried and purified by recrystallization from ethanol. Yield (78%), m.p. = 196-197 C, 177-179 C for compounds a and b respectively. General procedure for the synthesis of 4-aryl-6-phenyl or tolyl-2-Ssubstituted thio or (3-pyridyl) pyrimidine (6a-c), (7a-c), (8a-c) and (911) respectively (11) Sodium carbonate (0.2 gm) was added to vigorous stirred solution of substituted amidine hydrochloride (2 mole) in (20 ml) DMSO the mixture was stirred at 20 C for 10 min. The chalcones (3,5a,b) (1 mole) was added. The reaction mixture was heated at 80 C for 18 hrs. with an air stream bubbled through. The melting points and IR data were showed in Table (1). M. S. Al-Ajely & G. T. Sedeek & H. M. Al-Ajely