Synthesis of Bactericides via Carbon Nucleophilic Addition on 1,3-Diarylprop-2-enones as Michael Acceptors

Treatment of α,β-unsaturated ketones (I) with malononitrile in presence of ammonium acetate afforded 2-amino-4,6-diarylnicotinonitriles (II) which reacted with aq.alc.KOH, CS 2 (pyridine), CS 2 (EtOH/NaOH), phenyl isothiocyanate and guanidine hydrochloride to yield the corresponding heterocyclic products (III-VII) respectively.When I was allowed to react with cyanoacetanilide, ethyl chloroacetate, benzyl cyanide, 4-chlorobenzaldehyde and potassium cyanide, it gave the Michael adducts (VIII-X II).Fusion of X Ib with hydrazine hydrate afforded XIII whereas treatment of X Ib with hydrazine hydrate and/or hydroxylamine hydrochloride gave X IVa and b respectively.The evaluation of the minimal inhibitory concentration (MIC) of some of the synthesized compounds was As an extension of our program to study the addition reactions on α,β-unsaturated aromatic ketones (chalcones) 1-4 as one of the most important classes of conjugate acceptors, we describe in this work onestep and efficient routes which constitute convenient syntheses of heterocyclic compounds (some of which have biological activities) from the above mentioned readily obtainable chalcones.Thus, when 1-(2,4dimethoxyphenyl)-3-(4' -chlorophenyl)-and/or 3-(3' ,4' -methylenedioxyphenyl)prop-2-enone (Ia and/or Ib) was allowed to react with malononitrile in a 1:1 molar ratio in the presence of excess AcONH 4 , it yielded 2-amino-4,6-diarylnicotinonitriles (IIa and b) respectively. 5When the nicotinonitriles (IIa and/or IIb) were subjected to heating with aq.ethanolic 20% potassium hydroxide, hydrolysis of the cyano functionality occurred to afford 2-amino-4,6-diarylnicotinamides (IIIa and b) respectively.The reaction of nicotinonitriles (IIa and b) with carbon disulfide afforded a product depending upon the reaction conditions and permits the synthesis of some new fused thiazines and pyrimidine-2,4-dithiones.When the reaction was carried in refluxing pyridine, the isolated products were identified as 1H-5-aryl-7-(2,4-dimethoxyphenyl)-4-iminopyrido[2,3-d]thiazine-2-thione derivatives (IVa,b) respectively.On the other hand, when carried out.compound (IIa) was allowed to react with carbon disulfide in refluxing ethanol in the presence of sodium hydroxide followed by acidification with 20% HCl, 1H,3H-5-(4' -chlorophenyl)-7-(2,4-dimethoxyphenyl)pyrido[2,3-d]pyrimidine-2,4-dithione (V) was obtained. 6,7This reaction represents the synthetic method of choice to synthesise the pyrimidinedithiones.A heterocylic ring transformation was observed when the thiazinthione (IVa) was boiled with aq.ethanolic 20% sodium hydroxide solution followed by acidification with 20% HCl since it isomerized to pyrimidinedithione (V) which was identified by mp, mixed mp, IR spectra and TLC comparison.Treatment of 2-aminonicotinonitriles (IIa and/or IIb) with phenyl isothiocyanate and/or guanidine hydrochloride in refluxing dry pyridine and absolute ethanol in the presence of sodium acetate respectively resulted in the corresponding pyrido[2,3-d]pyrimidine-2-thiones (VIa and b) and 2-guanidopyridine derivatives (VIIa and b), unfortunately we did not obtain the desired product, pyrido[2,3-d]pyrimidine derivative (VII' ), which assumed to be formed via the cycloaddition of amino group to the cyanide group.Authentic samples of the latter products were also obtained by treatment of IIa and b with urea and/or thiourea in refluxing ethanol (Scheme 1).Ar = C 6 H 3 (OMe)-2,4 2 2 1 P h -N = C = S VII' EtOH/ NaOH CS 2 HCl NaOH Scheme 1 a, Ar = C 6 H 4 Cl-4 b, Ar = C 6 H 3 (O 2 CH 2 )-3,4 VII N N CN Ar Ar H 2 N NH 2 EtOH NH H 2 N NH