Intermolecular cyclization of cinnamoyl isothiocyanate: A new synthetic entry for pyrimidine, triazine, and triazole candidates

An efficient and facile protocol for the synthesis of azine and azole ring systems was reported. Whereas, reaction of cinnamoyl isothiocyanate with <i>N</i>-nucleophile containing compounds (namely, <i>p</i>-aminophenol (<b>2</b>), <i>N</i>¹-phenylbenzene-1,4-diamine (<b>5</b>) and <i>p</i>-aminoacetophenone (<b>8</b>)) tolerated thiourea derivatives <b>3, 6</b>, and <b>9</b>, respectively. The later compounds underwent intramolecular cyclization upon treatment with EtONa to give pyrimidinethiones <b>4, 7</b>, and <b>10</b>, respectively, in moderate yield (74–79%). Compound <b>9</b> underwent intramolecular cyclization and condensation upon reaction with NaOH and benzaldehyde to give pyrimidinethione <b>12</b>. Thiosemicarbazides <b>14</b> and <b>19</b> were obtained through reaction of heteroallen <b>1</b> with 2,4-dinitrophenylhydrazine <b>13</b> and hydrazone <b>18</b>, respectively. Compound <b>14</b> was cyclized to pyrimidinethione <b>15</b> and triazine derivatives <b>17</b> through its reaction with EtONa at room temperature and refluxing temperature, respectively. Finally, base mediated and oxidative cyclization of thiourea derivative <b>19</b> with EtONa, Br₂/AcOH, and Pb(OAc)₂ afforded thiadiazole <b>20</b>, benzothiazolotriazole <b>21</b>, and triazolethione <b>22</b> derivatives, respectively.