Pyridine Derivatives as Insecticides: Part 6. Design, Synthesis, Molecular Docking, and Insecticidal Activity of 3-(Substituted)methylthio-5,6,7,8-tetrahydroisoquinoline-4-carbonitriles Toward <i>Aphis gossypii</i> (<i>Glover</i>, 1887)

Three new series of 3-(substituted)methylthio-4-cyano-5,6,7,8-tetrahydroisoquinolines were designed and synthesized starting from readily available materials, 7-acetyl-4-cyano-1,6-dimethyl-6-hydroxy-8-(4-pyridyl, 3-pyridyl, phenyl, 4-methoxyphenyl, or 4-chlorophenyl)-5,6,7,8-tetrahydrosoquinoline-3(2<i>H</i>)-thiones <b>2a</b>-<b>e</b> in high yields and very pure states. Thus, compounds <b>2a</b>-<b>e</b> were reacted with some chloro reagents, namely, <i>N</i>-aryl-2-chloroacetamides <b>3a</b>-<b>f</b> and <i>N</i>-(naphthalen-2-yl)-2-chloroacetamide (<b>3g</b>) under mild basic conditions to give the first two series of the target compounds, 3-(<i>N</i>-aryl)carbamoylmethylthio-5,6,7,8-tetrahydroisoquinoline-4-carbonitriles <b>4a</b>-<b>l</b> and <b>5a</b>-<b>e</b>, respectively. Reaction of compounds <b>2d</b>,<b>e</b> with ethyl chloroacetate under the same conditions gave the other series, 3-ethoxycarbonyl-methylthio-5,6,7,8-tetrahydroisoquinoline-4-carbonitriles <b>6d</b>,<b>e</b>. Structural formulas of all of the new compounds were elucidated and confirmed by elemental and spectral analyses. The insecticidal activity of all synthesized 5,6,7,8-tetrahydrosoquinolines toward the nymphs and adults of <i>Aphis gossypii</i> were screened. The results revealed the promising insecticidal activity of some tested compounds. Moreover, the structure-activity relationships as well as molecular docking of some representative compounds were evaluated.