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 Aphis gossypii (Glover, 1887)

Abstract

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(2H)-thiones 2a–e in high yields and very pure states. Thus, compounds 2a–e were reacted with some chloro reagents, namely, N-aryl-2-chloroacetamides 3a–f and N-(naphthalen-2-yl)-2-chloroacetamide (3g) under mild basic conditions to give the first two series of the target compounds, 3-(N-aryl)carbamoylmethylthio-5,6,7,8-tetrahydroisoquinoline-4-carbonitriles 4a–l and 5a–e, respectively. Reaction of compounds 2d,e with ethyl chloroacetate under the same conditions gave the other series, 3-ethoxycarbonyl-methylthio-5,6,7,8-tetrahydroisoquinoline-4-carbonitriles 6d,e. 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 Aphis gossypii 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.