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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 H )-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.

Ethyl 5-cyano-1,6-dihydro-2-methyl-4-(2'-thienyl)-6-thioxonicotinate ( A ) was synthesized and reacted with ethyl chloroacetate in the presence of sodium acetate or sodium carbonate to give ethyl 5-cyano-6-((2-ethoxy-2-oxoethyl)thio)-2-methyl-4-(2'-thienyl)nicotinate ( 1a ) or its isomeric thieno[2,3- b ]pyridine 2a . 3-Aminothieno[2,3- b ]pyridine-2-carboxamide 2b was also synthesized by the reaction of A with 2-chloroacetamide. The reaction of 1a with hydrazine hydrate in boiling ethanol gave acethydrazide 3 . Heating ester 1a with hydrazine hydrate under neat conditions afforded 3-amino-1 H -pyrazolo[3,4- b ]pyridine 10 . Compounds 2b , 3, and 10 were used as precursors for synthesizing other new thieno[2,3- b ]pyridines and pyrazolo[3,4- b ]pyridines containing mainly the ethyl nicotinate scaffold. Structures of all new compounds were confirmed by elemental and spectral analyses. Most of the obtained compounds were evaluated for their insecticidal activity toward the nymphs and adults of Aphis gossypii (Glover,1887). Some compounds such as 4 , 9b, and 9c showed promising results. The effect of some sublethal concentrations, less than LC 50 , of compounds 4 , 9b, and 9c on the examined Aphis was subjected to a further study. The results demonstrated that exposure of A. gossypii nymphs to sublethal concentrations of compounds 4 , 9b, and 9c had noticeable effects on their biological parameters, i.e., nymphal instar duration, generation time, and adult longevity. The highest concentration C1 of all three compounds increased the nymphal instar duration and generation time and decreased adult longevity and vice versa.

Ethyl 5-cyano-1,6-dihydro-2-methyl-4-styryl-6-thioxonicotinate, its piperidinium pyridine-6-thiolate and 3-acetyl-5-cyano-1,6-dihydro-2-methyl-4-styryl-6-thioxopyridine were used as starting materials for synthesizing novel series of S-substituted methylthiopyridine-5-carbonitriles and thieno[2,3-b]pyridines with expected biological activity. Also, some novel thieno[2,3-c][2,7]naphthyridinones were synthesized. Moreover, 1,7-diamino-8,9-dihydro-5-methyl-8-phenyl-3H-pyrazolo[3,4-c][2,7]naphthyridine-6(7H)-one was synthesized by heating ethyl 5-cyano-1,6-dihydro-2-methyl-4-styryl-6-thioxonicotinate with hydrazine hydrate 99% under neat conditions. The obtained promising aminopyrazolo[3,4-c][2,7]naphthyridine-6(7H)-one was used as a precursor to get other novel derivatives with expected biological and medicinal importance. Structures of all new compounds were elucidated by elemental and spectral analysis. [ABSTRACT FROM AUTHOR]