Synthesis and insecticidal activity of 1,2,4-oxadiazole and 1,2,4-thiadiazole derivatives

Abstract

A series of 5-substituted 1,2,4-oxadiazoles and 1,2,4-thiadiazoles were prepared as muscarinic acetylcholine receptor agonists and evaluated for their insecticidal activity. These derivatives were synthesized through sequential reactions consisting of the condensation of pyridinecarboamides or pyridinecarbothioamides with N,N-dimethylacetamide dimethyl acetal, cyclization with hydroxylamine, quaternization by alkyl halide and reaction with sodium borohydride. All 1,2,4-oxadiazoles and 1,2,4-thiadiazoles synthesized were evaluated for insecticidal activity and their structure-activity relationships are discussed. It was discovered that many compounds were active against representative insects such as Nilaparvata lugens, Nephotettix cincticeps and Aphis craccivora. In particular, it was also found that 3-pyridyl-substituted derivatives of 1,2,4-oxadiazole and 1,2,4-thiadiazole exhibited good insecticidal activity against all the insects tested. Among the compounds evaluated, 3-methyl-5-(1,2,5,6-tetrahydropyridin-3-yl)-1,2,4-thiadiazole (9m-2) showed the highest activity against Nilaparvata lugens, and provided a high level of activity against the imidacloprid-resistant strain. Based on the preliminary binding assay using the binding inhibition of mAChR antagonist [ 3 H]NMS to the nerve-cord membranes as an index of the binding activity, 9m-2 exhibited a range of potencies for the insect muscarinic receptor.

Building 1,2,4‐Thiadiazole: Ten Years of Progress

“…[46] In the same year, Suzuki and colleagues described the synthesis of a series of 5-substituted 1,2,4-thiadiazoles, with the final objective of testing their insecticide activity. [47] The new derivatives were synthesized through sequential reactions consisting of the condensation of pyridinecarbothioamides with N,N-dimethylacetamide dimethyl acetal, cyclization with hydroxylamine, quaternization with alkyl halides, and treatment with sodium borohydride. Scheme 27 shows the synthetic route to 5-(1,2,5,6-tetrahydropyridin-3-yl)-and 5-(piperidin-3-yl)-1,2,4-thiadiazoles 75 and 76, respectively, and their intermediates 73 and 74.…”

“…Synthetic approach to the production of 1,2,4-thiadiazoles 75 and 76. [47] Similarly, 5-(pyridin-4-yl)-1,2,4-thiadiazole (78), 5-(1,2,5,6-tetrahydropyridin-4-yl)-1,2,4-thiadiazole (80), and 5-(piperidin-4yl)-1,2,4-thiadiazole (81) were synthesized from thioisonicotinamide (77), as shown in Scheme 28. Peculiarly, in the reaction of 2-thiopicolinamide (82), the obtained pyridinium salt 84 could not be reduced to 5-(1,4,5,6-tetrahydropyridin-2-yl)-1,2,4thiadiazole (85) with sodium borohydride under similar conditions.…”

Turning renewable resources into value-added products: Development of rosin-based insecticide candidates

“…1. Meanwhile, thiadiazole heterocyclic group has been documented to show a wide range of bioactivities, for instance, insecticidal, antimicrobic, antifungal, antineoplastic, herbicidal, etc (Gomha et al, 2015;Lin et al, 2014;Popiołek et al, 2015;Sobhy et al, 2012;Suzuki et al, 2011;Wang et al, 2011). Enlightened by all of the descriptions above, 37 rosin-based amide derivatives containing thiadiazole group were synthesized.…”

Suzuki-Miyaura Coupling Reactions of 3,5-Dichloro-1,2,4-thiadiazole

“…1,2 The role played by the 1,2,4-thiadiazole unit includes that of reactive warhead in irreversible enzyme inhibitors, 3 a scaffold role in more conventional enzyme inhibition 4 and binding to human muscarinic receptors. 5 More recently, 1,2,4-thiadiazoles have been optimized as inhibitors of inducible nitric oxide synthase and have shown efficacy against acute inflammation and chronic neuropathic pain, 6 have shown affinity for insect muscarinc receptor(s) and hold promise as insecticides 7 and have been demonstrated to have chemoprotective potential as a result of inhibition of aromatase and NF-κB. 8 The synthetic methodology employed to make these various systems is limited.…”