Larvicides are insecticides designed to kill insects during their larval stage. Among the mosquito species, Culex quinquefasciatus is particularly associated with various vector-spread diseases in several regions. These types of diseases have economic and social impacts worldwide. Mosquitoes are an important transmission vector for several diseases, particularly malaria 17, 18. However, the present study focused on the grindstone green chemistry method in order to overcome the abovementioned challenges in the preparation of Mannich base derivatives. In addition, some of the known green trends in Mannich reactions consist of ball milling without solvents 12, using ionic liquid mediums 13, using ionic liquids reinforced with nanoparticles 14, or applying enzymes under bio-catalytic conditions 15, 16. Other challenges include synthetic methodologies such as ultrasound or microwave irradiation, the use of Lewis acids or bases, and the use of solubilizing agents or surfactant-type catalysts 11. Mannich-type reactions face significant challenges in terms of reaction time, reaction conditions, toxicity, catalyst requirements, and separation and determination of the purity of final product(s). The met type of tyrosinase is an enzymatic form wherein two cupric ions are bridged by one or two tiny ligands, along with water molecules or hydroxide ions, while the enzyme is at rest and acting as a catalyst. The met type signifies a condition wherein copper atoms only at the active site have been oxidised but have not been bound by dioxygen. Dioxygen bonds as a peroxide ion in the oxy form in the µ-ŋ 2:ŋ 2 side-on bridging mode. The active core of the deoxy type contains two cuprous ions, which attach dioxygen to produce the oxy form. The dicopper core of this type-3 copper protein takes three redox forms 3, 4, 5, 6, 7, 8. Tyrosinase, alongside catechol oxidase 9 and hemocyanin 10, belongs to the type 3 copper protein class. Mushroom tyrosinase, which has a dinuclear copper active centre, catalyses the hydroxylation and subsequent oxidation reactions that convert phenol to the related ortho-quinone as well as the oxidation of catechol to quinone 3, 4, 5, 6, 7, 8. We will now focus on Mannich reactions, which are a widely studied type of reaction in the organic and medicinal chemistry domains 2. developed a range of chemical reactions carried out by simply grinding or triturating the solids together 1. Of the several green chemistry methodologies, the grindstone chemistry technique is a simple practice for the preparation of chemical compounds. For instance, as a scientist in chemical industries or academia, one could focus on protecting nature by employing green chemistry to produce various chemical and pharmaceutical active ingredients. It is both the legal and moral obligation of every human to protect planet Earth by undertaking activities that would prevent contamination of our planet and thereby protect it for future generations. In the broadest sense, human beings are part of nature however, our activity is often understood and interpreted as a category that is unique and separate from the rest of the natural phenomena. Lead molecules are important for their larvicidal properties and application as insecticides. Molecular docking studies also supported the finding that 1i is a potent larvicide with higher binding energy than the control (− 10.0 vs. quinquefasciatus and was non-toxic to non-target aquatic species. Compound 1i was found to possess a high larvicidal activity against C. Compounds 1a, 1e, 1f, 1j, and 1k were found to be highly toxic, whereas 1i was not toxic in antifeedant screening. Compound 1i (1-(5-oxo-1,5-diphenylpent-1-en-3-yl)-3-(3-phenylallylidene)thiourea) was notably more active (LD 50: 28.5 µM) against Culex quinquefasciatus than permethrin(54.6 µM) and temephos(37.9 µM), whereas compound 1i at 100 µM caused 0% mortality in Oreochromis mossambicus within 24 h in an antifeedant screening, with ichthyotoxicity determined as the death ratio (%) at 24 h. In this study, a total of 17 compounds ( 1a–1q) were synthesised, and their larvicidal and antifeedant activities were evaluated. The synthesised compounds were identified by FTIR, 1H NMR, 13C NMR, mass spectrometry, and elemental analysis. This method showed a high yield under mild reaction conditions. 1,5-diphenylpent-4-en-1-one derivatives were synthesised using the grindstone method with Cu(II)-tyrosinase used as a catalyst.