Solvent and Catalyst‐Free One‐Pot Synthesis of Tetrahydropyrimidine Analogs for Their Larvicidal Activity and Structural Insights
A series of ester derivatives of (6-methyl-4-phenyl-2-thioxo-1, 2, 3, 4-tetrahydropyrimidin-5-yl)(piperidin-1-yl) methanone (6a-6k) have been synthesized using a solvent and catalyst-free one-pot two-step synthetic method. These 11 molecules have been characterized by spectroscopic techniques such as FT-IR, NMR (<sup>1</sup>H and <sup>13</sup>C), and single-crystal x-ray structural analysis. The Hirshfeld surface and 2D fingerprint plot elucidated the intermolecular interactions and their contribution to crystal packing. Furthermore, the computational calculations, such as FMOs and MEP, revealed the global reactivity descriptors and sites for noncovalent interactions, such as hydrogen bonding, respectively, in these pharmacophores. Among these derivatives, the 6h molecule, which bears -CF<sub>3</sub> on the phenyl ring, has piperidine substitution on the ester group and contains a thiourea moiety, demonstrated the best larvicidal activity against Anopheles arabiensis, achieving a 94% mortality rate compared to the standard sample Temephos (98%).
Authors
- Katharigatta Narayanaswamy Venugopala (ORCID: https://orcid.org/0000-0003-0680-1549)
- Rahul D. Nagdeve (ORCID: https://orcid.org/0000-0001-9695-0833)
- Sandeep Chandrashekharappa (ORCID: https://orcid.org/0000-0003-2475-7270)
- Jyoti Swarup Thakur (ORCID: https://orcid.org/0000-0002-5935-6592)
- Susanta K. Nayak (ORCID: https://orcid.org/0000-0002-3175-9007)
- Viresh Mohanlall (ORCID: https://orcid.org/0000-0002-0103-7089)
- Osama I. Alwassil (ORCID: https://orcid.org/0000-0002-6572-8321)
- Deepak Chopra (ORCID: https://orcid.org/0000-0002-0018-6007)
- Keshab M. Bairagi (ORCID: https://orcid.org/0000-0002-7996-9601)
- Raquel Miranda Gleiser (ORCID: https://orcid.org/0000-0003-0726-2639)
- Manashi Panda (ORCID: https://orcid.org/0009-0007-6772-167X)
- Abdulaziz Almulhim (ORCID: https://orcid.org/0000-0002-3727-7543)
- Rohit Bhowal (ORCID: https://orcid.org/0000-0002-6688-8378)
Institutions
- Universidad Nacional de Córdoba (AR)
- Visvesvaraya National Institute of Technology (IN)
- Durban University of Technology (ZA)
- King Saud bin Abdulaziz University for Health Sciences (SA)
- Indian Institute of Science Education and Research, Bhopal (IN)
- Gondwana University (IN)
- National Institute of Pharmaceutical Education and Research (IN)
- King Faisal University (SA)
Publication Details
- Journal
- Archiv der Pharmazie
- Published
- 2025-12-01
- DOI
- https://doi.org/10.1002/ardp.70162
- Primary Topic
- Multicomponent Synthesis of Heterocycles
- Type
- article
- Field-Weighted Citation Impact
- 0.00