Three novel tetra substituted p‑tert-butylthiacalix[4]arene derivatives (3, 4, and 5) with five coordinating carbonyl groups at the lower rims were synthesized. Accordingly, diethyl tetra-t‑butyl‑trihydroxy-tetrathia-tetrabenzenacyclooctaphanyl)oxy)malonate react with ethyl bromoacetate, phenacyl bromide and 2‑chloro-N-(p-tolyl)acetamide, to produce new p‑tert-butylthiacalix[4]arenes in of 60, 90, and 80% yields, respectively. The molecular structures of the products were verified using FT-IR, ¹H NMR, and ¹³C NMR spectroscopy. Metal ions such as Na⁺, K⁺, Cs⁺, Hg²⁺, Cd²⁺, Pb²⁺, Ni²⁺, Co²⁺, Cu²⁺, and Ag⁺ are easily chelated by the new thiacalixarene derivatives using liquid-liquid extraction technique. These compounds surprisingly show high efficiency in liquid-liquid extraction of alkali, heavy, and transition metal ions. Uptake efficiencies of 71.00% (for Co(II)), 46.00% (for Cu(II), and 15.00% (for Hg(II)) were attained by thiacalixarene 3, 4, and 5. These derivatives were subjected to DFT-based computational analysis with the aim of increasing the efficiency with which thiacalixarene (as a nucleophilic) interacts with the metal ion (3, 4, and 5 in the role of electrophile).