We report here the results of a study to understand the formation mechanism of single crystals of the transition metal chalcogenide, CuS, at the water-toluene interface through an interfacial reaction. Systematic measurements carried out using synchrotron x-ray scattering, electron microscopy, atomic force microscopy and calorimetric techniques clearly show that nano-crystallites of CuS form within a few minutes at the interface as the reagents are brought from the organic (upper) and aqueous (lower) layers to the interface, then crystallization of CuS proceeds over a few hours only by reorganization, despite the large excess available in both upper and lower liquid phases. The interface confinement and passivation by organics is critical here in the formation of single crystals having sizes of 6 and 200 nm along the normal and in-plane directions of the liquid-liquid interface.