Two-dimensional (2D) correlation spectroscopy is a powerful method to study the intermolecular interactions between different molecules/functional groups. In the present paper, variable concentrations were selected to construct 2D synchronous spectrum for studying the weak intermolecular interactions in solutions. Mathematical analysis performed on 2D synchronous spectra using variable concentration as an external perturbation shows that the "Orthogonal Sample Design Scheme" is necessary for eliminating the interfering cross peaks in 2D synchronous spectra. The authors prepared four mixed-solutes-solutions whose concentration series satisfy the "Orthogonal Sample Design Scheme" for each chemical system and the consequent 2D synchronous spectrum was calculated from the corresponding four 1D spectra. Thus, by 1D & 2D FTIR spectra together with solid grinding reaction, the intermolecular interactions in two chemical systems (Sodium 2-Aminobenzoate/NdCl3 in aqueous solution, and 2-ethylhexyl phosphonic acid mono 2-ethylhexyl ester (PC88A)/Naphthenic Acid (NA) in heptane solution) were studied, where the intermolecular interactions only induce subtle spectral variations in conventional 1D spectra. First, the cross peaks between f-f transition bands of Nd3+ ion at 521, 574, 741, 795 and 865 nm and pi-pi transition band of Sodium 2-Aminobenzoate at 308 nm in 2D synchronous spectrum confirm the coordination interaction between Sodium 2-Aminobenzoate and Nd3+. Solid grinding reaction between Sodium 2-Aminobenzoate and NdCl3 and FTIR spectra of the product indicate that the vibration bands of amino, carboxyl groups from sodium 2-aminobenzoate show considerable changes. Based on the spectral result above, a conclusion is drawn that Nd3+ can coordinate with Sodium 2-Aminobenzoate by amino and carboxyl groups. Second, the cross peaks between POH stretching band of PC88A at 983 cm(-1) and COOH stretching band of NA at 1 710 cm(-1) in 2D spectra confirm the interaction between PC88A and NA. Subtraction spectrum demonstrates that when PC88A is mixed with NA in heptane solution, and P=O stretching band of PC88A shifts from 1 199 to 1161 cm(-1), and POH stretching band shifts from 983 to 965 cm(-1). Based on the spectral result above, a conclusion was made that PC88A and NA can interact with each other by forming new assemblies with POH and COOH groups.