A number of phenyl-substituted derivatives of 4-phenylamino-pent-3-en-2-one, APO-NPh, were synthesized. Their structures, intramolecular hydrogen bond strength, vibrational assignment, fluorescence, NMR, and UV spectra were studied by the help of density functional theory (DFT) and time-dependent density functional theory(TD-DFT) calculations, at the B3LYP/6-311++G** level, and also experimental techniques. The 2-fluoro, and 2,6-dimethyl derivatives showed reduced intramolecular hydrogen bond strength, while the 4-nitro, 4-ethyl ester increased it and 3-chloro and 3-bromo showed no change in comparison to APO-NPh. For the assignment of IR and Raman spectra of APO-NPh, isotope effects, GaussView animation, and potential energy distributions (PED) contributions were used. Also, for the best assignment, the 4-amino-3-penten-2-one (APO) and their VEDA's PED contributions were compared. Since in the titled molecules the NH stretching are covered by the aliphatic and aromatic CH stretching motions, the NH stretching frequencies were estimated using experimental ND stretching frequencies. The estimated frequencies are in good agreement with other theoretical and experimental results for intramolecular hydrogen bond strength. According to the frequency shifts upon deuteration for APO and APO-NPh, the assignment by the GaussView animation and VEDA's PED contributions show no important difference, except for the NH rocking, which appeared at 1320 cm−1. The theoretical results predicted two conformers for the ortho and meta substituted compounds. The X-ray result for the 2-fluoro derivative (3) shows that the major form is the one with fluorine closest to NH. TD-DFT and fluorescence results confirmed that aminoketone, iminoketone tautomerism is likely in the first excited state.