Synthesis,spectroscopy, computational study and prospective biological activity of two novel 1,3,2-diazaphospholidine-2,4,5-triones

The preparation of two new 1,3,2-diazaphospholidine-2,4,5-triones is reported. Thus, 2-chloro-1,3,2-diazaphospholidine-2,4,5-trione ClP(O)(NHC(O)C(O)NH) (I)] and 2-benzylamino-1,3,2-diazaphospholidine-2,4,5-trione C₆H₅CH₂NHP(O)(NHC(O)C(O)NH) (II)] have been synthesized by the reaction of POCl₃ with the corresponding carboxylic diamide salts. The characterization of the compound I was performed by multinuclear (¹H, ¹³C, ³¹P) NMR and FTIR spectroscopies, elemental analysis and also mass spectrometry. Both compounds show two signals at room temperature in the low field region of the ¹H NMR spectrum, which collapsed to a single peak when the temperature is increased. Dynamic NMR (¹H DNMR) and quantum chemical studies were performed to gain insight from this conversion process. The free activation energies, calculated at the coalescence temperatures are 18.51 and 17.45 kcal/mol for compounds (I) and (II), respectively, which are associated with a tautomeric interconversion process, most likely between the lactam and lactim forms. The relative energy, molecular geometry and vibrational properties of several plausible tautomers were analyzed by using quantum chemical calculations at the HF/6-311G** and B3LYP/6-311++G** levels of the theory. The nuclear magnetic shielding tensors have been calculated for both tautomeric forms using the gauge independent atomic orbital (GIAO) method at the B3LYP/6-311++G(3df,2p) level of approximation. A biological activity prediction using the PASS software shows that compound (I) can be characterized by a superb anti-HIV activity whereas compound (II) is a very good antineoplastic.