DFT and FT-IR study reveals electronic and optical traits of a pyrimidine compound

Chemists have combined laboratory spectroscopy with quantum mechanical calculations to build a detailed picture of 4,6-dimethyl-2-hydroxy pyrimidine, a small heterocyclic molecule built around a six-membered ring containing two nitrogen atoms. The compound was synthesized in a single step from urea and 2,4-pentanedione in water, with trifluoroacetic acid added to the hot reaction mixture followed by two hours of reflux. The product, obtained as a light pink solid in 97.5 percent yield with a melting point of 202 to 205 degrees Celsius, was characterized by proton and carbon-13 nuclear magnetic resonance spectroscopy as well as Fourier-transform infrared spectroscopy, and then subjected to a battery of density functional theory calculations at the B3LYP/6-31G(d,p) level.

The infrared work formed the experimental backbone of the study. The spectrum was recorded in the 450 to 4000 wavenumber range using a potassium bromide pellet method, and the molecule, which contains 17 atoms, was predicted to exhibit 45 fundamental vibrations. Because the theoretical calculations describe an isolated molecule in the gas phase while the measurements were made on a solid, the raw computed wavenumbers ran higher than the observed values. The researchers therefore applied a scaling factor of 0.9679 to correct for basis set limitations and neglected anharmonicity, and used potential energy distribution analysis to connect individual computed modes with the measured bands.

The agreement between theory and experiment was close. The correlation coefficient between the scaled calculated and observed wavenumbers reached 0.9977, which the authors describe as a strong match. Specific assignments followed the familiar logic of vibrational spectroscopy. The band at 3702 wavenumbers in the observed spectrum was attributed to O-H stretching, matching a predicted value of 3662.38 wavenumbers with full potential energy contribution. Aromatic carbon-hydrogen stretching of the pyrimidine ring was calculated at 3111 wavenumbers and matched the observed band at 3062. Carbon-carbon skeletal stretches, methyl group stretching and bending modes, carbon-nitrogen stretches, and carbon-oxygen stretches were all assigned in the same way, with the experimental bands at 1634, 1570, 1490, 1366, 1282, 1420, and 1072 wavenumbers aligning with their computed counterparts.

Geometry optimization at the same level of theory showed an almost planar pyrimidine ring, which the authors say facilitates electron delocalization within the ring system. The shortest computed bond length belonged to the O5-H11 bond at 0.9801 angstroms and the smallest bond angle to H16-C8-H17 at 106.79 degrees, while the longest bond was C2-C8 at 1.5024 angstroms and the widest angle was N1-C6-N9 at 127.133 degrees. The computed bond lengths and angles were reported to be consistent with values published for other pyrimidine derivatives, and the nitrogen atoms in the heterocyclic ring were noted to influence the electronic structure and redistribute electron density across the molecule.

Frontier molecular orbital analysis placed the highest occupied molecular orbital at minus 8.96 electron volts and the lowest unoccupied molecular orbital at minus 4.46 electron volts, giving an energy gap of 4.50 electron volts. According to the authors, this gap indicates moderate chemical stability and the potential for intramolecular charge transfer. The HOMO was found to sit mainly over the electron-rich part of the molecule, acting as an electron donor, while the LUMO lay over the electron-deficient portion and acted as an electron acceptor. Deeper and higher adjacent orbitals, HOMO-1 and LUMO+1, were also mapped because they contribute to electronic transitions in conjugated systems. From these orbital energies, and using Koopmans’ theorem, the team derived a set of global reactivity descriptors including electronegativity, chemical potential, global hardness, softness, and the electrophilicity index.

Those descriptors painted a picture of a reactive molecule. The softness value came out low at 0.444, while the computed electrophilicity index of 10.011 was described as indicating a strong electrophilic character that may influence the compound’s chemical reactivity and its possible interactions with biological targets. A complementary local analysis using condensed Fukui functions, local softnesses, and local electrophilicity indices, calculated with Hirshfeld population analysis, identified which atomic sites are most vulnerable to which kind of attack. Sites C3 and O5 showed high values of the nucleophilic-attack descriptors, whereas C7, C8, N1, and N9 showed high values of the electrophilic-attack descriptors, giving a site-by-site reactivity map for the molecule.

A natural bond orbital study provided direct evidence of intramolecular charge transfer. The second-order perturbation analysis quantified stabilization energies for donor-acceptor interactions between occupied bonding orbitals or lone pairs and unoccupied antibonding orbitals. Among the reported interactions, electron donation from the pi orbital of the N1-C2 bond to the antibonding pi orbital of C6-N9 carried a stabilization energy of 39.94 kilojoules per mole, donation from the pi orbital of C3-C4 to the antibonding orbitals of N1-C2 and C6-N9 gave 36.08 and 11.13 kilojoules per mole, and donation from the second lone pair of the oxygen atom to the antibonding pi orbital of C6-N9 gave 40.79 kilojoules per mole. The largest values involved antibonding donors, with the pi star orbital of N1-C2 donating to the pi star orbital of C3-C4 at 193.99 kilojoules per mole and the pi star orbital of C6-N9 donating to the antibonding orbitals of N1-C2 and C3-C4 at 242.85 and 94.57 kilojoules per mole. The authors interpret these comparatively high stabilization energies as evidence of extensive electron delocalization within the pi framework of the heterocyclic ring.

The nonlinear optical assessment centered on the first-order hyperpolarizability, computed at the same B3LYP/6-31G(d,p) level. The molecule returned a dipole moment of 2.6026 debye, an average polarizability of 11.29 times ten to the minus 24 esu, and a first-order hyperpolarizability of 1.138 times ten to the minus 30 esu. Urea, the conventional benchmark in this field, has a dipole moment of 1.3732 debye and a first hyperpolarizability of 0.3728 times ten to the minus 30 esu at the same basis set, so the title compound exceeds the reference on both counts. The authors note that the high beta value and non-zero dipole moment suggest the compound may be a good candidate for nonlinear optical materials, a class of substances used in photonics, switching, modulation, and frequency conversion, although these are computed values for a single molecule rather than measurements on a bulk material or device.

Molecular electrostatic potential mapping added a spatial dimension to the reactivity analysis. The surface showed a major positive potential region, colored blue, around the hydrogen atom of the hydroxyl group, marking it as the site for nucleophilic attack, while negative potential regions, colored red or yellow, appeared around the oxygen and nitrogen atoms of the pyrimidine ring, marking sites for electrophilic attack. The authors conclude that the heteroatoms in the ring play the primary role in the molecule’s charge distribution, and that the positive regions around hydrogen atoms raise the probability of nucleophilic interactions while the negative regions around oxygen and nitrogen favor electrophilic and intermolecular interactions.

Finally, the team ran a drug-likeness screen using Lipinski’s rule of five with the Molinspiration tool. The molecule passed every criterion: a molecular weight of 124.14 grams per mole, a topological polar surface area of 46.01, one hydrogen bond donor, three hydrogen bond acceptors, and a calculated logP of 0.78, with no violations of the rule. The authors attribute this favorable profile to the low molecular weight and moderate polarity conferred by the nitrogen and oxygen heteroatoms, and suggest the values indicate good solubility, membrane permeability, and potential oral bioavailability. They are careful to frame this as a computational prediction of physicochemical properties rather than evidence of biological activity or therapeutic benefit; no biological testing was performed in this study. Taken together, the synthesis, the vibrational assignments with their near-perfect correlation, the orbital and charge-transfer analysis, and the optical and drug-likeness estimates offer a consolidated computational and spectroscopic profile of a simple pyrimidine derivative whose electronic behavior, the authors argue, had not previously been examined in such a combined experimental and theoretical treatment.

Subject of Research: Density functional theory and spectroscopic analysis of the synthesized compound 4,6-dimethyl-2-hydroxy pyrimidine

Article Title: Spectroscopic and quantum mechanical studies of 4,6-dimethyl-2-hydroxy pyrimidine by density functional method

Article References: Khanam, H., Awasthi, N., Fatma, S., Mishra, A., Bishnoi, A., & Pandey, J. (2026). Spectroscopic and quantum mechanical studies of 4,6-dimethyl-2-hydroxy pyrimidine by density functional method. Discover Molecules, 3(1), Article 37. https://doi.org/10.1007/s44345-026-00064-w

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DOI: 10.1007/s44345-026-00064-w

Keywords: 4,6-dimethyl-2-hydroxy pyrimidine, density functional theory, FT-IR spectroscopy, B3LYP, frontier molecular orbitals, hyperpolarizability, nonlinear optics, natural bond orbital analysis, molecular electrostatic potential, Lipinski rule of five, pyrimidine, reactivity descriptors