Synthesis and Molecular Docking Studies of N,N-Dimethyl Arylpyranopyrimidinedione Derivatives

The synthesis of N,N-dimethyl arylpyranopyrimidinedione derivatives from aromatic aldehydes, N-methyl-1-(methylthio)-2-nitroethamine (NMSM) and 1,3-dimethyl barbituric acid, in the presence of piperidine as a catalyst, is reported. The reaction mechanism involves a Knoevenagel condensation, followed by Michael addition and intramolecular O-cyclization reaction sequence. The synthesized compounds were docked with human kinesin Eg5 protein to calculate binding energy, inhibition constant and H-bond interaction. All the compounds show good binding affinity towards the protein, with significant docking score.

Recent Advances in the Application of Barbituric Acid Derivatives in Multicomponent Reactions

Barbituric acid is a pyrimidine heterocyclic organic compound, which is pharmacologically active. It is important to build structures containing various medicinal activities. This compound attracts the scientific research community in organic synthesis. It can be used in the synthesis of polyheterocyclic, natural, medicinal compounds, and organic sensors. Herein, the utilization of barbituric or thiobarbituric acid in multicomponent reactions is reported from 2016-2021 in this manuscript.

As Antimicrobial Agents: Synthesis, Structural Characterization and Molecular Docking study of Barbituric Acid Derivatives from Phenobarbital

In spite of phenobarbital has been used in various medical fields as hypnotics, anxiolytics, and anticonvulsants, it also contains active functional groups that can be reacted to form other products as dyes, polymers, antimicrobial and anti-antioxidants agents. A series of barbituric acid derivatives containing 1,2,3,4-Tetrazoline moiety were synthesized from phenobarbital. Phenobarbital 1 as raw starting material was reacted with acrylonitrile compound to give diacetonitrile derivative 2, this compound was treated in two ways, urea and thiourea to form barbituric acid derivatives containing oxadiazole and thiadiazole ring 3, 4 respectively. The Schiff bases derivatives 5, 6 (a-c) were synthesized from reacting the latter compounds with three aromatic aldehydes. In the final step, the barbituric acid derivatives containing 1,2,3,4Tetrazoline moiety 7, 8 (a-c) were prepared by cycloaddition reaction between different Schiff bases derivatives and sodium azide. The compounds were characterized by Melting point, 13 C-NMR, 1 H-NMR and FTIR techniques. Also, the result compounds were tested against two kinds of bacteria and two kinds of fungi. Most of the prepared derivatives were showed a high and clear effect against different types of bacteria and fungi. Molecular docking of final barbituric acid derivatives 7, 8 (a, b) were investigated with Molegro Virtual Docker (MVD).

An Efficient Microwave-Assisted Synthesis Method of Novel Bi2O3 Nanostructure and Its Application As a High-Performance Nanocatalyst in Preparing Benzylidene Barbituric Acid Derivatives

In this study, controllable and optimal microwave irradiation has been used to synthesize the novel nanostructures of Bi2O3 under environmental conditions. The final products had a thermal stability of 210 °C, an average particle size distribution of 85 nm, and surface area of 783 m2/g. The high thermodynamic stability of Bi2O3 nanostructures were confirmed by TG and DSC analyses. The nanostructure nature of compounds, most importantly, the use of effective, cost effective and rapid synthesis route of microwave have created significant physiochemical properties in the Bi2O3 products. These unexpected properties have made the possibility of potentials application of these products in various fields, especially in nanocatalyst applications. It is well-documented that, as Lewis acid, bismuth nanocatalyst exhibits a great catalytic activity for the green synthesis of some bio-active barbituric acid derivatives using precursors with electron-donating or –withdrawing nature in high yields (80-98%). After incorporating this catalyst into the aqueous media, all the reactions were completed within 2-3 min at room temperature. The main advantages of this method are practical facility, the availability of starting materials, and low costs besides the catalyst reusability. Additionally, the catalyst synthesis process may be carried in the aqueous media during a short period with medium to high yields. The obtained results have opened a new window for development of a novel nanocatalyst with practical application.

Formations of bimolecular barbituric acid complexes through hydrogen bonding interactions: DFT analyses of structural and electronic features

Formations of bimolecular barbituric acid (BA) complexes through hydrogen-bonding (HB) interactions were investigated in this work. BA has been known as a starting compound of pharmaceutical compounds developments, in which the molecular and atomic features of parent BA in homo-paring with another BA molecule were investigated here. The models were optimized to reach the stabilized structures and their properties were evaluated at the molecular and atomic scales. Density functional theory (DFT) calculations were performed to provide required information for achieving the goal of this work. Six dimer models were obtained finally according to examining all possible starting dimers configurations for involving in optimization calculations. N-H . . . O and C-H . . . O interactions were also involved in dimers formations besides participation of the X-center of parent BA in interaction. Molecular and atomic scales features were evaluated for characterizing the dimers formations. As a consequence, several configurations of BA dimers were obtained showing the importance of performing such structural analyses for developing further compounds from BA.

NiO nanoparticles: A highly efficient catalyst for the one-pot three-component synthesis of pyrano [2, 3-d] pyrimidine derivatives in green media.

: NiO nanoparticles are utilized to effectively strengthen annulated pyrano [2, 3- d] pyrimidine synthesis through primary Knoevenagel, following Micheal and ultimate heterocyclization reactions of aldehyde, malononitrile, and barbituric acid. The characteristics of NiO nanoparticles are identified using advanced techniques, such as IR, UV, EDX, XRD, SEM, and TEM. The nano-NiO particles are mostly below < 100 nm in size with uniform spherical shapes. The adopted approach is advantages thanks to its simple processing, relatively short reaction time, often good to high average yields, convenient workability, and environmental friendliness.

Investigating Functionalization Impacts on Structural Features of Barbituric Acid Derivatives: DFT Approach

Density functional theory (DFT) calculations were performed to investigate electronic and structural properties of barbituric acid (BA) and sixtheen of its derivatives to show impacts of structural functionalization on the features of parent BA. The models were optimized and the minimum energy structures were confirmed by frequency calculations. Molecular and atomic descriptors were evaluated for the optimized models, in which the results of formation binding strength and molecular orbital features indicated significance of such functionalization processes on the observed properties. The highest occupied and the lowest unoccupied molecular orbitals (HOMO and LUMO) and their related parameters all indicated magnitudes of changes from one molecule to another one. Furthermore, atomic scale quadrupole coupling constants (Cq) were evaluated for the nitrogen and oxygen atoms of BA compounds showing significance of structural functionalization impacts on the atomic properties of parent BA. As a consequence, such structural analyses of BA compounds could show their characteristic features for further developments especially for their efficient pharmaceutical applications.