Solvent Influence on Absorption Spectra and Tautomeric Equilibria of Symmetric Azomethine-Functionalized Derivatives: Structural Elucidation and Computational Studies

A new series of azomethine-functionalized compounds was synthesized from the condensation of 2-hydroxy-1,3-propanediamine and 2-thienylcarboxaldehydes in the presence of a drying agent. The derivatives were spectroscopically characterized by NMR, LC-MS, UV/Vis, IR and elemental analysis. Variable temperature ¹H-NMR (−60 to +60 °C) was performed to investigate the effect of solvent polarity; the capability of solvent to form H-bond was found to dramatically influencing the tautomerization process of the desired structures. The calculated thermochemical parameters (ΔH₂₉₈, ΔG₂₉₈ and ΔS₂₉₈) at DFT and MP2 levels of theory explained that 3 b exists in equilibrium with two tautomers. The basis of the electronic absorptions was pursued through Time-Dependent Density-Functional Theory (TD-DFT). Analysis of the structural surfaces was inspected and the molecular electrostatic potential (MEP) demonstrated that the three functionalized compounds were relatively analogous in the electronic distributions. Furthermore, the electrophilic and nucleophilic centers lying on the molecular surfaces were probably playing a key-role in stabilizing the compounds through the nonclassical C−H⋅⋅⋅π interactions and hydrogen bonding. The impact of solvent polarity on absorption spectra were investigated via solvatochromic shifts. For instance, compound 3 c displayed a gradual shift of the maximum absorption to the red area when the solvent polarity was increased, recording a 21 nm of bathochromic shift. In contrast, no significant solvent-effect on 3 a and 3 b was observed. The solvation relation was pursued between Gutmann's donicity numbers the experimental λ_max; exhibited almost positive linear performance with a minor oscillation, that ascribe to the possible weak interface between the molecules of solute and designated solvents. The bandgap energy of all products were assessed experimentally using optical absorption spectra following Tauc approach, giving −4.050 ( 3 a ), −3.900 ( 3 b ) and −3.210 ( 3 c ) eV. However, the ΔE were computationally figured out from TD-DFT simulation to be −4.258 ( 3 a ), −4.022 ( 3 b ) and −3.390 ( 3 c ) eV.     

DFT structural and optical nonlinear investigations of a synthesized new azo β-diketone dye

A new azo β-diketone (NA1) compound is synthesized by coupling reaction of 4-aminoantipyrine with acetylacetone. The NA1 compound is characterized via FTIR, Mass, ¹H NMR and ¹³C NMR spectroscopies. The keto-enol tautomers of the compound electronic structures and energies are investigated using density functional theory (DFT) via B3LYP method/6-311G (d,p) level. The NA1 compound nonlinear optical (NLO) properties are studied via the diffraction patterns (DPs) and the Z-scan where the compound nonlinear index of refraction (NIR), the optical limiting (OLg) property using 473 nm visible, low power, continuous (cw) laser beam are used while the all-optical switching (AOS) property is studied using two laser beams of wavelengths 473 nm and 532 nm.     

Prebiotic Route to Thymine from Formamide—A Combined Experimental–Theoretical Study

Synthesis of RNA nucleobases from formamide is one of the recurring topics of prebiotic chemistry research. Earlier reports suggest that thymine, the substitute for uracil in DNA, may also be synthesized from formamide in the presence of catalysts enabling conversion of formamide to formaldehyde. In the current paper, we show that to a lesser extent conversion of uracil to thymine may occur even in the absence of catalysts. This is enabled by the presence of formic acid in the reaction mixture that forms as the hydrolysis product of formamide. Under the reaction conditions of our study, the disproportionation of formic acid may produce formaldehyde that hydroxymethylates uracil in the first step of the conversion process. The experiments are supplemented by quantum chemical modeling of the reaction pathway, supporting the plausibility of the mechanism suggested by Saladino and coworkers.     

α‐ZrP/Uracil/Cu2+ nanoparticles as an efficient catalyst in the Morita‐Baylis‐Hillman reaction

A facile synthesis of uracil‐Cu²⁺ nanoparticles immobilized on alpha‐zirconium hydrogen phosphate (α‐ZrP), abbreviated as α‐ZrP/Uracil/Cu²⁺, was presented. This compound was synthesized by the thermal method and used as a reusable catalyst for the Morita‐Baylis‐Hillman reaction without any additives. First, (3‐ iodopropyl) trimethoxysilane as a linker is reacted with α‐ZrP support to give the α‐ZrP/IPTMOS. Addition of uracil and then the addition of copper (II) acetate to α‐ZrP/IPTMOS results in the production of selected catalyst. The Morita‐Baylis‐Hillman reaction catalyzed by α‐ZrP/Uracil/Cu^{2 +} demonstrated high product yield, short reaction time and a straightforward work‐up. The catalyst with enough outside surface was easily recovered using centrifugation and reused five times without a significant reduction in its activity.     

A new sample preparation and separation combination for the precise,accurate, and simultaneous determination of uracil and dihydrouracil in human plasma by reversed‐phase HPLC

We have developed an efficient procedure and detection method using reversed‐phase high‐performance liquid chromatography for the simultaneous measurement of uracil and dihydrouracil in human plasma. The procedure, including chromatographic conditions and sample preparation, was optimized and validated. Optimization of the sample preparation included deproteinization, extraction, and cleanup. A new sample preparation method which resulted in an improved extraction yield of analytes and significantly reduced interference at low‐wavelength UV detection was developed. The developed method was validated for specificity, linearity, limits of detection and quantitation, precision, and accuracy. All calibration curves showed excellent linear regression (R ² > 0.9990) within the testing range. The limit of detection for uracil and dihydrouracil was 2.5 and 5.0 ng/mL, respectively. The extraction yields were >94% for uracil and 91% for dihydrouracil. Intra‐ and interassay precision and accuracy for uracil and dihydrouracil were lower than 8% at all tested concentrations. The proposed method was successfully applied to measure plasma concentrations of uracil and dihydrouracil in colorectal cancer patients scheduled to receive fluoropyrimidine‐based chemotherapy.     

Synthesis,characterization and theoretical evaluations of HMDS promoted chemoselective O-alkylation of uracils

The sodium salts of the conjugated bases of uracils undergo highly chemoselective O⁴-monoalkylation when treated with various alkyl halides in dry DMF, while the use of methyl iodide results in N¹+N³-dimethylation. Theoretical evaluations of the chemo- and regioselectivity along with X-ray crystallographic data are presented.     

The stability and reactivity of activated acryloylcarbamates as reagents for the synthesis of N‐1 substituted thymine and uracil – an NMR and DFT study

The mechanism of the decomposition of acryloylcarbamates 7a–b yielding highly reactive isocyanates 3a–b was proposed based on NMR measurements and quantum chemical calculations. A good agreement between the experimental kinetic data and DFT calculations allowed us to demonstrate that the stability of 7a–d depends on the presence of methyl in the acryloyl moiety and the position of the nitro group in the nitrophenolic part of the molecule. Furthermore, the reactivity of 7a–d with weakly nucleophilic and sterically hindered 2,4,6‐tri‐tert‐butylaniline was explored by ¹H NMR demonstrating the usefulness of reagents 7a–d offering access to a variety of 1‐N‐substituted uracils and thymines with potentially interesting biological properties. Copyright © 2010 John Wiley & Sons, Ltd.     

An efficient and regioselective one-pot multi-component synthesis of pyrimido[4,5-d]pyrimidine derivatives in water

Pyrimido[4,5-d]pyrimidine derivatives 4 have been prepared in an efficient and regioselective manner in water via multi-component reaction of isothiocyanate 1, aromatic aldehyde 2, N,N-dimethyl-6-amino uracil 3 in the presence of p-toluenesulfonic acid (p-TSA) as a Lewis acid catalyst.     

Absorption spectra of azobenzenes simulated with time‐dependent density functional theory

Using time‐dependent density functional theory and the polarizable continuum model, we have simulated the absorption spectra of an extended series of azobenzene dyes. First, we have determined a theoretical level optimal for this important class of dyes, and it turned out that a C‐PCM‐CAM‐B3LYP/6‐311+G(d,p)//C‐PCM‐B3LYP/6‐311G(d,p) approach represents an effective compromise between chemical accuracy and computational cost. In a second stage, we have compared the theoretical and experimental transition energies for 46 n → π^☆ and 141 π → π^☆ excitations. For the full set, that spans over a 302–565 nm domain, we obtained a mean absolute deviation of 13 nm (0.10 eV) and a linear correlation coefficient of 0.95, illustrating the accuracy of our approach, though some significant outliers pertained. In a last step, the impact of several modifications, that is, trans/cis isomerization, variation of the acidity of the medium and azo/hydrazo tautomerism have been modeled with two functionals. © 2010 Wiley Periodicals, Inc. Int J Quantum Chem, 2010     

Convenient Synthesis of 5‐Aryl Uracils

A convenient one‐step synthesis of 5‐aryl uracils has been developed. The procedure involves heating ethyl 3‐hydroxy‐2‐arylpropenate with urea at 130°C, followed by base‐catalyzed cyclization. The method is simple and high yielding.