Acetanilide Research Articles

Chiral organic molecular structures supported by planar surfaces.

We employ the molecular dynamics simulations to study the dynamics of acetanilide (ACN) molecules placed on a flat surface of planar multilayer hexagonal boron nitride. We demonstrate that the ACN molecules, known to be achiral in the three-dimensional space, become chiral after being placed on the substrate. Homochirality of the ACN molecules leads to stable secondary structures stabilized by hydrogen bonds between peptide groups of the molecules. By employing molecular dynamics simulations, we reveal that the structure of the resulting hydrogen-bond chains depends on the isomeric composition of the molecules. If all molecules are homochiral (i.e., with only one isomer being present), they form secondary structures (chains of hydrogen bonds in the shapes of arcs, circles, and spirals). If the molecules at the substrate form a racemic mixture, then no regular secondary structures appear, and only curvilinear chains of hydrogen bonds of random shapes emerge. A hydrogen-bond chain can form a zigzag array only if it has an alternation of isomers. Such chains can create two-dimensional (2D) regular lattices or 2D crystals. The melting scenarios of such 2D crystals depend on density of its coverage of the substrate. At 25% coverage, melting occurs continuously in the temperature interval 295-365K. For a complete coverage, melting occurs at 415-470 K due to a shift of 11% of all molecules into the second layer of the substrate.

Reaction of Polyamide Membrane Model Monomers with Chlorine Dioxide: Kinetics, Pathways, and Implications.

Aromatic polyamide (PA) based membranes are widely used for reverse osmosis (RO), but they can be degraded by free chlorine used for controlling the biofouling prior to RO treatment. Kinetics and mechanisms for the reactions of PA membrane model monomers, i.e., benzanilide (BA), and acetanilide (AC), with chlorine dioxide (ClO2) were investigated in this study. Rate constants for the reactions of ClO2 with BA and AC at pH 8.3 and 21°C were determined to be (4.1±0.1)×10-1 M-1.24 s-1 and (6.0±0.1)×10-3 M-1 s-1, respectively. These reactions are base assisted with a strong pH dependence. The activation energies of BA and AC degradation by ClO2 were 123.7 and 81.0 kJ mol-1, respectively. This indicates a relatively strong temperature dependence in the studied temperature range of 21-35 °C. The presence of bromide and natural organic matter does not promote the degradation of model monomers by ClO2. BA was degraded by ClO2 via two pathways: (1) the attack on the anilide moiety with the formation of benzamide (major pathway) and (2) oxidative hydrolysis to benzoic acid (minor pathway). A kinetic model was developed to simulate the degradation of BA and formation of byproducts during ClO2 pretreatment, and simulations agree well with the experimental data. Half-lives of BA treated by ClO2 were 1-5 orders of magnitude longer than chlorine under typical seawater treatment conditions. These novel findings suggest the potential application of ClO2 for controlling biofouling ahead of RO treatment at desalination treatments.

Chemometric quality assessment of Paracetamol and Phenylephrine Hydrochloride with Paracetamol impurities; comparative UV-spectrophotometric implementation of four predictive models

Spectrophotometric data analysis using multivariate approaches has many useful applications. One of these applications is the analysis of active ingredients in presence of impurities. Four chemometric-assisted spectrophotometric methods, namely, principal component regression (PCR), partial least-squares (PLS), artificial neural networks (ANN) and multivariate curve resolution-alternating least squares (MCR-ALS) were proposed and validated. The developed chemometric methods were compared to resolve the severely overlapped spectrum of Paracetamol (PAR) and Phenylephrine HCl (PHE) along with PAR impurities namely, P-Aminophenol (PAP), P-Nitrophenol (PNP), Acetanilide (ACT) and P-Chloroacetanilide (CAC). The four multivariate calibration methods succeeded in simultaneous determination of PAR and PHE with further quantification of PAR impurities. So, the proposed methods could be used with no need of any separation step and successfully applied for pharmaceutical formulation analysis. Furthermore, statistical comparison between the results obtained by the proposed chemometric methods and the official ones showed no significant differences.

The Role of Hydrogen Bonding in Paracetamol-Solvent and Paracetamol-Hydrogel Matrix Interactions.

The photophysical and photochemical properties of antipyretic drug – paracetamol (PAR) and its two analogs with different substituents (acetanilide (ACT) and N-ethylaniline (NEA)) in 14 solvents of different polarity were investigated by the use of steady–state spectroscopic technique and quantum–chemical calculations. As expected, the results show that the spectroscopic behavior of PAR, ACT, and NEA is highly dependent on the nature of the solute–solvent interactions (non-specific (dipole-dipole) and specific (hydrogen bonding)). To characterize these interactions, the multiparameter regression analysis proposed by Catalán was used. In order to obtain a deeper insight into the electronic and optical properties of the studied molecules, the difference of the dipole moments of a molecule in the ground and excited state were determined using the theory proposed by Lippert, Mataga, McRae, Bakhshiev, Bilot, and Kawski. Additionally, the influence of the solute polarizability on the determined dipole moments was discussed. The results of the solvatochromic studies were related to the observations of the release kinetics of PAR, ACT, and NEA from polyurethane hydrogels. The release kinetics was analyzed using the Korsmayer-Peppas and Hopfenberg models. Finally, the influence of the functional groups of the investigated compounds on the release time from the hydrogel matrix was analyzed.

Capillary zone electrophoresis as a quality assessment tool of paracetamol and phenylephrine hydrochloride in presence of paracetamol impurities.

The combination of paracetamol (PAR) and phenylephrine HCl (PHE) is a common pharmaceutical combination intended to manage symptoms of every day cold. Since paracetamol is susceptible to degradation or some manufacturing-related impurities, its stability should be monitored continuously. The developed method in this study for the determination of PAR and PHE in presence of PAR impurities is considered a quality assessment tool especially when PAR impurities can be quantitatively determined. A capillary zone electrophoresis (CZE) method was optimized and validated for simultaneous determination of PAR and PHE in presence of PAR impurities namely, p-Aminophenol (PAP), p-Nitrophenol (PNP), Acetanilide (ACT) and p-Chloroacetanilide (CAC) with further quantification of these toxic impurities. Factors that affect the separation quality such as pH, buffer and applied voltage were optimized. The separation was carried out using 20 mM phosphate buffer (pH 8). The linearity was reached over concentration ranges of 30-250 μg/mL, 1-40 μg/mL, 2-50 μg/mL, 2-50 μg/mL, 2-50 μg/mL and 2-50 μg/mL for PAR, PHE, PAP, PNP, ACT, and CAC, respectively, with accuracy ranging from 99.06% to 100.62%. After validation, the method was applied for pharmaceutical formulation analysis with RSD <2%. Moreover, statistical comparison with the official methods confirms that the method is a viable alternative for quality assessment of this combination.

Validated specific HPLC-DAD method for simultaneous estimation of paracetamol and chlorzoxazone in the presence of five of their degradation products and toxic impurities

This work demonstrates a specific and reliable HPLC with diode array detection (DAD) method for the simultaneous estimation of paracetamol (PAR) and chlorzoxazone (CZ) in the presence of five of their degradation products and toxic impurities; namely; 4-aminophenol (AP), 4-nitrophenol (NP), acetanilide (AT), 4-chloroacetanilide (CA) and 2-amino-4-chlorophenol (ACP). Successful chromatographic separation was accomplished using Waters Symmetry C8 column (3.9 × 150 mm, 5 μm) with gradient elution of the mobile phase consisting of 0.05 M phosphate buffer pH 7.5 and methanol. The gradient elution started with 5% (by volume) methanol ramped up linearly to 50% in 10 min, and then maintained at this percentage afterward till the end of the run. The mobile phase was pumped at a flow rate of 1.0 mL/min. The multiple wavelength detector was adjusted at 244 and 285 nm to quantify PAR and CZ, respectively. Additionally, the wavelength 270 nm was found suitable for monitoring the separation of the entire mixture of PAR, CZ, and their impurities. Seven peaks eluted with excellent resolution at retention times 3.4, 5.7, 8.0, 10.1, 10.8, 13.5, and 14.4 min for AP, PAR, NP, AT, ACP, CZ, and CA, respectively. Performance of the proposed method was validated with respect to linearity, range, precision, accuracy, specificity, robustness, detection, and quantitation limits. Calibration curves were linear in the ranges of 10–75 and 10–100 µg/mL for PAR and CZ, respectively with correlation coefficients not less than 0.9998. The proposed method proved to be specific and stability indicating by the resolution of both drugs from their degradation products and toxic impurities. Validated HPLC method was successfully applied to the analysis of PAR and CZ in their combined capsules dosage form, and assay results were favorably compared with a published reference HPLC method. DAD served as an efficient tool for peak identity and purity verification.

Preparation and oil lubrication of polyvinylidene fluoride (PVDF) nanospheres

Polymer block materials usually have good lubricating properties and their nano particles as lubricants are well anticipated. However, the preparation processes of polymer nanoparticles are complicated and their applications are confined. The evaluation of particles size and preparation process of polyvinylidene fluoride (PVDF) nanospheres are described. Reducing the number of PVDF chains when forming a crystal ball does often make the diameter smaller. The preparation process undergoes crystal nucleation, crystal growth and separation, to form nano particles. In this study, PVDF nanospheres were prepared under acetanilide (AA) solvent, which played an important role to separate and disperse PVDF nanospheres. Meanwhile, TGA, FT-IR, XRD and XPS characterizations revealed that AA was inside the PVDF nanospheres. In order to obtain pure PVDF nanoparticles, AA was washed by anhydrous ethanol. A strategy was proposed to promote the preparation method. Polymer nanoparticles were stably dispersed and their agglomeration was controlled. In the present work, a series of tribological tests were applied to evaluate the lubrication effect of PVDF nanoparticles. The results manifested that PVDF nanoparticles with low concentration possessed good lubricating property because of their film formation on the contact surface. The lubricating mechanism of PVDF nanoparticles was illuminated. The current study has potential applications in preparing polymer nanoparticles with good lubrication.

Experimental FTIR and theoretical investigation of the molecular structure and vibrational spectra of acetanilide using DFT and dispersion correction to DFT

The FTIR spectrum of acetanilide (ACN) is recorded and analyzed. The optimized molecular structures, harmonic vibrational wavenumbers and corresponding vibrational assignments of the ACN are computationally examined by using the B3LYP density functional theory method together with the standard 6-311[Formula: see text]G([Formula: see text],[Formula: see text]) basis set. From the calculations, the ACN is predicted to exist predominantly in trans configuration with the relative energy, rotational barrier, and population of 2.8[Formula: see text]kcal/mol, 14.8[Formula: see text]kcal/mol, and 99.5%, respectively. The optimized structure shows that the amide group (CO–NH) of trans-ACN adopts a planar peptide-like conformation. The effect of the incorporation of dispersion correction to the B3LYP on the calculated equilibrium structure and vibrational spectra of ACN is investigated. The highest occupied and the lowest unoccupied molecular orbitals, IR intensities and molecular electrostatic potential results are reported. In addition, reliable vibrational assignments have been made on the basis of Potential Energy Distribution (PED) using VEDA4 program. Simulated IR spectrum are compared with the experimental FTIR and FT-Raman spectra. Energy decomposition analysis (EDA) revealed that Pauli repulsion is responsible for the increased stability of the trans over the cis isomer.

The effect of tailor-made additives on crystal growth of methyl paraben: Experiments and modelling

In this study, methyl paraben (MP) was selected as the model component, and acetaminophen (APAP), p-methyl acetanilide (PMAA) and acetanilide (ACET), which share the similar molecular structure as MP, were selected as the three tailor-made additives to study the effect of tailor-made additives on the crystal growth of MP. HPLC results indicated that the MP crystals induced by the three additives contained MP only. Photographs of the single crystals prepared indicated that the morphology of the MP crystals was greatly changed by the additives, but PXRD and single crystal diffraction results illustrated that the MP crystals were the same polymorph only with different crystal habits, and no new crystal form was found compared with other references. To investigate the effect of the additives on the crystal growth, the interaction between additives and facets was discussed in detail using the DFT methods and MD simulations. The results showed that APAP, PMAA and ACET would be selectively adsorbed on the growth surfaces of the crystal facets, which induced the change in MP crystal habits.

Modified procedure for the synthesis of 2-chloroquinoline-3-carbaldehydes using phosphorus pentachloride

ABSTRACTAn alternative, convenient, and efficient procedure for the synthesis of 2-chloroquinoline-3-carbaldehyde was carried out by the action of Vilsmeier’s reagent on acetanilides using phosphorus pentachloride as chlorinating agent in place of phosphoryl chloride, obtaining good yields for activated acetanilides. The optimal conditions for this reaction requires only 4.5 equivalents of phosphorus pentachloride, 3 equivalents of N,N-dimethylformamide, and 1 equivalent of the corresponding acetanilide at 100 °C for approximately 4 h.

Inclusion Complexation of Acetanilide into the β-Cyclodextrin Nanocavity: A Computational Approach

Host–guest inclusion complexation of acetanilide (AA) into the β-cyclodextrin (β-CD) nano-hydrophobic cavity has been investigated using computational technique. Two different orientation of guest (AA) into host (β-CD) are considered for the inclusion of AA in to the nanocavity through the 2o rim of β-CD. The energy differences in the inclusion process are calculated using PM3 semi-empirical method. By the investigation of stabilization energies, it is found that the “orientation 1” in which the benzene ring of AA oriented towards 2o rim of β-CD nanocavity is the stable complex. The conclusions obtained from the computational analysis are in good correlation with the docking analysis.

Positronium formation studies in crystalline molecular complexes: Triphenylphosphine oxide – Acetanilide

Hydrogen bond formation in the triphenylphosphine oxide (TPPO), acetanilide (ACN) supramolecular heterosynton system, named [TPPO0.5·ACN0.5], has been studied by Positron Annihilation Lifetime Spectroscopy (PALS) and supported by several analytical techniques. In toluene solution, Isothermal Titration Calorimetry (ITC) presented a 1:1 stoichiometry and indicated that the complexation process is driven by entropy, with low enthalpy contribution. X-ray structure determination showed the existence of a three-dimensional network of hydrogen bonds, allowing also the confirmation of the existence of a 1:1 crystalline molecular complex in solid state. The results of thermal analysis (TGA, DTA and DSC) and FTIR spectroscopy showed thatthe interactions in the complex are relativelyweaker than those found in pure precursors, leading to a higher positronium formation probability at [TPPO0.5·ACN0.5]. These weak interactions in the complex enhance the possibility of the n- and π-electrons to interact with positrons and consequently, the probability of positronium formation is higher. Through the present work is shown that PALS is a sensible powerful tool to investigate intermolecular interactions in solid heterosynton supramolecular systems.

Investigations of Interhydrogen Bond Dynamical Coupling Effects in the Polarized IR Spectra of Acetanilide Crystals

This Article presents the investigation results of the polarized IR spectra of the hydrogen bond in acetanilide (ACN) crystals measured in the frequency range of the proton and deuteron stretching vibration bands, nu(N-H) and nu(N-D). The basic spectral properties of the crystals were interpreted quantitatively in terms of the "strong-coupling" theory. The model of the centrosymmetric dimer of hydrogen bonds postulated by us facilitated the explanation of the well-developed, two-branch structure of the nu(N-H) and nu(N-D) bands as well as the isotopic dilution effects in the spectra. On the basis of the linear dichroic and temperature effects in the polarized IR spectra of ACN crystals, the H/D isotopic "self-organization" effects were revealed. A nonrandom distribution of hydrogen isotope atoms (H or D) in the lattice was deduced from the spectra of isotopically diluted ACN crystals. It was also determined that identical hydrogen isotope atoms occupy both hydrogen bonds in the dimeric systems, where each hydrogen bond belongs to a different chain. A more complex fine structure pattern of nu(N-H) and nu(N-D) bands in ACN spectra in comparison with the spectra of other secondary amides (e.g., N-methylacetamide) can be explained in terms of the "relaxation" theory of the IR spectra of hydrogen-bonded systems.

Stability-Indicating Simultaneous Determination of Paracetamol and Three of Its Related Substances Using a Direct GC/MS Method

A simple, direct, and selective stability-indicating GC/MS procedure was developed for the simultaneous determination of paracetamol (PR) and three of its related substances: 4-aminophenol (4-AP), acetanilide (AD), and 4'-chloroacetanilide (4-CA). The method involved resolution of the underivatized compounds using a 100% dimethylpolysiloxane (Rtx-1) column, and MS detection was carried out in the electron-impact mode. The four compounds were completely resolved in less than 11 min. The fragmentation pathways for the four compounds were described, and the structures of the major fragment ions peaks were proposed. Quantification of the analytes was based on measuring their peak areas. The reliability and analytical performance of the proposed method including linearity, range, precision, accuracy, and detection and quantification limits were statistically validated. Calibration curves were linear over the ranges 75-500, 25-350, 25-350, and 25-350 microg/mL for PR, 4-AP, AD, and 4-CA, respectively. The proposed method was successfully applied for the determination of PR and its related substances in laboratory-prepared mixtures of different proportions. Also, it was applied for the assay of PR in several commercially available pharmaceutical formulations with recoveries of 98.95-100.76%.

Femtosecond IR Pump-Probe Spectroscopy of Nonlinear Energy Localization in Protein Models and Model Proteins

This paper reviews our experimental and theoretical efforts toward understanding vibrational self-trapping of the amide I and N-H mode of crystalline acetanilide (ACN), other similar hydrogen-bonded crystals, as well as of model peptides. In contrast to previous works, we used nonlinear IR spectroscopy as the experimental tool, which is specifically sensitive to the anharmonic contributions of the intramolecular interactions (as the nonlinear IR response of set of harmonic oscillators vanishes exactly). Our work reconfirms the previous assignment of the two bands of the amide I mode of ACN as being a self-trapped and a free exciton state, but in addition also establishes the lifetimes of these states and identifies the relevant phonons. Furthermore, we provide evidence for vibrationally self-trapped states also in model alpha-helices. However, given the short lifetime, any biological relevance in the sense of Davydov's initial proposal can probably be ruled out.

Thermodynamic quantities of solvation and dilution for some acetanilide derivatives in octanol and water mutually saturated

Based on published thermodynamic quantities for solution, partitioning and sublimation of acetanilide (ACN), acetaminophen (ACP) and Phenacetin (PNC), the thermodynamic quantities for drugs solvation in octanol-saturated water (W(ROH)) and water-saturated octanol (ROH(W)) as well as the drugs dilution in ROH(W) were calculated. The Gibbs energies of solvation were favourable in all cases. The respective enthalpies and entropies were negative indicating an enthalpy-driving for the solvation process in all cases. On the other hand, the Gibbs energies of dilution were favourable for ACP and PNC but unfavourable for ACN, whereas the respective enthalpies and entropies were negative for ACP and PNC but positive for ACN indicating enthalpy-driving for the dilution process in the case of the former drugs and entropy-driving for the latter. From the obtained values for the transfer processes, an interpretation based on solute-solvent interactions was developed.

Thermodynamic quantities of solvation and dilution for some acetanilide derivatives in octanol and water mutually saturateds

Based on published thermodynamic quantities for solution, partitioning and sublimation of acetanilide (ACN), acetaminophen (ACP) and Phenacetin (PNC), the thermodynamic quantities for drugs solvation in octanol-saturated water (W(ROH)) and water-saturated octanol (ROH(W)) as well as the drugs dilution in ROH(W) were calculated. The Gibbs energies of solvation were favourable in all cases. The respective enthalpies and entropies were negative indicating an enthalpy-driving for the sol- vation process in all cases. On the other hand, the Gibbs energies of dilution were favourable for ACP and PNC but unfavourable for ACN, whereas the respective enthalpies and entropies were negative for ACP and PNC but positive for ACN indicating enthalpy-driving for the dilution process in the case of the former drugs and entropy-driving for the latter. From the obtained values for the transfer process- es, an interpretation based on solute-solvent interactions was developed.

Infrared absorption spectra of molecular crystals: Possible evidence for small-polaron formation?

The temperature dependence of the position of the so-called anomalous band peaked at 1650 cm - 1 in the IR-absorption spectrum of crystalline acetanilide (ACN) is theoretically investigated within the small-polaron theory. Its pronounced shift towards the position of the normal band is predicted with the rise of temperature. Interpretation of the IR-absorption spectra in terms of small-polaron model has been critically assessed on the basis of these results.

Quantum vibrational polarons: Crystalline acetanilide revisited

We discuss a refined theoretical description of the peculiar spectroscopy of crystalline acetanilide (ACN). Acetanilide is a molecular crystal with quasi-one-dimensional chains of hydrogen-bonded units, which is often regarded as a model system for the vibrational spectroscopy of proteins. In linear spectroscopy, the $\mathrm{C}\mathrm{O}$ stretching (amide I) band of ACN features a double-peak structure, the lower of which shows a pronounced temperature dependence which has been discussed in the context of polaron theory. In nonlinear spectroscopy, both of these peaks respond distinctly differently. The lower-frequency band exhibits the anharmonicity expected from polaron theory, while the higher-frequency band responds as if it were quasiharmonic. We have recently related the response of the higher-frequency band to that of a free exciton [J. Edler and P. Hamm, J. Chem. Phys. 117, 2415 (2002)]. However, as discussed in the present paper, the free exciton is not an eigenstate of the full quantum version of the Holstein polaron Hamiltonian, which is commonly used to describe these phenomena. In order to resolve this issue, we present a numerically exact solution of the Holstein polaron Hamiltonian in one dimension (1D) and 3D. In 1D, we find that the commonly used displaced oscillator picture remains qualitatively correct, even for relatively large exciton coupling. However, the result is not in agreement with the experiment, as it fails to explain the free-exciton band. In contrast, when taking into account the 3D nature of crystalline acetanilide, certain parameter regimes exist where the displaced oscillator picture breaks down and states appear in the spectrum that indeed exhibit the characteristics of a free exciton. The appearance of these states is a speciality of vibrational polarons, whose source of exciton coupling is transition dipole coupling which is expected to have opposite signs of interchain and intrachain coupling.

Molecularly Imprinted Polymers with p‐Acetaminophenol and Its Positional Isomers as Templates

In this study, molecularly imprinted polymers (MIP) with p‐acetaminophenol (p‐AMP) and its positional isomers as templates were synthesized. Several structural analogues, phenol, acetanilide (AN), p‐nitrophenol (p‐NP) and p‐aminophenol (p‐AP) were chosen to study the selectivity of the MIPs in different mobile phases. In addition, the separation of the positional isomers was also investigated. The experimental results showed that, in the mobile phase with less polarity, the retention of the compounds was increased greatly on both blank polymer and the MIPs, thus leading no enhancement in the imprinting effect and selectivity. In addition, the use of dichloromethane/acetonitrile as the mobile phase favors the separation of the positional isomers, and baseline separation can be achieved only on the column based on the polymer imprinted with m‐acetaminophenol (m‐AMP) as a template.