The solvent-free synthesis of 1,4-dihydropyridines under ultrasound irradiation without catalyst

The condensation of aldehydes, ethyl acetoacetate and ammonium acetate result 1,4-dihydropyridines in 82–99% yields under ultrasound irradiation without solvent and catalyst at room temperature. Compared with conventional methods, the main advantages of the present procedure are milder conditions, shorter reaction time and higher yields.     

Sonochemical and photochemical oxidation of organic matter

Recent developments in sonochemistry have led us to study its use to treat water and wastewater. The effects of ultrasound wave in hydrophilic chemical oxidations are mainly due to hydroxyl radical production during the cavitation-induced water decomposition. Currently, the sonochemical destruction of aromatic compounds in water solution is obtained with low rates. The aim of this work is to evaluate the efficiency of the sonochemical effect in conjunction with a photochemical irradiation. Taking phenol as an example, the combined action of sonochemistry and photochemistry has been considered in a ‘sonuv’ reactor. An important enhancement of the degradation rate of phenol has been observed. It may be the result of three different oxidative processes: direct photochemical action, high frequency sonochemistry and reaction with ozone (produced by UV irradiation of air). The process has been successfully tested to lower the chemical oxygen demand of a municipal wastewater.     

Synthesis, in vitro antitubercular activity and 3D-QSAR study of 1,4-dihydropyridines

In continuation of our research program on new antitubercular agents, this article is a report of the synthesis of 97 various symmetrical, unsymmetrical, and N-substituted 1,4-dihydropyridines. The synthesized molecules were tested for their activity against M. tuberculosis H ₃₇Rv strain with rifampin as the standard drug. The percentage inhibition was found in the range 3–93%. In an effort to understand the relationship between structure and activity, 3D-QSAR studies were also carried out on a subset that is representative of the molecules synthesized. For the generation of the QSAR models, a training set of 35 diverse molecules representing the synthesized molecules was utilized. The molecules were aligned using the atom-fit technique. The CoMFA and CoMSIA models generated on the molecules aligned by the atom-fit method show a correlation coefficient (r ²) of 0.98 and 0.95 with cross-validated r ²(q ²) of 0.56 and 0.62, respectively. The 3D-QSAR models were externally validated against a test set of 19 molecules (aligned previously with the training set) for which the predictive ${r^{2} (r^{2}_{\rm pred})}$ is recorded as 0.74 and 0.69 for the CoMFA and CoMSIA models, respectively. The models were checked for chance correlation through y-scrambling. The QSAR models revealed the importance of the conformational flexibility of the substituents in antitubercular activity.     

Solid-state photodimerization of 4-aryl-1,4-dihydropyridines studied by C CPMAS NMR spectroscopy

¹³C CPMAS NMR spectroscopy has been applied to monitor the solid-state reaction of two different photodimerizing 4-phenyl-1,4-dihydropyridines yielding a cage dimer in one case and an anti-dimer in the other case. The spectra of the reacting monomers exhibit a magnetical inequivalence of chemically equivalent CO and C2/4 carbon atoms caused by a rotation of the pseudoaxially oriented 4-phenyl substituent out off the plane through N1, C3, C8 which could be determined by X-ray crystal structure analyses of the centrosymmetrically arranged monomers. The ¹³C CPMAS NMR monitoring of the cage dimer formation proves that the reaction takes place in two steps via a syn-dimer for which a non-symmetrical structure was derived from the spectrum. The non-symmetrical structure was confirmed by X-ray crystal structure analysis of one structurally related derivative. A centrosymmetric structure for both the finally formed cage dimer and the anti-dimer of the other monitored photoreaction was proved by their spectra with one set of signals for each half of the dimers, respectively. Thus, conformational properties of the molecules as well as the symmetry of the products can be directly derived from the ¹³C CPMAS NMR spectra.     

Stepwise aromatic nucleophilic substitution in continuous flow. Synthesis of an unsymmetrically substituted 3,5-diamino-benzonitrile library

Aromatic or heteroaromatic ring precursors with 2–3 identical functionalities are often used in sequential derivatization depending on the reactivity difference or the selective execution of the reaction such as nucleophilic aromatic substitution. Continuous flow chemistry offers an enhanced parameter space (pressure and temperature) with rapid parameter optimization that ensures selectivity in many cases. We developed a flow chemistry procedure to carry out a stepwise aromatic nucleophilic substitution of difluoro-benzenes having an activating group in meta position to the fluorines. The mono-aminated products were obtained in high yield and selectivity in an extremely short reaction time, while applying higher temperature, longer reaction zone (or time), and employing higher excess of another amine reactant, the subsequent introduction of the second amino group was also successfully achieved leading to an unsymmetrically substituted 3,5-diamino-benzonitrile library.     

Ultrasound-assisted oxidation of dibenzothiophene with phosphotungstic acid supported on activated carbon

Phosphotungstic acid (HPW) supported on activated carbon (AC) was applied to catalyze deep oxidation desulfurization of fuel oil with the assist of ultrasound. The sulfur-conversion rate was evaluated by measuring the concentration of dibenzothiophene (DBT) in n-octane before and after the oxidation. Supporting HPW on AC has been verified to play a positive role in UAOD process by a series of contrast tests, where only HPW, AC or a mixture of free HPW and AC was used. The influences of catalyst dose, ultrasound power, reaction temperature, H₂O₂:oil volume ratio and the reuse of catalyst on the catalytic oxidation desulfurization kinetics were investigated. The DBT conversion rate of the reaction catalyzed by supported HPW under ultrasound irradiation was higher than the summation of the reactions with HPW only and AC only as catalyst. With the increase of loading amount of HPW on AC, ultrasound power, H₂O₂:oil volume ratio and reaction temperature, the catalytic oxidation reactivity of DBT would be enhanced. The optimum loading amount of HPW was 10%, exceed which DBT conversion would no longer increase obviously. DBT could be completely converted under the optimized conditions (volume ratio of H₂O₂ to model oil: 1:10, mass ratio of the supported HPW to model oil: 1.25%, temperature: 70 °C) after 9 min of ultrasound irradiation.     

Ultrasound assisted electrochemical oxidation of substituted toluenes

Investigations on ultrasound assisted electrochemical syntheses demonstrate the positive influence of ultrasound on the achievable current density, selectivity and yield, but there is still a lack of investigations concerning the ultrasound influence on electroorganic syntheses. Especially the determining parameters like operation conditions and reactor geometry are not well defined for an industrial application. Therefore, the electrooxidation of substituted toluenes to their corresponding benzaldehydes via electrochemical conversion to the dialkylacetals, which is a reaction of great interest in industrial production, is studied with and without sonification of the working electrode.Experiments in a test-cell are done to evaluate the fundamental characteristics of the combined use of ultrasound and electrooxidation. A strong dependency of the current densities on the applied ultrasound power and a shift of oxidation potentials to lower values are achieved. Work is extended by theoretical investigations concerning the ultrasound field.For technical interesting syntheses a high electrode area-reactor volume ratio is demanded. This is achieved by an experimental sono-electrochemical gap cell with an electrode distance of only a few millimetres and a sound source "face on" the working electrode. Synthesis experiments done with this experimental set-up show an increase in chemical yield.     

Synthesis of new tripodal Hantzsch 1,4-dihydropyridines under solvent-free condition and their conversion to the corresponding tripodal pyridines

A mixture of β-ketoester and tri-aldehydes in the presence of ammonium fluoride was converted to their corresponding tripodal 1,4-dihydropyridines under solvent-free condition with good yields. The obtained tripodal 1,4-dihydropyridines were also aromatized with oxone^®/NaNO₂/wet SiO₂ system under mild and heterogeneous conditions quantitatively.     

Iodobenzene diacetate (IBD) catalyzed an quick oxidative aromatization of Hantzsch-1,4-dihydropyridines to pyridines under ultrasonic irradiation

This project was undertaken to demonstrate the potential of iodobenzene diacetate for the oxidative aromatization of Hantzch-1,4-dihydropyridines under ultrasonic irradiation. All reactions were carried out under ultrasonic irradiation and results were compared with traditional method. Sonochemical switching was observed in case of oxidative aromatization of 4-n-alkyl substituted 1,4-DHP. Without sonication, dealkylation occurred in case of n-alkyl substituted 1,4-DHP (ionic mechanism) but under ultrasonic irradiation, n-alkyl group was not expelled (radical mechanism). However, secondary alkyl (isopropyl) and benzyl group were expelled under both conditions.     

Ultrasound-assisted hydrogenation of cinnamaldehyde

The hydrogenation, employing hydrogen gas, of cinnamaldehyde was performed using Pd-black and Raney Ni catalysts at 298+/-3 K in a water-cooled (jacketed) reaction vessel. Sampling at pre-determined time intervals and GC/MS analysis yielded time-dependent product state distribution information. A kinetic modeling of the data revealed that cinnamaldehyde was both hydrogenated directly to the final product benzenepropanol, as well as a fraction being converted to the intermediate benzenepropanal, where the latter was subsequently hydrogenated to benzenepropanol. Comparing the ultrasound-assisted and blank (stirred) experiments revealed that a higher maximum relative concentration of the intermediate benzenepropanal was formed in the ultrasound experiments compared to the stirred experiment. The activity of the ultrasound experiments compared to blank were 9-fold and 20-fold greater for the Pd-black and Raney Ni catalysts, respectively. Finally, an application of the Bell-Evans-Polanyi principle to yield an estimate of the ratio of rate coefficients for benzenepropanal and benzenepropanol formation was performed by considering chemical group energy differences and surface adsorption energy differences in the first mechanistic step of hydrogenation.     

Amine-functionalized graphene oxide nanosheets (AFGONs): an efficient bifunctional catalyst for selective formation of 1,4-dihydropyridines,acridinediones and polyhydroquinolines

Molecular Diversity - We report here selective formation of functionalized 1,4-dihydropyridines (DHP), acridinediones and polyhydroquinolines in high yields using amine-functionalized graphene...     

Ultrasound-assisted dyeing of cellulose acetate

The possibility of reducing the use of auxiliaries in conventional cellulose acetate dyeing with Disperse Red 50 using ultrasound technique was studied as an alternative to the standard procedure. Dyeing of cellulose acetate yarn was carried out by using either mechanical agitation alone, with and without auxiliaries, or coupling mechanical and ultrasound agitation in the bath where the temperature range was maintained between 60 and 80 °C.The best results of dyeing kinetics were obtained with ultrasound coupled with mechanical agitation without auxiliaries (90% of bath exhaustion value at 80 °C). Hence the corresponding half dyeing times, absorption rate constants according to Cegarra–Puente modified equation and ultrasound efficiency were calculated confirming the synergic effect of sonication on the dyeing kinetics. Moreover the apparent activation energies were also evaluated and the positive effect of ultrasound added to mechanical agitation was evidenced by the lower value (48 kJ/mol) in comparison with 112 and 169 kJ/mol for mechanical stirring alone with auxiliaries and without, respectively.Finally, the fastness tests gave good values for samples dyed with ultrasound technique even without auxiliaries. Moreover color measurements on dyed yarns showed that the color yield obtained by ultrasound-assisted dyeing at 80 °C of cellulose acetate without using additional chemicals into the dye bath reached the same value yielded by mechanical agitation, but with remarkably shorter time.     

Photophysical properties of a series of 4‐aryl substituted 1,4‐dihydropyridines

In this article, a series of Hantzsch 1,4‐dihydropyridines with different substituted aryl groups were synthesized and its spectral data obtained by UV–Vis absorption and fluorescence emission spectroscopies in solution. The dihydropyridines present absorption located around 350 nm and fluorescence emission in the blue–green region. A higher Stokes’ shift could be observed for the derivative 3b because of an intramolecular charge transfer in the excited state from the dimethylaniline to the dihydropyridine chromophores, which was corroborated by a linear relation of the fluorescence maxima (ν_max) versus the solvent polarity function (Δf) from the Lippert–Mataga correlation. A comparison between the experimental data and time‐dependent density functional theory‐polarizable continuum model calculations of the vertical transitions was performed to help on the elucidation of the photophysics of these compounds. For these calculations, the S₀ and S₁ states were optimized using Becke, three‐parameter, Lee–Yang–Parr/6‐31 G* and Configuration Interaction Singles/6‐31 G*, respectively. The predicted absorption maxima are in good agreement with the experimental; however, the theoretical fluorescence emission maxima do not match the experimental, which means that the excited specie cannot be related to neither a locally excited state nor to an aromatized structure. Copyright © 2012 John Wiley & Sons, Ltd.     

Synthesis of 5-alkylated barbituric acids and 3-alkylated indoles via microwave-assisted three-component reactions in solvent-free conditions using Hantzsch 1,4-dihydropyridines as reducing agents

Reaction of barbituric acids with aldehydes and dihydropyridines in one pot under microwave (MW) irradiation in the absence of solvent, affords 55–82% of the 5-benzylated barbituric acids. Use of alkyl nitriles or barbituric acids with indole-3-aldehyde and dihydropyridine (DHP) afforded 3-alkylated indoles in 57–76 % yield. In each case DHPs are converted to pyridines.     

Ultrasound-assisted one-pot synthesis of substituted coumarins catalyzed by poly(4-vinylpyridinium) hydrogen sulfate as an efficient and reusable solid acid catalyst

Poly(4-vinylpyridinium) hydrogen sulfate solid acid was found to be efficient catalyst for synthesis of substituted coumarins via Pechmann reaction using ultrasound irradiation at room temperature and neat condition in high yields with short reaction times. This methodology offers momentous improvements over various options for the synthesis of coumarins with regard to yield of products, simplicity in operation and green aspects by avoiding toxic catalysts and solvents. Further, the catalyst can be reused and recovered for several times.     

Ultrasound-assisted conversion of alpha-chitin into chitosan

This paper discusses the production of chitosan by applying high intensity ultrasound irradiation to alpha-chitin suspended in 40% aqueous sodium hydroxide. The average degree of acetylation (DA) of chitosan was determined by ¹H NMR spectroscopy and titrimetry while its viscosity average molecular weight (Mv) was calculated from the intrinsic viscosity as determined by capillary viscometry. The results show that fully acid-soluble chitosans (DA < 32%; 100,000 g/mol ? Mv ? 200,000 g/mol) are produced at very high yield (>95%) by applying non-isothermal ultrasound-assisted N-deacetylation process to alpha-chitin suspension (44 mg/mL). It is also shown that such a process is more efficient than thermochemical N-deacetylation, even being carried out at a lower temperature due to the effects of high intensity ultrasound irradiation.