Intensification of paracetamol (acetaminophen) synthesis from hydroquinone using ultrasound

Paracetamol (acetaminophen) is one of the most frequently used analgesic and antipyretic drugs. This work deals with ultrasound assisted synthesis (UAS) of paracetamol from hydroquinone using ammonium acetate as an amidating agent. The optimization of various reaction and ultrasound parameters was performed to minimize the energy and time requirement. UAS of paracetamol was achieved at a lower temperature (60 °C) and the time (150 min) without formation of salt as a byproduct, making reaction green and inherently safer. On the other hand, the conventional process requires high reaction temperature (220 °C) and time (15 h). The quantification of the product was done by using high performance liquid chromatography (HPLC). Optimization of parameters revealed that the percent yield of 57.72% can be obtained in 150 min by performing the reaction in the ultrasound bath at 22 kHz frequency, 60 °C temperature, hydroquinone to ammonium acetate and acetic acid in a molar ratio of 1:6:5, 125 W power, 50% duty cycle and agitation speed of 300 RPM. Hence, ultrasound assisted synthesis can be considered as a process intensification tool for the synthesis of paracetamol and possibly other pharmaceutical compounds.     

Synthesis of chalcone (3-(4-fluorophenyl)-1-(4-methoxyphenyl)prop-2-en-1-one): advantage of sonochemical method over conventional method

In this work, an attempt was made to synthesize chalcone (3-(4-fluorophenyl)-1-(4-methoxyphenyl)prop-2-en-1-one) by condensation of 4-fluorobenzaldehyde with 1-(4-methoxyphenyl)ethanone under basic conditions by using both conventional (NUS) and sonochemical (US) methods. A simple condensation reaction of 4-fluorobenzaldehyde and 1-(4-methoxyphenyl)ethanone using potassium hydroxide as a base was carried out for the study. The synthesized chalcone derivative was characterized for FTIR, NMR, elemental analyses and studied for XRD, PSM, TGA and SEM properties to evaluate its performance obtained under ultrasonic energy. It was observed that complete conversion to chalcone occurred in 10 min by sonochemical method and in 4h by conventional method. Also it was found that crystallinity of the US synthesized chalcone was found to be increased by 63% than that of NUS synthesized chalcone. Finally, it has been observed that chalcone synthesis using sonochemical method is an energy efficient technique over conventional method (almost 90% of energy saving).     

Comparative material study and synthesis of 4-(4-nitrophenyl)oxazol-2-amine via sonochemical and thermal method

The present paper deals with the synthesis of aminooxazole derivatives via thermal and ultrasonic methods using deep eutectic solvent as medium. It was observed that ultrasound-assisted method gave 90% yield in just 8 min as against 3.5 h required to get 69% yield by thermal method. One of the compounds 4-(4-nitrophenyl)-1,3-oxazol-2-amine synthesized by both methods were subjected to material characterization study via XRD, TGA and SEM analysis. It was observed that use of ultrasound not only increased the rate of reaction but also improved the quality of product obtained. The crystallinity of the product from ultrasound method was 21.12% whereas thermal method fetched only 8.33% crystallinity thereby improving crystallinity by almost 60%. In addition, sonochemical synthesis also saved more than 70% energy as depicted by energy calculations.     

Synergetic decolorization of azo dyes using ultrasounds,photocatalysis and photo-fenton reaction

In the present work, ultrasound irradiation, photocatalysis with TiO₂, Fenton/Photo-Fenton reaction, and the combination of those techniques were investigated for the decolorization of industrial dyes in order to study their synergy. Three azo dyes were selected from the weaving industry. Their degradation was examined via UV illumination, Fenton and Photo-Fenton reaction as well as ultrasound irradiation at low (20 kHz) and high frequencies (860 kHz). In these experiments, we investigated the simultaneous action of the ultrasound and UV irradiation by varying parameters like the duration of photocatalysis and ultrasound irradiation frequency. At the same time, US power, temperature, amount of TiO₂ photocatalyst and amount of Fenton reagent remained constant. Due to their diverse structure, each azo dye showed different degradation levels using different combinations of the above-mentioned Advanced Oxidation Processes (AOPs). The Photo-Fenton reagent is more effective with US 20 kHz and US 860 kHz for the azo dyes originated from the weaving industry at pH = 3 as compared to pH = 6.8. The combination of the Photo-Fenton reaction with 860 kHz ultrasound irradiation for the same dye gave an 80% conversion at the same time. Experiments have shown a high activity during the first two hours. After that threshold, the reaction rate is decreased. FT-IR and TOC measurements prove the decolorization due to the destruction of the chromophore groups but not complete mineralization of the dyes.     

Optimization and kinetic study of ultrasound assisted deep eutectic solvent based extraction: A greener route for extraction of curcuminoids from Curcuma longa

The use of deep eutectic solvents (DESs) as a new extraction medium is a step towards the development of green and sustainable technology. In the present study, nine DESs based on choline chloride acids, alcohols, and sugar were screened to study the extraction of curcuminoids from Curcuma longa L. Choline chloride and lactic acid DES at 1:1 M ratio gave the maximum extent of extraction. Further, DES based extraction was intensified using ultrasound. The impact of various process parameters such as % (v/v) water in DES, % (w/v) solid loading, particle size, ultrasound power intensity, and pulse mode operation of ultrasound was studied. The maximum curcuminoids yield of 77.13 mg/g was achieved using ultrasound assisted DES (UA-DES) based extraction in 20% water content DES at 5% solid loading and 0.355 mm particle size with 70.8 $W/{\mathit{cm}}^2$ power intensity and 60% (6 sec ON and 4 sec OFF) duty cycle at 30 ± 2 °C in 20 min of irradiation time. Kinetics of UA-DES extraction was explained using Peleg’s model and concluded that it is compatible with the experimental data. Additionally, anti-solvent (water) precipitation technique was applied, which resulted in 41.97% recovery of curcuminoids with 82.22% purity from UA-DES extract in 8 h of incubation at 0 °C. The comparison was made between conventional Soxhlet, batch, DES and UA-DES based processes on the basis of yield, time, solvent requirement, temperature, energy consumption, and process cost. The developed UA-DES based extraction can be an efficient, cost effective, and green alternative to conventional solvent extraction for curcuminoids.     

Synergism of sweeping frequency ultrasound and deep eutectic solvents pretreatment for fractionation of sugarcane bagasse and enhancing enzymatic hydrolysis

Sugarcane bagasse (SCB) is an abundant agricultural waste in China and the conversion of the waste into plethora of useful resources is very vital. To achieve this, fractionation of the waste is highly important in the biomass biorefinery. The present study aims at investigating the synergistic role of deep eutectic solvents (DES) with sweeping frequency ultrasound (SFUS) and fixed frequency ultrasound (FFUS) in the fractionation of SCB to enhance the enzymatic saccharification process. Therefore, the effects of ultrasound (US) and DES conditions on the pretreatment efficiency were investigated. Under optimum SCB pretreatment conditions, FFUS (40 kHz, 60 min) + DES (choline chloride (ChCl)-lactic acid (LA), 120 °C, 3 h) and SFUS (40 kHz, 60 min) + DES (ChCl-LA, 120 °C, 3 h), the lignin removal rates were 80.13 and 85.62%, respectively. The hemicellulose removal rates were 78.08 and 90.46%, respectively; and the contents of glucose, xylose and arabinose in the liquid fractions after FFUS + DES pretreatment were 7.07, 17.95 and 3.01%, respectively. However, the yield of glucose, xylose, and cellobiose after enzymatic hydrolysis of the SFUS + DES pretreated SCB were 86.76, 38.68, and 20.76%. Analytical studies revealed that the SFUS + DES pretreatment can effectively destroy the ultrastructure of SCB and reduce the crystallinity of cellulose. Furthermore, the mechanism of pretreatment with SFUS + DES was proposed, which confirmed the excellent performance of SFUS + DES. Thus, the application of SFUS + DES pretreatment was able to improve the removal of lignin and hemicellulose from SCBs.     

Ultrasound assisted intensification of biodiesel production using enzymatic interesterification

Ultrasound assisted intensification of synthesis of biodiesel from waste cooking oil using methyl acetate and immobilized lipase obtained from Thermomyces lanuginosus (Lipozyme TLIM) as a catalyst has been investigated in the present work. The reaction has also been investigated using the conventional approach based on stirring so as to establish the beneficial effects obtained due to the use of ultrasound. Effect of operating conditions such as reactant molar ratio (oil and methyl acetate), temperature and enzyme loading on the yield of biodiesel has been investigated. Optimum conditions for the conventional approach (without ultrasound) were established as reactant molar ratio of 1:12 (oil:methyl acetate), enzyme loading of 6% (w/v), temperature of 40 °C and reaction time of 24 h and under these conditions, 90.1% biodiesel yield was obtained. The optimum conditions for the ultrasound assisted approach were oil to methyl acetate molar ratio of 1:9, enzyme loading of 3% (w/v), and reaction time of 3 h and the biodiesel yield obtained under these conditions was 96.1%. Use of ultrasound resulted in significant reduction in the reaction time with higher yields and lower requirement of the enzyme loading. The obtained results have clearly established that ultrasound assisted interesterification was a fast and efficient approach for biodiesel production giving significant benefits, which can help in reducing the costs of production. Reusability studies for the enzyme were also performed but it was observed that reuse of the catalyst under the optimum experimental condition resulted in reduced enzyme activity and biodiesel yield.     

Ultrasound and microwave assisted synthesis of isoindolo-1,2-diazine: a comparative study

A comparative study, ultrasound (US) versus microwave (MW) versus conventional thermal heating (TH), for synthesis of isoindolo-1,2-diazine is described. The reaction pathway is fast, efficient and straight applicable, involving a Huisgen [3+2] dipolar cycloaddition of cycloimmonium ylides to 1,4-naphthoquinone. A feasible reaction mechanism for the obtaining of the fully aromatized tetra- and penta- cyclic isoindolo-1,2-diazine is presented. Under US irradiation the yields are much higher (sometimes substantially, by almost double), the reaction time decreases substantially, the reaction conditions are milder. The use of a generator with a higher nominal power induces higher yields and short reaction times. Overall the use of US it proved to be more efficient than MW or TH. A feasible explication for US efficiency is presented.     

Improved direct synthesis of TiO2 catalyst using sonication and its application for the desulfurization of thiophene

TiO₂ catalyst was synthesized in the presence of ultrasound (ultrasonic horn at 20 kHz frequency and 70% duty cycle) at different power (80 W to 120 W) and durations as well as surfactant concentration with an objective of establishing best conditions for achieving lowest particle size of the photocatalyst. Detailed characterization in terms of crystal phase, crystallinity, functional groups and morphology of the photocatalyst has been performed using SEM, XRD and FTIR analysis. It was demonstrated that sonication significantly reduced the particle size with high degree of sphericity and homogeneity as compared to conventionally synthesized TiO₂ with similar crystallinity in both cases. The catalytic performance was subsequently evaluated for the deep desulfurization of thiophene. Different desulfurization approaches including individual US (ultrasonic horn at 20 kHz frequency, 110 W power and 70% duty cycle) and UV irradiations, US/UV, US/UV/H₂O₂, US/UV/TiO₂ and US/UV/H₂O₂/TiO₂ were applied to evaluate the catalytic activity. The best approach was demonstrated as US/UV/H₂O₂/TiO₂ and also activity of catalyst synthesized using ultrasound was much better compared to conventionally synthesized catalyst. The studies related to different model solvents demonstrated lowest reactivity for toluene whereas n-hexane and n-octane resulted in complete desulfurization in 60 min and 50 min treatment respectively. The desulfurization followed pseudo first order reaction kinetics irrespective of the solvent used. Overall the work clearly demonstrated the efficacy of ultrasound in improving the catalyst synthesis as well as desulfurization of thiophene.     

Improved synthesis of aluminium nanoparticles using ultrasound assisted approach and subsequent dispersion studies in di-octyl adipate

The present work reports on an efficient and simple one pot synthetic approach for aluminium nanoflakes and nanoparticles based on the intensification using ultrasound and provides a comparison with the conventional approach to establish the cutting edge process benefits. In situ passivation of aluminium particles with oleic acid was used as the method of synthesis in both the conventional and ultrasound assisted approaches. The aluminium nanoflakes prepared using the ultrasound assisted approach were subsequently dispersed in di-octyl adipate (DOA) and it was demonstrated that a stable dispersion of aluminium nanoflakes into di-octyl adipate (DOA) is achieved. The morphology of the synthesized material was established using the transmission electron microscopy (TEM) analysis and energy dispersive X-ray analysis (EDX) and the obtained results confirmed the metal state and nano size range of the obtained aluminium nanoflakes and particles. The stability of the aluminium nanoflakes obtained using ultrasound assisted approach and nanoparticles using conventional approach were characterized using the zeta potential analysis and the obtained values were in the range of −50 to +50 mV and −100 to +30 mV respectively. The obtained samples from both the approaches were also characterized using X-ray diffraction (XRD) and particle size analysis (PSA) to establish the crystallite size and particle distribution. It was observed that the particle size of the aluminium nanoflakes obtained using ultrasound assisted approach was in the range of 7–11 nm whereas the size of aluminium nanoparticles obtained using conventional approach was much higher in the range of 1000–3000 nm. Overall it was demonstrated that the aluminium nanoflakes obtained using the ultrasound assisted approach showed excellent morphological characteristics and dispersion stability in DOA showing promise for the high energy applications.     

Preparation of 1,3-bis(allyloxy)benzene under a new multi-site phase-transfer catalyst combined with ultrasonication – A kinetic study

In the present work, kinetics of synthesis of 1,3-bis(allyloxy)benzene was successfully carried out by O-allylation of resorcinol with allyl bromide using aqueous potassium hydroxide and catalyzed by a new multi-site phase-transfer catalyst viz., 1,3,5,7-tetrabenzylhexamethylenetetraammonium tetrachloride, MPTC under ultrasonic (40 kHz, 300 W) assisted organic solvent condition. The pseudo first-order kinetic equation was applied to describe the overall reaction. Under ultrasound irradiation (40 kHz, 300 W) in a batch reactor, it shows that the overall reaction rate can be greatly enhanced to seven fold faster with ultrasound irradiation than without ultrasound. The present study provides a method to synthesize ethers by ultrasound assisted liquid–liquid phase-transfer catalysis condition.     

Ultrasound assisted synthesis of doped TiO2 nano-particles: Characterization and comparison of effectiveness for photocatalytic oxidation of dyestuff effluent

The present work deals with the synthesis of titanium dioxide nanoparticles doped with Fe and Ce using sonochemical approach and its comparison with the conventional doping method. The prepared samples have been characterized using X-ray diffraction (XRD), FTIR, transmission electron microscopy (TEM) and UV–visible spectra (UV–vis). The effectiveness of the synthesized catalyst for the photocatalytic degradation of crystal violet dye has also been investigated considering crystal violet degradation as the model reaction. It has been observed that the catalysts prepared by sonochemical method exhibit higher photocatalytic activity as compared to the catalysts prepared by the conventional methods. Also the Ce-doped TiO₂ exhibits maximum photocatalytic activity followed by Fe-doped TiO₂ and the least activity was observed for only TiO₂. The presence of Fe and Ce in the TiO₂ structure results in a significant absorption shift towards the visible region. Detailed investigations on the degradation indicated that an optimal dosage with 0.8 mol% doping of Ce and 1.2 mol% doping of Fe in TiO₂ results in higher extents of degradation. Kinetic studies also established that the photocatalytic degradation followed the pseudo first-order reaction kinetics. Overall it has been established that ultrasound assisted synthesis of doped photocatalyst significantly enhances the photocatalytic activity.     

Ultrasound assisted synthesis of highly active nanoflower-like CoMoS4 electrocatalyst for oxygen and hydrogen evolution reactions

Rapid technological development requires sustainable, pure, and clean energy systems, such as hydrogen energy. It is difficult to fabricate efficient, highly active, and inexpensive electrocatalysts for the overall water splitting reaction: the oxygen evolution reaction (OER) and hydrogen evolution reaction (HER). The present research work deals with a simple hydrothermal synthesis route assisted with ultrasound that was used to fabricate a 3D nanoflower-like porous CoMoS₄ electrocatalyst. A symmetric electrolyzer cell was fabricated using a CoMoS₄ electrode as both the anode and cathode, with a cell voltage of 1.51 V, to obtain a current density of 10 mA/cm². Low overpotentials were observed for the CoMoS₄ electrode (250 mV for OER and 141 mV for HER) at a current density of 10 mA/cm².     

Enhanced degradation of 2,4-dichlorophenol by ultrasound in a new Fenton like system (Fe/EDTA) at ambient circumstance

This study investigated the effect of ultrasound (US) enhancement on the degradation of 2,4-DCP in a new Fenton like system. An obviously synergistic effect was observed after introduction of US into the Fe/EDTA system. Good correspondences with pseudo-first-order kinetic were found in each reaction system. It was demonstrated that the degradation rate constant (k_obs) of DCP in US/Fe/EDTA was 7 and 32 times higher than those in Fe/EDTA and US system alone. Simultaneously, lower first-order k_obs was also obtained in the investigation of decomposition of EDTA. At 60 min reaction time, Removals of 81% TOC, complete DCP and 89% EDTA were achieved. Low molecular weight organic acids are identified as the main products, which contribute to the solution self-buffer at about pH 6.5 along with the reaction. In addition, the effect of initials condition, i.e., iron addition, EDTA dosage, DCP concentration and US input power as well as reaction temperature were studied and reaction activation energy (E_a) was also calculated.     

Ultrasound-assisted synthesis of pyrimidines and their fused derivatives: A review

The pyrimidine scaffold is present in many bioactive drugs; therefore, efficient synthetic routes that provide shorter reaction times, higher yields, and site-selective reactions are constantly being sought. Ultrasound (US) irradiation has emerged as an alternative energy source in the synthesis of these heterocyclic scaffolds, and over the last ten years there has been a significant increase in the number of publications mentioning US in either the construction or derivatization of the pyrimidine core. This review presents a detailed summary (with 140 references) of the effects of US (synergic or not) on the construction and derivatization of the pyrimidine core through classical reactions (e.g., multicomponent, cyclocondensation, cycloaddition, and alkylation reactions). The main points that were taken into consideration are as follows: chemo- and regioselectivity issues, and the results of conventional heating methods compared to US and mechanistic insights that are also presented and discussed for key reactions.     

Mechanism study of Single-Step synthesis of Fe(core)@Pt(shell) nanoparticles by sonochemistry

Transition metal (TM) core-platinum (Pt) shell nanoparticles (TM@Pt NPs) are attracting a great deal of attention as highly active and durable oxygen reduction reaction (ORR) electrocatalysts of fuel cells and metal-air batteries. However, most of the reported synthesis methods of TM@Pt NPs are multistep in nature, a significant disadvantage for real applications. In this regard, our group has reported a single-step method to synthesize TM@Pt NPs for TM = Mn, Fe, Co, and Ni by using sonochemistry, namely the UPS (ultrasound-assisted polyol synthesis) method. Previously, we proposed the mechanism of the formation of these TM@Pt NPs by UPS method, but rather in a rough sense. Some details are missing and the optimal conditions have not been established. In the present work, we performed detailed studies on the formation mechanism of UPS reaction by using Fe@Pt NPs as the model system. Effects of synthesis parameters such as the nature of metal precursor, conditions of ultrasound, and temperature profile as a function of reaction time were assessed, along with the analyses of intermediates during the UPS reaction. As results, we verified our previously proposed mechanism that, under appropriate conditions, Fe core is formed through the cavitation and implosion of the solvent, induced by the ultrasound, and the Pt shell is formed by the chemical reaction between Fe core and Pt reagent, independent from the direct effect of ultrasound. In addition, we established the optimal conditions to obtain a high purity Fe@Pt NPs in a high yield (>90% based on Pt), which may enable the increase of synthesis scale of Fe@Pt NPs, a necessary step for the real application of TM@Pt NPs.     

Applications of ultrasound in total synthesis of bioactive natural products: A promising green tool

Total synthesis is frequently compared to climbing as it provides a suitable route to reach a high point from the floor, the complex natural product from simple and commercially available materials. The total synthesis has a privileged position of trust in confirming the hypothetical complex structures of natural products despite sophisticated analytical and spectroscopic instrumentation and techniques that are available presently. Moreover, total synthesis is also useful to prepare rare bioactive natural products in the laboratory as several bioactive secondary metabolites are obtained in small quantities from natural sources. The artistic aspect of the total synthesis of bioactive natural products continues to be praised today as it may provide environmental protection through the concept of green or clean chemistry. The use of ultrasound waves as a non-polluting source of energy is of great interest in the field of sustainable and pharmaceutical chemistry as it differs from conventional energy sources in terms of reaction rates, yields, selectivities, and purity of the products. The present review highlights the application of ultrasound as a green tool in the total synthesis of bioactive natural products as well as this article is also aimed to offer an overview of natural sources, structures, and biological activities of the promising natural products for the first time from 2005 to 2020 elegantly.     

Selective synthesis of sulfoxides from sulfides using ultrasound

The present work aims at developing a new process to selectively synthesize sulfoxide from sulfides using ultrasound. Methyl phenyl sulfide (MPS) has been taken as a model reactant. The reaction has been carried out in ultrasonic bath with an operating frequency of 22 kHz and maximum power supply of 120 W with an actual power dissipation of approximately 40 W measured using calorimetric studies. Effect of various parameters such as presence and absence of catalyst, type of catalyst (catalysts used were sodium tungstate and ammonium molybdate), temperature, concentration of hydrogen peroxide, effect of molar ratio of MPS to H(2)O(2) has been investigated with an aim of obtaining the optimum conditions for the synthesis of sulfoxides. It was observed that the presence of catalyst is a must to achieve appreciable conversions. It was also observed that the periodic addition of stoichiometric amount of hydrogen peroxide instead of sudden addition of it (total quantity of hydrogen peroxide remains the same) gave better selectivity for sulfoxide. The maximum conversion achieved in the present work was approximately 88.42% with sulfone formation being only 0.4% indicating a 99.6% selectivity for the desired product i.e. sulfoxides.     

Enzymatic synthesis of ascorbyl palmitate in ultrasound-assisted system: process optimization and kinetic evaluation

This work is focused on the optimization of reaction parameters for the synthesis of ascorbyl palmitate catalyzed by Candida antarctica lipase in different organic solvents under ultrasound irradiation. The sequential strategy of experimental design proved to be useful in determining the optimal conditions for reaction conversion in tert-butanol system using Novozym 435 as catalyst. The optimum production was achieved at 70°C, ascorbic acid to palmitic acid molar ratio of 1:9, enzyme concentration of 5 wt% at 3h of reaction, resulting in an ascorbyl palmitate conversion of about 27%. Reaction kinetics for ascorbyl palmitate production in ultrasound device showed that satisfactory reaction conversions (～26%) could be achieved in short reaction times (2h). The empirical kinetic model proposed is able to satisfactorily represent and predict the experimental data.     

Ultrasound assisted enzyme catalyzed hydrolysis of waste cooking oil under solvent free condition

The present work demonstrates the hydrolysis of waste cooking oil (WCO) under solvent free condition using commercial available immobilized lipase (Novozyme 435) under the influence of ultrasound irradiation. The process parameters were optimized using a sequence of experimental protocol to evaluate the effects of temperature, molar ratios of substrates, enzyme loading, duty cycle and ultrasound intensity. It has been observed that ultrasound-assisted lipase-catalyzed hydrolysis of WCO would be a promising alternative for conventional methods. A maximum conversion of 75.19% was obtained at mild operating parameters: molar ratio of oil to water (buffer pH 7) 3:1, catalyst loading of 1.25% (w/w), lower ultrasound power 100 W (ultrasound intensity – 7356.68 W m⁻²), duty cycle 50% and temperature (50 °C) in a relatively short reaction time (2 h). The activation energy and thermodynamic study shows that the hydrolysis reaction is more feasible when ultrasound is combined with mechanical agitation as compared with the ultrasound alone and simple conventional stirring technique. Application of ultrasound considerably reduced the reaction time as compared to conventional reaction. The successive use of the catalyst for repetitive cycles under the optimum experimental conditions resulted in a loss of enzymatic activity and also minimized the product conversion.