Reaction Mass Efficiency Research Articles

An innovative and efficient method to synthesize meloxicam in one-step procedure with respect to the green chemistry

An improved procedure for the synthesis of meloxicam drug (methyl 4-hydroxy-2-methyl-2H-1,2-benzothiazol-2-amine-3-carboxylate 1,1-dioxide) was described in one-step using mainly impregnated montmorillonite K10 (MK10) with ZnCl2 as a heterogeneous catalyst. This innovative method was compared to the last described procedure employed in the manufacture of this anti-inflammatory drug by means of some metrics used in a first step of the evaluation process of the environmental impact of a chemical transformation. Apart from the yield, which was 90%, atom economy, waste, environmental factor, reaction mass efficiency and stoichiometric factor were calculated as 91.6%, 8.4%, 0, 8.1% and 1%, respectively. Interpretation of these metrics was given and highlighted the fact that the strategy used in the current study may be considered as an environmental-friendly and sustainable method that fits well in the green chemistry concepts.

Exploring TiO2 NPs as efficient catalyst for 1,6 Michael addition of 3-methyl-5-pyrazolone on 3-methyl-4-nitro-5-alkenyl isoxazoles and rapid synthesis of 3,3‐bis(indolyl)oxindoles in water

We here present a report on development of a column chromatography free, heterogenous titanium dioxide nanoparticles (TiO2 NPs) catalyzed 1, 6 Michael addition of 3-methyl-5-pyrazolone on 3-methyl-4-nitro-5-alkenyl isoxazoles and rapid synthesis of 3,3-di(indolyl)indolin-2-ones by reaction of indole on isatin at room temperature in water for the first time. Moderate to good yield was obtained in case of 1, 6 Michael addition reaction and quantitative yield in case of a 3,3‐bis(indolyl)oxindole products. A scale up experiment on gram scale was performed successfully for both the reactions. Recyclability experiment was carried out for 4 cycles and turn over frequency (TOF) calculation for each cycle are presented for both reactions, which clearly indicate the sustainability of the protocol. In addition, green chemistry matrices (atom economy, reaction mass efficiency (RME), E-factor, process mass intensity (PMI)) values suggest that the presented methodology is green and eco-friendly.

Toward the Selection of Sustainable Catalysts for Suzuki–Miyaura Coupling: A Gate-to-Gate Analysis

Reports of homogeneous and heterogeneous methods for Pd-catalyzed Suzuki–Miyaura coupling provide a vast data set to establish sustainability targets and parameters for future catalyst development. In this gate-to-gate inventory we estimate energy and palladium usage along with reaction mass efficiency (RME) for a range of palladium catalysts (both single- and multiuse) for the generation of (a) 4-phenylphenol from 4-iodophenol and phenylboronic acid or (b) 4-methoxybiphenyl from 4-chloroanisole and phenylboronic acid. Small differences were found in calculated energy usage, RME values, and non-palladium reagent toxicities. Palladium usage, however, varied substantially and stood out as the main differentiating consideration from a sustainability standpoint. Reusable heterogeneous catalysts still use more palladium when compared to ultra-low-loading homogeneous techniques that are effective for conversion of aryl iodides. For aryl chloride substrates, highly active and reusable heterogeneous catalysts bec...

An efficient solvent-free synthesis of 3-methyl-4-nitro-5-styrylisoxazoles using solid nano-titania

An efficient and solvent-free procedure for the synthesis of 3-methyl-4-nitro-5-styrylisoxazoles using nano-titania as solid support and recyclable catalyst is presented. This method provides clean, simple, solvent-free and useful alternative to synthesize styrylisoxazoles. The use of nano-titania provides excellent yield, leading to an easy separation and reuse of the catalyst up to four times without loss of yield. Also, the green matrices calculation shows low environment impact. The green chemistry matrices atom economy, reaction mass efficiency (RME), process mass intensity and E-factor are also calculated which show that this methodology is green and eco-friendly. The catalytic efficiency of heterogeneous TiO $$_2$$ NPs was successfully demonstrated by recyclability experiment (up to 4 cycles). The sustainability of the catalyst was tested by performing recyclability experiment up to 4 cycles. Calculated turn over frequency (TOF) for each cycle indicates the protocol as sustainable. An efficient and solvent-free procedure for the synthesis of 3-methyl-4-nitro-5-styrylisoxazoles using nano-titania as solid support and recyclable catalyst is presented. This method provides a useful alternative to synthesize styrylisoxazoles.

Scalable Synthesis of Cholesteric Glassy Liquid Crystals

Capable of nonabsorbing circular polarization of unpolarized incident light, cholesteric glassy liquid crystals consisting of hybrid chiral-nematic pendants to volume-excluding cores are potentially useful for the fabrication of various robust optical devices. As illustrated in this study, the well-oriented glassy film of enantiomeric Bz3ChN, with a glass transition at 73 °C and a cholesteric-to-isotropic transition at 295 °C, exhibits a selective reflection band centered at approximately 410 nm, an exceptional set of properties well suited for optical device exploration. To enable sustainable large-scale synthesis of this material class for widespread applications, a productive strategy has been established, requiring a mere three-step scheme with an overall yield, atom economy, and reaction mass efficiency at 34%, 33%, and 12%, respectively. While amenable to improvement, the resulting green chemistry metrics are encouraging as the first attempt.

Organic Transformations Induced by Hydrotalcite as Green Catalyst Useful in Pharmaceutical Industries

Background: Pharmaceutical industry is one of the most popular sectors known for spreading of pollution. Here the association with various bases belonging to either organic or inorganic for the enhancement of different transformation is a routine practice for manufacturing of active pharmaceutical ingredients and their intermediates. This results in the destruction of environment directly or indirectly because such bases are non-recoverable and non-recyclable. Methods: Present investigation has focused on the advantage of application of century old hydrotalcite as a green catalyst, which is recoverable and recyclable, in various organic transformations useful for the synthesis of some active pharmaceutical ingredients and their intermediates. Here the authors have identified research gap and disclosed novel green synthetic procedures catalyzed by hydrotalcite. Hydrolysis, oxidation, S-Alkylation, Knovengel condensation and peptide bonding transformations were tested in this protocol resulting in efficient, cost effective, eco-benign and industrially advantageous outcome. Conclusion: This methodology was assessed by Reaction Mass Efficiency, one of the green metrics, proving it to be eco-friendly as well as describing its financial importance which comes under green and sustainable practices. Keywords: Clay, green chemistry, hydrotalcite, organic transformations, reaction mass efficiency, sustainable procedures.

Metrics of Green Chemistry and Sustainability: Past, Present, and Future

The first green chemistry metrics—the E factor (kgs waste/kg product) and atom economy (mol wt of product/sum of mol wts of starting materials)—were introduced in the early 1990s and were actually green chemistry avant la lettre. In the last two decades, these two metrics have been adopted worldwide by both academia and industry. The E factor has been refined to distinguish between simple and complete E factors, for example, and to define the system boundaries. Other mass-based metrics such as process mass intensity (PMI) and reaction mass efficiency (RME) have been proposed. However, mass-based metrics need to be augmented by metrics which measure the environmental impact of waste, such as life cycle assessment (LCA), and metrics for assessing the economic viability of products and processes. The application of such metrics in measuring the sustainability of processes for the manufacture of pharmaceuticals and other fine chemicals is discussed in detail. Mass-based metrics alone are not sufficient to mea...

A green synthesis of unsymmetrical triarylmethanes via indium (III) triflate catalyzed Friedel Crafts alkylation of o-hydroxy bisbenzylic alcohols under solvent free conditions

Using indium (III) triflate as a mild Lewis acid catalyst, the Friedel Crafts alkylation of o-hydroxy bisbenzylic alcohols with aromatic/heteroaromatic arenes under solvent free conditions was achieved to give the corresponding unsymmetrical triarylmethanes in high yields (up to 80% yield). Calculation of the different green metrics for the above reaction revealed it to have high atom economy (94–96%), high reaction mass efficiency (66–77%) and high carbon efficiency (70–80%). The Lewis acid was found to be air and moisture tolerant. The protocol was found to be operationally simple and can be carried out in an “open-flask” leaving behind water as the sole by product. Gratifyingly the Lewis acid catalyst could be recycled and reused up to 5 catalytic cycles without compromising much on the yield thus further highlighting the importance of the protocol.

Green chemistry with process intensification for sustainable biodiesel production

Biodiesel as a renewable fuel has the potential to replace non-renewable fossil fuels and associated environmental pollution. The most commonly used method in biodiesel production is transesterification of virgin and used oil feedstock. However, the chemical reaction (transesterification) does not proceed spontaneously, which means excess reactants are required to move the reaction to completion. The biodiesel reaction efficiency can be improved by incorporating green chemistry principles and process intensification effects. Green chemistry principles can be used to design chemical products and processes that reduce or eliminate the use and generation of hazardous substances. Microwave- and ultrasound-enhanced biodiesel synthesis can improve the reaction efficiency due to higher product recovery, low by-product formation, and reduced energy consumption. In addition, utilization of green metrics such as E-factor, atom economy (utilization), mass intensity or mass productivity, and reaction mass efficiency can help design safer and highly efficient biodiesel synthesis. Green chemistry principles have been analyzed for other processes in greater details, but they are rarely discussed in the context of biodiesel production. Process intensification by microwave- and ultrasound-mediated biodiesel production was never discussed from the perspective of green chemistry and sustainable process development. This research review article discusses the role of green chemistry and process intensification in biodiesel production followed by specific examples and illustrations on green metrics of microwave- and ultrasound-enhanced biodiesel synthesis and the effect of catalysts and solvents including discussions on reaction kinetics and activation energy in detail for the first time in the literature.

Microwave-assisted synthesis of zirconium-based metal organic frameworks (MOFs): Optimization and gas adsorption

Microwave-assisted synthesis of zirconium (Zr) based metal organic frameworks (MOFs) were performed and the yield and porous property of UiO-67 was optimized by varying the quantity of the modulator (benzoic acid, BenAc and hydrochloric acid, HCl), reaction time and temperature. It was found that (i) an increase in the amount of modulator enhanced the specific surface area and pore volume of UiO-67 due to the promotion of linker deficiency; and (ii) the presence of modulators influenced the number of nuclei (and hence the crystal size) and nucleation time (and hence the yield). Optimum amounts of BenAc and HCl for synthesizing UiO-67 under microwave irradiation were determined as 40 mol equivalent and 185 mol equivalent (to Zr salt), respectively. In comparison to conventional solvothermal synthesis, which normally takes 24 h, microwave methods promoted faster syntheses with a reaction time of 2–2.5 h (at similar temperatures of 120 °C and 80 °C for BenAc and HCl, respectively). The thermal effect of microwave is believed to contribute to the fast synthesis of UiO-67 in the microwave-assisted synthesis. The reaction mass efficiency and space-time yield show that microwave heating promoted the simple yet highly efficient preparation of Zr-based MOFs. In addition, UiO-67 MOFs from different synthesis methods (i.e. the microwave-assisted and solvothermal method) were evaluated using single-component (CO2 and CH4) adsorption, showing comparable gas uptakes.

Assessment of Sustainability Indicators for Biodiesel Production

Biodiesel production may provide a sustainable route to reduce environmental pollution caused by fossil fuel consumption. In order to minimize environmental impacts of biodiesel production, the chemical process should be optimized to minimize waste generation and energy consumption. Therefore, it is important to design biodiesel chemical reactions and processes using green chemistry and green engineering principles to develop sustainable chemical processes. This study provides the results of the synergistic effect of microwave and ultrasound irradiations to produce biodiesel using ethanol or methanol as the alcohol donor. The biodiesel yields are presented along with their respective green metrics, such as atom economy, environmental factor (E-factor), atom economy (utilization) or atomic efficiency, mass intensity, reaction mass efficiency, atom utilization, and stoichiometric factor. These green metrics are crucial to determine the sustainability and environmental impact of biodiesel production. Evaluation of these green metrics indicates that methanol is a better alternative for biodiesel production provided it is derived from renewable sources. Sustainability indicator concepts used for biodiesel production in this study can be applied to various biofuels and other chemical reaction designs, synthesis and process development.

Reaction Scale and Green Chemistry: Microscale or Macroscale, Which Is Greener?

The different ways microscale and green chemistry allow reducing the deleterious impacts of chemistry on human health and the environment are discussed in terms of their different basic paradigms: green chemistry follows the ecologic paradigm and microscale the risk paradigm. A study of the synthesis of 1-bromobutane at macro- → microscale (109.3 → 10.9 g of the limiting reagent, butan-1-ol) showed that green chemistry mass metrics (AE, atom economy; RME, reaction mass efficiency; MI, mass intensity; E-factor, environmental factor; CEE, carbon efficiency) are unsuitable for evaluating the advantages of micro- versus macroscale. Poorer values of mass metrics at the microscale and the same green star at both scales showed that green metrics do not recognize that microscale improves safety. As so far no metrics have been proposed for evaluating this purpose, a new risk index (scale risk index, SRI) was developed for assessing the improvement of safety on downsizing the scale of synthesis experiments in chemi...

Hierarchically Porous Sphere-Like Copper Oxide (HS-CuO) Nanocatalyzed Synthesis of Benzofuran Isomers with Anomalous Selectivity and Their Ideal Green Chemistry Metrics

Development of nanocatalysts for a chemical reaction with ideal values in green chemistry metrics is considered to be a challenging task to achieve sustainable chemistry. With this aim, we herein report a hierarchically porous sphere-like copper oxide (HS-CuO) nanocatalyst to afford benzofuranamine and dihydro-benzofuranamine isomers with anomalous selectivity via O-annulated A3 coupling among salicylaldehydes, secondary amines, and alkynes followed by cycloisomerization in the absence of base and solvent. The anomalous selectivity of benzofuran isomers was dependent on the electronic factors of substituents on salicylaldehyde and the type of secondary amines used in the coupling reaction. The HS-CuO nanocatalyst was recycled five times without significant loss in its catalytic activity. The present method offers several advantages over the reported methods such as wide substrate scope with anomalous selectivity in the products, high yields in short reaction time, avoided the usage of extra reagents such as additives/bases, and showed ideal values of green chemistry metrics such as low E-factor and process mass intensity (PMI), high atom economy (AE), reaction mass efficiency (RME), and carbon efficiency (CE).

Decarboxylative Coupling Strategy To Afford N-Heterocycles Driven by Silica-Nanosphere-Embedded Copper Oxide (Cu@SiO2-NS)

An environmentally benign and surfactant-free method was developed for the preparation of porous silica nanospheres (SiO2 NS) from the hydrolysis of tetraethoxyorthosilicate (TEOS), using corn starch as a sacrificial template. The stabilization of malachite on SiO2 NS, followed by calcination at 600 °C, afforded silica-nanosphere-embedded copper oxide (Cu@SiO2-NS). The obtained Cu@SiO2-NS was found to be a versatile nanocatalyst for the decarboxylative coupling strategies to afford aromatic or aliphatic N-heterocycles such as aminoindolozines, pyrrolo[1,2-a]quinolones, and substituted pyrrolidine. The Cu@SiO2-NS was successfully recycled for six times without significant loss in its catalytic efficiency. The present method shows several advantages, such as being an environmentally benign approach for the catalyst preparation, being easy to handle, and having a wide substrate scope for decarboxylative couplings with excellent yields in short reaction time, and showed excellent green chemistry metrics, such as E-factor, process mass intensity (PMI), reaction mass efficiency (RME), carbon efficiency (CE), and comparatively high turnover number/turnover frequency (TON/TOF) values.

Visible Light‐Mediated Copper(I)‐Catalysed Aerobic Oxidation of Ynamides/Ynamines at Room Temperature: A Sustainable Approach to the Synthesis of α‐Ketoimides/α‐Ketoamides

AbstractA novel visible light‐mediated, copper‐catalysed aerobic oxidation of the C≡C bond in ynamides/ynamines at room temperature by using molecular oxygen as an oxidant is described. Overall, 23 examples were demonstrated with substrates having a wide range of functional groups. The current protocol can be readily scaled up to a preparative (1–2 g) scale with high yields (78–92%), high atom efficiency, and reaction mass efficiency. The mechanistic study shows that in‐situ formation of a copper(I)‐coordinated π‐complex (λmax=460 nm) is most probably the key light absorbing species responsible for the visible light‐induced oxidation of ynamides and ynamines. This sustainable oxidation approach allows the direct synthesis of potentially important novel α‐ketoimide/α‐ketoamide skeletons without the need of external oxidants (organic/inorganic oxidants) and generation of stoichiometric amounts of wastes.magnified image

Comparing Amide-Forming Reactions Using Green Chemistry Metrics in an Undergraduate Organic Laboratory

In this laboratory experiment, upper-division undergraduate chemistry and biochemistry majors investigate amide-bond-forming reactions from a green chemistry perspective. Using hydrocinnamic acid and benzylamine as reactants, students perform three types of amide-forming reactions: an acid chloride derivative route; a coupling reagent promoted method; and a boric acid catalyzed condensation. After isolation of the common product, students assess the reactions using the 12 Principles of Green Chemistry and several green chemistry metrics: atom economy; reaction mass efficiency; process mass intensity; and the EcoScale. In addition to assessing what route is the greenest, students also compare the metrics to discern what aspects of green chemistry each metric captures. In order to extend sustainability to economic considerations, the projected “front-end” cost of synthesizing a kilogram of the amide is calculated based on data from each reaction. The experimental work is conducted over two 3 h laboratory pe...

Exploring Green Chemistry Metrics with Interlocking Building Block Molecular Models

A classroom activity for learning green chemistry metrics with interlocking building blocks is described. The activity illustrates the strengths and weaknesses of conversion, selectivity, yield, atom economy, reaction mass efficiency, carbon efficiency, E-factor, and effective mass yield by counting, where appropriate, the number of molecular models built, the number of bricks used, or the number of connection points available. The activity is appropriate for students in general chemistry courses through advanced undergraduate green chemistry or industrial chemistry courses.

Assessing Process Mass Intensity and Waste via an aza-Baylis–Hillman Reaction

A synthetic procedure is outlined where upper-level undergraduate organic chemistry students perform a two-week, semimicroscale aza-Baylis–Hillman reaction to generate an allylic sulfonamide product. Students evaluate several green chemistry reaction metrics of industrial importance (process mass intensity (PMI), E factor, and reaction mass efficiency) and specifically learn the pivotal role that PMI plays in improving operational sustainability. Advantages and disadvantages of the various metrics are highlighted within the context of a multicomponent transformation eliciting current research activity.

Catalytic Transfer Hydrogenation of Castor Oil

The main thickening agent or soap in multipurpose grease, lithium 12-hydroxystearate, is a chemical commodity for the auto industry. This compound is obtained from castor oil via a series of chemical transformations. The first step, hydrogenation of castor oil, has been developed into a laboratory experiment for second-year undergraduate organic chemistry. Students are introduced to catalytic transfer hydrogenation (CTH) as a method to reduce a carbon–carbon double bond in ricinoleic acid, the main fatty acid in castor oil. Students perform a comparative analysis based on calculation of several green metrics: atom economy, E factor, reaction mass efficiency, CO2 emissions, and costs. The product, hydrogenated castor oil, is characterized by several techniques: 1H NMR and IR spectroscopy, and melting point.

BATTERY OF METRICS FOR EVALUATING THE MATERIAL GREENNESS OF SYNTHESIS REACTIONS

The use of a battery of three mass metrics (atomic economy - AE, reaction mass efficiency - RME, and mass intensity - MI) for systemic evaluation of the material greenness of synthesis reactions is presented. Material greenness is discussed in terms of materialization/dematerialization of the reaction system and also according to the first two Principles of Green Chemistry, and is shown to involve two components: atomic greenness (incorporation of the atoms provided by reagents into the product, evaluated by AE and RME); and massic greenness (global mass of reagents and non-stoichiometric materials, evaluated by MI, related to the production of residues).