Reaction Mass Efficiency Research Articles

Development of a Sustainable Catalytic Ester Amidation Process

We describe the development of a sustainable ester amidation process. Base and solvent screening, combined with the application of Design of Experiments methodology was employed to identify an optimized set of reaction conditions using a sustainable protocol. Utilizing these optimized conditions, treatment of a range of ester derivatives with amino alcohols in the presence of a catalytic quantity of potassium phosphate deploying iso-propanol as solvent results in the highly efficient generation of a range of amido-alcohol derivatives in good to excellent yield, accompanied with excellent reaction mass efficiency (RME).

On the Probability That Ring-Forming Multicomponent Reactions Are Intrinsically Green: Setting Thresholds for Intrinsic Greenness Based on Design Strategy and Experimental Reaction Performance

This paper describes in detail the determination of the likelihood that a given generalized chemical reaction may be considered intrinsically “green” based on design strategy. Justification is given for setting threshold constraints on reaction yield and kernel reaction mass efficiency (RME) performances at greater than 80% and greater than 61.8%, respectively, for intrinsically green reactions. These criteria are applied to a survey of 60 named ring-forming multicomponent reactions (MCRs) and 2000+ such reactions reported in the literature from 2003 to 2011. Patterns among various ring construction motifs are discussed. Results show that 5- and 6-membered monocyclic rings are most commonly made by [2+2+1] and [3+2+1] cycloadditions where 57% and 76% of them, respectively, have a 100% chance of being intrinsically green from a design perspective. Similarly, the [4.3.0] and [4.4.0] skeletons are the most common fused bicyclic structures made by MCR strategies where 38% and 59% of them, respectively, have a...

Evaluation of the synthesis of 1-(pentafluorophenyl)-4,5-dihydro-1H-pyrazoles using green metrics

1-(Pentafluorophenyl)-4,5-dihydro-1H-pyrazoles were synthesized from the cyclocondensation reactions of 4-alkoxy-1,1,1-trihalo-3-alken-2-ones (CX3C(O)CH=C(R1)OR, where X = F, Cl; R = Me, Et; R1 = H, Me, Et, n-Pr, i-Pr, n-Bu, i-Pent, Ph, 4-Cl-C6H4, 4-Br-C6H4, 4-F-C6H4) with pentafluorophenyl hydrazine. Pyrazoles were obtained under microwave irradiation in solvent-free conditions or under conventional heating in the ionic liquid 1-butyl-3-methylimidazolium tetrafluoroborate, [BMIM][BF4]. These procedures furnished products in moderate to good yields in a short reaction time. Atom economy, reaction mass efficiency (RME), and environmental factor (E-factor) were determined for the cyclocondensation reaction performed under microwave (MW)/solvent-free and under conventional thermal heating/[BMIM][BF4] conditions. RME and E-factor indicated that the solvent-free procedure is invariably less green than [BMIM][BF4] when the isolated product was considered.

H3PO4/metal halide induces a one-pot solvent-free esterification–halogenation of glycerol and diols

As part of our continued effort to achieve the synthesis of halohydrin esters from polyols by a sustainable method, here we report on a multicomponent inorganic acid-mediated solvent-free synthesis. The synthesis was designed to ensure few waste materials. Using this approach, the process shows a low E-factor and a high reaction mass efficiency. The new process involves the preparation of a reaction mixture containing either a fatty acid or fatty material, glycerol or diol, a halide salt and H3PO4. This mixture is heated at 100 °C for 48 h, yielding up to 88% of halohydrin ester. The process also allows recovery of pyrophosphate salts, compounds that have various applications in agriculture, and in the pharmaceutical, chemical and food industries.

Evaluation of several catalytic systems for the epoxidation of methyl oleate using H2O2 as oxidant

The interest of epoxidation of fatty esters lies in the production of renewable and biodegradable intermediates. A plethora of epoxidizing conditions have been reported in the literature, but it remains difficult to evaluate their relative efficiency and sustainability. To this aim, we present here an evaluation of several catalytic systems for the epoxidation of methyl oleate, together with a green metrics study using atom economy (AE), reaction mass efficiency (RME), material recovery parameter (MRP), yield and reaction time as main parameters. This study reveals the distinct efficiency of the fatty ester epoxidation systems presented in this work. The use of hydrogen peroxide (H2O2) together with fluorinated solvents and aryldiselenide compounds as catalysts was found to be the most efficient methodology. Enzymatic epoxidation also arises as an efficient alternate way to obtain methyl 9,10-epoxystearate. CALB immobilized onto silica has shown a good activity and improved recyclability with respect to Novozym 435.

A comparison of green chemistry metrics for two methods of bromination and nitration of bis-pyrazolo[3,4-b;4′,3′-e]pyridines

Abstract Green chemistry metrics (E-factor, atom economy, reaction mass efficiency) and the EcoScale have been compared for conventional heating and microwave assisted bromination and nitration of bis-pyrazolo[3,4-b;4′,3′-e]pyridines. The major advantages in microwave-assisted reactions in relation to traditional evaluation of the process have encompassed higher yields, shorter reaction time and higher selectivity. The microwave-assisted reactions have shown better green chemistry parameters and EcoScale ranks than those in conventionally heated reactions. Mass reaction efficiency values have been critical for considering ‘green’ the reactions conducted under traditional conditions. Additional advantages of using microwaves, not considered in calculated parameters, include easier purification of the reaction mixture and isolation of the product.

Green synthesis of 5‐substituted‐1,3,4‐thiadiazole‐2‐thiols as new potent nitrification inhibitors

Abstract magnified image A fast, efficient synthesis of 5‐substituted‐1,3,4‐thiadiazole‐2‐thiols was successfully developed, assessed using green chemistry matrices, and compounds were screened for their in vitro nitrification inhibitory activity. The greener method was superior with higher energy efficiency, E(nvironmental) factor, atom economy, atom efficiency, carbon efficiency, and reaction mass efficiency. J. Heterocyclic Chem., (2010).

Ionic Liquids and Green Chemistry: A Lab Experiment

Although ionic liquids have been investigated as solvents for many applications and are starting to be used in industrial processes, only a few lab experiments are available to introduce students to these materials. Ionic liquids have been discussed in the context of green chemistry, but few investigations have actually assessed the degree of their greenness. This experiment combines two research areas, ionic liquids and ecological assessment, in an advanced undergraduate lab course. The modular combination of these two research areas allows for the adaptation of the timetable and content. Two ionic liquids are synthesized, and the method of heating (microwave-assisted vs convective), temperature, time, and alkylating agent are varied. In addition to the yield, simple metrics (atom economy, reaction mass efficiency, E-factor) in combination with energy efficiency, prices of chemicals, and ecological impacts of the materials are considered. It is the goal of this experiment to help students realize that a synthetic method leading to quantitative yields is not a priori green: other factors (nature of reactants, energy consumption, etc.) must be assessed as well.

Sustainable Chemistry Metrics

Green chemistry has developed mathematical parameters to describe the sustainability of chemical reactions and processes, in order to quantify their environmental impact. These parameters are related to mass and energy magnitudes, and enable analyses and numerical diagnoses of chemical reactions. The environmental impact factor (E factor), atom economy, and reaction mass efficiency have been the most influential metrics, and they are interconnected by mathematical equations. The ecodesign concept must also be considered for complex industrial syntheses, as a part of the sustainability of manufacturing processes. The aim of this Concept article is to identify the main parameters for evaluating undesirable environmental consequences.

Loss Prevention and Waste Minimization with Cascade-Engineered Green Synthesis of Bisphenol-A from Cumene Hydroperoxide and Phenol using Heteropoly Acid-Supported Clay Catalysts

Bisphenol-A (BPA), an important raw material for the synthesis of epoxy resins and other polymers, is conventionally synthesised by acid-catalysed condensation of phenol and acetone, which produces 28 known byproducts. This leads to heavy costs for purification of the final product and loss of raw material. Phenol itself is almost exclusively manufactured via the three-step Hock process which includes vapour-phase isopropylation of benzene to cumene, autoxidation of cumene to cumene hydroperoxide (CHP), and finally the highly exothermic liquid acid-catalysed cleavage of CHP to acetone and phenol. The second step in the Hock process produces around 35% w/w CHP, which is then concentrated to 80% w/w. There are inherent process hazards involved in the manufacture and/or concentration of CHP, leading to run-away situations and explosions. Cascading these two series reactions in a single pot using the same catalyst fits elegantly into the concept of waste minimization and results in a greener and cleaner environment with added economic incentives. Traditionally, single-pot synthesis overlooks the concepts of atom economy, reaction mass efficiency and the environmental impact factor which are of prime importance to any methodology desiring to be called “green synthesis”. In this work, a novel technique of BPA synthesis from CHP and phenol was engineered in a single pot by using 20% w/w dodecatungstophosphoric acid (DTP) supported on acidic clay (K-10) at 100 °C, wherein CHP produced in cumene itself and was used along with phenol to make BPA. The process is atom economical, producing water as a coproduct. In comparison with the traditional process of making BPA from phenol and acetone, there is 58% enhancement in yield and 33% enhancement in BPA selectivity. There is also a 28% improvement in reaction mass efficiency and 25% reduction in the environmental impact factor. Along with preserving the atom economy, the hazard involved in the concentration and handling of CHP, which has resulted in numerous accidents in process industries, has been eliminated. In the current process CHP produced from cumene by the Hock process is used as such without separation, and this strategy avoids the hazards of concentration and costs of separation. Finally, a comprehensive parametric sensitivity was also done, and a Langmuir−Hinshelwood−Hougen−Watson (LHHW) model was developed to describe the reaction mechanism. The theoretical predictions were found to match the experimental data.

PEER REVIEW ORIGINAL RESEARCH: EHS & LCA assessment for 7-ACA synthesis A case study for comparing biocatalytic & chemical synthesis

Abstract A Green Technology Comparison framework incorporating a life cycle approach and sustainability metrics has been used to compare the performance, and the environment, health, safety, and life cycle impacts of two synthetic methods used to produce 7-aminocephalosporic acid (7-ACA). The routes under study were a chemical synthetic process and a two-enzyme catalyzed process, both starting from the potassium salt of cephalosporin C. Cradle-to-gate life cycle impact estimations were performed using the Fast Life Cycle Assessment of Synthetic Chemistry (FLASC™) tool and following modular gate-to-gate methodology. The results compare the synthetic efficiency, environment, health, safety, and life cycle metrics for a mature chemical process and a more recent but less developed enzymatic process for making 7-ACA. The chemical process has a higher yield, but a significantly lower reaction mass efficiency and half the mass productivity of the enzymatic process. The chemical process uses more hazardous materi...

Integration of Solventless Reaction in a Multi‐Step Process: Application to an Efficient Synthesis of PA‐824

AbstractIn order to improve redundant synthetic processes, the integration of a solventless reaction has proved to be useful for gaining high reaction mass efficiency (RME) as well as reducing the amount of solvents. This concept was applied to synthesis of PA‐824, a potential antituberculosis drug. Thus, the solventless ring‐opening reaction of glycidyl silyl ether with dinitroimidazole was connected to succeeding solution reactions. The ring‐opening of glycidol followed by selective silylation of the primary hydroxy group under solventless conditions was also feasible. As a consequence, the overall yield of the target compound was nearly tripled, and thus the RME values were increased more than 2.5 times while the amount of necessary solvents was decreased to less than 1/3.

On the Use of "Green" Metrics in the Undergraduate Organic Chemistry Lecture and Lab To Assess the Mass Efficiency of Organic Reactions

This article describes a novel approach to evaluate the complete reaction mass efficiency (RME) and raw material cost (RMC) of any chemical transformation through the implementation of an Excel spreadsheet in a tax-form style and an easy graphical representation of the results. The complete equation for evaluating RME is presented. Students and their lab instructors will be able to see at once the material performance of their laboratory reaction and evaluate critically which of the four parameters (reaction yield, atom economy, stoichiometric factor, and material recovery parameter) needs further optimization to bring about a �greener� synthesis plan. The effect of material recovery options on RME and RMC are also given. The methodology is applied to a wide variety of organic reaction types and key trends in the material efficiency performances are summarized.

On Using Tree Analysis to Quantify the Material, Input Energy, and Cost Throughput Efficiencies of Simple and Complex Synthesis Plans and Networks: Towards a Blueprint for Quantitative Total Synthesis and Green Chemistry

Synthetic plans or networks may be depicted as trees in a graph-theoretical sense. When drawn in a systematic way according to a defined convention key “green” metrics relating to the efficiency of performance of a synthesis to a target molecule may be easily obtained by inspection, that is, by a “connect-the-dots” approach. Example metrics include the cumulative and overall reaction mass efficiency (RME), the overall raw materials cost (RMC), and the fraction of total energy input directed to product (FTE). Throughout this paper kernel metrics are used to determine and compare the intrinsic efficiencies of synthetic plans since these depend directly on the nature of the chemical transformations and not on ancillary variables such as solvent usage, etc. Histograms of these metrics versus reaction stage allow for the easy determination of the mass-, cost-, and input energy-determining steps for a given synthesis plan. Other useful parameters that can be determined from a synthesis tree include the degree o...

Unification of Reaction Metrics for Green Chemistry II: Evaluation of Named Organic Reactions and Application to Reaction Discovery

The concept of minimum atom economy (AE)min and maximum environmental impact factor Emax is introduced and applied to a database of more than 400 named organic reactions by employing generalized Markush structures as a means of gauging worst-case scenarios for waste production for chemical reactions. The scope of the method can be extended to evaluate “green” performances for any chemical reaction once all byproducts are identified. From the inverse relationship connecting AE and Emw (environmental impact factor based on molecular weight) and an analogous one connecting RME (reaction mass efficiency) and E (Sheldon environmental impact factor), a minimum value of AE or RME equal to the golden ratio, 0.618 (or 61.8%), is suggested as a threshold metric for gauging the true “greenness” of reactions. The rationale for this is that this condition is met when the magnitude of AE exceeds that of Emw and similarly when RME exceeds E. Probabilities for achieving this condition are also determined for several orga...

Unification of Reaction Metrics for Green Chemistry: Applications to Reaction Analysis

A formalism is presented which unifies key reaction metrics associated with “greenness” in chemical reactions with respect to raw materials usage. The fundamental basis of this treatment begins with balanced chemical reactions in which byproducts are identified. The primary or kernel metrics are reaction yield, scale of reaction, stoichiometric factor (SF), and Trost's atom economy (AE). The stoichiometric factor is a new metric that is defined to account for reactions run under nonstoichiometric conditions, that is, with one or more reagents in excess. A general relation for reaction mass efficiency (RME) is derived which shows that this metric is a composite of the aforementioned primary metrics and takes into account solvent usage in the reaction and postreaction phases (workup and purification). The Sheldon environmental impact factor E is treated at various levels of complexity according to what is constituted as waste and is shown to be related to RME by a simple inverse expression. A flowchart is presented which shows other simple relationships connecting all metrics. Raw material costs, optimum conditions for recycling or reclaiming catalysts and reaction and postreaction solvents, and the handling of reactions giving isomeric products are also assessed. General algorithms are proposed for determining kernel reaction metrics for linear and convergent sequences that can be used to compare the intrinsic, or best-case scenario, green performances of synthetic plans to a common target structure. All key relationships can be implemented in a spreadsheet format from which reaction histograms or “maps” can be generated. Individual reaction RME performances can be gauged, ranked, and decomposed according to AE, SF, and reaction yield kernel metrics. This allows for the easy identification of best and worst reactions in a process or sequence. Example applications of the present methodology include the following: (a) a comparative analysis of the synthesis of quinine by the classic Woodward−Rabe and the modern greener Stork methods; (b) the analysis of the industrial synthesis of sildenafil (Viagra) by a convergent strategy; and (c) the analysis of kinetic resolution of racemic alcohols by a successive oxidation and recycling reduction cycle.

Green Chemistry in Process Research and Development in Pharmaceutical Industry

AbstractFor Abstract see ChemInform Abstract in Full Text.

Effect of concentration of bed materials on combustion efficiency during incineration

The concentration of bed materials in a fluidized bed incinerator influences the reaction time, mass and heat transfer efficiency. These parameters significantly affect the combustion efficiency and the generation of pollutants in the waste incineration. This research studied the effect of concentration of bed materials on combustion efficiency during waste incineration. The size of bed materials, combustion temperature, and excess air factor were controlled to assess the concentration of carbon monoxide. The pressure drop was measured to evaluate the bed expansion and calculate the concentration of bed materials. Experimental results indicated that the concentration of carbon monoxide did not decrease with the decrease of residence time and increase of excess air factor. With higher heat transfer efficiency, the combustion time could be reduced and the combustion efficiency would be improved. The concentration of carbon monoxide at 700 °C was higher than that at 800 and 900 °C. The influence of heat transfer efficiency on combustion efficiency was significant as the operating temperature was higher than 700 °C. The concentration of carbon monoxide decreased with increasing static bed height. In addition, the size of bed materials affected the mixing and heat transfer efficiency in the sand bed. According to the result of experiment, the best particle size of bed materials was 770 μm.

医薬品原薬のプロセス研究および生産現場におけるグリーンケミストリーへの取り組み

Recently, green chemistry (GC) plays an important role for manufacturing active pharmaceutical ingredients (APIs) at pharmaceutical companies. For example, large amount of aluminum waste was originally involved and dichloromethane used as a solvent in the process of a new anticholinergic agent, Vamicamide (FK 176), useful for the treatment of urinary incontinence. Non-selective and tedious procedures for alkylation of quinazoline nucleous were used on a laboratory scale in the process of a novel aldose reductase inhibitor, Zenarestat (FK 366) developed for the remedy of diabetic complications. These problems must be excluded before realizing a truly efficient process on a large scale. New process involved much less amount of waste in the case of Vamicamide, and utilized regioselective alkylation reaction for Zenarestat. As a result, E-factor and reaction mass efficiency (RME) were dramatically improved. Herein, we report our efforts leading to an efficient, practical and environmentally friendly process amenable to a large scale synthesis.

Metrics to ‘green’ chemistry—which are the best?

A considerable amount has been written about the use of metrics to drive business, government and communities towards more sustainable practices. A number of metrics have also been proposed over the past 5–10 years to make chemists aware of the need to change the methods used for chemical syntheses and chemical processes. This paper explores several metrics commonly used by chemists and compares and contrasts these metrics with a new metric known as reaction mass efficiency. The paper also uses an economic analysis of four commercial pharmaceutical processes to understand the relationship between metrics and the most important cost drivers in these processes.