molecules
Review Azeotropes as Powerful Tool for Waste Minimization in Industry and Chemical Processes
Federica Valentini and Luigi Vaccaro *
Laboratory of Green S.O.C., Dipartimento di Chimica, Biologia e Biotecnologie, Università degli Studi di Perugia, Via Elce di Sotto 8, 06123 Perugia, Italy; [email protected] * Correspondence: [email protected]; Tel./Fax: +39-07-5585-5541
Academic Editor: Derek J. McPhee Received: 17 October 2020; Accepted: 10 November 2020; Published: 12 November 2020
Abstract: Aiming for more sustainable chemical production requires an urgent shift towards synthetic approaches designed for waste minimization. In this context the use of azeotropes can be an effective tool for “recycling” and minimizing the large volumes of solvents, especially in aqueous mixtures, used. This review discusses the implementation of different kinds of azeotropic mixtures in relation to the environmental and economic benefits linked to their recovery and re-use. Examples of the use of azeotropes playing a role in the process performance and in the purification steps maximizing yields while minimizing waste. Where possible, the advantages reported have been highlighted by using E-factor calculations. Lastly azeotrope potentiality in waste valorization to afford value-added materials is given.
Keywords: azeotrope; waste minimization; solvent recovery; azeotropic distillation; process design; waste valorization
1. Introduction The materials not incorporated into the final desired product and the energy required for conducting a process can be considered most trivially as the major direct origin of “waste” associated to chemical production. In addition, the possible formation of undesired isomers or byproducts also results in the generation of costly waste, that being in some cases hazardous, can limit the final application of the main product. In recent decades, many efforts have been aimed at highlighting the importance of a waste prevention approach rather than focusing on the definition and control of waste disposal techniques [1–3]. In the shift towards more sustainable chemical production, prevention must be the priority instead of the end-of-pipe treatment. Indeed, the Environmental Protection Agency (EPA) policy for waste minimization [4] does not consider relevant the incineration, encapsulation, or chemical oxidation procedures. Waste minimization hierarchically refers to:
Reduction at the source: generally requiring an important process modification to reduce or • eliminate the generation of waste and the use of hazardous materials. Recycling: consisting of contaminant removal from a useful fraction of waste to allow it to • be reused.
Waste minimization is also an economical opportunity, in fact by decreasing the amount of waste generated per month, the chemical industries can be more competitive in the market: according to the EPA’s Resource Conservation and Recovery Act (RCRA) they can actually reduce waste management costs. In the context of green chemistry, principles [5] and metrics [6,7] have been listed as guidelines and quantitative tools functional for the development of sustainable processes [7]. Among these,
Molecules 2020, 25, 5264; doi:10.3390/molecules25225264 www.mdpi.com/journal/molecules Molecules 2020, 25, x FOR PEER REVIEW 2 of 19 Molecules 2020, 25, 5264 2 of 18 In the context of green chemistry, principles [5] and metrics [6,7] have been listed as guidelines and quantitative tools functional for the development of sustainable processes [7]. Among these, E- E-factor [8] and Process Mass Intensity (PMI) [9], equivalent but from different perspectives, focus the factor [8] and Process Mass Intensity (PMI) [9], equivalent but from different perspectives, focus the attention toward the optimization of the resources used by comparing the mass of materials used or of attention toward the optimization of the resources used by comparing the mass of materials used or waste produced in relation to the mass of product obtained. From this comparison it emerges that the of waste produced in relation to the mass of product obtained. From this comparison it emerges that pharmaceutical industry produced the highest amount of waste [10]. Most of the waste is constituted the pharmaceutical industry produced the highest amount of waste [10]. Most of the waste is by solvents (80–90%) [10] that are generally used in huge amounts at all stages and especially during constituted by solvents (80–90%) [10] that are generally used in huge amounts at all stages and the purification steps necessary to isolate the product in high purity. especially during the purification steps necessary to isolate the product in high purity. A careful choice of the solvent used as reaction medium in combination with an efficient A careful choice of the solvent used as reaction medium in combination with an efficient recovery and reuse technique is essential in the definition of modern tools for chemical production recovery and reuse technique is essential in the definition of modern tools for chemical production aiming at the minimization of its environmental impact [11]. Both in the context of “recycling” and aiming at the minimization of its environmental impact [11]. Both in the context of “recycling” and “reduction at source”, azeotropes can actively play an effective role. While the formation of azeotrope “reduction at source”, azeotropes can actively play an effective role. While the formation of azeotrope can sometimes be considered an issue that may lead to additional issues in the separation process, can sometimes be considered an issue that may lead to additional issues in the separation process, on onthe the other other side side the the peculiar peculiar properties properties of ofsubstances substances to tocombine combine together together to toform form azeotropes azeotropes may may be be usedused toto developdevelop more eeffectiveffective processes in chemistry and and chemical chemical engineering. engineering. InIn this this contribution contribution it it will will be be highlighted highlighted how how azeotropes azeotropes can can be be an an effective effective tool tool for for waste waste minimizationminimization in chemical process processes.es. In In particular, particular, it it will will show show their their role role in in (i) (i) the the recovery recovery and and reuse reuse ofof complexcomplex mixtures of solvents, ( (ii)ii) the the field field of of process process modification modification to to prevent prevent waste waste production, production, andand (iii)(iii) thethe synthesis of materials based o onn waste waste valorization. valorization. 2. Azeotropes for Waste Recovery and Reuse 2. Azeotropes for Waste Recovery and Reuse ByBy following the the EPA EPA policy policy for for waste waste minimization, minimization, when when the the“redesign” “redesign” of a process of a process is not is notpossible possible or complicate or complicated,d, recovery recovery and andreuse reuse of solvent of solvent waste waste is crucial. is crucial. As above As above mentioned, mentioned, the theformation formation of binary of binary or higher or higher-order-order azeotropes azeotropes may may constitute constitute a problem a problem for for solvent solvent recovery recovery by by distillation.distillation. An An option option could could be be distillation distillation under under different different pressure pressures,s, however, however, the the risk risk of of product product degradationdegradation andand alsoalso economiceconomic disadvantages,disadvantages, maymay lead lead to to the the definition definition of of azeotropic azeotropic distillation distillation as as an alternativean alternative effective effective route route [12]. [12]. Azeotropic Azeotropic distillation distillation (Figure (Figure1) may 1) may also involvealso involve an entrainer an entrainer (E) which (E) changeswhich change the volatilitys the volatility of the components of the components of the azeotrope of the azeotrope forming a forming new azeotrope. a new azeotrope. The azeotropic The distillation can be homogeneous or heterogeneous, depending if it involves a liquid liquid separation azeotropic distillation can be homogeneous or heterogeneous, depending if it involve−s a liquid−liquid ofseparation the new of azeotrope. the new azeotrope. When the When entrainer the entrainer is substituted is substituted with a solvent,with a solvent, the distillation the distillation is named is extractivenamed extractive distillation: distillation: the solvent the solvent interacts interacts with one with or moreone or components more components and changes and change their fugacitys their withoutfugacity formingwithout anyforming new any azeotrope new azeotrope [13]. [13].
(a) (b)
Figure 1. Schematic representation of (a) homogeneous azeotropic distillation; (b) heterogeneous Figure 1. Schematic representation of (a) homogeneous azeotropic distillation; (b) heterogeneous azeotropic distillation. azeotropic distillation. By combining the extractive distillation with heterogeneous azeotropic distillation a hybrid By combining the extractive distillation with heterogeneous azeotropic distillation a hybrid extractive-heterogeneous azeotropic distillation (Figure2) was proposed in 2004 [ 14]. One of the most extractive-heterogeneous azeotropic distillation (Figure 2) was proposed in 2004 [14]. One of the most important advantages of this hybrid distillation technology is that no additional solvents are added, important advantages of this hybrid distillation technology is that no additional solvents are added, and no new azeotropes are formed. Generally, water is present as auto-entrainer. and no new azeotropes are formed. Generally, water is present as auto-entrainer.
Molecules 2020, 25, 5264 3 of 18 Molecules 2020, 25, x FOR PEER REVIEW 3 of 19
FigureFigure 2. 2. SimplifiedSimplified representation representation of of extractive extractive-heterogeneous-heterogeneous azeotropic distillation.
Below are are reported reported significative significative examples examples on the on use the of use azeotropic of azeotropic distillation distillation for waste for recovery waste whenrecovery complex when mixtures complex of mixtures solvents of or solvents azeotropes or azeotropesare present. are Selected present. examples Selected reflect examples most reflectof the commonmost of the problem commons of problems chemical ofindustries chemical and industries are complete and are with complete environmental with environmental and economic and evaluations.economic evaluations.
2.1. Homogeneous Azeotropic Distillation 2.1. Homogeneous Azeotropic Distillation The first first production of anhydrous ethanol with azeotropic distillation wa wass dated 1902 and was proposed by Young [15]. The addition of benzene to an ethanol water mixture forms a three-component proposed by Young [15]. The addition of benzene to an −ethanol−water mixture forms a three- azeotrope which boils at 64.85 C. This lower boiling point, compared with the ones of ethanol water component azeotrope which boil◦ s at 64.85 °C. This lower boiling point, compared with the ones− of ethanolazeotropes,−water allowed azeotrope the distillations, allowed t ofhe thedistil novellation azeotrope of the novel formed azeotrope by removing formed waterby removing from ethanol. water n fromIn addition, ethanol. the In addition, excess of the benzene excess could of benzene be easily could separated be easily fromseparated the alcohol from the by alcohol using by-hexane. using nAlthough-hexane. Although this method this proved method to proved be efficient to be and efficient opened and the opened way forthe the way development for the development of different of differentazeotropic azeotropic distillation distillation procedures, procedures nowadays the, nowadays use of benzene the use is unappealing of benzene and, is generally,unappealing it should and, generally,be avoided. it should be avoided. InIn this context, a a practical example of waste minimization deals with the nitrocellulose manufacturing facilityfacility ofof Taiwan Taiwan described described by by Liu Liu in 2003in 2003 [16 ].[16]. The The waste waste minimization minimizat assessmention assessment plan planapplied applied at the satellite at the satellite plant in Taiwan plant in allowed Taiwan for allow the reductioned for the of wastereduc attion source of waste and minimized at source waste, and minimizeresultingd in waste increased, resulting productivity in increased of the facility. productivity The alcohol of the rectification facility. The by alcohol azeotropic rectification distillation by azeotropicwas part of distillation the recovery was/recycle part of program.the recover Iny/recycle 1978, ethanol program. was In replaced1978, ethanol with was isopropyl replaced alcohol with isopropyl(IPA) as a alcohol dehydrating (IPA) agent.as a dehydrating After concentration agent. After of concentration the spent IPA of by the the spent two-phase IPA by column the two system,-phase the formation of ternary azeotrope water IPA benzene allowed the recovery of up to 4 tons of IPA column system, the formation of ternary azeotrope− − water−IPA−benzene allowed the recovery of up to(99% 4 tons+) daily. of IPA From (99%+) 1990 todaily. 1996 From several 1990 alternatives to 1996 several were evaluated, alternatives and were a novel evaluated, rectification and unita novel was rectificationbuilt due to bothunit increasedwas built productiondue to both and increased the toxicity production of benzene. and Thethe newtoxicity rectification of benzene. plan The adopted new rectificationfrom the task plan force adopted replaced from benzene the task with force cyclohexane replaced and benzene the benefits with fromcyclohexane this decision and the allowed benefits the fromrecovery thisin decision two years allowed of the USD the recover 260,000y invested in two foryears the of new the rectification USD 260,000 unit. invested for the new rectificationIn 2018, unit. You and coworkers proposed and compared by technoeconomic analyses different azeotropicIn 2018, distillation You and designs coworkers to separate proposed light and oil compared waste into bysingle technoeconomic components analyses [17]. Light different oil is azeotropican organic distillatio waste fromn designs Nylon plantto separate production light oil and waste is composed into single of componentsn-pentanol, cyclohexanone[17]. Light oil is and an organiccyclohexene waste oxide, from compounds Nylon plant that production are difficult and to separate is composed using conventional of n-pentanol, distillation cyclohexanone due to their and cyclohexenesimilar boiling oxide, points. compounds that are difficult to separate using conventional distillation due to their Bysimilar using boiling water point as entrainer,s. the authors designed six different configurations for azeotropic distillationBy using and water carried as outentrainer rigorous, the simulations, authors designed making six use different of theAspen configurations Plus software for azeotropic platform. distillationThe composition and carried of the lightout rigorous oil was setsimulation as 35.4%s, of makingn-pentanol, use of 31.8% the Aspen of cyclohexanone, Plus software and platform. 32.8% of Thecyclohexene composition oxide of in the accordance light oil was with set data as 35.4% from Yueyang of n-pentanol, Branch 31.8% of Sinopec of cyclohexanone, Corp. Strict parametersand 32.8% ofabout cyclohexene purity degree oxide of the in recovered accordance chemicals with data (more from than Yueyang 95%), their Branch amounts of (more Sinopec than Corp. 92.5%) Strict and parametersamount of theabout entrainer purity (atdegree least of 98%) the needed recovered to be chemicals fulfilled when(more designingthan 95%), the their process amounts separation. (more thanWith the92.5%) results and obtained amount from of the the entrainer simulations (at andleast technoeconomic 98%) needed to analyses, be fulfilled it emerged when thatdesigning azeotropic the processdistillation separation. may save With around the 7%results of the obtained total annual from coststhe simulations in comparison and with technoeconomic conventional analyses, distillation. it emerged that azeotropic distillation may save around 7% of the total annual costs in comparison with 2.2. Heterogeneous Azeotropic Distillation conventional distillation. In cellulose acetate manufacturing, an important operation is the dehydration of acetic acid. 2.2.Water Heterogeneous and acetic acidAzeotropic do not D formistillation an azeotrope, and their boiling points are very similar, making In cellulose acetate manufacturing, an important operation is the dehydration of acetic acid. Water and acetic acid do not form an azeotrope, and their boiling points are very similar, making
Molecules 2020, 25, 5264 4 of 18 conventional distillation too expensive for accomplishing the recovery of pure acetic acid. For this reason, several studies have been performed using heterogeneous azeotropic distillation [18,19]. Although these studies were focused on an optimization of the process design, an evaluation of operating costs and control of azeotropes are needed for a more comprehensive definition of a sustainable protocol. Indeed, process design and product design must be performed interactively to give a global evaluation of costs and the environmental quality of the entire process. In 2005 Diwekar and Xu conducted a multiobjective optimization combining process and product design to evaluate the operability of the system and the environmental impact (EI) based on LD50 (lethal dose for 50% of the tested population) and LC50 (lethal concentration for 50% of the tested population) for the continuous separation of an acetic acid water mixture using heterogeneous − azeotropic distillation [20]. The authors selected seven different environmentally benign entrainers (ethyl acetate, propyl acetate, isopropyl acetate, methyl propyl ketone, methyl isopropyl ketone, diethyl ketone, and methyl propionate) for the formation of minimum boiling point azeotropes. By considering different objectives and solvents different distillation schemes were given. The results obtained evidenced that the highest amount of recovered acetic acid was obtained by using methyl isopropyl ketone, while the best EI for LC50 and LD50 was obtained with methyl propionate and isopropyl acetate, respectively. Chien and coworkers focused their attention on the selection of the best entrainer for acetic acid recovery in different percentages, considering the impact on total annual costs [21,22]. In 2004 the authors selected the best entrainer for the separation of an acetic acid water mixture 1:1 [21]. Between − ethyl acetate, iso-butyl acetate, and n-butyl acetate the authors selected the latter as best entrainer for the high ratio and purity of the acetic acid obtained. The implementation of this heterogeneous azeotropic distillation reduced the total annual cost by 55% of the value obtained for conventional distillation. Although the results obtained in this study were interesting, a typical waste stream still contained a low amount of acetic acid. For this reason, the authors in 2006 designed an alternative system for a more reasonable 8:2 water acetic acid mixture [22]. The need for a preconcentrator column was also − investigated and its impact on total annual costs evaluated. Indeed, in industrial processes, the addition of a preconcentrator column in combination with the heterogeneous azeotropic distillation is common. After careful evaluation of different parameters and configurations, the optimal design consists of a single azeotropic distillation column with aqueous reflux stream. In this configuration a decrease in total annual costs of about 25% has been reached in comparison with the preconcentrator design. As above mentioned, the pharmaceutical industry produces the highest amount of solvent waste and a typical example of this waste stream treatment consists of the recovery of ethyl acetate-isooctane mixture. This mixture features a low boiling point azeotrope (76.3 ◦C). In 2014, Gerbaud and coworkers screened 13 entrainers, among 60 candidates, for the recovery of high purity compounds through heterogeneous azeotropic distillation [23]. Among these, only acetonitrile and methanol were selected as effective entrainers for heterogeneous azeotropic distillation in a rectifying column configuration. After evaluating of the miscibility gap of the heterogeneous azeotrope, the composition of the entrainer isooctane azeotrope and the temperature differences between the other possible − azeotropes, acetonitrile was selected as the best entrainer. Indeed, acetonitrile allows a decrease in operational time with an increment in yield. This study was the first example of heterogeneous azeotropic distillation for the recovery of ethyl acetate-isooctane mixture. Furthermore, the authors validated the method in a batch distillation column configuration at laboratory scale. Another growing industry at a global scale concerns the production of semiconductors for screens. One of the major contributors to waste associated with these processes, consists of the photoresistor thinners, i.e., propylene glycol monomethyl ether (PGME) and propylene glycol monomethyl ether acetate (PGMEA). Although these components are generally retrieved by distillation, the formation of their azeotropes with water makes the recovery of these representative photoresistor thinners difficult and energy demanding. In 2016, Lee and coworkers proposed the combination of heterogeneous azeotropic distillation with a dividing wall column (DWC) [24] technology for the purification and Molecules 2020, 25, 5264 5 of 18 recovery of PGME and PGMEA [25]. The authors investigated several configurations before selecting the heterogeneous azeotropic dividing wall column as the most energy and cost saving system for recovery of the photoresistor thinners. Indeed, they were able to save 33.1% of energy with an impact on the total annual costs of about 20% [25]. The energy savings in the combination of DWC technology with azeotropic distillation had already been observed, also in the dehydration of ethanol [26], bioethanol [27], acetic acid [28] and in the separation of pyridine water toluene mixtures [29]. − − 2.3. Hybrid Extractive-Heterogeneous Azeotropic Distillation A more complex industrial issue is related to the separation of nonideal quaternary mixtures. The waste streams studied by Mizsey in 2004 were six different nonideal mixtures composed of ethanol (EtOH), ethyl acetate (EtOAc), isopropyl acetate (IPOAc), methyl-ethyl-ketone (MEK), iso-propanol (IPOH), acetone and water (H2O) [14]. These solvents generate binary and ternary azeotropes and have been divided into three groups (Table1). The authors gave general important guidelines for separating each group by using water as auto-entrainer with hybrid extractive- heterogeneous azeotropic distillation.
Table 1. Groups of nonideal mixtures with number of azeotropes formed.
Mixture n. Binary Azeotropes n. Ternary Azeotropes Water, EtOH, MEK, acetone 3 1 Group 1 Water, EtOH, EtOAc, acetone 3 1 Water, EtOH, EtOAc, IPOAc 5 2 Group 2 Water, EtOH, MEK, IPOAc 5 2 Water, EtOH, EtOAc, MEK 6 3 Group 3 Water, IPOH, EtOAc, MEK 6 3
Below are listed the general strategies for each group without considering dehydration of EtOH and IPOH:
Group 1: acetone does not form any azeotropes with other components; from the economic point • of view it is preferable to separate it with conventional distillation before proceeding through extractive heterogenous distillation to separate the remaining solvents by using additional water as auto-entrainer. Group 2: when a couple of solvents which do not form azeotropes, but their azeotropes are present • with other components, extractive-heterogeneous azeotropic distillation with two subsequent conventional distillations is the preferred way to recover single components. Group 3: when a binary azeotrope is present between the components of the mixtures, the best way • for solvent separation is two extractive-heterogeneous azeotropic distillations with subsequent conventional distillation.
This novel hybrid distillation allows the separation of complex mixtures and is a promising tool for the recovery of solvents from the waste stream with a reduced environmental impact. To better understand the role of this new hybrid azeotropic distillation, a comparison with the conventional treatment, i.e., recovery or incineration, has been reported by the same authors in 2006 considering both environmental and economic impact [30]. A life-cycle assessment (LCA) consideration was expanded for different options of treatment of a nonideal mixture (EtOH, EtOAc, IPOAc, water) from a printing company by using Eco-indicator 99 life-cycle impact assessment methodology [31]. This method allows the assignment of a single score to the environmental impact. Focusing only on incineration and recovery by conventional distillation alternatives, economic and environmental impacts are not in agreement. Indeed, from the economic point of view, recovery is the preferable option, however, the high energy demand for separating this nonideal mixture is too high Molecules 2020, 25, 5264 6 of 18 to be considered sustainable. This contradictory evidence is the driving force of green engineering to design more sustainable recovery processes. On the other hand, from these calculations, emerges the only option which leads to both economic and sustainability benefits: extractive-heterogeneous azeotropic distillation [30]. Extractive-heterogeneous azeotropic distillation is not only limited to the separation of minimum boiling point azeotropes but is useful also when those with maximum boiling points are present. Based on industrial problems, Toth and coworkers investigated the separation of two nonideal mixtures containing chloroform [32]. Chloroform generates maximum boiling point binary azeotropes both with acetone and EtOAc. After careful simulation and experimental verifications, the authors proved for the first time in 2019 the efficiency in separation of maximum boiling point azeotrope recovering chloroform at 99.5% purity.
2.4. Azeotropes and Membrane Technologies in Water-Containing Waste Treatment Wastewater treatment is a complex common issue for several industries and it is also linked to the worldwide increasing demand for fresh water. Industrial wastewater comes from reverse osmosis of brine and requires the employment of membrane technologies [33,34]. Among these technologies, pervaporation is also widely employed in the removal of volatile organic compounds (VOC), dehydration of organic solvents and separation of organic mixtures [35–40]. In addition, the pervaporation approach has many advantages in the sustainable dehydration and recovery of solvents (e.g., avoids the use of entrainer, high selectivity), although a major limit can be related to the relatively high costs of membranes. To solve this issue, hybrid technologies have been developed [41–43]. In 2018 a study by Andre and coworkers about the separation of an isobutanol water mixture, − emerged that the choice of a separation process strictly depends on the product composition requirement [44]. Moreover, the ranking position of a separation technology cannot be easily standardized due to social and technological factors. The authors compared different separation methods and also their combination: azeotropic distillation, azeotropic distillation extended with heat integration, pervaporation, distillation assisted pervaporation and distillation assisted pervaporation with heat integration. Multi-Criteria Decision Analysis, comprehensive of Political, Economic, Social and Technological (PEST) analysis, gave similar results to those obtained from LCA considerations. Besides considering 98.8 w/w% of isobutanol it is clear how pervaporation is the favorable choice in comparison with azeotropic distillation, by increasing to 99.9 w/w% their relative ranking position is unclear, while the hybrid combination of distillation-assisted pervaporation with heat integration is without any doubt the most convenient separation alternative in both cases. In 2019 similar considerations have been highlighted by Toth for the selection of the separation technology of an ethyl acetate ethanol water highly nonideal mixture [42]. Four different combinations − − of separation techniques have been economically compared considering the total annual costs (TAC). Hybrid extractive-heterogeneous azeotropic distillation allowed a reduction of the energy requirement in combination with pervaporation confirming the importance of the combination of different methodologies for saving money and energy in waste purification. Recently this combination has shown itself to be efficient also in the separation of other nonideal three-component mixtures: ethyl acetate methanol water and isobutyl acetate methanol water [43]. − − − − 3. Azeotropes in Organic Synthesis for Waste Minimization In the realm of modern organic synthesis, the strategies for minimizing the production of waste play a key role for a competitive economic and environmental chemical production and especially in the preparation of fine chemicals, modern materials or pharmaceutically active ingredients (APIs). The peculiar chemical physical properties of azeotropes may be useful also to maximize catalyst − stability and performance, for the continuous removal of byproducts, and also to influence the selectivity of the process. As above mentioned, the waste stream derived from chemical processes is mainly Molecules 2020, 25, 5264 7 of 18 constituted by solvents and this is even more evident when an aqueous mixture is used as a medium Molecules 2020, 25, x FOR PEER REVIEW 7 of 19 as their recovery may be difficult or impossible. It is noteworthy that the use of aqueous organic mixturesIn this section (H2O withit will tetrahydrofuran be shown how (THF), the latter dimethylformamide can be efficiently (DMF), substituted ethanol by (EtOH),azeotropes acetonitrile both in (MeCN),purification etc.) steps is all butand rare as a in reaction routine laboratory medium ( practiceSection but3.3.). also Below at an are industrial reported level. relevant In this examples section it willwhere be shownthe use howof azeotropes the latter canhas bealso effi ledciently to significant substituted improvement by azeotropess in both the inefficiency purification of a stepssynthetic and asprocedure a reaction (Section medium 3.1.) (Section and or 3.3 a ).purification Below are reportedprocess ( relevantSection 3 examples.2.). where the use of azeotropes has also led to significant improvements in the efficiency of a synthetic procedure (Section 3.1) and or a purification3.1. Azeotropes process Steer O (Sectionrganic S3.2ynthesis).
3.1. AzeotropesThe use of Steer biocatalysts Organic for Synthesis esterification processes is a very efficient process, however their facile inactivation constitutes a limitation for their use in larger scale application. In addition, considering The use of biocatalysts for esterification processes is a very efficient process, however their facile the high costs of enzymes, preserving their stability is of fundamental importance to minimize the inactivation constitutes a limitation for their use in larger scale application. In addition, considering costs of the entire process. With this aim, Vulfson and coworkers developed a synthetic strategy to the high costs of enzymes, preserving their stability is of fundamental importance to minimize the improve catalyst tolerance and allow its efficient reuse [45]. The authors found an improved catalytic costs of the entire process. With this aim, Vulfson and coworkers developed a synthetic strategy to activity and stability in the Novozyme 435 biocatalyst when tert-butanol/n-hexane minimum boiling improve catalyst tolerance and allow its efficient reuse [45]. The authors found an improved catalytic point azeotrope was employed in the synthesis of sorbitan esters. The use of this azeotrope did not activity and stability in the Novozyme 435 biocatalyst when tert-butanol/n-hexane minimum boiling only allow for the reduction of the operating temperature, thus improving the preservation of the point azeotrope was employed in the synthesis of sorbitan esters. The use of this azeotrope did not enzyme, but also for removal of the water formed during the reaction facilitating the process. only allow for the reduction of the operating temperature, thus improving the preservation of the The use of azeotropes for the removal of byproducts, especially those that can negatively affect enzyme, but also for removal of the water formed during the reaction facilitating the process. the course of the reaction, has been widely investigated. For example, Wang and Li reported in 2010 The use of azeotropes for the removal of byproducts, especially those that can negatively affect the use of azeotropic agents to remove methanol formed during the synthesis of glycerol carbonate the course of the reaction, has been widely investigated. For example, Wang and Li reported in 2010 (3) from glycerol (1) and dimethyl carbonate (DMC, 2) allowing the reduction of the equivalent of the the use of azeotropic agents to remove methanol formed during the synthesis of glycerol carbonate (3) carbonylation agent [46]. Glycerol carbonate is a value-added chemical which can be produced by from glycerol (1) and dimethyl carbonate (DMC, 2) allowing the reduction of the equivalent of the carbonylation of glycerol, the main byproduct of biodiesel production [47,48]. Generally, when the carbonylation agent [46]. Glycerol carbonate is a value-added chemical which can be produced by carbonylation of 1 is performed with DMC (2), an excess of the latter is required. In addition, the carbonylation of glycerol, the main byproduct of biodiesel production [47,48]. Generally, when the excess of 2 and methanol formed during the process, must be distilled for an efficient recovery of the carbonylation of 1 is performed with DMC (2), an excess of the latter is required. In addition, the excess desired product 3. On the other hand, excess of DMC may lead to side reactions resulting in the of 2 and methanol formed during the process, must be distilled for an efficient recovery of the desired decrease of the yield in glycerol carbonate (3). Low yields and an excess of reactants contribute both product 3. On the other hand, excess of DMC may lead to side reactions resulting in the decrease to the non-sustainability of the process generating waste and the requirement of additional energy of the yield in glycerol carbonate (3). Low yields and an excess of reactants contribute both to the costs for the recovery of the pure product. The authors proposed to exploit azeotropic distillation for non-sustainability of the process generating waste and the requirement of additional energy costs the continuous remotion of methanol formed during the reaction with the aim of shifting the for the recovery of the pure product. The authors proposed to exploit azeotropic distillation for the equilibrium of the reversible transesterification process towards the product (Scheme 1) [46]. In these continuous remotion of methanol formed during the reaction with the aim of shifting the equilibrium conditions 98% of pure glycerol carbonate was obtained by using 1:1 ratio between glycerol and of the reversible transesterification process towards the product (Scheme1)[ 46]. In these conditions DMC. 98% of pure glycerol carbonate was obtained by using 1:1 ratio between glycerol and DMC.
Scheme 1. Waste-minimized synthesis of glycerol carbonate as a value-added chemical. Scheme 1. Waste-minimized synthesis of glycerol carbonate as a value-added chemical. Another common example of the use of azeotropes to remove byproduct and shift the equilibrium towardsAnother product common by water example removal, of Dean the Stark use ofapparatus azeotropes is used to in remove the acetalization byproduct of aldehydes and shift andthe − ketonesequilibrium (4). Intowards 2015, Azzena product and by coworkerswater removal, developed Dean a−Stark novel apparatus catalyst/solvent is used system in the asacetalization a sustainable of alternativealdehydes and to the ketones common (4). In toluene 2015, /Azzenap-toluenesulfonic and coworkers acid developed [49]. The authors a novel catalyst/solvent employed ammonium system saltsas a sustainable as insoluble alternative acidic catalysts to the incommon cyclopenthyl toluene/ methylp-toluenesulfonic ether (CPME), acid a green [49]. The substitute authors to employed the most commonammonium ethereal salts as solvents, insoluble which acidic forms catalysts a minimum in cyclopenthyl boiling point methyl heterogeneous ether (CPME), azeotrope a green with substitute water to the most common ethereal solvents, which forms a minimum boiling point heterogeneous azeotrope with water (bp 83 °C) (Scheme 2). The peculiar hydrophobicity of CPME makes this solvent almost insoluble in water, making them easy to separate and allowing an 85% recovery of the solvent. With this catalyst/solvent system they were able to perform efficient acetalization of 4 with easy recycling of ammonium salt, reducing in this way the waste production.
Molecules 2020, 25, 5264 8 of 18
(bp 83 ◦C) (Scheme2). The peculiar hydrophobicity of CPME makes this solvent almost insoluble in water, making them easy to separate and allowing an 85% recovery of the solvent. With this catalyst/solvent system they were able to perform efficient acetalization of 4 with easy recycling of Molecules 2020, 25, x FOR PEER REVIEW 8 of 19 Moleculesammonium 2020, salt,25, x FOR reducing PEER REVIEW in this way the waste production. 8 of 19
Scheme 2.2. Acetalization under Dean−StarkStark conditions using CPME as a green alternative. Scheme 2. Acetalization under Dean−Stark conditions using CPME as a green alternative. Azeotropes may be useful tools also in transfer hydrogenation reactions. The use of formic Azeotropes may be useful tools also in transfer hydrogenation reactions. The use of formic acid/triethyl amine azeotrope is widely employed to improve the performance of formic acid as a acid/triethyl amine azeotrope is widely employed to improve the performance of formic acid as a safer H H22--sourcesource [50 [50––5454],], while while recently recently it ithas has been been observed observed how how the theazeotrope azeotrope EtOH EtOH−waterwater may mayshift safer H2-source [50–54], while recently it has been observed how the azeotrope EtOH−water− may shift shift the reaction selectivity [43]. Indeed, in 2019 Vaccaro, Piermatti and Pica realized a switchable the reaction selectivity [43]. Indeed, in 2019 Vaccaro, Piermatti and Pica realized a switchable chemo- chemo-selective Au-based heterogeneous catalyst and used this system in the reduction of nitroaromatic selective Au-based heterogeneous catalyst and used this system in the reduction of nitroaromatic compounds with NaBH44 (Scheme 33))[ [55].55]. When When absolute absolute ethanol was used as a medium the reaction compounds with NaBH4 (Scheme 3) [55]. When absolute ethanol was used as a medium the reaction proceeded selectively towards the sole formation of the corresponding aniline (8). On the contrary, proceeded selectively towards the sole formation of the corresponding aniline (8). On the contrary, the employment of EtOHEtOH−water azeotrope completely shift shifteded the selectivity with the sole formation the employment of EtOH−water azeotrope completely shifted the selectivity with the sole formation of the azoxy derivatives (9) giving the possibility to isolate these important chemicals in high yields of the azoxy derivatives (9) giving the possibility to isolate these important chemicals in high yields using a single catalytic system. using a single catalytic system.
Scheme 3. Different reaction pathways for reduction of nitroaromatic compounds promoted by Scheme 3. Different reaction pathways for reduction of nitroaromatic compounds promoted by EtOH EtOH azeotrope. azeotrope. 3.2. Azeotropes in Purification Process 3.2. Azeotropes in Purification Process Glucaric acid is a bioderived platform molecule derived from the catalytic oxidation of glucose. Glucaric acid is a bioderived platform molecule derived from the catalytic oxidation of glucose. DespiteGlucaric the great acid is interest a bioderived for this platform chemical molecule as a key derived ingredient from forthe catalytic several industrialoxidation specialties,of glucose. Despite the great interest for this chemical as a key ingredient for several industrial specialties, it is Despiteit is commercialized the great interest only asfor K this and chemical Ca glucarate as a salts.key ingredient Reproducible for several procedures industrial for the specialties, obtainment it ofis commercialized only as K and Ca glucarate salts. Reproducible procedures for the obtainment of the commercializedthe pure crystalline only form as K ofandd-glucaric Ca glucarate acid salts. (11) areReproducible extremely rareprocedures due to thefor the equilibrium obtainment with of the pure crystalline form of D-glucaric acid (11) are extremely rare due to the equilibrium with the purecorresponding crystalline lactones form of (12, D-glucaric 13, 14). The acid dehydration (11) are extremely leading to rare lactones due to is thefurther equilibrium promoted with by high the corresponding lactones (12, 13, 14). The dehydration leading to lactones is further promoted by high correspondingtemperatures, generallylactones (12, employed 13, 14). The for water dehydration removal. leading For this to lactones purpose, is Armstrong further promoted and coworkers by high temperatures, generally employed for water removal. For this purpose, Armstrong and coworkers temperatures,developed an easygenerally method employed to obtain for pure water crystalline removal.11 Forexploiting this purpose, minimum Armstrong boiling pointand coworkers azeotrope developed an easy method to obtain pure crystalline 11 exploiting minimum boiling point azeotrope developedacetonitrile anwater easy [method56]. Starting to obtain from pure commercially crystalline available 11 exploiting glucarate minimum salts (10 boiling) the authors point azeotrope employed acetonitrile−−water [56]. Starting from commercially available glucarate salts (10) the authors Amberlyst-15acetonitrile−water (H+ ) [56].exchange Starting resin from to promote commercially the formation available of 11 , glucarate when the salts addition (10) of the acetonitrile authors employed Amberlyst-15 (H+) exchange resin to promote the formation of 11, when the addition of employedallows the Amberlyst drying of- the15 (H product+) exchange at a lower resin temperatureto promote the without formation any formationof 11, when of the byproducts addition orof acetonitrile allows the drying of the product at a lower temperature without any formation of acetonitrileadditional gains allows in energy the dry demanding of the (Scheme product4). With at a thislower set-up temperature the authors without were able any to formation isolate up to of byproducts or additional gains in energy demand (Scheme 4). With this set-up the authors were able byproducts98% of pure or dry additionald-glucaric gain acids (in> 99.96%).energy demand The reproducibility (Scheme 4). ofWith this this method set-up leads the toauthors further were study able of to isolate up to 98% of pure dry D-glucaric acid (>99.96%). The reproducibility of this method leads tolife-cycle isolate assessmentup to 98% of and pure technoeconomic dry D-glucaric analysisacid (>99.96%). for the preparationThe reproducibility of pure crystallineof this methodd-glucaric leads to further study of life-cycle assessment and technoeconomic analysis for the preparation of pure toacid further starting study from of glucoselife-cycle oxidation assessment [57 ].and Effi technoeconomiccient strategies a fornalysis high for yield the product preparation isolation of pure are, crystalline D-glucaric acid starting from glucose oxidation [57]. Efficient strategies for high yield crystallineindeed, powerful D-glucaric and sustainableacid starting tools from for glucose waste minimization. oxidation [57]. Efficient strategies for high yield product isolation are, indeed, powerful and sustainable tools for waste minimization.
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d SchemeScheme 4 4. .4 Purification.Purification Purification of of DD--glucaric-glucaricglucaric acid by azeotropical azeotropical removal removal of of water. water. Eisenbraun and coworkers developed an efficient method for Wolff Kishner reduction employing EisenbraunEisenbraun and and coworkers coworkers developed developed an efficient method method for for− Wolff Wolff−Kishner−Kishner reduction reduction diethylene glycol (DEG) which forms bilayer azeotropes with products [58]. The Wolff Kishner employingemploying diethylene diethylene glycol glycol (DEG) (DEG) which which forms bilayer azeotropes azeotropes with with products products [58]. − [58]. The The reductionWolffWolff−Kishner−Kishner allows reduction for reduction the obtainment allows allows for offor methylene tthehe obtainobtain groupsment from of of methylenemethylene carbonylic groupsfunctionalities groups from from carbonylic making carbonylic this reactionfunctionalitiesfunctionalities extremely making making useful this this in organicreaction reaction chemistry extremely extremely and usefuluseful several in organicorganic modifications chemistrychemistry have and and been several several largely modifications modifications applied over thehavehave years. been been Glycols largely largely were applied applied generally over over the employedthe years.years. toGlycolsGlycols allow anwere increase generally in the employedemployed reaction temperaturet oto allow allow an an andincrease increase facilitate in in thethe reaction removal reaction temperature of temperature water [59 –and 61and] facilitate formedfacilitate during thethe removalremoval the reaction, of water and [59[59–– also6161]] formed formed removal during during of excess the the reaction, ofreaction, hydrazine and and hydratealsoalso removal removal [61]. However,of of excess excess of due of hydrazine hydrazine to the extreme hydratehydrate conditions [61]. However, of these duedue conditions, toto thethe extreme extreme further conditions improvementsconditions of of these these were desirable.conditions,conditions, Eisenbraun further further improvements improvements and coworkers w wereere therefore desirable.desirable. proposed Eisenbraun an easy andand waycoworkerscoworkers to perform therefore therefore the Wolproposed proposedff-Kishner an an reductioneasyeasy way way employing to to perform perform azeotropic thethe WolffWolff distillation--KishnerKishner reduction reduction with the employing preservation azeotropic azeotropic of KOH, distillation distillation recycling withthe with excess the the hydrazinepreservationpreservation hydrate of of KOH, KOH, and recycl arecycl portioninging the the of DEGexcess excess (Scheme hydrazinehydrazine5)[ 58hydrate]. The andand authors a a portion portion found of of thatDEG DEG products (Scheme (Scheme (5)17 5) )[58]. from[58]. dimethoxybenzaldehydeTheThe authors authors found found that that products products (15) and ( (17 2170-acetonaphthone)) from from dimethoxybenzaldehydedimethoxybenzaldehyde form a heterogeneous ( (1515) )and and azeotrope 2′ 2′-acetonaphthone-acetonaphthone with diethylene form form glycola heterogeneousa heterogeneous and hydrazine azeotrope azeotrope hydrate. with with This diethylene diethylene consideration glycolglycol allowsand hydrazine the continuous hydrate. hydrate. separation This This consideration consideration of products allows allows from the continuous separation of products from the reaction mixture and recover DEG and hydrazine thethe reactioncontinuous mixture separat andion recover of products DEG andfrom hydrazine the reaction hydrate. mixture The and possibility recover to DEG preserve and hydrazine KOH and hydrate. The possibility to preserve KOH and reuse hydrazine hydrate for several consecutive runs, reusehydrate. hydrazine The possibility hydrate to for preserve several consecutiveKOH and reuse runs, hydrazine in combination hydrate with for the several 85% ofconsecutive DEG recovered, runs, in combination with the 85% of DEG recovered, make this process a sustainable alternative which makein combination this process with a sustainablethe 85% of alternativeDEG recovered, which make minimizes this process waste a by sustainable reducing reactantalternative costs which and minimizes waste by reducing reactant costs and reaction time as well. reactionminimize times waste as well. by reducing reactant costs and reaction time as well.
Scheme 5. Continuous Wolff Kishner reduction recovering and reusing hydrazine hydrate and − diethyleneScheme 5.glycol Continuous (DEG) by Wolff heterogeneous−Kishner reduction azeotropic recovering distillation and of reusing product hydrazine17. hydrate and Schemediethylene 5. Continuous glycol (DEG) Wolff by heterogeneous−Kishner reduction azeotropic recovering distillation and of product reusing 17 hydrazine. hydrate and 3.3. Azeotropes Enable Waste Prevention diethylene glycol (DEG) by heterogeneous azeotropic distillation of product 17. 3.3.The Azeotropes ever-increasing Enable Waste interest Prevention in the carbon fiber market is due to the peculiar properties of these3.3. Azeotropes materialsThe ever E-increasingnable and broadWaste interest applicabilityPrevention in the carbon range fiber [62]. market Among is diduefferent to the precursors, peculiar properties polyacrylonitrile of these is the most employed, however a key limitation factor for its application is related to the high materialsThe ever and-increasing broad applicability interest in rangethe carbon [62]. fiber Among market different is due precursors, to the peculiar polyacrylonitrile properties of is these the cost of its key-ingredient, acrylonitrile. Its cost is strictly related to the synthetic strategies used materialsmost employed, and broad however applicability a key limitation range [62]. factor Among for its different application precursors, is related polyacrylonitrileto the high cost of is its the (propylene ammoxidation), which also lead to the formation of several byproducts [63–65]. The need mostkey -employed,ingredient, however acrylonitrile. a key Its limitation cost is strictly factor related for its toapplication the synthetic is related strategies to the used high (propylene cost of its for a more sustainable synthesis, preferably based on renewable feedstock, is steering the research keyammoxidation),-ingredient, acrylonitrile. which also lead Its costto the is formation strictly related of several to thebyproducts synthetic [63 strategies–65]. The need used for (propylene a more towards a biomass-based production of acrylonitrile (19)[66,67]. Recently, Naskar, Beckham and ammoxidation),sustainable synthesis, which alsopreferably lead to based the formation on renewable of several feedstock, byproducts is steering [63– 65the]. researchThe need towards for a more a coworkers proposed an integrated synthesis with subsequent polymerization without the need for any sustainablebiomass-based synthesis, production preferably of acrylonitrile based on renewable(19) [66,67]. feedstock, Recently, Naskar,is steering Beckham the research and coworkers towards a biomass -based production of acrylonitrile (19) [66,67]. Recently, Naskar, Beckham and coworkers
Molecules 2020, 25, x FOR PEER REVIEW 10 of 19
Molecules 20202020, 2525, 5264x FOR PEER REVIEW 10 of 19 18 proposed an integrated synthesis with subsequent polymerization without the need for any additionalproposed acrylonitrile an integrated isolation/purification synthesis with subsequent [68]. The authors polymerization used the acrylonitrile without the synthesized need for any by nitrilationadditional ofacrylonitrile methyl acrylate isolation/purification isolation (18)/ purificationdirectly in the [[68].68 polymerization]. The authors used step the (Scheme acrylonitrile 6), minimizing synthesized energy by andnitrilation material of methyl costs for acrylate acrylonitrile ( 18) directly purification. in the polymerizationAcrylonitrile forms step a(Scheme ternary 6 6)azeotrope),, minimizingminimizing with energyene waterrgy and materialmethanolmaterial costscosts (MeOH) for for acrylonitrile acrylonitrile 20, therefore purification. purification. it separates Acrylonitrile Acrylonitrile and can be forms used forms ain ternary aemulsion ternary azeotrope azeotrope polymerization with with water water with and MeOHmethanoland methanol as (MeOH)chain (MeOH) transfer20, therefore 20 agent., therefore This it separates setit separates-up andhas several can and be can usedenvironmental be in used emulsion in emulsion advantages polymerization polymerization, such with as reduced MeOH with operationalasMeOH chain as transfer chain cost s agent.transfer avoiding This agent. purification, set-up This has set several -minimizedup has environmental several energy environmental demand advantages, and advantages substitution such as reduced, such of conventional operationalas reduced thiolcostsoperational-based avoiding chaincost purification,s avoidingtransfer agents purification, minimized with MeOH energyminimized as demand a coproduct energy and demand substitution (20) formed and substitution of in conventional the nitrilation of conventional thiol-based step. The authorschainthiol-based transfer calculate chain agentsd transfer that with the agents use MeOH of with19 as−20 aMeOH− coproductwater/azeotrope as a coproduct (20) formed impacts (20 in) formedon the the nitrilation total in the process nitrilation step. for The about step. authors 40%The ofcalculatedauthors the imported calculate that the d electricity that use ofthe19 use and20 of 35% water19− 20 of/−azeotrope water/azeotrope the heat demand.impacts impacts on This the wasteon total the process- minimizedtotal process for about method for 40%about for of 40% the − − productionimportedof the imported electricity of polyacrylonitrile electricity and 35% and of copolymer the 35% heat of demand. the showed heat This comparable demand. waste-minimized This efficiency waste method- minimizedwith conve for the ntional method production methods for the of allowingpolyacrylonitrileproduction high of polyacrylonitrilemolecular copolymer weight showed copolymer and comparablelow polydispersity showed effi comparableciency of withthe obtainedefficiency conventional material. with methods conve ntional allowing methods high molecularallowing high weight molecular and low weight polydispersity and low polydispersity of the obtained of material. the obtained material.
Scheme 6. Polyacrylonitrile polymerization by azeotropic distillation of 19 obtained from nitrilation ofScheme 18. 6. Polyacrylonitrile polymerization polymerization by by azeotropic azeotropic distillation distillation of 19 ofobtained 19 obtained from from nitrilation nitrilation of 18. of 18. ParticularParticularlyly int intriguingriguing is the direct utilization of aqueous azeotropes as the reaction medium for processParticular modificationmodificationly intriguing aimed is at the waste direct minimization utilization of [[55,6955 aqueous,69––7575].]. azeotropes as the reaction medium for processIn 2013 modification a silica silica-base-base aimed heterogeneous at waste minimization catalyst was [55,69 employed –75]. in Suzuki cross cross-coupling-coupling and the role of ratio In 2013 of EtOH:waterEtOH a silica:water-base mixture heterogeneous in the catalytic catalyst performance was employed has in been Suzuki investigated cross-coupling [[69].69]. The and authors the role foundof ratio the of best EtOH reaction :water mixtureconditions in thein in batchcatalytic the performance employment hasof of the the been EtOH:water EtOH:water investigated mixture mixture [69]. The in in 1:1 1:1authors ratio. ratio. Thisfound medium medium the best selection selectionreaction is conditions isbased based on theon in search thebatch search the for theemployment for complete the complete dissolutionof the dissolutionEtOH:water of both organic of mixture both and organic in inorganic1:1 ratio. and inorganicreagentsThis medium or reagents additives. selection or additives. Anyway, is based comparing Anyway, on the searchcomparing aqueous for EtOH theaqueous complete azeotrope EtOH dissolutionwith azeotrope absolute ofwith EtOH,both absolute organic yield EtOH, of and the yieldproductinorganic of increasesthe reagents product significantly. or additives. increases Despite Anyway, significantly. the comparing heterogeneous Despite aqueous the catalyst heterogeneous EtOH showing azeotrope good catalyst with recyclability absolute showing EtOH, undergood recyclabilitytheyield optimized of the under product batch the conditions, increases optimized the significantly. batchauthors conditions, aimed Despite to further the the authors heterogeneous minimize aimed the to environmental catalyst further show minimizeing impact good the of environmentaltherecyclability Suzuki cross-coupling under impact the of optimizedthe by Suzuki employing batchcross flow- coupling conditions, technology by employing the (Scheme authors 7flow ). aimed technology to further (Scheme minimize 7). the environmental impact of the Suzuki cross-coupling by employing flow technology (Scheme 7).
Scheme 7. FlowFlow approach approach for for the the waste waste-minimized-minimized Suzuki reaction in aqueous EtOH azeotrope. Scheme 7. Flow approach for the waste-minimized Suzuki reaction in aqueous EtOH azeotrope. The flow flow set set-up-up was was designed designed with with the the intention intention of exploiting of exploiting the thewell well-established-established “release “release and and catch” mechanism of Pd-catalysts [76,77]. Two different reactors were separately filled with K CO catch”The mechanism flow set-up of was Pd- catalystsdesigned [76,77]. with the Two intention different of exploitingreactors were the wellseparately-established filled “releasewith K22 COand33 base and Pd-based catalyst; the mixture of reactants in EtOH aqueous azeotrope was cyclically pumped basecatch” and mechanism Pd-based of catalyst; Pd-catalysts the mixture[76,77]. Two of reactants different in r eactors EtOH aqueouswere separately azeotrope filled was with cyclically K2CO3 until complete conversion was achieved. The use of azeotrope was found to be essential for the strategy, pumpedbase and until Pd- basedcomplete catalyst; conversion the mixture was achieved. of reactants The use in of EtOH azeotrope aqueous was azeotrope found to be was essential cyclically for in fact, K CO is insoluble in this medium and therefore acts as a heterogeneous system able to scavenge thepumped strategy,2 until 3in complete fact, K2CO conversion3 is insoluble was in achieved. this medium The useand of therefore azeotrope acts was as afound heterogeneous to be essential system for the boronic acid formed during the reaction allowing the product to be isolated in pure form without ablethe strategy, to scavenge in fact, the Kboronic2CO3 is acidinsoluble formed in thisduring medium the reaction and therefore allowing acts the as product a heterogeneous to be isolated system in an additional purification step. Solid base therefore can be charged into a reactor separated from the pureable toform scavenge without the an boronic additional acid purification formed during step. the Solid reaction base thereforeallowing canthe beproduct charged to beinto isolated a reactor in pure form without an additional purification step. Solid base therefore can be charged into a reactor
Molecules 2020, 25, 5264 11 of 18 Molecules 2020, 25, x FOR PEER REVIEW 11 of 19 separatedcatalyst allowing from the easy catalyst preservation allowing of easy the preserv efficiencyation of theof the catalytic efficiency system of the and catalytic easy recovery system ofand it. easyProduct recover is isolatedy of it. Product by simple is isolated distillation by simple of EtOH distillation azeotrope of thatEtOH can azeotrope be recovered that can and be resulting recovered in andE-factor resulting values in between E-factor 3.5–3.9. values Commonbetween 3.5 E-factor–3.9. Common values calculated E-factor forvalues previously calculated reported for previously protocols werereported in the protocols range ofwere 3180 in the5100 range due of to 3180 the utilization−5100 due to of the mixtures utilization of solvents of mixtures used of for solvents running used the − forreaction, running for the the work-up reaction, procedure for the work and-up the procedure required purification and the required steps. The purificatio combinationn steps. of flow The combinationtechnology [78 of] flow and azeotropetechnology medium [78] and significantly azeotrope medium decrease significantly waste production decrease for waste the Pd-catalyzed production forSuzuki the Pd cross-coupling-catalyzed Suzuki allowing cross a- 99%coupling E-factor allowing minimization a 99% E- [factor69]. minimization [69]. A similar protocol was employed by Vaccaro Vaccaro and coworkers us usinging zirconium phosphate glycine diphosphonate nanosheets nanosheets as as support support for for Pd Pd nanoparticles for for Suzuki Suzuki cross cross-coupling-coupling reaction reaction [70]. [70]. The use use of of EtOH EtOH aqueous aqueous azeotrope azeotrope was found was found to be essential to be essential for leaching for minimization leaching minimization and preserving and preservingthe catalyst the for several catalyst consecutive for several runs.consecutive Simple rundistillations. Simple of distillationthe azeotropic of the reaction azeotropic media reaction allowed mediapure crystalline allowed pure products crystalline to be obtainedproducts with to be an obtained E-factor with value an of E 3.2.-factor value of 3.2. GenerallyGenerally,, cross cross-coupling-coupling reactions reactions are are performed performed in toxic in toxic dipolar dipolar aprotic aprotic solvents solvents such as such DMF as (dimethylDMF (dimethylformamide)formamide) and NMP and NMP(N-methyl (N-methyl-2-pyrrolidone),-2-pyrrolidone), the employment the employment of these of solvents, these solvents, often coupledoften coupled with water with waterto dissolve to dissolve inorganic inorganic salts, salts,reflect reflectss an unsustainable an unsustainable waste waste generation generation for their for completetheir complete removal removal from fromproducts. products. Among Among solvent solventss which which can be can used be usedas su asbstitute substitutess for DMF for DMF and NMP,and NMP, acetonitrile acetonitrile is of is great of great interest interest due due to to the the possibility possibility of of form forminging a a minimum minimum boiling boiling point azeotrope with water.water. VaccaroVaccaro and and coworkers coworkers employed employed a a synthetic synthetic strategy strategy for for waste waste minimization minimization of ofSonogashira Sonogashira cross-coupling cross-coupling (Scheme (Scheme8) 8) by by using using recoverable recoverable aqueous aqueous acetonitrile acetonitrile azeotrope azeotrope asas thethe reaction medium and a heterogeneous recoverable catalystcatalyst/base/base systemsystem [[71].71].
Scheme 8. SonogashiraSonogashira reaction reaction in aqueous acetonitrile azeot azeotrope.rope.
The synthetic strategy reported [71] [71] a achieveschieves E E-factor-factor values from 8 to 20 with an 82% waste minimization if compared with the protocol that useusess a homogeneous base. TheThe use use of of polymer polymer-- supported piperazine piperazine base base in in combination combination with with acetonitrile acetonitrile azeotrope azeotrope significatively significatively decrease decreasess Pd leachingPd leaching,, maximizing maximizing the the recovery recovery and and reuse reuse of ofthe the catalyst. catalyst. Indeed, Indeed, it itis is well well known known that that DMF DMF and and NMP may stabilize met metalal released released in in solution solution leading leading to to a a tedious tedious procedure procedure for for product product purification. purification. Due to the synthetic importance of the Mizoroki Heck cross-coupling reaction in pharmaceutical Due to the synthetic importance of the −Mizoroki−Heck cross-coupling reaction in pharmaceuticaland opto-electronic and industries,opto-electronic two industries, waste-minimized two waste flow-minimized protocols flow have protocols been developed have been in devacetonitrileeloped in/water acetonitrile/water azeotrope with azeotrope different with Pd-heterogeneous different Pd-heterogeneous catalysts using catalysts polymer using supported polymer supportedtriethylamine triethylamine as the base as (Scheme the base9)[ (Scheme72,73]. The 9) [72,73]. flow reactor The flow was packed reactor with was apacked dispersion with of a dispersionheterogeneous of heterogeneous base and Pd-catalyst base and and Pd- thencatalyst a mixture and then of iodobenzenea mixture of iodobenzene (24) and methyl (24) acrylateand methyl (18) acrylatein acetonitrile (18) in water acetonitrile azeotrope water was azeotrope pumped atwas 130 pumped◦C. When at potassium130 °C. Whenα-zirconium potassium phosphate α-zirconium was phosphateemployed aswas support employed for Pdas support nanoparticles for Pd [ 73nanoparticles] an E-factor [73] value an ofE-factor 4.6 was value obtained, of 4.6 was while obtained, slightly whilehigher valuesslightly (7–12) higher were values measured (7–1 with2) were silica-supported measured ionicwith liquid silica- forsupported Pd stabilization ionic liquid was employed for Pd stabilizationas support [72 was]. In employed both cases as the support azeotrope [72]. acetonitrile In both cases water the was azeotrope recovered acetonitrile to 95%, allowing water pure was recoveredproducts to to be 95% obtained, allowing without pure the products need of to additional be obtained steps. without The developed the need protocolof additional highlighted steps. The the deveperformanceloped protocol of azeotrope highlighted in waste the prevention: performance all the of input azeotrope materials in have waste been prevention: recovered all or theeffi ciently input materialstransformed have minimizing been recovered the environmental or efficiently impact transformed of this usefulminimizing tool for the C–C environmental bond formation. impact of this useful tool for C–C bond formation.
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Scheme 9. Mizoroki−Heck cross coupling in aqueous acetonitrile azeotrope. Scheme 9.9. Mizoroki−HeckHeck cross cross coupling coupling in in aqueous aqueous acetonitrile azeotrope azeotrope.. Most important for an effective− sustainable approach, the use of renewable feedstock is essential to reduceMost the important carbon footprint for an effective eff ofective the sustainablechemical synthesis. approach, theIndeed, use of therenewable replacement feedstock of is fossil essential -derived with tobiomass reduce- thederivedthe carboncarbon solvents footprintfootprint plays ofof thethe a crucial chemicalchemical role synthesis.synthesis. in the design Indeed, of themore replacement sustainable of fossil-derivedsynthesisfossil-derived [79,80]. withFurfuryl biomass-derivedbiomass alcohol-derived is a solventsclear liquid plays with a crucial high role boiling in the pointdesign design (171 of of more more °C) sustainable sustainablederived from synthesis synthesis the treatment [79,80]. [79,80]. of hemicelluloseFurfuryl [81]. alcohol This biomass is a clear- derived liquid with chemical high boiling is miscible point (171with ◦°C) C)several derived organic from the solvents treatment and offorms a minimumhemicellulose boiling [[81].81 ].point ThisThis biomass-derivedbiomassazeotrope-derived with chemical chemicalwater (bp isis misciblemiscible 98.5 °C). with with For several several the first organic organic time solvents solvents in 2016 and and the forms forms furfuryl a minimum boiling point azeotrope with water (bp 98.5 C). For the first time in 2016 the furfuryl alcohol alcohola minimum aqueous boilingazeotrope point w azeotropeas used in with copper water-catalyzed (bp ◦98.5 azide°C). For–alkyne the first cycloaddit time in 2016ion the(Scheme furfuryl 10) by aqueous azeotrope was used in copper-catalyzed azide–alkyne cycloaddition (Scheme 10) by Vaccaro Vaccaroalcohol and aqueous coworkers azeotrope [74]. wTheas used authors in copper proved-catalyzed the efficiency azide–alkyne of this cycloaddit reactionion medium (Scheme 10)obtaining by and coworkers [74]. The authors proved the efficiency of this reaction medium obtaining good yields goodVaccaro yields ofand product coworkers with [74]. different The authors substrates. proved In theaddition, efficiency the ofpresence this reaction of a portion medium of obtaining water in the ofgood product yields with of product different with substrates. different Insubstrates. addition, In the addition, presence the of presence a portion of of a waterportion in of the water azeotrope in the azeotrope allowed the product to precipitate making the purification procedure easier. Indeed, allowedazeotrope the allow producted the to precipitate product to making precipitate the purification making the procedure purification easier. procedure Indeed, simple easier. filtration Indeed, simplewassimple filtration necessary filtration was to obtain was necessary necessary pure products to to obtain obtain (29) and pure pure 81% products of initial ( azeotrope29(29) ) and and 81% was 81% of recovered of initial initial azeotrope and azeotrope reused was for was recoveredseveralrecovered and consecutive and reused reused for runs for several without several consecutive consecutive any loss in eruns ffirunsciency. without any any loss loss in in efficiency. efficiency.
Scheme 10. Copper-catalyzed azide–alkyne cycloaddition in recoverable furfuryl alcohol water Scheme 10. Copper-catalyzed azide–alkyne cycloaddition in recoverable furfuryl alcohol water Schemeazeotrope 10. C asopper reaction-catalyzed medium azide. –alkyne cycloaddition in recoverable furfuryl alcohol water azeotropeazeotrope as reaction as reaction medium medium.. This improved synthetic strategy allows a decrease of 96% of the waste generated for this process resultingThis improved in an E-factorE -syntheticfactor value strategy of 4.3. allowsThe use a of decrease furfuryl of alcohol 96% of water the waste azeotrope generated is environmentally for this process resultingadvantageous in an E-fac not tor only value because of 4.3. of its The easy use recovery of furfuryl and alcohol reuse but water also forazeotrope the life-cyclelife-cycle is environmentally assessment advantageousconsideration not about only thebecause employment of its easy of biomass recovery derived and solvents.solvents.reuse but also for the life-cycle assessment considerationThe f furfurylurfuraboutyl thealcohol alcohol employment chemical chemical structureof structure biomass make make derived its its use use solvents. interesting interesting also also as asa bidentate a bidentate ligand ligand for formetalThe metal f urfurcomplexes. complexes.yl alcohol In 2018 Inchemical 2018Vaccaro Vaccaro structure and coworkers and coworkersmake tested its use tested the interesting efficiency the efficiency of also furfuryl ofas furfuryl a alcoholbidentate alcohol and ligand other and for oxygen-containing bidentate ligands in copper-catalyzed Ullman-type cross-coupling reactions metalother complexes. oxygen-containing In 2018 Vaccaro bidentate and ligands coworkers in copper-catalyzed tested the efficiency Ullman-type of furfuryl cross-coupling alcohol reactions and other (Scheme 11) [75]. The best reaction conditions for the coupling of iodoarene derivates (24) with oxygen(Scheme-containing 11)[75 ]. bidentate The best ligands reaction conditions in copper for-catalyzed the coupling Ullman of iodoarene-type cro derivatesss-coupling (24 ) reaction with s heteroaromatic or aliphatic amine (30) were obtained with furfuryl alcohol and tetrahydrofurfuryl (Schemeheteroaromatic 11) [75]. The or aliphatic best reaction amine (30 conditions) were obtained for the with coupling furfuryl of alcohol iodoarene and tetrahydrofurfuryl derivates (24) with alcohol as as ligands. ligands. Due Due to tothe the possibil possibilityity of form of forminging aqueous aqueous azeotrope azeotropess with withwater water,, the authors the authors chose heteroaromatic or aliphatic amine (30) were obtained with furfuryl alcohol and tetrahydrofurfuryl choseto perform to perform the Ullman the Ullman coupling coupling reaction reaction in in furfuryl furfuryl alcohol alcohol azeotrope. azeotrope. In In addition, addition, several alcohol as ligands. Due to the possibility of forming aqueous azeotropes with water, the authors chose experiments were were conducted conducted to to evaluate evaluate the the influence influence of furfuryl of furfuryl alcohol alcohol by changing by changing its ratio its ratiowith to performwithwater. water. Optimal the Optimal Ullman results results in coupling terms in terms of conversion reaction of conversion inwere furfuryl were obtained obtained alcohol only only by azeotrope.using by using the theazeotropic azeotropicIn addition, mixture mixture several to experimentstoefficiently efficiently were synthetize synthetize conducted 23 23 different di tofferent evaluate products products the with withinfluence low low environmental environmental of furfuryl impact.alcohol impact. The Theby authorschanging authors were were its able ratio to with water.recover Optimal 93% results of furfuryl in terms alcohol of azeotrope conversion minimizing were obtained E-factorE-factor only values by to using 9.7. T This thehis constitutes azeotropic the mixture first first to efficientlyexample synthetize in in which which both23 bothdifferent reaction reaction mediumproducts medium and with ligand and low ligand could environmental be could easily be recovered impact. easily recovered and The reused, authors and minimizing were reused able, to recoverwasteminimizing 93% generation. of furfuryl waste generation. alcohol azeotrope minimizing E-factor values to 9.7. This constitutes the first example in which both reaction medium and ligand could be easily recovered and reused, minimizing waste generation.
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Scheme 11. Ullman-type cross-coupling in recoverable furfuryl alcohol water azeotrope. SchemeScheme 11. 11.UllmanUllman-type-type cross cross-coupling-coupling in in recoverable furfuryl furfuryl alcohol alcohol water water azeotrope. azeotrope. 4.4. AzeotropesAzeotropes inin MaterialMaterial SynthesisSynthesis for WasteWaste ValorizationValorization 4. Azeotropes in Material Synthesis for Waste Valorization WhenWhen wastewaste minimizationminimization is not possible,possible, a powerful tool for minimizing the environmental impactWhenimpact ofwasteof chemistrychemistry minimization isis thethe abilityability is tonotto transformtransform possible, wastewaste a powerful stream into tool value-addedvalue for -minimizingadded materials. the I Inenvironmentaln this this field field impactazeotropesazeotropes of chemistry may may alsoisalso the playplay ability a a crucial crucial to transform role. role. Below Below waste are are stream reported into two two value significant significant-added example examplesmaterials.s of of I n waste waste this field azeotropesvalorizationvalorization may driven drivenalso play byby azeotropes.azeotropes. a crucial role. Below are reported two significant examples of waste valorizationFlyFly ashdriven ash derived derived by azeotropes. from from oil shale oil shale processing processing is a serious is a serious environmental environmental pollutant. pollutant. Gan and coworkers Gan and reportedFlycoworkers ash in derived 2010reported the fromuse in 2010 of oil oil the shale shale use ash of processing (OSA)oil shale as aluminaash is (OSA) a serious source as alumina in environmental the preparation source in the of pollutant. gamma-alumina preparation Gan of and gamma-alumina nano-powder (Scheme 12) [82]. Alumina nanoparticles found applications in coworkersnano-powder reported (Scheme in 2010 12 )[the82 ].use Alumina of oil shale nanoparticles ash (OSA) found as alumina applications source in di ffinerent the fieldspreparation from of catalysisdifferent tofields ceramics from ascatalysis well as to their ceramics use as as absorbents. well as their The use authors as absorbents. combined The ultrasound authors technologycombined gamma-alumina nano-powder (Scheme 12) [82]. Alumina nanoparticles found applications in withultrasound azeotropic technology distillation with to a azeotropicfford good distillation size distribution to afford of γ -alumina. good size Indeed, distribution sonication of γ- promotedalumina. different fields from catalysis to ceramics as well as their use as absorbents. The authors combined theIndeed, contact sonication between promoten-butanold the and contact hydrogel between preventing n-butanol aggregate and hydrogel formation, preventing while azeotropic aggregate ultrasounddistillationformation, technology while efficiently azeotropic with removed azeotropic distillation water adsorbed efficiently distillation on remove particle to affordd water surfaces. good adsorbed sizeThis on workdistribution particle represents surface of aγs.- validThisalumina. Indeed,alternativework sonication represents for OSA promotea valid valorization. alternatid the ve contact for OSA between valorization. n-butanol and hydrogel preventing aggregate formation, while azeotropic distillation efficiently removed water adsorbed on particle surfaces. This work represents a valid alternative for OSA valorization.
SchemeScheme 12. Waste OSA valorization to γ--aluminaalumina particles.
ExpandedExpanded polystyrene polystyrene is a a non-biodegradable non-biodegradable material widely employed in in packaging that that constitutesconstitutes aa serious seriousScheme environmental environmental 12. Waste issue. issue. OSA Amongvalorization the two to γ - alternativesalumina particles. for expanded polystyrene recyclingrecycling areare energyenergy recoveryrecovery byby incinerationincineration and valorization by its use as a raw raw material material;; the the latter latter isExpandedis usuallyusually expensiveexpensive polystyrene whilewhile is incinerationincineration a non-biodegradable maymay generategenerate material hazardous widely chemicals. employed In In 2016 2016 Varughese Varughesein packaging and and that constituteMangalaraMangalaras a serious developeddeveloped environmental aa sustainablesustainable approach issue. Among for synthetized the two value value-added alternatives-added polystyrene polystyrene for expanded particles particles polystyrene with with micro-micro- oror nano-sizenano-size fromfrom expandedexpanded polystyrenepolystyrene waste through an emulsificationemulsification−diffusiondiffusion sequence sequence recycling are energy recovery by incineration and valorization by its use as a raw− material; the latter (Scheme 13)[83]. The authors employed bioderived d-limonene to dissolve polystyrene and performed is usually(Scheme expensive 13) [83]. while The incineration authors employed may generate bioderived hazardous D-limonene chemicals. to dissolve In 2016 polystyrene Varughese and and emulsificationperformed emulsification in aqueous inmedium, aqueous after medium, adding after an excess adding of an water excess to promote of water the to promoteprecipitation the Mangalara developed a sustainable approach for synthetized value-added polystyrene particles with ofprecipitation new polystyrene of new particles polystyrene (diff particlesusion), the (diffusion), recovery the of drecovery-limonene of wasD-limonene performed was atperformed a relatively at micro- or nano-size from expanded polystyrene waste through an emulsification−diffusion sequence lowa relatively temperature low temperature thanks to the thanks formation to the of formatid-limoneneon of waterD-limonene heterogeneous water heterogeneous azeotrope (bp azeotrope 97.4 ◦C). (SchemeThe(bp yield97.4 13) °C). and [83]. The size The yield eff ectauthors and of size the polystyreneeffect employed of the polystyrene particles bioderived were particles D found-limonene w toere be found dependent to dissolve to be dependent on the polystyrene amount on the of and performedpoly(vinylamount emulsification of alcohol),poly(vinyl employed alcohol), in aqueous as employed a biodegradable medium, as a biodegradable after emulsification adding emulsification stabilizer.an excess Up stabilizer. of to water 70% of Up tod -limoneneto promote 70% of the precipitationemployedD-limonene of for employednew the polystyrene expanded for the polystyrene expanded particles polystyrene(diffusion), valorization valorization the was recovery efficiently was of recoveredefficiently D-limonene makingrecovered was thisperformed making novel at a relativelyapproachthis novel low a approach sustainable temperature a sustainable alternative thanks alternative toto the the conventional formati to the onconventional of mechanical D-limonene mechanical recycle water and recycle heterogeneous incineration. and incineration. azeotrope (bp 97.4 °C). The yield and size effect of the polystyrene particles were found to be dependent on the amount of poly(vinyl alcohol), employed as a biodegradable emulsification stabilizer. Up to 70% of D-limonene employed for the expanded polystyrene valorization was efficiently recovered making this novel approach a sustainable alternative to the conventional mechanical recycle and incineration.
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SchemeScheme 13. 13.Synthesis Synthesis of of value-added value-added polystyrenepolystyrene particles from from expanded expanded polystyrene polystyrene waste waste and and solventsolvent recovery recovery through through azeotropic azeotropic distillation. distillation.
5. Conclusions5. Conclusions and and Future Future Outlook Outlook InIn the the shift shift towards towards more more sustainable sustainable chemicalchemical production production several several efforts efforts have have been been mad madee to to developdevelop synthetic synthetic technologies technologies aimed aimed at at waste waste minimization.minimization. In In this this review review we we have have tried tried to tohighlight highlight andand discuss discuss the the possible possible role role of azeotropesof azeotropes both both in wastein waste recovery recovery and and reuse, reuse, as alternativesas alternative tos theto the more employedmore employed end-of-pipe end treatments:-of-pipe treatment incineration,s: incineration, and in process and in modification. process modification. Lastly, a few Lastly, examples a few of theirexamples use in wasteof their valorization use in waste have valorization been reported. have been reported. SignificantSignificant examples examples in the the use use of ofazeotropic azeotropic distillation distillation for solvent for solvent recovery recovery from the from waste the wastestream stream have been have discussed been discussed,, highlighting highlighting both the environmental both the environmental and economic and gains economic considering gains consideringhomogeneous homogeneous azeotropic azeotropicdistillation, distillation, heterogeneous heterogeneous azeotropic distillation azeotropic and distillation hybrid extractive and hybrid- extractive-heterogeneousheterogeneous azeotropic azeotropic distillation. distillation. MoreMore importantly, importantly, by by following following EPA EPA hierarchy, hierarchy, the process modification modification design design for for “sourc “sourcee reduction” is a fundamental strategy. In this context it has been highlighted the importance of reduction” is a fundamental strategy. In this context it has been highlighted the importance of azeotropes to assist organic synthesis by preserving catalysts or in the purification processes for the azeotropes to assist organic synthesis by preserving catalysts or in the purification processes for isolation of pure product by minimizing waste and energy or also with their use as recoverable the isolation of pure product by minimizing waste and energy or also with their use as recoverable reaction media. reaction media. In addition, examples of the use of azeotropes for the implementation of a sustainable approach to Inwaste addition, valorization examples have of been the discusse use of azeotropesd. for the implementation of a sustainable approach to wasteDespite valorization azeotropes have proving been discussed. to be a powerful tool for waste minimization during the different syntheticDespite steps, azeotropes there are proving a small tonumber be a powerful of examples tool in forliterature waste that minimization consider the during carbon the footprint different syntheticand LCA steps, of the there solvents are a employed. small number In the ofse examples optics, azeotropes in literature of biomass that consider-derived the chemi carboncals should footprint andbe LCA further of theemployed solvents to increase employed. the Insustainability these optics, of azeotropesknown, less ofenvironmentally biomass-derived effective chemicals protocols. should be further employed to increase the sustainability of known, less environmentally effective protocols. Author Contributions: Writing—review and editing, F.V. and L.V. All authors have read and agreed to the Authorpublished Contributions: version of theWriting—review manuscript. and editing, F.V. and L.V. All authors have read and agreed to the publishedFunding: version This research of the manuscript. was funded by MIUR, grant AMIS—“Dipartimenti di Eccellenza—2018–2022”. Funding: This research was funded by MIUR, grant AMIS—“Dipartimenti di Eccellenza—2018–2022”. Acknowledgments: The Università degli Studi di Perugia and MIUR are acknowledged for financial support to Acknowledgments:the project AMIS, throughThe Universit the programà degli “Dipartimenti Studi di Perugia di E andccellenza MIUR—2018 are acknowledged–2022”. for financial support to the project AMIS, through the program “Dipartimenti di Eccellenza—2018–2022”. Conflicts of Interest: The authors declare no conflict of interest. Conflicts of Interest: The authors declare no conflict of interest.
References References 1. Brundtland, C.G. Our Common Features, The World Commission on Environmental Development: Oxford 1. Brundtland, C.G. Our Common Features, The World Commission on Environmental Development; Oxford University Press: Oxford, UK, 1987. 2. UniversityBurnett, Press:M.L. The Oxford, Pollu UK,tion 1987. Prevention Act of 1990: A Policy Whose Time Has Come or Symbolic 2. Burnett,Legislation? M.L. The Environ. Pollution Manag. Prevention 1998, 22, Act213– of224 1990:, doi:10.1007/s002679900098. A Policy Whose Time Has Come or Symbolic Legislation? 3. Environ.Farr, J.R. Manag. A Hat,1998 a Rapier,, 22, 213–224. a Knife, [CrossRefand a Dagger.] A Tale of Two Murders; Duke University Press: Durham, 3. Farr,NC, J.R. USA, A Hat, 2005; a pp. Rapier, 40–53, a Knife,doi:10.1215/9780822387145 and a Dagger. In A- Tale004. of Two Murders; Duke University Press: Durham, 4. NC,U.S. USA, Environmental 2005; pp. 40–53. Protection [CrossRef Agency.] Report to Congress: Minimization of Hazardous Waste; EPA/530-SW- 4. U.S.86- Environmental033; OSW and ER: Protection Washington, Agency. DC, USA,Report 1986. to Congress: Minimization of Hazardous Waste; EPA/530- 5. SW-86-033;Anastas, P.; OSW Warner, and ER:J. Green Washington, Chemistry DC,Theory USA, and 1986. Practice; Oxford University Press: Oxford, UK, 1998. 5. Anastas, P.; Warner, J. Green Chemistry Theory and Practice; Oxford University Press: Oxford, UK, 1998.
Molecules 2020, 25, 5264 15 of 18
6. Constable, D.J.C.; Curzons, A.D.; Cunningham, V.L. Metrics to ‘green’ chemistry—Which are the best? Green Chem. 2002, 4, 521–527. [CrossRef] 7. Curzons, A.D.; Mortimer, D.N.; Constable, D.J.C.; Cunningham, V.L. So you think your process is green, how do you know? Using principles of sustainability to determine what is green–a corporate perspective. Green Chem. 2001, 3, 1–6. [CrossRef] 8. Sheldon, R.A. Organic Synthesis; Past, Present and Future. Chem. Ind. 1992, 903–906. 9. Constable, D.J.C.; Curzons, A.D.; Dos Santos, L.M.F.; Geen, G.R.; Kitteringham, J.; Smith, P.; Hannah, R.; McGuire, M.A.; Webb, R.L.; Yu, M.; et al. Green Chemistry Measures for Process Research and Development. Green Chem. 2001, 3, 7–9. [CrossRef] 10. Jimenez-Gonzalez, C.; Ponder, C.S.; Broxterman, Q.B.; Manley, J.B. Using the Right Green Yardstick: Why Process Mass Intensity Is Used in the Pharmaceutical Industry To Drive More Sustainable Processes. Org. Process. Res. Dev. 2011, 15, 912–917. [CrossRef] 11. Curzons, A.; Constable, D.; Cunningham, V. Solvent selection guide: A guide to the integration of environmental, health and safety criteria into the selection of solvents. Clean Technol. Environ. Policy 1999, 1, 82–90. [CrossRef] 12. Fien, G.-J.A.F.; Liu, Y.A. Heuristic Synthesis and Shortcut Design of Separation Processes Using Residue Curve Maps: A Review. Ind. Eng. Chem. Res. 1994, 33, 2505–2522. [CrossRef] 13. Fink, J. Processes; Elsevier: Amsterdam, The Netherlands, 2016; pp. 185–223. 14. Szanyi, A.; Mizsey, P.; Fonyo, Z. Novel hybrid separation processes for solvent recovery based on positioning the extractive heterogeneous-azeotropic distillation. Chem. Eng. Process. Process. Intensif. 2004, 43, 327–338. [CrossRef] 15. Young, S. LXXIII.—The preparation of absolute alcohol from strong spirit. J. Chem. Soc., Trans. 1902, 81, 707. [CrossRef] 16. Liu, H.-L. Waste Minimization At A Nitrocellulose Manufacturing Facility. Int. J. Environ. Stud. 2003, 60, 353–361. [CrossRef] 17. Zhou, H.; Cai, Y.; You, F. Systems Design, Modeling, and Thermoeconomic Analysis of Azeotropic Distillation Processes for Organic Waste Treatment and Recovery in Nylon Plants. Ind. Eng. Chem. Res. 2018, 57, 9994–10010. [CrossRef] 18. Wasylkiewicz, S.K.; Kobylka, L.C.; Castillo, F.J. Optimal design of complex azeotropic distillation columns. Chem. Eng. J. 2000, 79, 219–227. [CrossRef] 19. Pham, H.N.; Doherty, M.F. Design and synthesis of heterogeneous azeotropic distillations—III. Column sequences. Chem. Eng. Sci. 1990, 45, 1845–1854. [CrossRef] 20. Xu, W.; Diwekar, U.M. Environmentally Friendly Heterogeneous Azeotropic Distillation System Design: Integration of EBS Selection and IPS Recycling. Ind. Eng. Chem. Res. 2005, 44, 4061–4067. [CrossRef] 21. Chien, I.-L.; Zeng, K.-L.; Chao, H.-Y.; Liu, J.H. Design and control of acetic acid dehydration system via heterogeneous azeotropic distillation. Chem. Eng. Sci. 2004, 59, 4547–4567. [CrossRef] 22. Chien, I.-L.; Kuo, C.-L. Investigating the need of a pre-concentrator column for acetic acid dehydration system via heterogeneous azeotropic distillation. Chem. Eng. Sci. 2006, 61, 569–585. [CrossRef] 23. Ooms, T.; Vreysen, S.; Van Baelen, G.; Gerbaud, V.; Rodríguez-Donis, I. Separation of ethyl acetate–isooctane mixture by heteroazeotropic batch distillation. Chem. Eng. Res. Des. 2014, 92, 995–1004. [CrossRef] 24. Asprion, N.; Kaibel, G. Dividing wall columns: Fundamentals and recent advances. Chem. Eng. Process. Process. Intensif. 2010, 49, 139–146. [CrossRef] 25. Chaniago, Y.D.; Harvianto, G.R.; Bahadori, A.; Lee, M. Enhanced recovery of PGME and PGMEA from waste photoresistor thinners by heterogeneous azeotropic dividing-wall column. Process. Saf. Environ. Prot. 2016, 103, 413–423. [CrossRef] 26. Sun, L.; Chang, X.-W.; Qi, C.-X.; Li, Q.-S. Implementation of Ethanol Dehydration Using Dividing-Wall Heterogeneous Azeotropic Distillation Column. Sep. Sci. Technol. 2011, 46, 1365–1375. [CrossRef] 27. Kiss, A.A.; Suszwalak, D.J.P.C. Enhanced bioethanol dehydration by extractive and azeotropic distillation in dividing-wall columns. Sep. Purif. Technol. 2012, 86, 70–78. [CrossRef] 28. Le, Q.-K.; Halvorsen, I.J.; Pajalic, O.; Skogestad, S. Dividing wall columns for heterogeneous azeotropic distillation. Chem. Eng. Res. Des. 2015, 99, 111–119. [CrossRef] 29. Wu, Y.C.; Lee, H.-Y.; Huang, H.-P.; Chien, I.-L. Energy-Saving Dividing-Wall Column Design and Control for Heterogeneous Azeotropic Distillation Systems. Ind. Eng. Chem. Res. 2014, 53, 1537–1552. [CrossRef] Molecules 2020, 25, 5264 16 of 18
30. Benko, T.; Szanyi, A.; Mizsey, P.; Fonyo, Z. Environmental and economic comparison of waste solvent treatment options. Open Chem. 2006, 4, 92–110. [CrossRef] 31. Goedkoop, M.; Spriensma, R. The Eco-indicator 99, a Damage Oriented Method for Life Cycle Assessment; Methodolgy Report; Pre Consultants: Amersfoort, The Netherlands, 2000. 32. Toth, A.J.; Szilagyi, B.; Haaz, E.; Solti, S.; Nagy, T.; Szanyi, A.; Nagy, J.; Mizsey, P. Enhanced separation of maximum boiling azeotropic mixtures with extractive heterogeneous-azeotropic distillation. Chem. Eng. Res. Des. 2019, 147, 55–62. [CrossRef] 33. Selim, A.; Toth, A.J.; Fozer, D.; Haaz, E.; Mizsey, P. Pervaporative desalination of concentrated brine solution employing crosslinked PVA/silicate nanoclay membranes. Chem. Eng. Res. Des. 2020, 155, 229–238. [CrossRef] 34. Toth, A.J. Modelling and Optimisation of Multi-Stage Flash Distillation and Reverse Osmosis for Desalination of Saline Process Wastewater Sources. Membranes 2020, 10, 265. [CrossRef] 35. Valentínyi, N.; Cséfalvay, E.; Mizsey, P. Modelling of pervaporation: Parameter estimation and model development. Chem. Eng. Res. Des. 2013, 91, 174–183. [CrossRef] 36. Haáz, E.; Valentinyi, N.; Tarjani, A.J.; Fozer, D.; Andre, A.; Mohamed, S.A.K.; Rahimli, F.; Nagy, T.; Mizsey, P.; Deák, C.; et al. Platform Molecule Removal from Aqueous Mixture with Organophilic Pervaporation: Experiments and Modelling. Period. Polytech. Chem. Eng. 2018, 63, 138–146. [CrossRef] 37. Castro-Muñoz, R.; Galiano, F.; Figoli, A. Recent advances in pervaporation hollow fiber membranes for dehydration of organics. Chem. Eng. Res. Des. 2020, 164, 68–85. [CrossRef] 38. Valentínyi, N.; Mizsey, P. Comparison of pervaporation models with simulation of hybrid separation processes. Period. Polytech. Chem. Eng. 2014, 58, 7–14. [CrossRef] 39. Toth, A.J.; Gergely,F.; Mizsey,P.Physicochemical treatment of pharmaceutical process wastewater: Distillation and membrane processes. Period. Polytech. Chem. Eng. 2011, 55, 59. [CrossRef] 40. Valentinyi, N.; Andre, A.; Haaz, E.; Fozer, D.; Toth, A.J.; Nagy, T.; Mizsey, P. Experimental investigation and modeling of the separation of ternary mixtures by hydrophilic pervaporation. Sep. Sci. Technol. 2019, 55, 601–617. [CrossRef] 41. Szilágyi, B.; Trang, D.T.H.; Fózer, D.; Selim, A.; Haáz, E.; Toth, A.J. Modelling of Hybrid Method for VOC Removal from Process Wastewater: Distillation and Hydrophilic Pervaporation. Period. Polytech. Chem. Eng. 2020, 64, 364–370. [CrossRef] 42. Toth, A.J. Comprehensive evaluation and comparison of advanced separation methods on the separation of ethyl acetate-ethanol-water highly non-ideal mixture. Sep. Purif. Technol. 2019, 224, 490–508. [CrossRef] 43. Haaz, E.; Szilagyi, B.; Fozer, D.; Toth, A.J. Combining extractive heterogeneous-azeotropic distillation and hydrophilic pervaporation for enhanced separation of non-ideal ternary mixtures. Front. Chem. Sci. Eng. 2020, 14, 913–927. [CrossRef] 44. Andre, A.; Nagy, T.; Toth, A.J.; Haaz, E.; Fozer, D.; Tarjani, J.A.; Mizsey, P. Distillation contra pervaporation: Comprehensive investigation of isobutanol-water separation. J. Clean. Prod. 2018, 187, 804–818. [CrossRef] 45. Sarney, D.B.; Barnard, M.J.; Virto, M.; Vulfson, E.N. Enzymatic synthesis of sorbitan esters using a low-boiling-point azeotrope as a reaction solvent. Biotechnol. Bioeng. 1997, 54, 351–356. [CrossRef] 46. Li, J.; Wang, T. Coupling reaction and azeotropic distillation for the synthesis of glycerol carbonate from glycerol and dimethyl carbonate. Chem. Eng. Process. Process. Intensif. 2010, 49, 530–535. [CrossRef] 47. Jindapon, W.; Ruengyoo, S.; Kuchonthara, P.; Ngamcharussrivichai, C.; Vitidsant, T. Continuous production of fatty acid methyl esters and high-purity glycerol over a dolomite-derived extrudate catalyst in a countercurrent-flow trickle-bed reactor. Renew. Energy 2020, 157, 626–636. [CrossRef] 48. Gérardy, R.; Debecker, D.P.; Estager, J.; Luis, P.; Monbaliu, J.-C.M. Continuous Flow Upgrading of Selected C2–C6 Platform Chemicals Derived from Biomass. Chem. Rev. 2020, 120, 7219–7347. [CrossRef][PubMed] 49. Azzena, U.; Carraro, M.; Mamuye, A.D.; Murgia, I.; Pisano, L.; Zedde, G. Cyclopentyl methyl ether–NH4X: A novel solvent/catalyst system for low impact acetalization reactions. Green Chem. 2015, 17, 3281–3284. [CrossRef] 50. Mujahed, S.; Valentini, F.; Cohen, S.; Vaccaro, L.; Gelman, D. Polymer-Anchored Bifunctional Pincer Catalysts for Chemoselective Transfer Hydrogenation and Related Reactions. ChemSusChem 2019, 12, 4693–4699. [CrossRef][PubMed] 51. Soni, R.; Jolley, K.E.; Clarkson, G.J.; Wills, M. Direct Formation of Tethered Ru(II) Catalysts Using Arene Exchange. Org. Lett. 2013, 15, 5110–5113. [CrossRef][PubMed] Molecules 2020, 25, 5264 17 of 18
52. Zimbron, J.M.; Dauphinais, M.; Charette, A.B. Noyori–Ikariya catalyst supported on tetra-arylphosphonium salt for asymmetric transfer hydrogenation in water. Green Chem. 2015, 17, 3255–3259. [CrossRef] 53. He, B.; Zheng, L.; Phansavath, P.; Ratovelomanana-Vidal, V. Rh III -Catalyzed Asymmetric Transfer Hydrogenation of α-Methoxy β-Ketoesters through DKR in Water: Toward a Greener Procedure. ChemSusChem 2019, 12, 3032–3036. [CrossRef] 54. Soni, R.; Cheung, F.K.; Clarkson, G.C.; Martins, J.E.D.; Graham, M.A.; Wills, M. The importance of the N–H bond in Ru/TsDPEN complexes for asymmetric transfer hydrogenation of ketones and imines. Org. Biomol. Chem. 2011, 9, 3290–3294. [CrossRef] 55. Ferlin, F.; Cappelletti, M.; Vivani, R.; Pica, M.; Piermatti, O.; Vaccaro, L. Au@zirconium-phosphonate nanoparticles as an effective catalytic system for the chemoselective and switchable reduction of nitroarenes. Green Chem. 2019, 21, 614–626. [CrossRef] 56. Armstrong, R.D.; Kariuki, B.M.; Knight, D.W.; Hutchings, G.J. How to Synthesise High Purity, Crystalline d-Glucaric Acid Selectively. Eur. J. Org. Chem. 2017, 2017, 6811–6814. [CrossRef] 57. Thaore, V.B.; Armstrong, R.D.; Hutchings, G.J.; Knight, D.W.; Chadwick, D.; Shah, N. Sustainable production of glucaric acid from corn stover via glucose oxidation: An assessment of homogeneous and heterogeneous catalytic oxidation production routes. Chem. Eng. Res. Des. 2020, 153, 337–349. [CrossRef] 58. Eisenbraun, E.J.; Payne, K.W.; Bymaster, J.S. Multiple-Batch, Wolff Kishner Reduction Based on Azeotropic − Distillation Using Diethylene Glycol. Ind. Eng. Chem. Res. 2000, 39, 1119–1123. [CrossRef] 59. Herr, C.H.; Whitmore, F.C.; Schiessler, R.W. The Wolff-Kishner Reaction at Atmospheric Pressure. J. Am. Chem. Soc. 1945, 67, 2061–2063. [CrossRef] 60. Soffer, M.D.; Soffer, M.B.; Sherk, K.W. A Low Pressure Method for Wolff—Kishner Reduction. J. Am. Chem. Soc. 1945, 67, 1435–1436. [CrossRef] 61. Huang, M. A Simple Modification of the Wolff-Kishner Reduction. J. Am. Chem. Soc. 1946, 68, 2487–2488. [CrossRef] 62. Frank, E.; Steudle, L.M.; Ingildeev, D.; Spörl, J.M.; Buchmeiser, M.R. Carbon Fibers: Precursor Systems, Processing, Structure, and Properties. Angew. Chem. Int. Ed. 2014, 53, 5262–5298. [CrossRef][PubMed] 63. Grasselli, R.K. Fundamental Principles of Selective Heterogeneous Oxidation Catalysis. Top. Catal. 2002, 21, 79–88. [CrossRef] 64. Grasselli, R.K.; Tenhover, M.A. Ammoxidation. In Handbook of Heterogeneous Catalysis; Wiley: Hoboken, NJ, USA, 2008; pp. 3489–3517. 65. Centi, G.; Perathoner, S.; Trifirò, F. V-Sb-oxide catalysts for the ammoxidation of propane. Appl. Catal. A Gen. 1997, 157, 143–172. [CrossRef] 66. Grasselli, R.K.; Trifirò, F. Acrylonitrile from Biomass: Still Far from Being a Sustainable Process. Top. Catal. 2016, 59, 1651–1658. [CrossRef] 67. Karp, E.M.; Eaton, T.R.; Nogué, V.S.I.; Vorotnikov, V.; Biddy, M.J.; Tan, E.C.D.; Brandner, D.G.; Cywar, R.M.; Liu, R.; Manker, L.P.; et al. Renewable acrylonitrile production. Science 2017, 358, 1307–1310. [CrossRef] 68. Meek, K.M.; Eaton, T.R.; Rorrer, N.A.; Brandner, D.G.; Manker, L.P.; Karp, E.M.; Biddy, M.J.; Bratis, A.D.; Beckham, G.T.; Naskar, A.K. Emulsion polymerization of acrylonitrile in aqueous methanol. Green Chem. 2018, 20, 5299–5310. [CrossRef] 69. Pavia, C.; Ballerini, E.; Bivona, L.A.; Giacalone, F.; Aprile, C.; Vaccaro, L.; Gruttadauria, M. Palladium Supported on Cross-Linked Imidazolium Network on Silica as Highly Sustainable Catalysts for the Suzuki Reaction under Flow Conditions. Adv. Synth. Catal. 2013, 355, 2007–2018. [CrossRef] 70. Kozell, V.; Giannoni, T.; Nocchetti, M.; Vivani, R.; Piermatti, O.; Vaccaro, L. Immobilized Palladium Nanoparticles on Zirconium Carboxy-Aminophosphonates Nanosheets as an Efficient Recoverable Heterogeneous Catalyst for Suzuki–Miyaura and Heck Coupling. Catalyst 2017, 7, 186. [CrossRef] 71. Kozell, V.; McLaughlin, M.; Strappaveccia, G.; Santoro, S.; Bivona, L.A.; Aprile, C.; Gruttadauria, M.; Vaccaro, L. Sustainable Approach to Waste-Minimized Sonogashira Cross-Coupling Reaction Based on Recoverable/Reusable Heterogeneous Catalytic/Base System and Acetonitrile Azeotrope. ACS Sustain. Chem. Eng. 2016, 4, 7209–7216. [CrossRef] 72. Petrucci, C.; Strappaveccia, G.; Giacalone, F.; Gruttadauria, M.; Pizzo, F.; Vaccaro, L. An E-Factor Minimized Protocol for a Sustainable and Efficient Heck Reaction in Flow. ACS Sustain. Chem. Eng. 2014, 2, 2813–2819. [CrossRef] Molecules 2020, 25, 5264 18 of 18
73. Petrucci, C.; Cappelletti, M.; Piermatti, O.; Nocchetti, M.; Pica, M.; Pizzo, F.; Vaccaro, L. Immobilized palladium nanoparticles on potassium zirconium phosphate as an efficient recoverable heterogeneous catalyst for a clean Heck reaction in flow. J. Mol. Catal. A Chem. 2015, 401, 27–34. [CrossRef] 74. Rasina, D.; Lombi, A.; Santoro, S.; Ferlin, F.; Vaccaro, L. Searching for novel reusable biomass-derived solvents: Furfuryl alcohol/water azeotrope as a medium for waste-minimised copper-catalysed azide–alkyne cycloaddition. Green Chem. 2016, 18, 6380–6386. [CrossRef] 75. Ferlin, F.; Trombettoni, V.; Luciani, L.; Fusi, S.; Piermatti, O.; Santoro, S.; Vaccaro, L. A waste-minimized protocol for copper-catalyzed Ullmann-type reaction in a biomass derived furfuryl alcohol/water azeotrope. Green Chem. 2018, 20, 1634–1639. [CrossRef] 76. Gruttadauria, M.; Giacalone, F.; Noto, R. “Release and catch” catalytic systems. Green Chem. 2013, 15, 2608–2618. [CrossRef] 77. Mahmoudi, H.; Valentini, F.; Ferlin, F.; Bivona, L.A.; Anastasiou, I.; Fusaro, L.; Aprile, C.; Marrocchi, A.; Vaccaro, L. A tailored polymeric cationic tag–anionic Pd(ii) complex as a catalyst for the low-leaching Heck–Mizoroki coupling in flow and in biomass-derived GVL. Green Chem. 2019, 21, 355–360. [CrossRef] 78. Ferlin, F.; Lanari, D.; Vaccaro, L. Sustainable flow approaches to active pharmaceutical ingredients. Green Chem. 2020, 22, 5937–5955. [CrossRef] 79. Vaccaro, L. Green Shades in Organic Synthesis. Eur. J. Org. Chem. 2020, 2020, 4273–4283. [CrossRef] 80. Gao, F.; Bai, R.; Ferlin, F.; Vaccaro, L.; Li, M.; Gu, Y. Replacement strategies for non-green dipolar aprotic solvents. Green Chem. 2020, 22, 6240–6257. [CrossRef] 81. Sun, D.; Sato, S.; Ueda, W.; Primo, A.; García, H.; Corma, A. Production of C4 and C5 alcohols from biomass-derived materials. Green Chem. 2016, 18, 2579–2597. [CrossRef] 82. An, B.; Ji, G.; Wang, W.; Gan, S.; Xu, J.; Gao, G.; Li, G. Azeotropic distillation-assisted preparation of nanoscale gamma-alumina powder from waste oil shale ash. Chem. Eng. J. 2010, 157, 67–72. [CrossRef] 83. Mangalara, S.C.H.; Varughese, S. Green Recycling Approach To Obtain Nano- and Microparticles from Expanded Polystyrene Waste. ACS Sustain. Chem. Eng. 2016, 4, 6095–6100. [CrossRef]
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