Perspective

pubs.acs.org/journal/ascecg

Intensifying Multiphase Reactions and Reactors: Strategies and

Examples
Ranjeet P. Utikar†,* and Vivek V. Ranade*,‡
†
Department of Chemical Engineering, Curtin University, GPO Box U1987, Perth WA 6845, Australia
‡
School of Chemistry and Chemical Engineering, Queen’s University of Belfast, Belfast BT9 5 AG, United Kingdom

ABSTRACT: Intensification is intrinsic to better chemical

and process engineering and has always been used in practice.
Multiphase reactions and reactors are ubiquitous in chemical
and allied industries and are of great economic and ecological
importance. There is a great scope for intensifying multiphase
reactions and reactors for realizing productivity enhancements,
which are crucial for sustainable manufacturing. These
enhancements can be in terms of increased throughput; better
yield, conversion, and selectivity; smaller environmental
footprint; and intrinsically safer operations. The advances in
intensified reactors, especially microreactors and microfluidic
devices, have created significant awareness about intensifica-
tion in recent decades. In this article, we discuss different
strategies for intensifying multiphase reactions and reactors based on the published information. A variety of tools and examples
are presented to showcase the potential of intensification. We have found the efforts toward intensification of multiphase
reactions and reactors very rewarding academically as well as professionally. We hope that this article will further stimulate
interest in this area and pave the way toward realizing next generation productivity for chemical and allied industries.
KEYWORDS: Process intensification, Multiphase reactors, Microreactor, Sustainable process development

■ INTRODUCTION
Chemical and allied industries are crucial for sustaining and
very early in our research careers. Professor M. M. Sharma of
UDCT (now called Institute of Chemical Technology,
enhancing quality of life as they touch the lives of everyone Mumbai) is one of the pioneers in intensifying multiphase
every day. The chemical industry faces its biggest challenges in reactions. He introduced one of us (V.V.R.) to intensification
rising raw material costs, depleting feedstocks, and stricter and the benefits of it more than three decades ago (when
environmental regulations. These challenges also open up process intensification had not become the buzz word as it is
significant opportunities for innovation. It is essential to today). In his classic book1 he has discussed several examples of
continuously focus on significant improvements in productivity intensification of multiphase reactions. In one of his papers with
via process innovations for conserving raw materials, catalysts, almost the same title as this article,2 he has discussed several
energy, and water. To enhance productivity, and thus economic examples of intensifying reactions. These works and the
impact, it is important that the chemical (and biological) references cited therein are a must read for anyone interested
transformations in a chemical process are carried out in the best in intensifying multiphase reactions.
possible way that is intrinsically safe and has a smaller Continuous improvement has been the cornerstone of the
environmental footprint. A vast majority of such trans- process industry and has resulted in significant advances in
formations involve multiphase reactions and reactors. There- several process areas. For example, advances in materials and
fore, there is immense scope for intensifying multiphase heat exchanger configurations have tremendously improved the
reactions and reactors for realizing productivity enhancements. energy efficiency of sulfuric acid plants over recent years.
Intensification may be broadly defined as the ability to obtain Compared to a traditional double-catalyst double-absorption
better results in terms of purity, conversion, and yield of the process cycle, where almost 40% low level heat is wasted in an
desired product by manipulating rates of relevant transport acid cooling system, modern processes such as Monsanto
processes and chemical reactions so as to enhance overall
performance (more throughput, better quality, less energy
Special Issue: Asia-Pacific Congress on Catalysis: Advances in
consumption, less waste, safer, etc.). This usually translates into
Catalysis for Sustainable Development
a reduced cost, which has been the main driver behind
intensification. It is therefore in a sense intrinsic to better Received: December 11, 2016
chemical and process engineering and has always been used in Revised: February 4, 2017
practice. We were fortunate to get introduced to intensification Published: February 15, 2017

© 2017 American Chemical Society 3607 DOI: 10.1021/acssuschemeng.6b03017

ACS Sustainable Chem. Eng. 2017, 5, 3607−3622
ACS Sustainable Chemistry & Engineering Perspective

Figure 1. Intensification of multiphase reactions and reactors.

Enviro-Chem’s Heat Recovery System and Outokompus heat intensifying reactions. Rather than focusing on such specific
recovery system offer recovery of over 95% of the process heat efforts on intensifying reactions, in this article, published studies
as steam. Recently, there has been significant effort to develop on intensification of multiphase reactions and reactors are
scalable technologies for the synthesis of carbon-neutral critically analyzed and useful strategies for intensification are
ammonia by conversion of intermittent energies (e.g., solar extracted.
and wind).3 The new developments allow ammonia plants to For any chemical reaction to occur, a reactor has to carry out
behave like energy plants, a drastic shift from the traditional several tasks such as bring reactants into intimate contact with
centralized, large-scale, capital- and energy-intensive Haber- each other as well as the active sites on a catalyst, provide an
Bosch process. appropriate environment (pressure, temperature, and concen-
In this article, we focus on some of the recent work on tration) for adequate time, and allow for timely removal of
intensification. Stankiewicz and Moulijn4 have defined the products. Naturally, successful reactor engineering requires
modern interpretation of process intensification as “the bringing together better chemistry and better engineering.
development of novel apparatuses and techniques that are Better chemistry is achieved through understanding of
expected to bring dramatic improvements in manufacturing and thermodynamics, catalysis, and reaction pathways (Figure 1).
processing, substantially decreasing equipment size, energy While engineering can be improved via insights into fluid
consumption, or waste production, and ultimately resulting in dynamics, mixing, and heat and mass transfer, and real time
cheaper, sustainable technologies”. The definition is still heavily process monitoring and control. Thus, it is important to
biased toward new apparatuses and methods than on other combine the understanding of chemistry and catalysis with key
avenues of intensification advocated by Sharma2 and others. It reaction engineering expertise in order to realize the true
also covers a broader scope beyond chemical reactions. In this potential of intensification via the following two avenues:
article, we restrict the scope to intensification of chemical • Intensifying chemical reactions: This can be carried out
reactions and reactors. Intensification of other processes such as in a variety of waysimproved catalysts (replace reagent
separations, unless they are intimately linked to reactions, is not based processes), better process routes, improved
included. solvents (supercritical media, ionic liquids), better
The advancement in intensified devices including micro- process windows (concentrations, temperature, pressure,
reactors and microfluidic devices has created significant hype etc.), improved atom efficiency, and alternative pathways
and awareness about process intensification in recent decades.
to prevent waste.
Nevertheless, adoption of microdevices-based technologies by
• Intensifying transport processes: New ways of process
industry is slow. Hundreds of research papers and many books
and monographs are now available in this area. Owing to the intensification can come from improved underlying flows
continuous research, researchers and practicing engineers now and associated transport processes (via experiments and
better understand the limitations and strengths of process computational models) to ensure delivery of materials
intensification technologies and continuous processing. As a and energy at the right time and right place at length and
consequence, more informed use and research plans for time scales, which are appropriate to the reaction rather
enhancing adoption and relevant development of process than driven by the process.
intensification technology have emerged. There is a gradual but In the following section, we briefly review published studies
certain expansion of scope of research and development from and attempt to capture key strategies for intensification. It
microdevices to milli- or even centi-scale devices, which has should be mentioned here that the major fraction of work on
considerably enhanced the potential for adoption in practice. intensification realized in practice does not get published
Recently, Ranade et al.5 have described the development of because of the proprietary and confidential nature of the work.
MAGIC (modular, agile, intensified, and continuous) reactors Even the small fraction that gets published covers such a broad
and their applications for intensifying variety of reactions. They range that it is almost impossible to present an all-
have also discussed key drivers, factors, and tools available for encompassing review in a single article. Naturally, the emphasis
3608 DOI: 10.1021/acssuschemeng.6b03017
ACS Sustainable Chem. Eng. 2017, 5, 3607−3622
ACS Sustainable Chemistry & Engineering Perspective

on certain topics and the selection of examples is rather biased monochlorioacetic acid by hydrogenation to avoid cumbersome
and is directly related to our own research interests and and expensive fractional crystallization. The hydrogenation step
experience. We have, however, made an attempt to evolve can, however, be eliminated by using extractive distillation with
general guidelines, which will be useful for generically a suitable extractant.8 Many other examples of a similar nature
addressing intensification of multiphase reactions/reactors. can be identified. However, these are not considered in the
Some comments on the path forward are also included at the present article. Another alternative to eliminate the hydro-
end. genation step or to reduce selectivity toward DCA is to use

■ STRATEGIES FOR INTENSIFICATION

There are thousands of industrially relevant processes involving
tubular millireactors and control backmixing to such an extent
that formation of DCA is within an acceptable limit. Such
intensification strategies are considered here.
multiphase reactions. There are many books and resources that Intensification of Multiphase Reactions. One of the
highlight and cite many such reactions. For example, most obvious ways of intensifying reactions limited by intrinsic
Doraiswamy and Sharma in their two-volume book1 have kinetics is to select an appropriate operating process window.
listed hundreds (if not thousands) of reactions. Doraiswamy6 in For reactions of positive order, using higher temperature,
his treatise on organic synthesis engineering discussed many reactant concentrations, and higher catalyst or promoter
reactions. More recently, Joshi and Ranade7 have listed several concentration wherever permissible, will lead to higher rates.
industrially relevant multiphase reactions in their edited book One needs to be aware that intensification through this obvious
on industrial catalytic processes for fine and specialty chemicals. route may lower selectivity toward desired product. The
Instead of giving examples of such reactions here, the reader is operating process window therefore needs to be optimized.
referred to these sources and references cited therein. There are several examples of such a strategy in published
Multiphase reactions and reactors can be classified in a literature and practice. For example, recently, Garkhedkar et al.9
variety of ways. One may classify these based on involved have reported a significant intensification in the effective
reactions like hydrogenations, oxidations, esterification, alkyla- reaction rate of hydrogenation of cinnamaldehyde to cinnamyl
tion, halogenation, diazotization, and so on. One may also alcohol without jeopardizing selectivity by appropriate selection
classify these on more generic reaction types such as gas− of reactant concentration, catalyst and promoter concentra-
liquid, liquid−liquid, gas−liquid−solid, liquid−solid, gas−solid, tions, and hydrogen partial pressure. We do not discuss this
and solid−solid reactions or reactor types such as stirred strategy further in this article since it is commonly used even
reactors, bubble column reactors, three-phase fluidized beds, for single-phase reactions. Instead, we focus our attention on
packed beds, fluidized beds, jet loop reactor, rotor-stator three widely used strategies for intensifying multiphase
reactor, tubular reactors, and so on. Significant efforts around reactions, namely, catalyst design, solvent design, and
the world continue to enhance and intensify the wide range of elimination of equilibrium limitations.
multiphase reactions and reactors. It is almost impossible to Catalyst Design. Major advances and step changes for
keep track of all the published literature and critically review it. intensification of multiphase reactions will, no doubt, continue
No such attempt is made here. Instead, we used the limited and to emerge from catalysis. A catalyst provides an alternative
arguably biased exposure to the published and unpublished route of reaction where the activation energy is lowered.
work to which we are privy to bring out key strategies of Catalysts enhance rates of chemical reactions without affecting
intensification. chemical equilibrium. Catalysts could be homogeneous
As mentioned earlier, these strategies are broadly grouped (catalyst and substrate in same phase) or heterogeneous
into intensification of reactions and intensification of transport catalysis (solid catalyst and substrate is a gas and/or liquid).
processes. Obviously, the two strategies are not completely Most of the homogeneously catalyzed systems also involve the
independent of each other. Any intensification strategy needs to presence of an immiscible phase and therefore are multiphase
first identify a performance-limiting step and then make an reactions.
attempt to eliminate those limitations. For example, if in a The role of catalyst becomes significantly more important
reactor rates of transport processes, such as mixing, are much when multiple reactions are thermodynamically feasible. In
higher than the reaction rate, intensification of reaction is an such cases, an appropriate catalyst manipulates the reaction
appropriate strategy. After intensification of the underlying rates in such a way that selectivity toward the desired product
reaction, rates of transport processes may become limiting, and increases. The catalyst performance is usually quantified using
intensification of transport processes may become an activity (rate of reaction), selectivity (toward desired product),
appropriate strategy. Intensification is thus a continuous activity and stability (deactivation, regeneration, reusability, life). With
and, depending on relative rates of underlying reactions and recent advances in molecular modeling, our understanding
transport processes at the time of consideration, an appropriate about atomic- and molecular-scale transformations around
strategy has to be selected. Key strategies used for intensifying catalyst sites through which a catalyst influences the overall
reactions and reactors (transport processes) are briefly outlined performance has improved significantly. It has enabled us to
in the following section. tailor catalysts for the desired performance. In many cases,
Before we proceed to discuss strategies for intensification, it bifunctional catalysts are used to achieve desired selectivity. For
may be useful to highlight here that one of the best strategies example, Talwalkar et al.10 used a bifunctional ion-exchange-
for intensification of reactions is avoiding the reaction resin catalyst for effective hydrogenation of diisobutylene
altogether! For example, consider a case of the monochloro- (DIB). DIB is generally available as an equilibrium mixture of
acetic acid (MCA) process. Conventionally, MCA is manufac- its isomers 2,4,4-trimethylpent-1-ene (TMP-1) and 2,4,4-
tured by chlorination of acetic acid in bubble columns or trimethylpent-2-ene (TMP-2). The terminal double bond in
sectionalized bubble columns. This is an autocatalytic reaction, TMP-1 gets hydrogenated substantially more quickly than the
and invariably some dichloroacetic acid (DCA) is formed in internal double bond in TMP-2; therefore, the isomerization of
bubble columns or similar reactors. The DCA is converted to TMP-2 to TMP-1 is essential to achieve higher rates and yields
3609 DOI: 10.1021/acssuschemeng.6b03017
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Figure 2. Examples of solvent designs for intensification: (a) Enhancing effective rate by adding immiscible liquid (Sharma2). (b) Use of
thermomorphic solvent for facilitating separation of homogeneous catalysts (Behr et al.17). (c) Solid−solid reactions in a screw extruder (Crawford
et al.22).

of hydrogenation. The selectivity and effective rate was several options such as CO2-expanded solvents, supercritical
intensified using a catalyst that is active for hydrogenation as solvents (CO2 and water), ionic liquids, and so on.
well as simultaneous isomerization. In many applications, it is beneficial to add a second
The subject of catalyst design as a strategy to enhance immiscible solvent in the reaction system either to intensify the
multiphase reactions is very complex and broad. It is not reaction rate or to facilitate easy separation of catalyst/products.
possible to do justice to the subject by including a short Sharma2 have demonstrated that addition of a second
subsection in this article. Instead, we refer readers to Joshi and immiscible liquid phase can significantly intensify rates of
Ranade7 and references cited therein for gaining deeper gas−liquid reactions. The second liquid phase has higher
appreciation and advances in this area. We would like to solubility for the gas and may be dispersed or emulsified. The
mention here two different examples of catalyst designs for the additional phase provides an extra mode of transport of the
purpose of illustration. The designing of “chiral” metal surfaces solute gas and thus enhances the rate. For example, Mehra15
has significant potential and could form a basis for developing and Mehra et al.16 report almost 30 times enhancement of the
solid catalysts for region-specific chemistry (see review by specific rates of alkaline hydrolysis of solid esters2,4-
Mallat et al.11 for several examples and references on this dichlorophenyl benzoate, p-chlorophenyl benzoate, and phenyl
subject). Another example is of crystal lattice engineering to benzoatein the presence of a second emulsified liquid phase
develop active and selective catalysts for converting biomass- (Figure 2a). In solid−liquid systems, Doraiswami and Sharma1
derived polyols by Jin et al.12 Using this approach, a bimetallic and Sharma2 have reported a large enhancement in the rates of
nanocatalyst was designed by synthesizing copper-based absorption of gases such as isobutylene, but-1-ene, and
nanocatalysts on a reduced graphene oxide support. The propylene into emulsions of an additional liquid phase in
catalytically active {111} facet was realized as the dominant aqueous sulfuric acid as well as microemulsions/micellar
surface by lattice-match engineering. It is hoped that such new solutions. Thus, addition of a second immiscible liquid can
be effectively used for intensifying a large variety of multiphase
methodologies for designing catalysts may open new vistas for
reactions.
exploiting graphene-based supports and improved metal-based
An example of a solvent design to derive the benefits of a
catalysts for a variety of heterogeneous catalytic reactions. Yet
high activity homogeneous catalyst without the associated
another possibility of enhancing the performance of a catalyst is difficulties of separation of a homogeneous catalyst is to use a
by designing appropriate supports for the catalyst. Jin et al.13 thermomorphic solvent (TMS) system. A TMS consists of at
have designed a heterogeneous support (TiO2) for bimetallic least two solvents with different polarity.17 As shown in Figure
PtCu catalysts where the support is apparently acting as a 2b, the solvents are immiscible at low temperature and form a
“‘ligand’” for the formation of nuclei, thus generating well- single homogeneous reaction phase at higher temperatures. An
dispersed Pt and Cu particles. They have demonstrated order of appropriate system can be chosen such that the catalyst is
magnitude enhancement in oxidation activity with improved predominantly soluble in one solvent and the other solvent has
selectivity for catalytic synthesis of glucaric acid by oxidation of higher affinity toward the product. Dreimann et al.18 have
gluconic acid/glucose (using oxygen as oxidant). Creative and reported selection of a TMS system for hydroformylation
synergistic design of support and catalyst will open up new reactions to reduce the difficulties in downstream separation
possibilities for developing greener and intensified processes. significantly.
Solvent Design. Solvents are routinely used for carrying out Another interesting way of intensifying multiphase reactions
reactions and influence not just the rates and productivity but is by selecting an appropriate solvent that allows efficient
also environmental impact. Solvents influence solubility of removal of heat liberated due to reactions and eliminates heat
reactants, may interact with the catalyst, and may act as a heat transfer limitations to increase the effective rate. For example,
carrier helping in providing heat for endothermic reactions or Deshpande and Dixit19 disclose a new process for polyolefins
managing heat liberated in exothermic reactions. There is an where polymerization occurs in a suspended phase, which
increasing emphasis on identifying better solvents that offer allows viscosity to remain within limits and provides effective
higher productivity of reaction with lower environmental mixing and heat transfer. Use of acetic acid for oxidation of
impact. Gadge and Bhanage14 have recently reviewed the paraxylene is a well-known example of effectively using
selection of solvents and reaction media. They have discussed evaporation of a solvent for removing heat of a reaction.
3610 DOI: 10.1021/acssuschemeng.6b03017
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Recently Ranade et al.20 have disclosed a way of intensifying reactors by the following three strategies: intensifying mixing,
hydrogenation of nitrobenzene via use of an evaporating heat transfer, and mass transfer.
solvent. Intensification of Mixing. There are several ways to intensify
While the use of solvents offers advantages, they effectively mixing controlled reactions. Most of these efforts are directed
reduce reactant concentration and may reduce productivity of toward reducing characteristic length scales of diffusion and
reactor if the reactor is operating under kinetically limiting mixing. For turbulent flows, it is achieved by enhancing and
conditions. In such a case, alternative ways of carrying out the concentrating turbulent energy dissipation rates. For laminar
reaction with minimal or no solvents can be explored. The flows, the length scales are usually reduced by realizing folding
grinding of solid reactants is emerging as an alternative to and refolding of the lamellar structure and reducing thickness of
conventional solvent-intensive methods. James et al.21 provide a the lamellas. Some of the augmentation of mixing and other
critical review of mechanochemical synthesis. Recently, transport processes are summarized by Ranade et al.5 A variety
order(s) of magnitude higher space time yields over conven- of high shear mixers using rotor-stator flows can be used for
tional methods have been reported by using screw extruders intensifying micromixing controlled reactions (such as polyur-
(Figure 2c) for the continuous synthesis of various metal ethane reactions). A large number of innovative designs of
complexes, including metal organic frameworks (MOFs).22,23 static mixers have also been developed for intensifying mixing
Overcoming Equilibrium Limitations by Combining controlled reactions. Besides these conventional ways of
Reaction and Separation. Many reactions used in practice intensifying, many new ideas have been proposed and are
are reversible in nature and often the conversion is limited by used to intensify mixing.
thermodynamic equilibrium considerations. Integration of Novel micromixers have been proposed for realizing faster
possible ways of removing one of the products from the mixing in laminar flows.31,32 Recently, Boroun and Larachi33
reacting mass is often the way to intensify such reactions. proposed the use of magnetic nanofluid actuation by rotating
Distillation, chromatography, and membrane separations are magnetic fields for intensifying liquid mixing. They have shown
the most studied separation processes integrated with reactors that the mixing index can be tripled compared to that obtained
to facilitate in situ product removal for shifting reaction without a magnetic field. Boroun and Larachi34 have also
equilibrium in forward direction. Recently, Reddy et al.24 discussed the possibility of tailoring the physical chemistry of
compared two multifunctional reactors, reactive distillation and magnetic nanoparticles (MNPs) for enhancing transport rates.
chromatographic reactors, for the production of C1−C4 In the future, it may be possible to use bifunctional magnetic
carboxylic esters. There are several examples of reactive nanomaterials that simultaneously carry out catalysis as well as
distillation including the celebrated methyl acetate process by intensify local mixing.
Intensify Heat Transfer. Many reactions used in practice are
Eastman.4 Stripping is used for removal of products and
highly exothermic, and often the ability to remove heat
intensification of urea alcoholysis reactions in the dialkyl
liberated from reactions controls the achievable productivity.
carbonates process.25,26 Fernandez et al.27 have shown that use
Many times such exothermic reactions are deliberately carried
of a membrane reactor can significantly enhance conversion
out at low temperatures (at low reaction rates) to match the
and purity of produced hydrogen for a methane-reforming
rate of heat liberation with the rate of heat removal. Enhancing
reaction. Membrane reactors have also been shown to be useful the heat removal capacity, mainly by significantly enhancing the
in intensifying biotransformations and enhancing selectiv- heat transfer area, may intensify such reactors. Heat transfer
ity. 28,29 These examples provide useful guidelines for area per unit volume of reactor is inversely related to the
intensifying equilibrium-limited multiphase reactions and characteristic length scale of the reactor cross-section. Most of
reactors. the process intensification efforts are focused on devising new
Intensifying Multiphase Reactors. Several factors reactor types having smaller characteristic length scales. By
influence overall performance of a multiphase reactor. The reducing the characteristic length scales of heat transfer
extent of backmixing (from completely mixed to a plug flow) in channels to around 0.01 m and less, the heat removal capacity
the reactor, mode of operation (batch, semibatch, and can be enhanced to 1000 kW/m3. The obvious choice of
continuous), and reactor configuration (single versus multiple) reactors for systems requiring such large heat removal capacity
influence the reactor performance for single as well as is therefore tubular (topologically) reactors. Several designs of
multiphase systems. Specific strategies that are relevant for such topologically tubular reactors have been proposed.
intensifying multiphase reactors are discussed here. Obvious One of the simplest designs is a pinched tube disclosed by
strategies such as changing the reactor configuration, which are Kulkarni and Ranade35 (Figure 4b). Pinched tubes have shown
generic in nature, are not discussed. For example, recently Atias to offer enhanced heat transfer and reduced axial dispersion,
et al.30 disclosed use of two reactor configurations for which make them suitable for carrying out exothermic
epoxidation. Epoxidation involves two steps: etherification reactions.36−38 Joshi et al.39 have demonstrated safe operations
and dehalohydrogenation (epoxidation). Unlike the conven- with several multiphase exothermic reactions using pinched
tional process, where both the steps take place in the same tube reactors. Andersson et al.40 have developed a novel
reactor, intensification is achieved by splitting the reaction into intensified reactor for liquid−liquid reactions that has
two reactors.30 They further intensify the liquid−liquid eventually lead to a compact plate heat-exchanger cum reactor
epoxidation step by using a high shear mixer for carrying out from Alfa Laval. Such strategies can be used to intensify heat
the epoxidation step. The strategies like carrying out the transfer-limited multiphase reactions and reactors.
reaction into two reactors, which is generic and useful for Intensify Mass Transfer. Many multiphase reactions are
homogeneous reactions, are not discussed here. However, the limited by mass transfer. For different multiphase reactors,
strategies like using a high shear mixer for intensifying the different intensification strategies for mass transfer are required.
liquid−liquid epoxidation reaction are discussed in the Generically, these involve reducing diffusion time scales and
following. Here, we discuss the intensification of multiphase enhancing mass transfer area. For example, one of the ways of
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intensifying gas−liquid−solid reactions in trickle bed reactors is the involvement of an additional immiscible fluid phase wherein
use of an in-line monolithic reactor.41 Here, the catalytic reactor catalysts are “immobilized”, the pseudobiphasic reaction system
is not a separate vessel but is an integral part of the pipeline in is able to provide significant enhancement in mass transport.
the form of a wash-coated monolith in which the reaction This results in higher yield and selectivity with residence time
between the predispersed gas and the liquid takes place. A of a few minutes. The approach can be extended to other
significant reduction of the equipment size can be achieved due similar catalytic reactions, incorporating both homogeneous
to much greater catalytic effectiveness in the wash-coated and heterogeneous catalysts.

■
monoliths compared to conventional trickle beds.
Pollington et al.42 demonstrate continuous-flow structured TOOLS AND EXAMPLES OF INTENSIFICATION OF
reactors for the oxidation of glycerol under mild conditions MULTIPHASE REACTIONS/REACTORS
using a gold/carbon catalyst. Compared to autoclave studies,
monolith and mesoscale structured down-flow slurry bubble The strategies discussed in the previous section are quite
column designs lead to 1 and 2 orders of magnitude intuitive and are often discussed in textbooks. There are variety
enhancement in the reaction rate, respectively. The monolith of tactics and tools that can be used to implement these
reactor offers structured contact of gas−liquid and solid strategies successfully in practice. We have cited some of the
reacting phases that results in enhanced interaction between tools and examples while describing these strategies. In this
bubbles and particles compared to a thin channel slurry bubble section, an additional discussion on tools with examples is
column where the solid phase is allowed to freely move within included. Considering the vast scope and wide variety of
the channel. Consequently, much higher selectivity to glyceric multiphase reactions/reactors, obviously only a small fraction of
acid is observed in the monolith reactor compared to the thin such tools/examples can be discussed here. We hope that
channel slurry bubble column. discussion conveys the general flavor and provides useful
Several well-known catalytic reactions such as hydrogenation, pointers for wider applications. The discussion is organized
Fischer−Tropsch synthesis, oxidation, etc. have been carried along the lines of different tools/tactics that may be useful for
out in micropacked bed reactors. Pennemann and Kolb43 implementing multiple strategies discussed in the previous
present a review on the operation of microstructured reactors section. Emphasis is on intensification of multiphase reactions/
for selective oxidation reactions. Faridkhou et al.44 present an reactors via transport processes or operating window rather
overview of mass transfer and hydrodynamics in micropacked than on catalyst and solvent design.
beds. Topologically Tubular Reactors and Continuous
For gas−liquid reactions, smaller bubbles can substantially Processing. In recent years, there has been a significant
improve gas−liquid mass transfer. For example, in a new type push in the fine and specialty chemicals sector to convert batch
of static mixing element,45,46 screens/grids are used to obtain processes to continuous processes using small topologically
interfacial areas as high as 2200 m2/m3 (compared to 200−400 tubular reactors offering substantially higher mixing and heat
m2/m3 in bubble column). These screens have also shown to be and mass transfer rates. Many books and monographs on this
very effective in promoting liquid−liquid mass transfer and area have been published besides hundreds of research papers.
reached values greater than 4 s−1 at low specific energy Several research institutes and universities throughout the
consumption rates. A similar concept is also proposed47,48 for world have programs based on continuous-flow synthesis and
generating smaller bubbles in bubble columns. manufacturing at various levels. Recently, Ranade et al.5 have
Using small channel reactors, Enache et al.49 demonstrate highlighted the use of topologically tubular reactors (so-called
intensification of homogeneously catalyzed gas−liquid reac- MAGIC tubes) with millimeter- or centimeter-scale character-
tions. Solvent-free hydroformylation of cyclododecatriene using istic dimensions. Different possible ways of augmenting mixing
a homogeneous catalyst carried out in a heat-exchange (HEx) and transport rates of such tubular reactions were also
reactor with millimeter-scale thin channels is shown to be an discussed. A simple idea like pinching of tubes has been
order of magnitude faster than that in a stirred batch autoclave. shown to improve mixing and heat/mass transfer. Pinched tube
Operation in the HEx reactor eliminates mass transfer reactors and AmAR reactors35 have been extensively used for
limitations, and the observed turnover frequency is independ- intensifying several multiphase reactions including nitration52
ent of catalyst concentration. On the contrary, the catalyst and diazotization.53 These MAGIC tubes derived from
productivity in the autoclave is a function of its concentration commercially available tubing can significantly reduce the cost
indicating mass transfer limitations. The selectivity to the of manufacturing while retaining the major advantages offered
desired monoaldehyde product is also higher in the HEx by narrow channel reactors.
reactor. Joshi et al.39 have demonstrated the use of tubular reactors
Metal-catalyzed gas−liquid reactions such as hydrogenation, for very efficient synthesis of a large family of beta amino
carbonylation, and hydroformylation are ubiquitous in crotonates. The higher heat and mass transfer rates offered by
pharmaceutical and fine chemical production. Typical gas− the tubular reactors allow reactions at much higher temper-
liquid reactions are performed in stirred batch reactors, where atures compared to conventional semibatch reactors. This
the gaseous reactant is pressurized in the headspace above the results in orders of magnitude reduction in required residence
stirred liquid phase containing the substrates and catalysts, and time compared to the batch time required with a semibatch
are often hindered by heat and mass transport limitations due system. Kulkarni and co-workers have developed continuous-
to low specific interfacial areas. Such limitations can be flow nitrations using fuming nitric acid. For example, Sharma et
mitigated through the use of micro/millireactors as platforms al.52 present intensification of nitration of o-xylene with only
for multiphase organic syntheses due to the tremendous fuming nitric acid as the nitrating agent. They demonstrate that
transport acceleration inherent in these small-scale flowing the use of a multisection reactor comprising tubes of different
systems. A triphasic segmented flow millireactor is reported50,51 diameters for different sections is more economical than a
for intensifying metal catalyzed gas−liquid reactions. Despite reactor comprising a single tube size.
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Tonkovich and Deshmukh54 have intensified the hydro- system is used for removing most of the phase transfer catalyst
cracking process for conversion of solid wax (typically the from the desired organic effluent stream while reducing the
C20+ fraction of the FT hydrocarbon product, produced in a amount of extraction solvent required.
Velocys microchannel reactor) to produce diesel and other Jeong et al.63 have intensified transformation of natural
liquid fuel products. Process intensification was demonstrated lignocellulosic biomass resources by developing an integrated
with an order of magnitude increase in catalyst productivity, 10 continuous two-step microfluidic system as a platform for direct
to 30 h−1 WHSV. The flow regime of the gas−liquid interaction conversion of fructose to diverse furan chemicals with excellent
was tailored to meet the requirements of a thin liquid film and yields. A sequential two-step process is utilized to complete the
enhanced productivity per unit catalyst weight. Despite the high dehydration of fructose in the surface acid catalyst followed by
WHSV, complete conversion of the solid hydrocarbon fraction four types of HMF conversion in a binary or ternary phase with
was obtained, and varying the feed WHSV is shown to have an magnetic-based heterogeneous catalysts using residence time of
influence on the final fuel product. Operating conditions can be few minutes to one hour. This transformation platform was
carefully selected to obtain a tailored fuel product. extended to ternary oxidation and hydrogenolysis reactions in
The application of various reaction conditions in micro- the tube-in-tube system for the production of DFF and DMF.
reactors using segmented flow can dramatically increase the In particular, the supported catalysts on the magnetic Fe3O4
reaction rates for a simple biphasic hydrolysis.55 The approach particles enabled easy positioning of an appropriate amount of
is effective in intensifying homogeneous reactions such as catalyst at the inner wall of the microchannel using an external
diazotation/Heck reaction as well. Continuous processing is magnet. This approach appears to be promising for trans-
also found to be effective in intensifying photochemical forming natural lignocellulosic biomass resources to meet
reactions relevant to organic synthesis, materials, and water industrial requirements.
treatment.56 Heitmann64 has presented process intensification work at
Damm et al.57 show high-temperature continuous-flow Clariant and highlighted that the work has enabled the design
synthesis of adipic acid from cyclohexene, cyclohexanol, and of a modular container-based (pilot) plant for intensified
cyclohexanone using aqueous H2O2 and tungstic acid as the continuous production processes. A flexible modular container
catalyst without using any phase transfer catalysts (PTCs). The plant is currently being engineered for performing amidation
absence of PTC greatly simplifies downstream processing. The and esterification reactions. Modular container plants can create
intensified process based on H2O2 potentially offers an opportunities to change the way of thinking about new
attractive way of manufacturing adipic acid without N2O processes and new production facilities besides offering
emissions (as in conventional process). Oxidation using air or advantages in terms of safety, efficiency, and product quality.
oxygen are often limited by mass transfer effects that can Continuous reactors have also facilitated intensified and safe
adversely affect reaction kinetics and selectivity or lead to production of hazardous reactions and reagents. Singh et al.65
irreversible decomposition of a catalyst. There is also a have developed a continuous zero exposure system for
possibility of formation of flammable mixtures of oxygen and chloromethyl methyl ether chemistry involving a carcinogenic
solvent vapor. Therefore, despite showing versatility and reagent. It relies on a novel membrane-free SiNWs micro-
promise on a laboratory scale, these aerobic oxidations are separator to allow for the separation of low boiling chemicals by
not widely used in specialty chemicals and the pharmaceutical simple heating in a continuous-flow manner. This total process
sector. Recent advances in continuous processes using small concept including an integrated system and procedure can be
diameter tube or plate reactors are expected to change this. easily extended to other carcinogenic, explosive, toxic, or
Gutman et al.58 developed a continuous-flow N-demethylation noxious regents. Movsisyan et al.66 report recent examples of
with molecular oxygen as the oxidant. The catalytic oxidative hazardous reactions successfully carried out in continuous-flow
demethylation with molecular oxygen offers an atom-economic reactors. As demonstrated in this review, new advances in
and environmentally benign alternative to traditional proce- reactor technology make hazardous chemistry accessible.
dures. Gemoets et al.59 have reviewed continuous-flow liquid Karande et al.67 review microreactors for biocatalytic
phase oxidation chemistry in microreactors using oxygen, applications. During the past decade, there has been a rapid
hydrogen peroxide, ozone, and other oxidants. Relevant mass rise in integrating microfluidic reactors and biocatalytic
and heat transfer phenomena are discussed to facilitate reactions for various applications. The combination of
judicious choices for a suitable reactor. Besides the safety miniaturized technologies and microfluidics allows coupling of
aspects, the scale-up potential is also described. Erdmann et scale- and time-dependent phenomena for bioprocess intensi-
al.60 report the first continuous cross-dehydrogenative homo- fication. Dimensionless numbers are discussed, which help
coupling of an unactivated arene using oxygen as the sole identify rate-limiting steps and offer opportunities to enhance
oxidant. Use of microreactor technology enables operations at the overall reaction performance in solid−liquid biocatalytic
elevated temperatures and pressures with significant reduction reactions. This integrated concept is realized in a case study
in required residence time.61 based on the biocatalytic conversion of styrene to (S)-styrene
Peer et al.62 report intensification of biphasic alcohol oxide using catalytic biofilms.
oxidation with hydrogen peroxide using a solvent-free It is of course possible to intensify multiphase reactors by
continuous reactor with in-line separation of the tungsten converting batch mode to continuous mode even without using
polyoxometalate catalyst and phase transfer catalyst from the tubular reactors. For example, van Alsten et al.68 have
product. Zinc-substituted polyoxotungstate in combination intensified a hydrogenation reactor by making it continuous
with the selected phase transfer catalyst drives the oxidation using two stirred tank reactors in series. A dinitro intermediate
reaction to completion within a short residence time (5−10 in a smoking cessation drug is reduced in a two-reactor
min). Corning flow reactors with in-line membrane-based continuous stirred tank train to the diamine product. The two
liquid−liquid extraction units at the reactor outlet are used for reactors operate within different regimes: The upstream reactor
scale-up. A three-stage countercurrent liquid−liquid extraction exhibits hydrogen mass transfer limited behavior, and the
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Figure 3. Some examples of enhancing interphase contact: (a) Three levels of porosity reactor (van Hasselt et al.130). (b) Siphon reactor (Gelhausen
et al.84). (c) Segmented reactor (Liedtke et al.87).

downstream reactor shows substrate concentration limited external absorber was used to contact gas and liquid. Similarly,
behavior. By manipulating reaction conditions in the two Tan et al.72 have intensified catalytic hydrogenation of
continuous reactors (catalyst, temperature, and substrate ethylanthraquinone by passing the gas−liquid microdispersion
concentration), significant improvements over conventional system through a packed bed reactor. Values of two orders of
batch processing are achieved. Recently, Rode et al.69 have magnitude of the overall volume mass transfer coefficient
converted batch hydrogenation of nitrobenzene to para-amino (compared to the conventional trickle bed reactors) were
phenol to a continuous process with significant enhancement in achieved in the microdispersion reaction system.
productivity. Another way of intensifying gas−liquid reactions is instead of
Interphase Transport Rates. It is obvious that enhancing sparging gas into a liquid phase is to significantly enhance gas−
the interphase contact will improve transport rates and liquid mass transfer by spraying liquid droplets into a gas phase.
therefore intensify multiphase reactions/reactors. Several differ- Subramanian et al.73 have disclosed such a spray reactor for a
ent ways and ideas have been developed for intensifying selective oxidation process. This involves introducing small
interphase contacts. These may include reduction in character- droplets of liquid reaction mixture having oxidizable reactant,
istic dimensions, enhancing local energy dissipation rates, use of catalyst, and solvent into a reaction zone containing oxygen and
spatially or temporally periodic flows, etc. It must, however, be diluent gas at a suitable reaction temperature and pressure.
mentioned here that intensifying mass transfer will not Several other new types of reactors have been proposed to
necessarily lead to performance enhancement all the time. intensify transport rates and therefore multiphase reactions/
Sometimes you may need an optimal value of mass transfer to reactors. Some of these such as monolith reactors and
get better selectivity. topologically tubular reactors were mentioned earlier. Grase-
This is illustrated by an example discussed by Lohokare et mann et al.74 reported a modified bubble column staged by
al.70 In this example, the liquid phase reactant (A) is structured catalytic layers with integrated crossflow microheat-
hydrogenated in the presence of a catalyst to give partially exchangers (HEX) (Figure 4d). The HEX integrated within a
hydrogenated liquid phase molecules of B and completely staged bubble column reactor (SBCR) with catalytic layers
hydrogenated molecule C. B is the desired product. The made of Pd/ZnO on sintered metal fibers showed a high
selectivity toward B was maximized by operating the reactor in specific productivity in the solvent-free hydrogenation of 2-
a mass transfer controlled regime by realizing an appropriately methyl-3-butyn-2-ol. Despite the observed influence of external
low value of mass transfer coefficients (kLa). Intensifying mass mass transfer on the overall catalyst performance, the SBCR
transfer in this case will lower selectivity toward B. An optimal productivity was several orders of magnitude above the values
value of the mass transfer coefficient was realized by using an obtainable in conventional reactors.
external loop gas lift reactor that can keep a catalyst suspended Rehm et al.75 developed a microstructured falling film reactor
at lower values of gas superficial velocity (and therefore at lower for the dye-sensitized photochemical conversion of 1,5-
values of gas−liquid mass transfer coefficient) than a conven- dihydroxynaphthalene to juglone. This continuous-flow micro-
tionally used stirred or bubble column slurry reactor. reactor enables the efficient contacting of a gas and a liquid
There are of course several cases, where intensifying mass phase in combination with external irradiation by high-power
transfer or heat will enhance reaction/reactor performance. LED arrays. Two sensitizers were used for the photochemical in
Some ideas for realizing such enhancement in transport rates situ generation of singlet oxygen as a key step in the synthesis
are discussed in the Intensifying Multiphase Reactors section. of the natural product juglone. The dye-sensitized activation of
Some more examples and tools are discussed here. One of the molecular oxygen offers an important strategy to incorporate
ways of intensifying multiphase reactions/reactors is separating oxygen into molecules under mild reaction conditions. The
the reaction and mass transfer step and independent intensified gas−liquid contacting and uniform irradiation
intensifying strategies for these two operations. For example, offered by a falling film reactor offer an attractive way to
Otterstatter et al.71 have used an absorber−fixed bed reactor implement this in practice. Use of thin plate photoreactors
combination for intensifying oxidative esterification. Instead of (rectangular chambers illuminated from both sides) have
relying on gas−liquid mass transfer in a trickle bed reactor, an yielded significantly higher productivity of microalgae com-
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Figure 4. Some examples of intensified reactors: (a) Rotor-stator spinning disk (Visscher et al.77). (b) Pinched tube reactor (Sharma et al.38). (c)
Cavitation reactor (Ranade et al.98). (d) Structured bubble column reactor (Grasemann et al.74).

pared to conventional shallow raceway ponds. Possible than in the region with the liquid film on the rotor. This reactor
synchronization among random cell motion, the intrinsic has a good potential for scaling up as gas and liquid can be co-
rate-limiting steps for photosynthesis, and the time scale for fed from one rotor-stator unit to another without the need for
photon harvesting may allow further possible enhancement in redistribution of the gas.
productivity of such thin photobioreactors.76 Subramanian et al.80 and Harting et al.81 discuss an inclined
Several new reactors concepts such as three levels of porosity rotating fixed bed reactor for process intensification of
reactor (Figure 3a) have been proposed for intensification of heterogeneous catalytic multiphase reactions. The basic idea
multiphase reactions/reactors. Introducing new reactor con- of the new concept is to superimpose reactor inclination and
cepts in process industries is a lengthy process. Industry is rotation. The superimposed rotation of the inclined reactor
reluctant to introduce novel chemical reactor types in existing results in a catalyst wetting intermittency through periodic
processes when replacement is not essential. Many of the new immersion of the catalyst packing into the accumulated liquid
reactor concepts therefore remain at the laboratory scale. phase. Several advantages such as periodic refreshment of the
Besides the topologically tubular reactors and their different liquid at the catalyst surface and product removal, efficient
versions as the Amar Reactors mentioned earlier, there are transfer of the reaction heat to the liquid, improved access and
many new concepts relying on rotating components. These transfer of the gas phase to the drained catalyst section, and less
reactors essentially rely on centrifugal forces for intensifying crucial role of the gas−liquid distributor due to forced flow
transport rates. Visscher et al.77 provide a review of the current pattern may be foreseen. Dashilborun et al.82 present a low
state-of-the-art in the field of rotating reactors. Their main shear rotating reactor concept that promises more flexible
advantages and disadvantages are presented, including the adjustment of pressure drop, liquid saturation, liquid residence
typical operational conditions (residence time, rotational speed, time, and back-mixing at constant flow rates. The implementa-
energy consumption). tion of such a reactor concept will, however, increase
The rotor-stator spinning disc reactor (rs-SDR, Figure 4a) is complexity of operation and will require significant additional
one such multiphase reactor that aims to intensify transport investments. The additional complexity and costs have to be
processes by applying centrifugal forces and high-shear counterbalanced by enhanced performance.
conditions. It combines the features of a classical spinning One of the other strategies proposed for enhancing transport
disk with a liquid film on the rotor78 and those of a rotor-stator rates in trickle bed reactors is use of periodic flows. Dietrich et
spinning disk reactor.79 In this new configuration, gas and al.83 have recently shown that performance of a trickle bed
liquid are co-fed through an inlet in the top stator. It is shown reactor for reactions limited by the mass transfer of the gaseous
that gas−liquid mass transfer mainly takes place in the reactant can be improved by modulation of the hydrodynamics.
dispersed region between the rotor and the bottom stator, It was recommended to realize a higher proportion of the void
and the volumetric mass transfer rate is up to 6 times larger channels with vigorously fluctuating values of the liquid hold-up
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for intensifying performance. It is also possible to use spatially magnetic fields, and high gravity fields has been identified as a
nonuniform distribution instead of temporally nonuniform key approach for process intensification.89 Stefanidis and
distribution of liquid to realize similar intensification. Care has Stankiewicz90 give a broad overview of alternative energy
to be taken, however, to ensure that macroscale maldistribution sources for process intensification. While there are a few
does not arise in the process. They have reported more than examples of commercialization of alternate energy sources,91
150% enhancement in reaction rates via this strategy. widespread industrial adoption of these energy sources closely
Gelhausen et al.84 further modified this concept by proposing depends on the robustness, safety, flexibility, and capital and
a novel concept, referred to as the “Siphon Reactor” (Figure operating costs. Here, we discuss a few key examples.
3b). This reactor comprises a fixed catalyst bed in a siphoned Heating techniques such as microwave, ultraviolet, and other
reservoir, which is periodically filled and emptied. This serves to electromagnetic processing methods deliver more useful heat to
alternate liquid−solid and then gas−liquid mass transfer the product reducing waste. They also offer control of
processes. By manipulating the duration of each phase, mass additional process parameters such as electromagnetic
transfer can be harmonized with the reaction. Residence time frequency, energy input, and spatial extent making them
experiments demonstrate that, in contrast to periodically more flexible. As the interaction of electromagnetic energy with
operated trickle bed reactors, the static liquid hold-up is matter varies from material to material, electromagnetic
exchanged frequently and uniformly due to the complete processing techniques can enable entirely new or enhanced
homogeneous liquid wetting. Periodic operations have also manufactured products and have been widely employed in
been suggested for intensifying other reactions/reactors. For chemistry as an energy source. Ramirez ́ et al.92 describe
example, Nikolic et al.85 have shown periodic operation with ethylene epoxidation in microwave heated structured reactors.
modulation of inlet concentration and flow rate for improving They use a catalyst that also acts as a MW susceptor. By rapid
reactor performance. They have illustrated this with an example selective heating of the catalyst, significant energy savings can
of a hydrolysis reaction of acetic anhydride. be achieved. Benaskar et al.93 give a cost analysis of production
Trickle beds also suffer from plugging by fine particles in of 2-acetoxybenzoic acid as aspirin and 4-phenoxypyridine as an
liquid feed. Hamidipour and Larachi86 developed a strategy antibiotic precursor in Vancocin production using a combina-
based on modulation of electrical conductivity in kaolin/ tion of microprocessing and microwave heating. They
kerosene suspensions for countering plugging of trickle bed emphasize the need to approach process design in a holistic
reactors/hydrotreaters. The suspension stability was remarkably manner rather than focusing only on the reaction. The advent
enhanced through ON−OFF concentration modulation of an of tailored magnetic nanoparticles (MNP) has opened a whole
electrolyte-based kerosene conductivity improver and resulted
new avenue of exploiting magnetism for intensifying multiphase
in an efficient bed-cleaning strategy under operating conditions.
reactions and reactors. Boroun and Larachi34 list various
Periodic additions of the conductivity improver enabled fines
opportunities and challenges in utilizing MNPs for intensifica-
and deposits to gain momentarily large and similar electrical
tion. Cravatto et al.94 describe use of sound energy for
charges undoing, or impeding, multilayer deposition. The
intensifying catalytic reactions in water, assisted by ultrasound
strategy was shown to be effective in mitigating deposition and
and/or hydrodynamic cavitation. Cavitational implosion
in preventing filtration-induced flow maldistribution
One may also think of providing a nonstochastic micro- generates mechanical and chemical effects such as cleaning of
reactor alternative to the conventional trickle bed reactor. the catalyst surface and formation of free radicals by sonolysis
Liedtke et al.87 have demonstrated the enhancement in solid− of water. They present an overview of sonochemical reactions
liquid mass transfer in small diameter segmented flow reactors in water (oxidation, bromination, aza-Michael, C−C couplings,
(Figure 3c). They demonstrate that slug length and particle size MCR, and aldol reactions) for furthering the progress of
(as long as particles are bigger than 50 μm) have no influence organic synthesis using harmless and greener sound energy.
on mass transfer. The mass transfer coefficient depends mainly Chakma and Moholkar95 have demonstrated intensification of
on overall flow velocity and an adequate circulation of solid degradation of azo and nonazo dyes using sonochemical
particles in the liquid phase. For well-suspended particles, methods. Gaikwad and Gogate96 demonstrated the use of
higher Sherwood numbers up to 8.75 could be realized. For ultrasound-assisted production of biodiesel using heteroge-
gas−liquid systems where the reactor could be operated at neous catalysts. Dubey and Gogate97 reported ultrasound-
higher two phase velocities, Sherwood numbers up to 15 were assisted selective O-alkylation of vanillin with benzyl chloride to
obtained. Losey et al.88 could increase the overall mass transfer form 4-benzyloxy-3-methoxybenzaldehyde. The work has
coefficient for gas−liquid absorption by more than 2 orders of clearly established a superior process for synthesis based on
magnitude (compared with values reported for traditional the use of ultrasonic irradiations with higher yields as compared
multiphase packed bed reactors) by using a microfabricated to the conventional approach. Ranade et al.98 disclose a
packed bed reactor consisting of 10 channels loaded with hydrodynamic cavitation device based on a vortex diode for a
catalyst particles. wide range of effluent treatment applications (Figure 4c).
Alternative Energy Sources. For many multiphase The use of alternative energy sources for intensification will
reactions/reactors, heating contributes significantly toward find increasing applications in the coming years. It is important
process heating requirements. Consequently, minimizing philosophically to think about possible ways of harnessing low
waste heat losses as well as recovery and use of waste heat entropy energy sources like electricity for enhancing selectivity
provide an avenue for intensification. Alternatively, instead of toward the desired product. Electrochemical technologies and
heating the environment, delivering the energy directly where it processes are still relatively untapped despite the successes for
is required improves energy efficiency significantly. Use of large processes like chlor-alkali and aluminum. Developments
selective heating techniques like alternating electromagnetic in electrochemical synthesis and methods in the last couple of
fields at different operating frequencies (microwave, ultraviolet, decades are expected to open new opportunities for intensified
plasma, ultrasound), acoustic and hydrodynamic cavitation, electrochemical manufacturing of chemicals.99
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Computational Modeling. Computational modeling can example is the methanol to olefins (MTO) reactor. The design
make significant contributions toward realizing potential of the MTO reactor is based on the FCC reactors albeit with
intensification of multiphase reactions/reactors. These compu- quite different hydrodynamics. Unlike the FCC reactor, coke
tational tools may range from molecular modeling on one hand deposition in a MTO reactor may occur over tens of minutes or
(for design and optimization of catalysts) to life cycle analysis more. Lu et al.111 have developed an efficient approach to
tools on the other hand (for selecting appropriate process model MTO reactors by coupling CRE models with CFD
routes) with reactor engineering models and computational models. With the new approach, simulated values of methanol
flow models (CFM) as intermediate levels. CFM is being conversion agreed much better than those obtained with
increasingly used for intensifying multiphase reactions/reactors. simpler models (like CSTR model). Using this coupled CRE−
The role of computational flow modeling for enhancing reactor CFD approach, it was possible to carry out optimization of an
performance has been discussed extensively by Ranade.100 industrial MTO reactor based on detailed CFD simulations.
Some examples of using chemical reaction engineering as well Reaction engineering and CFD models are also often used to
as computational flow modeling for intensifying multiphase optimize degree of back-mixing and transport rates for
reactions/reactors are briefly mentioned here to illustrate the intensifying gas−liquid reactions in bubble columns and
potential of this tool. reactor−separators. For example, Chaudhari et al.112 used
Computational models have been extensively used for CFD models to quantify back mixing in bubble columns. The
enhancing intensification of fixed bed reactors. These may model was then used to design internal baffles to reduce back
range from using reaction engineering models to intensify mixing for realizing enhanced productivity. Similar sectionalized
reactions or regeneration of fixed bed reactors to using bubble columns were also used to enhance selectivity of
computational fluid dynamics (CFD)-based models of flow, monochloroacetic acid in a continuous chlorination bubble
heat transfer, and reactions around catalyst pellets to optimize column reactor. Lohokare et al.70 used reaction engineering and
shapes and sizes of pellets. For example, Hou et al.101 used CFD models for optimizing an external loop gas lift reactor.
computational models for optimization of a packed bed reactor Darda and Ranade113 used reaction engineering models for
carrying out the Sabatier reaction system. They obtained a simulating a reactive−distillation process for manufacturing
significant reduction in bed length (220 to 150 mm) and isophorone. The operations of an isophorone reactor were
pressure drop (2.62 to 1.64 kPa) for the same hydrogen optimized using the model for realizing enhanced selectivity
conversion by designing a concurrent preheating using the toward isophorone. Ranade et al.109 have used computational
model. This reflected significant advantages considering space models to optimize the performance of a reactor−separator for
applications of this reaction. Girotra and Ranade102 used cases where reactants and products are in vapor phase while
relatively simple models to intensify low temperature reactions occur in liquid phase with a homogeneous catalyst.
regeneration of a coked fixed bed reactor. The coked reactors Similar strategies were used to enhance the performance of a
are usually regenerated by gasification using air or oxygen dimethyl carbonate (DMC) reactor using a sectionalized
mixed with diluents like steam, nitrogen, or carbon dioxide. horizontal bubble column reactor.25 In this case, a stripping
Because of an exothermic coke combustion reaction, temper- agent was used to enhance selectivity toward DMC.
ature rise in the reactor is of primary concern. Girotra and Computational models have also been extensively used for
Ranade102 used the computational models to develop optimal intensifying reactions in stirred tank reactors.100,114 One
regeneration protocols that will minimize regeneration time example is cited here: Patwardhan et al.115 simulated a large
(down time from the manufacturing perspective) and energy industrial oxidation reactor using CFD. The CFD model gave
requirements. an adequately accurate prediction of the residence time
CFD models have been extensively used for eliminating distribution of the industrial-scale reactor. The computational
maldistribution in fixed bed reactors. For example, Ranade103 model was validated using the measured gas hold-up
has used the CFD model to minimize maldistribution by distribution in the industrial scale reactor (measured using
designing variable resistance support plates for a radial flow gamma ray tomography). The model was then used to identify
fixed bed reactor for isomerization. Unlike the bed-scale bottlenecks of the existing reactor. Several intensification
models, particle-resolved CFD simulations, where flow around strategies were involved and computationally investigated.
individual particles is simulated, can provide insights into The shortlisted solutions were implemented in the plant,
interactions of heat and mass transfer with chemical reactions which resulted in substantial monetary benefits. Many such
occurring on catalyst surface. Dixon et al.,104 Wehinger et al.,105 examples unfortunately do not get published or even patented.
and Karthik and Buwa106 used particle-resolved CFD models Computational models have also been used to intensify a
for understanding and improving reforming reactors. While variety of nonconventional reactors used by sectors other than
these simulations are computationally intensive, they provide process industries. For example, Ranade and Gupta116 have
insights that can be harnessed for intensification. demonstrated the use of CFD models to enhance the
Performance of fluidized bed reactors have been significantly performance of pulverized coal-fired boilers. Mujumdar and
enhanced using CFD models. For example, Ranade107 used Ranade117 have shown how reaction engineering and CFD
multiple computational models to redesign spargers and models can be coupled to enhance performance of cement
internals for regenerators of fluid catalytic cracking (FCC) kilns. Similar models were also used to intensify kilns used for
reactors to intensify regeneration process. Similarly, Nayak et manufacturing hydrofluoric acid (HF). Kuan and Witt118 have
al.108 demonstrate the use of CFD models to design improved used computational flow models to optimize supersonic
oil injection nozzles in FCC reactors. CFD models were also quenching of magnesium vapor for developing a carbothermal
shown to significantly enhance throughput of fluidized bed oxy- reduction process for magnesium. The model was validated
chlorination reactors by improving mixing and sparger grid using steam condensation data and applied to study supersonic
design.109 Lu et al.110 have shown that multiscale CFD models quenching of magnesium vapor in a laboratory-scale setup. The
could be used to optimize isoparafin reactor. Another recent model was used for designing and up-scaling processes that
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eventually resulted in CSIRO’s MagSonic carbothermal inherent safety practices. For example, certain intensification
magnesium technology. technologies require higher energy inputs or to be operated at
In their comprehensive review on multiphase reactors, Joshi higher temperatures. The processes may be more complex or
and Nandakumar119 suggest a paradigm shift by using high call for a more complex control system. These aspects call for
fidelity computational models for design and scale up instead of due attention to process safety and integrate those consid-
physical modeling and pilot plant testing. In order to achieve erations while evolving intensification strategies. Intensification
this, the computational models need to be capable of a priori of multiphase reactions and reactors may also significantly
prediction of process performance. Current computational enhance inherent process safety by reducing inventory of
models, especially for multiphase flows, rely on closure models hazardous materials and by realizing enhanced transport rates.
for realistic predictions. Many of the closure models (such as Etchells128 has discussed some examples of how process
drag) are derived from empirical correlations, and careful intensification has, or might have, improved safety. Some of the
validation is required limiting their ability as all-encompassing issues related to process safety that need to be considered while
design tools. The reliability of the computational models can be devising intensification strategies are also discussed.
improved by using the uncertainty quantification approach.120 At this juncture, it would be useful to re-examine the lessons
Reactions coupled with direct numerical simulation do away learned from our experience of intensification of multiphase
with the closure models but require enormous computational reactions and reactors. One of the most important lessons from
resources, and only simple and small geometries can be our experience is that it is extremely important to correctly to
simulated. Nevertheless, a well-calibrated and validated CFD the following:
model can be used to examine various designs and operating • identify and pose the problem
conditions and can substantially reduce the pilot-scale testing
and provide a reliable scale up. • analyze various key issues limiting rate of reactions/
There are numerous examples of applying computational performance of reactor under consideration
models for designing reactors and reactor internals for • select an appropriate intensification strategy with due
intensifying multiphase reactions. Several complex configura- consideration to process safety
tions of microreactors have been developed using these models. • collect relevant reaction and reactor engineering data and
The bottleneck in realizing these configurations is manufactur-
use computational models and develop implementation
ing processes. The manufacturability of reactors that incorpo-
rate new intensified process concepts can have a significant protocols
impact on their market and industry success.121 The new • implement the strategy in practice
advances in 3D printing technology122 can be harnessed to For any engineering discipline, the so-called Occam’s razor
optimize shapes of process equipment without concerns about always provides guidelines for selecting an appropriate strategy.
manufacturability. This opens up new tools for optimization. Occam’s razor can be stated as, “it is futile to do with more,
For example, Tao et al.123 present a hybrid optimization what can be done with less”. There are many instances where
method aiming to design the flow channel shape and achieve simple intensification strategies may provide elegant and
the desired objective. Similar approaches can be used to adequate solutions. It is, however, important to emphasize
automate optimization of reactor shapes and internals and their here the maxim that says “one should always try to make things
subsequent manufacturing via 3D printing technology. The as simple as possible (following the Occam’s razor) but not
technologies for additive manufacturing are growing at an simpler”. It may be necessary to develop more intricate
enormous pace. It is possible to use materials that can intensification strategies dependent on out of the box thinking.
withstand high temperatures and pressures and obtain micron- Distinguishing the “simple” and “simpler” intensification
scale resolution. Bikas et al.124 give a critical review of additive strategies is often the key for successful implementation.
manufacturing methods. Thompson et al.125 provide an Some of the examples cited here such as using MAGIC tubes
overview of trends, opportunities, considerations, and con- are useful to understand this distinction.
straints. Techniques such as stereolithography, metal cold The other important lesson is that it is beneficial and more
spraying, or electrodeposition are compatible with a large efficient to develop intensification strategies in a hierarchical
number of catalytic metals and can be used to mass produce way. It may be useful to undertake a stage-wise development,
tailored reactors. For example, Avril et al.126 demonstrate a validation, and implementation. Adequate and judicious use of
series of continuous-flow hydrogenations of alkenes and computational models is always helpful in realizing intensifica-
carbonyls using a tubular reactor with 3D-printed static mixers. tion in practice. Advances in software technology, enhanced
The static mixers are coated with a catalytic metal layer, which computing resources, and integrated tools encompassing CFD
can be inserted into standard stainless steel reactor tubing. codes with physical and chemical property databases to process
Monaghan et al.127 report development of 3D-printed lab-on- or reactor simulation tools allow evaluation of changes in the
chip devices that feature integrated optics. reactor hardware on overall process performance in the near
Discussion. There may of course be several other ways of future. Such capabilities will significantly influence intensifica-
intensification that are not touched upon here. We, however, tion strategies and the practice of tomorrow.
believe that the tools and examples discussed here provide The advances in manufacturing technologies have signifi-
useful pointers for wider applications. Here, we would like to cantly enhanced realization of complicated reactor geometries.
discuss few other relevant points related to intensification and However, uncertainty in scale-up can hinder adoption of new
share some of the lessons from our experience. technology and commercialization of efficient processes.
One of the important points, which must be kept in mind Powell129 has discussed the challenges in scale-up at length
while developing intensification strategies for multiphase from an industrial perspective. The key to a reliable scale-up lies
reactions and reactors, is related to process safety consid- in developing advances in computational models that can
erations. Conflicts may arise between intensification and some provide reliable and accurate a priori predictions.
3618 DOI: 10.1021/acssuschemeng.6b03017
ACS Sustainable Chem. Eng. 2017, 5, 3607−3622
ACS Sustainable Chemistry & Engineering Perspective

The overall approach of identification of the rate-limiting Dr. Ranjeet P. Utikar is senior lecturer at Curtin University, Australia.
step and removing the identified limitations often leads to Dr. Utikar’s work in the area of industrial flow modeling has resulted in
sequential steps of intensification of intrinsic chemical reaction direct measurable benefits to the chemical, environmental, and auto
rate and intensification of transport rates. If these two ways are industries and has been incorporated into proprietary commercial
explored together, a true synergy can be realized and such modeling and design systems. He has worked with several multina-
synergistic intensification can lead to leapfrogging in tionals on modeling, troubleshooting, and optimization of various unit
productivity. Finally, efficiencies and intensification avenues operations, as well as process development. Dr. Utikar has previously
need to be sought in all areas of a process and not just on worked at CSIR-NCL, University of Twente, and DSM Netherlands.
reactions and reactors for enhancing sustainability of the He is also an entrepreneur and is a founder of two companies:
chemical industry. Tridiagonal Solutions and Vivira Process Technologies Pvt., Ltd.

■ SUMMARY
The returns or benefits offered by intensification of multiphase
reactions and reactors often far exceed the cost of required
investments. We have made an attempt to provide some
insights on strategies for and some examples of intensification
of multiphase reactions and reactors. Intensification may be
realized by using basic ideas of chemistry and catalysis to make
modifications of existing reactor designs or operating protocols.
The discussion will hopefully help to select appropriate
strategies for intensification. The overall methodology of
achieving objectives of performance enhancement is discussed
with the help of examples. An attempt is made to evolve general
guidelines, which may be useful for solving practical
intensification projects. It is our experience that every time Dr. Vivek V. Ranade is a Professor of Chemical Engineering at the
our intensification efforts led to some benefits in practice it School of Chemistry and Chemical Engineering of Queen’s University
strengthened our interest and encouraged us to explore further Belfast. His research focus is on sustainable energy, water, and fine and
intensification opportunities. specialty chemicals. Previously, he led the chemical engineering and
Adequate attention to key issues mentioned in here and process development at National Chemical Laboratory, Pune. He has
creative use of strategies will make significant contributions in contributed significantly to chemical engineering science and practice
enhancing chemical reactor engineering. The field of by developing performance enhancement solutions, software products,
intensification of multiphase reactions and reactors is and fluidic devices for a variety of applications, which are
continuously evolving and being continuously updated. New commercialized, and by developing new insights and methodologies
advances may be assimilated using the framework discussed for MAGIC (modular, agile, intensified, and continuous) processes
here. We hope that this will further stimulate development of and plants. He has also worked at TUDelft, University of Twente, and
intensification strategies for multiphase reactions and reactors. ETH Zurich and cofounded two technology companies: Tridiagonal

■ AUTHOR INFORMATION
Corresponding Authors
Solutions and VIVIRA Process Technologies.

■ ACKNOWLEDGMENTS
*E-mail: r.utikar@curtin.edu.au (R.P.U.). We had contacted numerous researchers working in the area of
*E-mail: V.Ranade@qub.ac.uk (V.V.R.). intensification of multiphase reactions and reactors. We are
ORCID grateful to these researchers who provided their feedback and
Vivek V. Ranade: 0000-0003-0558-6971 suggested excellent intensification examples.
Notes
The authors declare no competing financial interest. ■ REFERENCES
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3622 DOI: 10.1021/acssuschemeng.6b03017

ACS Sustainable Chem. Eng. 2017, 5, 3607−3622