catalysts

Review
An Overview on the Production of Biodiesel Enabled by
Continuous Flow Methodologies
Claudia Carlucci

CNR-Institute of Nanotechnology (CNR-NANOTEC), c/o Campus Ecotekne, Via Monteroni, 73100 Lecce, Italy;
claudia.carlucci@nanotec.cnr.it

Abstract: Biodiesel was produced via transesterification reaction catalyzed by acids, bases, enzymes
or supercritical fluids. The catalysis was homogeneous or heterogeneous and the process could
be carried out in batch or using a continuous flow process. Microreactors allowed us to obtain
better control of the experimental variables, such as temperature, pressure and flow rate, carrying
out the reactions in safe conditions, avoiding exothermic and dangerous processes. The synthetic
methodologies in continuous flow, combined with other technologies as microwave irradiation or
ultrasounds, led to complete automation of the process with an increase in efficiency, also applicable
on an industrial scale.

Keywords: biodiesel; flow chemistry; microreactors; microwaves; ultrasound

1. Introduction
The main energy sources are represented by fossil fuels as coal, natural gas and oil.
Therefore, limited availability has prompted researchers to seek alternative and renewable
energy sources, such as solar, wind, hydro, nuclear and biomass energy. In particular,
Citation: Carlucci, C. An Overview biomass presents major advantages compared to sun, wind and hydro energies in terms of
on the Production of Biodiesel
operations and maintenance costs. The first two, in fact, represent variable and intermittent
Enabled by Continuous Flow
sources of energy; the last can be generated only in a few strategic points close to water
Methodologies. Catalysts 2022, 12,
sources. Biodiesel is an energy source that has received great attention in recent decades,
717. https://doi.org/10.3390/
with very similar properties compared to conventional diesel, but with the advantages of
catal12070717
being renewable, biodegradable, less toxic and environmentally friendly [1].
Academic Editors: Changwei Hu and Biodiesel is safer, contains fewer sulfur compounds and presents a higher flash point,
Mohammad Mozahar Hossain does not produce any carbon dioxide emission, emits 80% less hydrocarbons and 50% less
Received: 26 May 2022
toxic particles, does not contain petroleum residues and can be mixed with conventional
Accepted: 27 June 2022
diesel. In particular, a blend containing 80% petroleum and 20% biodiesel (B20) is used in
Published: 29 June 2022
diesel engines without significant modifications [2].
The choice of raw materials is one of the most important aspects to consider in the
Publisher’s Note: MDPI stays neutral
production of biodiesel, with a considerable contribution to the cost of production. In
with regard to jurisdictional claims in
Europe, the most used raw material is rapeseed oil. The first-generation materials are
published maps and institutional affil-
mainly edible crops. The second generation use cooking oils, animal fats, pork lard and
iations.
beef tallow. The third generation, on the other hand, are algae. In particular, microalgae
play a very important role in the production of biodiesel, with numerous advantages, such
as a higher oil content compared to other crops and eco-friendliness. The algae have no
Copyright: © 2022 by the author.
environmental impact, requiring a small area with a rapid growth and undeveloped lands
Licensee MDPI, Basel, Switzerland. to be cultivated without requiring the use of pesticides [3].
This article is an open access article On the other hand, the use of macroalgae for producing biofuels relies on the availabil-
distributed under the terms and ity and huge seasonal patterns. The biomass of macroalgae differs by species, geographical
conditions of the Creative Commons region and season, and by yields and product types generated, which depend on the
Attribution (CC BY) license (https:// process technology [4].
creativecommons.org/licenses/by/ Biodiesel production is carried out through various processes. In direct mixing, the
4.0/). raw material is mixed with diesel. However, this process presents disadvantages such as a

Catalysts 2022, 12, 717. https://doi.org/10.3390/catal12070717 https://www.mdpi.com/journal/catalysts

Catalysts 2022, 12, 717 2 of 31

high viscosity and the acidic value of the final product, the content of free fatty acids (FFA)
and the formation of rubber, making it difficult to use the final product as a fuel. The use of
microemulsions involves oils mixed with an emulsifying agent, usually a short-chain alcohol.
This process, however, forms carbon deposits in the engine and causes incomplete combus-
tion. The catalytic cracking, or pyrolysis, is the catalytic transformation, in the absence of air
or oxygen, of an inedible oil or animal fat into a product with combustible properties similar
to diesel. Biodiesel is characterized by a mixture of methyl esters of fatty acids (FAME),
obtained from lipids and alcohol through a catalyzed transesterification reaction [4].
The reaction takes place between a triglyceride and an alcohol, in the presence of a
suitable catalyst, obtaining FAMEs and glycerol. The reaction is reversible, and an excess of
alcohol is necessary to shift the balance towards the production of the products. Usually, the
alcohols used are methanol or ethanol thanks to their chemical and physical characteristics
and lower cost. When the reaction is carried out, the speed of the reaction, the nature of
the reactants, the concentration, temperature, pressure and the mechanism of the reaction
are analyzed [5].
The reaction occurs in the presence of enzymes, homogeneous or heterogeneous,
alkaline or acidic catalysts, and in supercritical conditions. The process consists of three
consecutive and reversible reactions, in which triglycerides are converted into diglycerides,
then into monoglycerides, and finally into glycerol. An ester is produced in each of the
three reactions. Thus, starting from a molecule of triglyceride at the end of the overall
reaction, three molecules of esters are obtained and glycerol is produced as a byproduct
(Scheme 1) [6].

Scheme 1. General scheme of the transesterification reaction in the presence of methanol.

The transesterification, or alcoholysis, is the most widely used method on an industrial

scale due to its ease of execution, efficiency and low cost [7].
In the presence of a high content of FFA in the oil, transesterification must be preceded
by esterification, in which an alcohol reacts with an FFA with the formation of an ester [8].

2. Transesterification Reaction
2.1. Homogeneous Base Catalyzed Transesterification
The homogeneous, easily available and cheap alkaline catalyst is the most used
in the production of biodiesel, thanks to its ability to react at low temperatures and at
atmospheric pressure, allowing high conversion in a short time. However, the catalyst
presents the disadvantage of being used only with a FFA content of less than 3% (w/w)
and a water content of less than 0.05%. Otherwise, the reaction with FFA affords the
saponification, leading to the deactivation of the catalyst and a reduction in the conversion
yield of FAME [9].
The most used alkaline catalysts are NaOH, CH3 ONa and KOH. The reaction mech-
anism for base-catalyzed transesterification consists of three steps. In the first step, the
Catalysts 2022, 12, 717 3 of 31

formation of an alkoxide, a strong nucleophile, occurs. The alkoxide attacks the electrophilic
carbon of the ester group, forming an alkyl ester. The catalyst is deprotonated, while the
proton attached to the diglyceride anion until the formation of glycerol and alkyl esters
is completed [10].

2.2. Homogeneous Acid Catalyzed Transesterification

Homogeneous acid catalysis results not affected by the presence of FFA and both es-
terification and transesterification occur simultaneously. This represents a great advantage
for the use of low-cost raw materials, generally containing high concentrations of FFA. The
acid catalyst is more efficient when the amount of FFA in the oil is higher than 1% (w/w).
Furthermore, the homogeneous acid catalyst is cheaper than the alkaline catalyst, which
requires an additional step to convert the FFA into methyl esters [9].
However, the acid-catalyzed process also has disadvantages, including a slower re-
action rate, higher temperatures, a high molar alcohol/oil ratio, the separation process of
the catalysts and environmental and corrosion problems. In the first phase, the carbonyl
group is protonated; subsequently, the carbocation undergoes a nucleophilic attack by
methanol with the formation of a tetrahedral intermediate, followed by the loss of a proton.
The sequence is repeated twice with the formation of the final products, biodiesel and
glycerol. The reaction catalyzed by a homogeneous acid is about 4000 times slower than
that catalyzed by a homogeneous base. To determine whether it is more convenient to use
a basic or acid catalyst, it is necessary to evaluate the FFA content in the oil used as raw
material. Therefore, for oils containing high amounts of FFA, a two-step process is required.
In the first step, the FFA are converted into FAME with the use of acids to reduce the FFA
levels to 1% (w/w); in the second phase, transesterification takes place through the use
of bases. Esterification is a relatively slow reaction that can be sped up by using a higher
amount of acid catalyst. The disadvantage of this two-phase process is the additional phase
required to remove the catalyst in both cases [11].

2.3. Heterogeneous Base Catalyzed Transesterification

Homogeneous catalysts present disadvantages such as energy consumption, saponifi-
cation reaction, difficult separation from the reaction mixture and cleaning of the catalyst
and products. These problems are solved with the use of heterogeneous catalysts. Several
synthetic catalysts based on alkali metals (Na, K) hydroxides, alkaline earth metal oxides
(Ca, Mg, Sn, Zn) and salts impregnated on alumina have been studied. The system consists
of a solid homogeneous catalyst and two phases constituted by immiscible liquids. The
transesterification reaction catalyzes by calcium hydroxide, using methanol as a reagent. In
the first phase, there is the formation of the methoxide anion. In the second step, the attack
of the carbon of the carbonyl group by the methoxide anion occurs with the formation of an
intermediate, which rearranges in the third phase with the formation of more stable com-
pounds as the ester and the diglyceride anion. Afterwards, there is the attack of the cation
by the diglyceride anion, with the formation of the diglyceride and CaO. Then, the catalyst
is finally regenerated, and the mechanism is repeated two more times, until biodiesel and
glycerol are obtained. Heterogeneous solid catalysts, which are easily recoverable and
reusable, do not require a separation step, but they are less effective than homogeneous
catalysts. The heterogeneous catalyst reacts in a different phase, the energy and costs for
the recovery of the homogeneous catalyst are reduced and a higher yield of biodiesel and
of glycerol purity as a by-product are obtained [12].

2.4. Heterogeneous Acid Catalyzed Transesterification

The use of solid acid catalysts, such as zeolites, ion-exchange resins, sulfated metal
oxides and sulfated carbon fibers, presents several advantages. These catalysts are not
influenced by the FFA content; esterification and transesterification occurs simultaneously;
the biodiesel washing phase is not necessary; the separation of the catalyst from the reaction
medium is easier (therefore the product is less contaminated); the catalyst is regenerated
Catalysts 2022, 12, 717 4 of 31

and recycled more easily and the problem of corrosion is reduced. The heterogeneous
acid catalyst requires higher temperatures and pressures, and a higher alcohol/oil molar
ratio compared to homogeneous catalyst. However, in the case of heterogeneous catalysts,
less pollutants are produced, and production costs are reduced. However, the heteroge-
neous acid catalyst is less active and requires longer reaction times compared to alkaline
heterogeneous catalysts [13].
In recent years, the development of new catalytic strategies in the production of
biodiesel has seen an increase in the use of silica. It can be used as a support on which to
load acid sulphonic catalysts, which have shown promising catalytic activity. The function-
alization of silica nanoparticles was operated through the insertion of inert alkyl chains
(C3, C8 and C18) and active residues of propylsulfonic acid to obtain optimal amphiphilic
and catalytic characteristics [14].

2.5. Transesterification Catalyzed by Enzymes

The use of enzymes as biocatalysts in the production of biodiesel allows this method
to work in moderate conditions, significantly reducing production costs. The enzymes are
used in their immobilized form to maintain the catalytic activity without contaminating
the finished product.
Enzymes show numerous advantages such as biodegradability, reusability, simulta-
neous conversion of FFA and triglycerides into biodiesel, absence of by-products, mild
working conditions, easier separation and recovery of the product. Furthermore, reactions
such as saponification and hydrolysis are prevented and a low oil to alcohol molar ratio
is required. However, enzymes present disadvantages, such as high cost, longer reaction
time, inhibition by methanol and limited regeneration of themselves.
Enzymes require less energy compared to a process involving the use of a chemical
catalyst. Furthermore, enzymes such as lipases are insensitive to the FFA content and afford
a very pure final product. However, the glycerol produced limits the yield of the process,
as accumulated in the reactor, increasing the viscosity and deposition on the surface of the
immobilized lipase, preventing the access of the substrates to the active site of the enzyme.
Hence, the continued removal of glycerol from the reaction mixture is required but
using co-solvents the production speed enhances with the increase in the hydrophobicity
of the solvent [15].
Immobilization occurs when the enzyme is bound to a solid support, and the substrates
pass beyond that support, converting into products. Immobilized enzymes have numerous
advantages over free enzymes, such as the possibility of frequent use, favorable separation
from the solution, higher stability of the enzyme and higher purity of the products [16].
The methods of immobilizing enzymes are adsorption, covalent bond technique,
entrapment and immobilization of the entire cell [17].
Transesterification catalyzed by enzymes involves two phases. In the first, the lipase
hydrolyzed fatty acids, triglycerides, diglycerides and monoglycerides, and in the second
phase, the esterification of alcohol occurs with the release of fatty acids [18].

2.6. Transesterification in Supercritical Conditions

Supercritical fluids have intermediate characteristics between gas, such as viscosity
and diffusibility, and liquid, such as density [19].
The non-catalyzed transesterification in supercritical conditions is completed in a few
minutes. The transesterification of triglycerides with alcohol is usually a heterogeneous
reaction that occurs at controlled temperatures due to the incomplete miscibility of polar
and apolar compounds.
Under supercritical conditions, however, the mixture becomes a single homogeneous
phase, thanks to the low dielectric constant of the supercritical methanol, accelerating the
reaction, because there is no mass transfer phase that limits the reaction rate. Another
positive consequence of the use of supercritical conditions is that alcohol is simultaneously
a reagent and an acidic catalyst. In this process, the addition of water is advantageous
Catalysts 2022, 12, 717 5 of 31

because it affords easier separation of products such as glycerol, which is more soluble in
water than methanol, thus improving the yield of biodiesel [20].
However, the synthesis of biodiesel through the use of supercritical methanol presents
disadvantages, such as the high cost of the equipment due to the high temperature (>400 ◦ C)
and pressure required that cannot be used on a large industrial scale. Then, co-solvents are
added to the mixture.
This technique allows a decrease in temperature and pressure as well as the amount of
alcohol used. The conversion of biodiesel depends on supercritical conditions (temperature
and pressure), purity of the reagent (content of water and fatty acids), source of alcohol
and molar alcohol/oil ratio.

3. Effect of the Different Parameters in the Biodiesel Production

3.1. Molar Ratio
In the reaction, the stoichiometric ratio of three moles of alcohol and one mole of
triglycerides allows us to obtain one mole of glycerol and three moles of biodiesel. However,
it is necessary to use an excess of alcohol to shift the reaction towards the formation of
the products. Initially, the yield of biodiesel increases with a molar ratio of alcohol/oil
up to 10:1, while an excessive increase in alcohol inhibits the reaction between oil and
catalyst. Under supercritical conditions, a higher alcohol/oil molar ratio, up to 40:1, is
required. Therefore, the transesterification within microreactors is positively influenced by
the increase in the molar ratio, but too high a molar ratio could lead to a decrease in the
biodiesel yield, probably because the alcohol acts as an emulsifying agent which causes a
part of the glycerol to remain in the biodiesel phase. Furthermore, the molar alcohol/oil
ratio depends on the type of reactor, the reaction conditions and the catalyst used [21].

3.2. Temperature
An increase in temperature leads to an increase in the reaction rate. In this way, a
greater yield is also obtained due to the reduction in the viscosity of the oil as the temper-
ature increases, resulting in better mixing of the oil with alcohol and faster separation of
glycerol from biodiesel. However, an excessive increase in temperature leads to a reduction
in the biodiesel yield. In fact, at higher temperatures, secondary reactions occur more
rapidly than transesterification and, as a result, a decrease in biodiesel yield is achieved [7].

3.3. Content of Water and Free Fatty Acids

Water determines the saponification, causing an increase in viscosity, formation of
gels and foams and a difficult separation of the glycerol. The content of water and FFA,
in addition to determining the formation of the soap, also allows the consumption of the
catalyst, resulting in a decrease in the yield of the alkyl ester. At the same time, however,
the presence of water has a positive effect on the yield of esters when methanol at room
temperature is replaced by supercritical methanol [6].

3.4. Cosolvent
The biggest obstacle in the transesterification of vegetable oils is the immiscibility of
alcohol and oil, which significantly slow down the reaction. To overcome this problem,
it is possible to use co-solvents, as acetone, THF, isopropanol, diethyl ether or carbon
dioxide. The addition of co-solvents to alcohol solves the problem of immiscibility by
increasing the contact between alcohol and oil but increases the number of purification
processes required [21].

4. Flow Chemistry
The constant increase in the costs of the environmental impact of production processes
has given considerable impetus to the search for new methodologies that reduced energy
consumption and decreased both the use of hazardous substances and the production of
waste, promoting a sustainable development model.
Catalysts 2022, 12, 717 6 of 31

Flow chemistry, in this context, represents a valid alternative to traditional methodolo-

gies, and is strategic technology to reduce the environmental impact of chemical processes,
due to more sustainable synthetic pathways. Microtechnologies enable the achievement of
safer and reproducible reactions with a significant reduction of costs and by-products [12].
Flow chemistry finds wide application in the preparation of organic and inorganic
compounds, drugs, natural products and sustainable materials [22].
In continuous flow chemistry, the reagents are introduced into a microreactor, which
allowed us to optimize the reaction parameters such as mixing, flow rate and residence
time. It is also possible to control the temperature and pressure conditions, the use of
solvents, the stoichiometry of the reaction and the work-up operations.
The advantages of this technology are better control of experimental variables and
reproducibility; easy separation of products from by-products; an increase in the reaction
rate, since the reactants can undergo rapid heat and mass transfer, which positively affect
productivity; better control of the heat exchange, thanks to the small size of the reactor
in which the reaction takes place; and of the temperature, avoiding a dangerous and
uncontrolled exothermic process.
In general, the reaction parameters such as temperature, pressure and flow rate are
easier to control compared to the batch process. When deciding whether to use the batch or
flow-through process, several factors need to be considered.
The most important element to evaluate is the safety of the process. The presence
of hazardous materials, heat exchange and high pressures present safety risks. These
risks are greatly controlled when using a continuous flow process, thanks to the small
volumes of reagents used. Contact with dangerous and toxic substances is also limited,
making the process safer for the operator. In addition, due to the short reaction time, it is
possible to perform reactions involving reactive intermediates that could not be used in the
batch process.
The optimization of temperature and reaction time is easier in the continuous flow
process, varying the reactor temperature and controlling the reaction time by the flow rate.
Considering the liquid–liquid reactions in batches, vigorous agitation produces emulsions,
with the production of droplets which, however, are not homogeneous in size. Therefore,
when a homogeneous emulsion is required, it is preferable to use a continuous flow process.
Another factor to consider when choosing the type of process to use is the reaction
rate. To obtain fast batch reactions, the temperature is lowered and the reagent is then
added. After a short stirring, to obtain homogeneity, the reaction mixture is heated up to
the temperature at which the reaction takes place.
However, when large amounts of products are obtained, some reactions have lower
yields due to poor miscibility and mass transfer.
In the flow method, on the other hand, faster mixing and a better heat transfer consid-
erably favor the yield of the reactions. Comparing a batch and a continuous flow reactor
with the same capacity, the tube has a larger surface area compared to a batch reactor.
Therefore, in the flow reactor there is a much higher surface/volume ratio. In this way,
heat is transferred to and from the reaction mixture much faster. Furthermore, in the batch
reactor the temperature is not homogeneous, causing an easier formation of undesired
by-products.
In batch processes, the time required for the reaction is closely related to the temper-
ature, while the continuous flow process parameters such as reactor volume and mass
flow rate are crucial. Stoichiometry in the flow reactor is determined by the concentration
of the reactants and the ratio between their flow rates. In the batch process, the stoi-
chiometry is instead determined by the concentration of the chemical reagents and their
volumetric ratio [23].
In the flow process, it is possible to produce a large amount of compounds via scaling
out by running up the process for a longer time, numbering up through multireactors in
parallel and scaling up the process in larger reactors [24].
Catalysts 2022, 12, 717 7 of 31

The transport system for reagents and fluids converges the substances up to the
mixing zone before entering the reactor, where the reaction takes place. The central zone is
connected to the quenching zone, with a control of the residence time. Before the collection
system, there is a pressure regulator to obtain the high pressure required. In addition,
optional analysis and purification systems are integrated. All these parts are interchanged
and rearranged in order to obtain a large number of possible combinations.

4.1. Types of Flow

Many important chemical transformations involve multiple phases such as gas–liquid,
solid–liquid, liquid–liquid or solid–liquid-gas phases. The mixing process is very important
and allows improvements in the reaction yield. In general, in a microfluidic system, the
surface area/volume ratio increases as the reactor size decreases.
In a multiphase system, the interfacial area plays a very important role in phase
transfer, which represents a limitation in the reaction rate. For gas–liquid mixtures, bubble,
bullet or annular flows are observed in microreactors. This system is influenced by the
flow rate, viscosity and properties of the channels. Gaseous reagents are usually used in
stoichiometric excess due to poor interfacial mixing, slowing down the reaction.
The microfluidic system eliminates headspace and increases the surface/volume ratio
of the reactor. The solid–liquid reaction is a heterogeneous reaction in which the separation
process of the two phases is easier. For solid–liquid reactions, three types of bed reactors
are used. The packed bed reactor has a column or channel, completely filled with a solid,
thus limiting the movement of the particles. The liquid flow inside this reactor is a “plug
flow”, but at high flow rates, it becomes turbulent.
In a fluidized bed reactor, the particles have a free flow and are suspended in the
channel thanks to the turbulent flow of the liquid phase. The mixed reactor shows average
characteristics between the two previous types. The movement of the solid at the bottom
of the reactor is limited, while the upper layers are suspended and mixed thanks to the
liquid phase. A solid–liquid mixture important for flow chemistry is one involving a
heterogeneous catalyst [25].
In fact, it is possible to carry out the reaction and separation in a single phase using a
packed bed reactor. In liquid–liquid mixtures, the most common types of flow are laminar
and projectile, and microcircuit or tubular reactors are used. In tubular reactors, laminar
flow is created when parallel phases do not interrupt their respective laminar flows.
In tubular reactors, however, a projectile flow is most often observed. It forms when
the perpendicular phase (phase 2) obstructs the channel, causing a build-up of pressure in
phase 1. When the pressure becomes sufficiently high, a droplet detaches, and this trend
is repeated several times, forming alternating bullets in each phase. The problem of the
liquid–liquid mixture is associated with maintaining a steady flow which, consequently,
leads to a shorter residence time.

4.2. Blending
Mixing is a process that describes how two phases interact together, highly influencing
the conversion and selectivity of the reaction. The reactions carried out in flow reactors and
in batches present different mixing mechanisms which, together with the kinetics of the
reaction, determined whether the flow conditions are favorable. The Reynolds number (Re)
is used to determine the type of flow that occurs in fluids [26].
When the values of Re are lower than 2 × 103 , there is a laminar flow; values higher
than 3 × 103 , on the other hand, indicate a turbulent flow. In some cases, the appearance of
vortices generated by the instability of the flow occur, even at relatively low values of Re,
when a certain critical value of the Dean number (De) exceeds
s
dh ρudh
De = Re Re = (1)
RC µ
Catalysts 2022, 12, 717 8 of 31

where ρ is the density, µ the viscosity of the fluid, u the velocity, dh the diameter of the
channel and RC the radius of curvature. This turbulence is useful for mixing, and therefore
for transport properties [27].

4.3. Temperature
For reactions that take less than 48 h at room temperature, it is sufficient to use
moderate temperatures (<80 ◦ C) in a batch reactor to reduce the reaction time to less than
an hour. If, on the other hand, the reaction that takes place at room temperature occurs in
more than 172 h, higher temperatures are required to reduce the reaction time, and this,
in a batch process, requires the use of a high-boiling solvent. This, however, limits the
choice of solvents to be used and, therefore, complicates the course of the reaction and the
purification of the product.
For reactions that require high temperatures, the use of closed containers allows
the use of solvents with a lower boiling point, since the solvent can be heated above its
boiling point. Both when the reactions require high and low temperatures, it is still more
appropriate to use the continuous flow process due to the lower temperature gradient and
the high surface/volume ratio of the reactor.

4.4. Residence Time

Residence time is the time necessary for the fluid to pass through the reactor. Residence
time for biodiesel production varies according to the type of microreactor used. In general,
however, an increase in residence time favors a higher yield of biodiesel. Under supercritical
conditions, the residence time is reduced to a few seconds by using supercritical methanol
in the absence of the catalyst. Complete conversion of triglyceride is achieved in a residence
time of five minutes. However, when the transesterification under supercritical conditions is
carried out in the presence of a homogeneous catalyst, the complete conversion is obtained
in less than 15 s.

4.5. Structure of the Reactor

It is possible to combine several chemical reactions in sequence in one process within
microreactors. A synthesis sequence in several phases takes place in several reactors ar-
ranged linearly, with the advantage that the intermediates are not isolated, but directly
transferred to the reactor in subsequent flow. However, the synthesis sequence has to be
divided into two or more partial sequences, and between each partial sequence the product
is isolated before being carried into the next sequence [22].
A continuous flow system is divided into eight zones: a fluid and reagent conveyor,
a mixer, a reactor, a quenching unit, a pressure regulator, a collector, an analyzer and a
purification system. The control of fluid movements is important because the residence
time and stoichiometry of the reagents are regulated.
In most cases, control is obtained through a pumping flow technique, where a pressure
difference is created between the inlet and outlet unit of the reactor. Mixing is active or
passive: in the first case, the input of external energy is used to improve mixing in the
reactor; in the second, the speed is proportional to the properties of the flow, pumping
speed, and physical path through the respective mixing units. The reactor is the central
unit in which the reactions take place.
There are three main types of reactors: a loop, a coil and a fixed-bed reactor. Accurate
control of the reaction time requires an appropriate quenching procedure, otherwise most
of the reactions or side reactions continue in the collecting flask, leading to undesirable
results. A back pressure regulator consists of special valves which allows operation to
occur at a constant system pressure. After depressurization, the reagents end up in a
collecting flask [26].
In general, in a continuous flow system, the reagents are pumped separately through
a micromixer into the reactor, with a temperature control [28].
Catalysts 2022, 12, 717 9 of 31

The reactors have channels or tubes with internal diameter sizes ranging from 10 µm
to a few mm. In particular, a microfluidic-type reactor (from 10 to 500 µm) and a minifluidic
type (from 500 µm to a few mm). The ability to transfer heat is greatly influenced by the
size of the channels. In fact, the more the diameter of the channels decreases, the more the
ability to transfer heat increases [29].

5. Reactors Used for Biodiesel Production

Conventional biodiesel production techniques required long reaction times, a high
alcohol/oil molar ratio and high costs due to the recovery of excess alcohol and the catalyst
used. However, several technologies developed have improved mixing and mass and
heat transfer. These technologies were also supported by the use of microreactors. Several
examples of transesterification carried out in flow reactors were studied and described and
different kind of reactors were explored and reported in the literature [18].

5.1. Microchannel Reactors

The microchannel reactors used to produce biodiesel usually consisted of a stainless-
steel capillary or a quartz tube. The reactor was connected to an HPLC pump, and the
other to a collection system, respectively. The temperature was controlled by immersing
the reactor in a water bath at a controlled temperature. This type of reactor allows us to
obtain rapid reaction rates, through the improvement of heat and mass transfer; a high
surface/volume ratio; and a short diffusion distance [30].
Jaree and coworkers studied the transesterification reaction of palm oil and methanol
in the presence of KOH in a microtube reactor. The optimal yield of 97.14% was achieved
with 1% (w/w) of the catalyst, with a temperature of 60 ◦ C, a molar ratio methanol/oil of
6:1 with a residence time of 5 s. A high yield of FAME was obtained with low residence
time, with a better performance obtained using a T-mixer compared to the J-mixer [31].
Martínez Arias and coworkers reported a continuous production of biodiesel from
castor oil and ethanol with different internal geometries of the microreactors, by using
Tesla-, Omega-, and T-shaped microchannels, with ethyl ester conversions of 96.7, 95.3 and
93.5%, respectively [32].
The best performances were obtained with Tesla- and Omega-shaped microreactors,
using NaOH of 1.0% (w/w) as catalyst at a reaction temperature of 50 ◦ C. The transesterifica-
tion reaction was studied in situ using a fiber-optic probe and monitored via near-infrared
spectroscopy (Figure 1).
The zigzag microchannel reactor presented smaller channels and more turns, which
enabled smaller droplets compared to those obtained with microchannel reactors with a T
or Y flow, thus allowing greater efficiency in the production of biodiesel, which is attributed
to the intensification of mass transfer through passive mixing [30].
Wen and coworkers fabricated zigzag microchannel reactors for continuous alkali-
catalyzed biodiesel synthesis (Figure 2) [33]. The methyl ester was obtained by using NaOH
as catalyst, with a yield of 99.5% and a residence time of 28 s, in the optimized conditions
within the zigzag microchannel reactor.
Kalu and coworkers produced biodiesel with different degrees of conversion using
homogeneous catalyst in the slit-channel reactor (Figure 3) [34].
Slit channel had higher active surface areas and low fabrication costs compared to
microreactors. The conversion of soybean oil to biodiesel, with a molar ratio of methanol to
oil of 9:1, a temperature of 56 ◦ C and a homogeneous sodium alkoxide catalyst amount of
1.2 w/w%, increased with channel depth and required an average residence time of only
28 s for complete product conversion, with a methyl ester yield of 99.5%.
Oliveira and coworkers investigated the transesterification of soybean oil in supercriti-
cal ethanol, using carbon dioxide as co-solvent, to produce fatty acid ethyl esters (FAEE) in
a continuous catalyst-free process [35].
Catalysts 2022, 12, 717 10 of 31

Figure 1. Transesterification reaction within (a) Omega shaped, (b) Tesla shaped and (c) t-shaped
microreactors.

Figure 2. Zigzag microchannel reactor.

Catalysts 2022, 12, 717 11 of 31

Figure 3. Slit-channel reactors.

The reaction was performed in a microtube reactor at a temperature between 523 and
598 K, a pressure range from 10 to 20 MPa, an ethanol to oil molar ratio from 20:1 and 40:1
and with a CO2 to substrates mass ratio between 0.05:1 and 0.2:1. The addition of CO2
increased the yield of the ethyl esters and the best results were obtained at 598 K, 20 MPa,
with an ethanol to oil molar ratio of 20:1 and using a co-solvent to substrate mass ratio
of 0.2:1.
Da Silva and coworkers studied a continuous catalyst-free process for the transesterifi-
cation of soybean oil in supercritical ethanol to produce fatty acid ethyl esters (FAEEs) [36].
The reactions were performed in a microtube reactor at a temperature between 523 and
598 K, with a pressure range from 10 to 20 MPa, with an ethanol to oil molar ratio from
10:1 to 40:1, with the addition of carbon dioxide as a co-solvent. The yields of ethyl esters
(70% w/w) obtained in the microtube reactor with an inner diameter 0.76 mm were higher
compared to a tubular reactor with an inner diameter of 3.2 mm and were not affected by
the use of CO2 as co-solvent.
Akkarawatkhoosith and coworkers used refined palm oil, ethanol and three different
co-solvents with different polarity values (THF, acetone and isopropanol) [37].
The influence on the purity of biodiesel was evaluated under different operating
conditions and was compared to the process without co-solvent. In the process, the co-
solvent was mixed with palm oil to obtain a homogeneous mixture at the desired weight
ratio. Subsequently, the mixture and ethanol were pumped separately into the T-way
micromixer by means of two HPLC pumps. The study was conducted at a temperature
between 220 and 350 ◦ C, with a residence time of 3.5 min, an alcohol/oil molar ratio of
23:1 and a co-solvent percentage of 20% (w/w). The results indicated that the percentage
of alkyl ester of fatty acids was influenced by the reaction temperature and the addition
of a co-solvent could lead to an increase in the percentage, compared to a system without
co-solvents, because a better homogeneity between oil and alcohol was obtained. However,
the type of co-solvent became less influential when the temperature exceeded 350 ◦ C, due
to the high rate of diffusion. Alkyl ester increased sharply as the reaction time increased.
The percentage exceeded 90% with the addition of any co-solvent when the residence time
was 8.5 min. Therefore, a long residence time with any co-solvent was used to obtain the
maximum yield. By varying the amount of co-solvent from 20 to 60% (w/w), the percentage
of alkyl ester reached 83%, for each type of co-solvent used. The highest percentage,
however, was obtained with acetone, which, due to its higher polarity, allowed for greater
homogeneity of the mixture. By varying the molar alcohol/oil ratio from 11:1 to 38:1, the
percentage of the acyl ester increased with each type of co-solvent, because the interfacial
area of the oil/alcohol mixture was greater when the molar ratio increased. Therefore,
in supercritical conditions, all three co-solvents used (acetone, THF, isopropanol) were
important to make the mixture homogeneous, thus accelerating the reaction rate. However,
when the temperature was high, and the residence time was long, the type of co-solvent
used did not affect the reaction.
Catalysts 2022, 12, 717 12 of 31

5.2. Packed Bed Reactor (PBR)

In the study conducted by Tran and coworkers, sunflower oil and Burkholderia lipase
were used in a packed bed reactor (PBR), in which the immobilized lipase was physically
trapped in the PBR column. The maximum values of triglyceride conversion and biodiesel
yield were obtained with a low flow rate value of 0.1 mL/min and did not exceed 67%.
This could be due to the characteristics of the lipase used and the accumulation of large
amounts of glycerol. Because of its viscosity, glycerol alters the diffusion process of the
product towards the lipase, preventing an increase in the biodiesel yield. However, it can be
improved by arranging several PBRs in series, with the simultaneous removal of glycerol
from each reactor [38].
Buasri and coworkers reported the transesterification of waste frying oil (WFO) in
packed bed reactor (PBR) with methanol, in the presence of KOH, supported on Jatropha
curcas fruit shell activated carbon (KOH/JS) (Figure 4) [39].

Figure 4. Packed bed reactor (PBR) for continuous process for biodiesel production.

In the optimized conditions, with a reaction temperature of 60 ◦ C, a methanol to oil

molar ratio of 16:1, a residence time of 2 h and catalyst bed height of 250 mm, a conversion
yield of 86.7% was achieved.
Chen and coworkers investigated the continuous-flow production of fatty acid methyl
esters, via the methanolysis of soybean oil, using methanol and potassium hydroxide as
the catalyst, within a rotating packed bed (RPB) reactor [40].
The optimized conditions were molar ratio of methanol to oil of 6:1, hydraulic retention
time of 0.72 min, and rotational speed in the rotating packed bed (RPB) system of 900 rpm.
This RPB system achieved a maximum yield of fatty acid methyl esters of 97.3% and
maximum productivity of fatty acid methyl esters of 0.828 mol/min.
Silva and coworkers investigated the transesterification of Jatropha oil in a continuous
catalyst-free process, using supercritical ethanol, performing the experiments in a packed-
bed tubular reactor (Figure 5) [41].
The experiments were performed at a temperature of 573 K, a pressure of 20 MPa
and keeping the mass ratio between ethanol and oil fixed at 1:1 for different residence
times. The presence of free fatty acids present in vegetable oil promotes faster reaction
kinetics due to simultaneous esterification and transesterification reactions. The addition
of water (10%) and n-hexane as a co-solvent decreased the decomposition of fatty acids
and increased the fatty acid ethyl ester yields (~90% w/w).
Baek and coworkers developed a heterogeneous catalyst characterized by a porous
phenolsulfonic acid–formaldehyde resin (PAFR) applied to the esterification of carboxylic
acids and alcohols, yielding 95% of esters without removing the water from the reaction
mixture. In particular, the esterification in water afforded the esters in high yield and
PAFR was more efficient compared to other homogeneous and heterogeneous catalysts.
The recyclability of the catalyst used in the PAFR-packed flow reactor developed for the
synthesis of carboxylic acids and FAME was four days (Figure 6) [42].
Catalysts 2022, 12, 717 13 of 31

Figure 5. Packed-bed tubular reactor.

Figure 6. PAFR-packed flow reactor.

Di Serio and coworkers reported the transesterification of soybean oil with methanol
in an autoclave and in a continuous packed bed reactor. The reaction was developed in the
presence of a commercial Mg/Al hydrotalcite at a temperature of 220 ◦ C, with a pressure
of 55 bar and a residence time of 6 min. Calcined Mg/Al hydrotalcite was deactivated
showing a decrease in the activity of 38% in 50 h but with a complete regeneration of the
catalyst after washing with acetone [43].
Halim and coworkers investigated the continuous procedure for transesterification of
waste cooking palm oil in an immobilized lipase packed bed reactor (Figure 7) [44].
The optimum conditions for the reaction were a 10.53 cm packed bed height and a
0.57 mL/min substrate flow rate. The response surface methodology (RSM) based on a
central composite rotatable design (CCRD) was adaptable for fatty acid methyl ester, and
the optimum predicted yield was 80.3% compared to the actual value of 79%.
Lee and coworkers investigated a continuous process for transesterification and esteri-
fication, using immobilized Candida rugosa and Rhizopus oryzae lipases in a packed-bed
reactor system (Figure 8) [45].
In the circulation system, the optimal reaction conditions were a reaction time of
3 h, a temperature of 45 ◦ C, a flow rate of 0.8 mL/min and water contents of 10% with a
conversion yield of biodiesel of 97.98%.
Catalysts 2022, 12, 717 14 of 31

Figure 7. Continuous packed bed reactor. F1 and F2 feed flow, C-FLAX tubing. F3 feed flow, stainless
steel piping; F3 feed flow, stainless steel piping; F4 transesterification product, stainless steel piping;
F5 transesterification product, stainless steel piping; F6 transesterification product, C-FLAX tubing;
T1 temperature for inlet the PBR; T2 temperature for outlet the PBR.

Figure 8. Continuous process with immobilized (a) and co-immobilized lipases (b).

5.3. Fixed Bed Reactor (FBR)

Echaroj and coworkers tested commercial and prepared Nickel–Molybdenum catalysts
(NiMo) in the deoxygenation of triglyceride content of palm oil within a fixed-bed reactor
at a reaction temperature between 573 and 613 K, with a pressure of 500 psi, a palm oil flow
rate of 0.02 mL/min and in the presence of a H2 flow rate of 200 mL/min. (Figure 9) [46].
Feng and coworkers developed a continuous esterification of free fatty acids from
acidified oil with methanol in the presence of a NKC-9 cation-exchange resin in a fixed-bed
reactor (Figure 10) [47].
In the optimized conditions after 500 h of continuous process, at 65 ◦ C, using a
methanol to oil ratio of 2.8:1, with a feed flow rate of 0.62 mL/min and a catalyst bed height
of 44 cm, a conversion of 98% into biodiesel was achieved. The water content in feedstock
and feed flow rate decreased the FFA conversion and the loss of sulfonic acid groups from
NKC-9 resin was not observed.
Lupton and coworkers reported an efficient method for the synthesis of biodiesel using
an integrated solid supported zirconium catalyst and polymer supported N-heterocycle
carbene (NHC) catalyst, connected with an intermediate drying column containing ground
3 Å molecular sieves, within an integrated flow system (Figure 11) [48].
Catalysts 2022, 12, 717 15 of 31

Figure 9. Fixed bed with high-pressure apparatus for deoxygenation reaction.

Figure 10. Apparatus for the transesterification reaction.

Figure 11. Reactor testing of biodiesel integrated flow system.

Catalysts 2022, 12, 717 16 of 31

The reaction occurred in Omnifit glass columns fitted in a Vapourtec flow device
equipped with temperature controller and pressure monitor. Vegetable oil, methanol and
THF were pumped through a first catalyst bed containing ZrCl4 /Ph-SBA-15, at 65 ◦ C, with
a flow rate of 11 mL/min and a residence time of 4 h. The produced water was removed in
an intermediate molecular sieve 3 Å column at room temperature, and finally the reaction
mixture passed through a second column containing the supported NHC catalyst at room
temperature. Both catalysts were robust, affording biodiesel in high yields from a wide
variety of sources.

5.4. Reactive Distillation (RD)

In reactive distillation, the chemical reaction and separation of the products took place
in a single unit. This technology had several advantages, such as a shorter reaction time;
did not require the use of excess alcohol; had lower production costs due to its small size;
and also did not require an additional unit of separation [30].
Thompson and coworkers studied a continuous-flow reactive distillation (RD) of
canola oil for the biodiesel production (Figure 12) [49].

Figure 12. Continuous-flow reactive distillation (RD).

The conditions investigated were a reaction time from 3.76 to 5.56 min, a tempera-
ture from 100 ◦ C to 130 ◦ C, a catalyst concentration of KOH and KOCH3 from 0.13 to
0.24 mol/mol and a feed molar ratio from 3.65:1 to 4.50:1, affording product yields from
41.5% to 94.9%, productivity from 16 to 55.8 kmol/m3 ·h (5.6 to 19.5 m3 /m3 ·h) and a range
from 4.44 to 29.1 mol/100 mol (0.19 to 1.27% w/w) of soap formation.
In another work, a closed-loop static mixer as a continuous-flow reactor for the trans-
esterification reactions of canola oil and methanol in biodiesel production was developed
(Figure 13) [50].
Canola methyl esters were produced using 1.5% of sodium methoxide as catalyst, a
reaction temperature of 60 ◦ C, with a methanol/glyceride molar ratio of 4:1 and a reaction
time of 30 min. This RD reactor showed shorter reaction time and higher unit productivity,
a much lower excess alcohol requirement and lower capital costs due to its smaller size
and the reduced need for alcohol recovery equipment, compared to batch and traditional
continuous-flow processes.
He and coworkers developed and investigated a novel reactor system using reactive
distillation (RD) for biodiesel preparation from canola oil and methanol, with NaOCH3 as
catalyst, at a column temperature of 65 ◦ C and with a molar ratio between methanol and
glyceride of 4:1 (Figure 14) [51].
Catalysts 2022, 12, 717 17 of 31

Figure 13. Closed-loop static mixer reactor.

Figure 14. Static mixer closed-loop system.

The reaction time inside the pre-reactor and the RD column was 3 min, and the produc-
tivity of the RD reactor system was about 6.6 m3 /h, which was from 20 to 30 times shorter
and from 6 to 10 times higher compared to batch and actual continuous-flow processes.
Assabumrungrat and coworkers performed biodiesel production from soybean oil
and methanol via reactive distillation processing using the commercial package Aspen
Plus1 (Figure 15) [52].

Figure 15. Biodiesel production with reactive distillation column using heterogeneous catalyst.
Catalysts 2022, 12, 717 18 of 31

The heterogeneous magnesium methoxide catalyst prevented neutralization, wastew-

ater disposal and salt waste processing, thus reducing operation processes and energy
consumption. The reactive distillation process catalyzed by magnesium methoxide required
153 kWh/t or 139.2 kWh/t of energy to produce biodiesel with a purity of 98% (w/w).
Agarwal and coworkers produced biodiesel from Karanja oil both in batch and continu-
ous reactors, using a helical tube reactor and a reactive distillation (RD) column (Figure 16) [53].

Figure 16. (a) Process for biodiesel production; (b) batch reactor; (c) helical tube reactor.

The continuous experimental conditions were a reaction temperature of 65 ◦ C, a

reaction time of 1 h, a methanol/oil molar ratio of 5:1, 0.8% (w/w) of KOH as catalyst and a
flow rate of 6.6 mL/min, with a maximum biodiesel yield of 96.6%. The residence times in
the helical tube reactor and RD column were 4 and 8 min, respectively.

5.5. Microwave Assisted Process

Microwave irradiation was able to accelerate chemical reactions, providing direct
energy to the reactants. Microwave heat transfer was more effective than conventional
heating, and the reaction was completed in a shorter time. Conventional heating was
limited due to the heterogeneous heating of the surface and depends on the thermal
conductivity of the materials, specific heat and density. In a conventional heating process,
the outer surface of the sample has a higher temperature, while the heat flows to the
innermost parts. With the use of microwaves, however, the situation was the opposite. The
most important disadvantage in this process was the low penetrating power of microwaves
in absorbent materials, which was only a few centimeters [18].
In general, the optimal microwave power values were between 300 and 700 W. A
further increase could cause the evaporation of alcohol, with a negative effect on the trans-
esterification reaction. The optimized temperature was 55–65 ◦ C, while an increase beyond
these values led to a decrease in yield due to the possible alteration of the triglyceride
structure. The optimal irradiation time was from one to seven minutes when a basic
homogeneous catalyst was used, with an optimal concentration of 1–1.3% w/w [54].
Ding and coworkers used palm oil and an acid catalyst as raw material using mi-
crowaves (up to a power of 150 W), affording an increase in biodiesel yield [55].
With a power of 60 W in one hour, a yield of 33% was obtained; while extending the
reaction time up to eight hours, a yield of 90% was obtained. Instead, using a value of 150 W
a yield of 98% was obtained in six hours. A further increase in microwave power (210 W)
did not lead to any increase in yield. The methanol/oil molar ratio in the transesterification
reaction is 3:1, but the reaction is reversible, so an excess of methanol is used to shift the
reaction towards product formation, thereby increasing the yield. A molar ratio greater
Catalysts 2022, 12, 717 19 of 31

than 12:1, however, leads to a gradual decrease in yield. Therefore, to obtain the maximum
yield (99%) a power of 150 W is used for microwaves, with a reaction time of six hours and
an alcohol/oil molar ratio of 11:1.
Gimbun and coworkers reported a transesterification reaction of waste cooking oil
(WCO) in a continuous microwave-assisted reactor (CMAR) (Figure 17) [56]. The results
from two-level factorial design showed that the methanol to oil molar ratio of 11.62:1, an
amount of 0.68% (w/w) of NaOCH3 catalyst and a reaction time of 4.47 min afforded a
biodiesel conversion of 97.13%.

Figure 17. Continuous microwave assisted reactor for the biodiesel production. Steam number
(S1–S11); valve label (V-1-V-4); pressure controller (PC); temperature indicator (TI); temperature
controller (TC); emergency stop button (ES); microwave irradiation controller (WC).

Leadbeater produced biodiesel using commercially available scientific microwave

apparatus. The reaction was conducted under atmospheric conditions, using vegetable or
waste oil, KOH 1% w/w as catalyst, with a molar ratio of methanol and oil of 6:1, with flow
rates of 7.2 L/min, in a 4 L reaction vessel. The continuous-flow microwave methodology
for the transesterification reaction resulted as more efficient compared to a conventional
heated apparatus with an overall conversion of 98.9% of biodiesel [57].
Gedanken used Con-Flow microwave synthesis to convert canola and sunflower oil to
fatty-acid esters and glycerol (Figure 18) [58].

Figure 18. Con-Flow microwave system.

Catalysts 2022, 12, 717 20 of 31

The Con-Flow system presented several advantages compared to batch microwave

ovens, using a considerable amount of reagents, withdrawing samples of the product
without stopping the process and the constant mixing of the reagents during the reaction,
as a result of the flow. The product yield in the Con-Flow system was 92% for canola and
89% for sunflower oil. Otherwise, the large-scale reactions within the batch microwave,
due to the limited penetration of the microwave radiation, showed reduced efficacy and
the advantage of the Con-Flow method was thus emphasized.
Encinar and coworkers investigated a microwave continuous-flow system for the
production of methyl esters from soybean oil (Figure 19) [59].

Figure 19. Microwave flow system setup.

The parameters evaluated in the transesterification reaction were the temperature

(50–110 ◦ C), the methanol/oil molar ratio (3:1, 6:1, 9:1 and 12:1) and the catalyst concentra-
tion (0.5%, 1% and 1.5% (w/w) of KOH). The optimized conditions, with 2 min residence
time and 200 W of power conversion, with a methanol/oil molar ratio of 12:1, a catalyst
concentration of 1% (w/w) and a final temperature of 70 ◦ C, afforded a conversion of 99%
to methyl ester.

5.6. Ultrasonic Assisted Process

The function of ultrasound was to provide the mechanical energy for mixing and
the activation energy necessary to start the transesterification reaction. Ultrasound was
divided into two classes: high frequency (1000–10,000 kHz) with low power, and low
frequency (20–1000 kHz) with high power, which was the most used class in the chemical
field. Ultrasound irradiation generated cavitation, which was defined as the formation,
growth and collapse of bubbles within a liquid, thus releasing a large amount of energy
in a small surrounding area. Cavitation provided enough activation energy to accelerate
the reaction rate. Furthermore, in reactions catalyzed by enzymes, a slight shockwave
generated by the cavitation bubbles helped the propagation of the substrates towards the
enzymes and contributes to the elimination of mass transfer resistance [60].
Therefore, the collapse of the cavitation bubbles generated microturbolence and the
breaking of the phase boundary. Thus, a microjet capable of determining the mixing of
immiscible reagents near the interphase was generated, and this led to the formation of
an emulsion. With the formation of the emulsion, both the interface and the mass transfer
between the two phases increased, making the reaction faster [61].
An ultrasonic reactor consisted of a main reaction compartment where the reagents (oil
and alcohol) and the catalysts were contained and an ultrasonic transducer, connected with
a controller, to generate ultrasonic waves. The reactants were transferred by specific pumps
at certain flow rates to the reaction compartment in which the ultrasonic waves generated
accelerated the mass transfer between the oil, alcohol and catalyst. The products were taken
Catalysts 2022, 12, 717 21 of 31

out of the reactor to settle in a separator, in which the biodiesel and glycerol were separated
by the force of gravity. The ultrasound-assisted process accelerated the reaction, obtaining
a high yield of biodiesel. This technique worked well if a homogeneous catalyst was used
because it was easily homogenized in the reaction mixture using ultrasonic waves. The
advantages of ultrasound-assisted transesterification were a shorter reaction time and lower
energy consumption compared to the conventional mechanical stirring method, an efficient
molar ratio of triglycerides and methanol and simplicity of execution [10]. However, this
technique had limitations. In some cases, the collapse of the bubble led to an accumulation
of energy in the hot spots which can inactivate the enzyme. Therefore, the application of
ultrasound increased the reaction temperature, unless a cooling treatment was not applied
at the same time. One possible solution was to associate an ultrasound-assisted system
with an agitator [60].
Vinatoru and coworkers investigated a continuous process for the production of
biodiesel from neat vegetable oil under high-power, low-frequency ultrasonic irradiation
(Figure 20) [62]. For a residence time of 20 min, the small reactor processed 7.8 L/h, while
the larger one afforded 19 L/h. Ultrasonic irradiation resulted as useful for large-scale
processing of vegetable oils. The highest conversion was achieved when a small reactor
and the shorter reaction time were employed.

Figure 20. Ultrasonic continuous transesterification process.

In the study conducted by Shinde and coworkers, rapeseed oil was used as a raw
material. The results of the conversion of triglycerides were analyzed by comparing the
use of ultrasound and mechanical agitation. Using CH3 ONa as catalyst at 0.5% (w/w),
at different molar ratios (6:1, 4:1, 3:1), with T = 35 ◦ C for ultrasound and T = 65 ◦ C
for mechanical stirring, it was observed that for the method that involved the use of
ultrasounds, the reaction time was shorter. The same observation was made using KOH
and NaOH as catalyst. In fact, the use of ultrasound improved mass transfer, thus increasing
the reaction rate [63].

5.7. Miscellaneous
Sansawang and coworkers realized a continuous process for scale-up biodiesel pro-
duction within a machine consisting of a tank of 25 L filled with used cooking oil and a
tank of 6.5 L with methanol and NaOH 1% w/w as catalyst (Figure 21) [64].
The complete reaction occurred at the end of the reactor with a production rate of
1.817 L/h. A hot water system with a temperature of 40, 50 and 60 ◦ C increased the
production rate to 3.15, 3.24 and 3.37 L/h, respectively.
Farid and coworkers reported the production of biodiesel from fats and oils within a
novel continuous gas–liquid reactor (Figure 22) [65].
Catalysts 2022, 12, 717 22 of 31

Figure 21. Diagram of biodiesel production process.

Figure 22. Continuous gas–liquid reactor.

Catalysts 2022, 12, 717 23 of 31

The high reaction rate of the process facilitated work up and the separation between
product and reactant. In fact, heated oil and fat were atomized and sprayed into a reaction
chamber with methanol vapor; thus, the product was separated continuously while the
excess of methanol streamed in the reactor. In the optimized conditions, 5–7 g of sodium
methoxide/L, with a flow rate of 17.2 L/h and 10 L/h for methanol and oil, respectively,
afforded a conversion of 94–96%.
Raston and coworkers reported a continuous flow conversion of sunflower oil within
a film vortex fluid device (VFD) at room temperature (Figure 23) [66].

Figure 23. Vortex fluidic device (VFD).

The optimization of the parameters prevented the use of co-solvent or complex cata-
lysts and saponification reaction, yielding biodiesel with high purity. The recyclability of
the catalyst, KOH 1M, was tested three times and the biodiesel, glycerol and catalyst were
easily separated after VFD processing.
Zhu and coworkers used a tube reactor system for continuous transesterification of
vegetable oil in the presence of supercritical methanol (Figure 24) [67].

Figure 24. Supercritical continuous reaction device.

The optimized conditions were a temperature of 310 ◦ C, a pressure of 35 MPa, a molar

ratio of 40:1 between alcohol and oil and a residence time of 25 min with a maximum
Catalysts 2022, 12, 717 24 of 31

production yield of 77% caused by the side reactions of unsaturated FAME at high reac-
tion temperature. However, with gradual heating, the methyl esters yield reached more
than 96%.
Ngamprasertsith and coworkers reported the continuous transesterification reaction of
coconut oil and palm kernel oil, using supercritical methanol without catalyst in a tubular
flow reactor (Figure 25) [68].

Figure 25. Tubular flow reactor.

The reactions were studied at a reaction temperature of 270, 300 and 350 ◦ C, at a
pressure of 10 and 19 MPa, with methanol/oils molar ratios of from 6:1 to 42:1. The best
conditions were at 350 ◦ C, with a molar ratio of methanol/oil of 42:1 and a space time of
400 s, with a methyl ester conversion of 95 and 96% (w/w) for coconut oil and palm kernel
oil, respectively.
Cheryan and coworkers used a continuous stirred-tank reactor (CSTR) system for
continuous transesterification of palm oil, using pumps for continuous delivery of oil and
catalyst and removal of products. The reaction was performed at 60 ◦ C, with potassium
hydroxide as catalyst, and the molar ratio between methanol and oil of 6:1. The yield of
methyl esters reached 97.3% with a residence time of 60 min, while higher residence times
decreased the production rate. (Figure 26) [69].

Figure 26. Continuous stirred-tank reactor (CSTR).

Catalysts 2022, 12, 717 25 of 31

Noureddini and coworkers investigated a continuous process in a pilot plant with

a motionless and a high-shear mixer for the conversion of triglycerides to methyl esters
higher than 98% (Figure 27) [70].

Figure 27. Flow diagram for the continuous transesterification process. Metering pumps (MP1. MP2,
MP3); pressure transducers (P1, P2); back pressure regulator (BPR); thermocouples (T1, T2, T3, T4);
residence tube (RT).

An excess of alcohol favored higher conversions, and higher catalyst (NaOH in methanol)
concentrations afforded higher conversions of methyl esters but increased the solubility in the
glycerol layer, thus reducing the amount of FAMEs separated by gravity settling.
Noriega and coworkers investigated biodiesel production in liquid–liquid film reactors
(LLFR) (Figure 28) [71].
In the liquid–liquid film reactor, the interfacial area is created without dispersing the
oil and alcohol phases in each other, using semi-structured packaging. This type of reactor
reduced separation time and increased process productivity. The optimized conditions
were a constant temperature of 55 ◦ C, with a concentration of 1% (w/w) of NaOH as catalyst
and a molar ratio methanol to oil of 6:1. The packing surface area to reaction volume ratio
ranged from 444 to 5333 m−1 , the vegetable oil flow rate from 5 to 40 g min−1 and the
reactor length from 0.25 to 1 m. The highest conversion and yield obtained were 99.9% and
97.5%, respectively, with a productivity of 2.5 m3 biodiesel m−3 h−1 .
Komers and coworkers reported a cascade of four flow-stirred reactors at a steady
state of 60 ◦ C for the continuous methanolysis of rapeseed oil catalyzed by KOH [72].
The optimal combination of initial conditions and the number and volumes of reactors
in the cascade afforded a rapeseed oil conversion of 98.5%.
Peterson and coworkers investigated continuous flow esterification to produce biodiesel
from rapeseed oil and ethanol (Figure 29) [73].
This system consisted of an empty spinning centrifuge placed in a reactor. The two
liquid phases, which were immiscible, were pumped into the annular zone between the
reactor and the centrifuge, where mixing took place. The mixture was then transferred to
the centrifuge, where the two phases were separated by centrifugal forces [74].
Catalysts 2022, 12, 717 26 of 31

Figure 28. Liquid–liquid film reactors (LLFR).

Figure 29. Flow path for the continuous flow system.

Catalysts 2022, 12, 717 27 of 31

The oil feed rate was 0.38 L/min and produced 945 L (250 gal) per batch.
Suranani and coworkers reported a continuous synthesis of biodiesel from fresh oil
(FO) and used cooking oil (CO) using a corning® Advanced FlowTM Reactor (AFR) similar
to a plug flow reactor (PFR) (Figure 30) [75].

Figure 30. Advanced FlowTM Reactor (AFR).

The reaction was performed in the presence of sulfuric acid 2% (w/w), with a tempera-
ture of 80 ◦ C and a feed flow rate of 30 mL/h, achieving a maximum oil conversion of 99
and 93% in AFRTM for FO and CO, respectively.
Nabetani and coworkers developed a non-catalytic transesterification of triglycerides
in a continuous-flow bubble column reactor (Figure 31) [76].

Figure 31. Continuous flow bubble column reactor. Vaporizer (VR); superheater (SH); bubble column
reactor (R1); level controller (LC1); condenser (Cd1); glass container for sample collector (F1); valves
(V1–V8); electrical heaters (H1–H5); temperature controllers (TC1–TC5); pipe on the top of F1 (O1);
pipe on the bottom of F1 (O2); inner pipe in the LC1 (O3).

The bubble column reactor was similar to reactive distillation, where oil was retained
in the liquid phase while the reaction products in the gas phase were continuously removed
from the reactive zone. The reaction was developed in a continuous-flow bubble column
reactor containing palm oil, with a liquid volume of 200 mL, in the presence of methanol
with feed flow rates of 1.5, 3.0, and 6.0 mL/min, and with reaction temperatures of 250,
270, and 290 ◦ C. The biodiesel productivity increased with the reaction temperature and
methanol feed flow rate, while the purity of the methyl ester decreased.
Catalysts 2022, 12, 717 28 of 31

To sum up the characteristics of the continuous flow technology, advantages and

drawbacks of the described reactors are reported in Table 1.

Table 1. Summary of reactors characteristics.

Reactor Advantages Drawbacks

Rapid reaction rates
Clogging
High heat and mass transfer
Microchannel Leakage between channels
High surface/volume ratio
High fabrication cost
Short diffusion distance
High conversion Side reactions
Packed Bed Reactor
Low operating costs Low temperature control
Fixed-Bed Reactor
Easy separation Difficult cleaning
Short reaction time Volatility constraints
Reactive Distillation Low alcohol amount Different steady-state
Low production costs column profiles
High heat Low penetrating power in
Microwave
Short reaction time absorbent materials
Short reaction time
Inactivation of the enzyme
Ultrasound Low energy consumption
Higher reaction temperature
Simplicity of execution
Easy operation
High-phase back mixing
Bubble Column Low maintenance costs
Difficult scale-up and design
Good mass transfer
High mass and heat transfer Difficult temperature control
Tubular Flow
Reduced production costs Difficult exothermic reaction
Easy temperature control
Low area heat transfer
Continuous Stirred-Tank Easy construction
Low heat transfer coefficients
Low operating costs

6. Conclusions
Over the years, flow chemistry assumed a crucial role both in academic research and in
the industrial field, offering a valid alternative to batch processes. Microreactors found wide
application in the production of biodiesel with a better control of experimental variables
and reproducibility, an increase in the reaction speed and a better control of heat exchange,
thus avoiding dangerous and uncontrolled exothermic processes. The continuous flow
technology carried out a sequence of chemical reactions in a single process, using several
reactors arranged linearly, with the advantage that the intermediates were not isolated but
directly transferred to the next reactor. The transesterification reaction can be performed
using a continuous flow process that allowed us to obtain biodiesel with a higher yield,
compared to conventional batch procedures, with better control of the reaction parameters
such as temperature, pressure and flow rate, carrying out the process in greater safety. The
continuous flow synthesis methods can be combined with other technologies, applicable
on an industrial scale, which contributed to the increased efficiency of the process.

Funding: This research received no external funding.

Acknowledgments: This work was supported by the Intervento cofinanziato dal Fondo di Sviluppo
e Coesione 2007–2013—APQ Ricerca Regione Puglia “Programma regionale a sostegno della special-
izzazione intelligente e della sostenibilità sociale ed ambientale—FutureInResearch”.
Conflicts of Interest: The authors declare no conflict of interest.
Catalysts 2022, 12, 717 29 of 31

References
1. Karthikeyan, C.; Karuppuchamy, S. Technologies for Biodiesel Production: A Review. Mater. Focus 2018, 7, 147–155. [CrossRef]
2. Konfo, T.R.C.; Agbangnan, D.C.P.; Sohounhloue, C.K.D. Comparative Study of Transesterification Processes for Biodiesel
Production (A Review). Elixir Appl. Chem. 2018, 120, 51235–51242.
3. Mofijur, M.; Rasul, M.G.; Hassan, N.M.S.; Nabi, M.N. Recent development in the production of third generation biodiesel from
microalgae. Energy Procedia 2019, 156, 53–58. [CrossRef]
4. Srivastava, N.; Srivastava, M.; Gupta, V.K.; Manikanta, A.; Mishra, K.; Singh, S.; Singh, S.; Ramteke, P.W.; Mishra, P.K. Recent
development on sustainable biodiesel production using sewage sludge. 3 Biotech 2018, 8, 245. [CrossRef] [PubMed]
5. Andreo-Martínez, P.; García-Martínez, N.; del Mar Durán-del-Amor, M.; Quesada-Medina, J. Advances on kinetics and thermo-
dynamics of noncatalytic supercritical methanol transesterification of some vegetable oils to biodiesel. Energy Convers. Manag.
2018, 173, 187–196. [CrossRef]
6. Demirbas, A. Progress and recent trends in biodiesel fuels. Energy Convers. Manag. 2009, 50, 14–34. [CrossRef]
7. Verma, P.; Sharma, M.P. Review of process parameters for biodiesel production from different feedstocks. Renew. Sustain. Energy
Rev. 2016, 62, 1063–1071. [CrossRef]
8. Trejo-Zárraga, F.; Hernández-Loyo, F.; Chavarría-Hernández, J.; Sotelo Boyás, R. Kinetics of Transesterification Processes for
Biodiesel Production. In Biofuels-State of Development; Biernat, K., Ed.; InTech: Rijeka, Croatia, 2018; pp. 149–179.
9. Ugwu, B.I.; Nnaji, J.C.; Simonyan, K.J.; Onukwuli, O.D. Advances in biodiesel synthesis: The role of various catalysts. Open J.
Eng. Sci. 2018, 1, 31–52.
10. Vyas, A.P.; Verma, J.L.; Subrahmanyam, N. A review on FAME production processes. Fuel 2010, 89, 1–9. [CrossRef]
11. Carlucci, C.; Andresini, M.; DeGennaro, L.; Luisi, R. Benchmarking Acidic and Basic Catalysis for a Robust Production of Biofuel
fromWaste Cooking Oil. Catalyst 2019, 9, 1050. [CrossRef]
12. Carlucci, C. A Focus on the Transformation Processes for the Valorization of Glycerol Derived from the Production Cycle of
Biofuels. Catalyst 2021, 11, 280. [CrossRef]
13. Hossain, M.N.; Chan, Y.; Seo, J. Optimization of biodiesel production from waste cooking oil using S–TiO2 /SBA-15 heterogeneous
acid catalyst. Catalysts 2019, 9, 67. [CrossRef]
14. Yang, B.; Leclercq, L.; Clacens, J.M.; Nardello-Rataj, V. Acid/amphiphilic silica nanoparticles: New eco-friendly Pickering
interfacial catalysis for biodiesel production. Green Chem. 2017, 19, 4552–4562. [CrossRef]
15. Taher, H. Biodiesel: Use of green feedstocks and catalysts. In Biorefinery; Bastidas-Oyanedel, J.R., Schmidt, J., Eds.; Springer:
Cham, Switzerland, 2019.
16. Moazeni, F.; Chen, Y.C.; Zhang, G. Enzymatic transesterification for biodiesel production from used cooking oil, a review. J. Clean.
Prod. 2019, 216, 117–128. [CrossRef]
17. Yucel, S.; Terzioglu, P.; Ozcimen, D. Lipase Applications in Biodiesel Production. Biodiesel—Feedstocks, Production and Applications;
InTech: Rijeka, Croatia, 2012; Chapter 8; pp. 209–250.
18. Tran, D.T.; Chang, J.S.; Lee, D.J. Recent insights into continuous-flow biodiesel production via catalytic and non-catalytic
transesterification processes. Appl. Energy 2017, 185, 376–409. [CrossRef]
19. Marre, S.; Roig, Y.; Aymonier, C. Supercritical microfluidics: Opportunities in flow-through chemistry and materials science.
J. Supercrit. Fluids 2012, 66, 251–264. [CrossRef]
20. Thangaraj, B.; Solomon, P.R.; Muniyandi, B.; Ranganathan, S.; Lin, L. Catalysis in biodiesel production—A review. Clean Energy
2018, 3, 2–23. [CrossRef]
21. Tiwari, A.; Rajesh, V.M.; Yadav, S. Biodiesel production in microreactors: A review. Energy Sustain. Dev. 2018, 43, 143–161.
[CrossRef]
22. Zhang, J.; Gong, C.; Zeng, X.; Xie, J. Continuous flow chemistry: New strategies for preparative inorganic chemistry. Coord. Chem.
Rev. 2016, 324, 39–53. [CrossRef]
23. Wegner, J.; Ceylan, S.; Kirschning, A. Flow chemistry—A key enabling technology for (multistep) organic synthesis. Adv. Synth.
Catal. 2012, 354, 17–57. [CrossRef]
24. Gutmann, B.; Cantillo, D.; Kappe, C.O. Continuous-flow technology—A tool for the safe manufacturing of active pharmaceutical
ingredients. Angew. Chem. Int. Ed. 2015, 54, 6688–6728. [CrossRef]
25. Carlucci, C.; DeGennaro, L.; Luisi, R. Titanium Dioxide as a Catalyst in Biodiesel Production. Catalysts 2019, 9, 75. [CrossRef]
26. Plutschack, M.B.; Pieber, B.; Gilmore, K.; Seeberger, P.H. The Hitchhiker’s Guide to Flow Chemistry. Chem. Rev. 2017, 117, 11796–11893.
[CrossRef] [PubMed]
27. Rossetti, I.; Compagnoni, M. Chemical reaction engineering, process design and scale-up issues at the frontier of synthesis: Flow
chemistry. Chem. Eng. J. 2016, 296, 56–70. [CrossRef]
28. De Souza, J.M. Impact of continuous flow chemistry in the synthesis of natural products and active pharmaceutical ingredients.
An. Acad. Bras. Cienc. 2018, 90, 1131–1174. [CrossRef] [PubMed]
29. Porta, R.; Benaglia, M.; Puglisi, A. Flow Chemistry: Recent Developments in the Synthesis of Pharmaceutical Products. Org.
Process Res. Dev. 2016, 20, 2–25. [CrossRef]
30. Qiu, Z.; Zhao, L.; Weatherley, L. Process intensification technologies in continuous biodiesel production. Chem. Eng. Process.
Process Intensif. 2010, 49, 323–330. [CrossRef]
Catalysts 2022, 12, 717 30 of 31

31. Kaewchada, A.; Pungchaicharn, S.; Jaree, A. Transesterification of Palm Oil in a Microtube Reactor. Can. J. Chem. Eng. 2016,
94, 859–864. [CrossRef]
32. Martínez Arias, E.L.; Fazzio Martins, P.; Jardini Munhoz, A.L.; Gutierrez-Rivera, L.; Maciel Filho, R. Continuous Synthesis and in
Situ Monitoring of Biodiesel Production in Different Microfluidic Devices. Ind. Eng. Chem. Res. 2012, 51, 10755–10767. [CrossRef]
33. Wen, Z.; Yu, X.; Tu, S.T.; Yan, J.; Dahlquist, E. Intensification of biodiesel synthesis using zigzag micro-channel reactors. Bioresour.
Technol. 2009, 100, 3054–3060. [CrossRef] [PubMed]
34. Kalu, E.E.; Chen, K.S.; Gedris, T. Continuous-flow biodiesel production using slit-channel reactors. Bioresour. Technol. 2011,
102, 4456–4461. [CrossRef] [PubMed]
35. Trentin, C.M.; Lima, A.P.; Alkimim, I.P.; da Silva, C.; de Castilhos, F.; Mazutti, M.A.; Oliveira, J.V. Continuous production of
soybean biodiesel with compressed ethanol in a microtube reactor using carbon dioxide as co-solvent. Fuel Processing Technol.
2011, 92, 952–958. [CrossRef]
36. Da Silva, C.; de Castilhos, F.; Oliveira, J.V.; Filho, L.C. Continuous production of soybean biodiesel with compressed ethanol in a
microtube reactor. Fuel Processing Technol. 2010, 91, 1274–1281. [CrossRef]
37. Akkarawatkhoosith, N.; Kaewchada, A.; Jaree, A. Enhancement of continuous supercritical biodiesel production: Influence of
co-solvent types. Energy Procedia 2019, 156, 48–52. [CrossRef]
38. Tran, D.T.; Lin, Y.J.; Chen, C.L.; Chang, J.S. Modeling the methanolysis of triglyceride catalyzed by immobilized lipase in a
continuous-flow packed-bed reactor. Appl. Energy 2014, 126, 151–160. [CrossRef]
39. Buasri, A.; Chaiyut, N.; Loryuenyong, V.; Rodklum, C.; Chaikwan, T.; Kumphan, N. Continuous Process for Biodiesel Production
in Packed Bed Reactor from Waste Frying Oil Using Potassium Hydroxide Supported on Jatropha curcas Fruit Shell as Solid
Catalyst. Appl. Sci. 2012, 2, 641–653. [CrossRef]
40. Chen, Y.H.; Huang, Y.H.; Lin, R.H.; Shang, N.C. A continuous-flow biodiesel production process using a rotating packed bed.
Bioresour. Technol. 2010, 101, 668–673. [CrossRef] [PubMed]
41. Silva, C.; Colonelli, T.A.S.; Silva, E.A.; Cabral, V.F.; Oliveira, J.V.; Cardozo-Filho, L. Continuous catalyst-free production of esters
from Jatropha curcas L. oil under supercritical ethanol. Braz. J. Chem. Eng. 2014, 31, 727–735. [CrossRef]
42. Baek, H.; Minakawa, M.; Yamada, Y.M.A.; Han, J.W.; Uozumi, Y. In-Water and Neat Batch and Continuous-Flow Direct
Esterification and Transesterification by a Porous Polymeric Acid Catalyst. Sci. Rep. 2016, 6, 25925. [CrossRef]
43. Di Serio, M.; Mallardo, S.; Carotenuto, G.; Tesser, R.; Santacesaria, E. Mg/Al hydrotalcite catalyst for biodiesel production in
continuous packed bed reactors. Catal. Today 2012, 195, 54–58. [CrossRef]
44. Halim, S.F.A.; Kamaruddin, A.H.; Fernando, W.J.N. Continuous biosynthesis of biodiesel from waste cooking palm oil in a
packed bed reactor: Optimization using response surface methodology (RSM) and mass transfer studies. Bioresour. Technol. 2009,
100, 710–716. [CrossRef] [PubMed]
45. Lee, J.H.; Kim, S.B.; Park, C.; Tae, B.; Han, S.O.; Kim, S.W. Development of batch and continuous processes on biodiesel production
in a packed-bed reactor by a mixture of immobilized Candida rugosa and Rhizopus oryzae lipases. Appl. Biochem. Biotechnol.
2010, 161, 365–371. [CrossRef] [PubMed]
46. Echaroj, S.; Sahasakmontri, T.; Suntikunaporn, M. Effect of NiMo Catalysts Preparation on the Deoxygenation of Palm Oil to
Green Diesel. Int. Proc. Chem. Biol. Environ. Eng. 2015, 88, 42–47.
47. Feng, Y.; Zhang, A.; Li, J.; He, B. A continuous process for biodiesel production in a fixed bed reactor packed with cation-exchange
resin as heterogeneous catalyst. Bioresour. Technol. 2011, 102, 3607–3609. [CrossRef] [PubMed]
48. Asadi, M.; Hooper, J.F.; Lupton, D.W. Biodiesel synthesis using integrated acid and base catalysis in continuous flow. Tetrahedron
2016, 72, 3729–3733. [CrossRef]
49. He, B.B.; Singh, A.P.; Thompson, J.C. Experimental optimization of a continuous flow reactive distillation reactor for biodiesel
production. Trans. ASAE 2005, 48, 2237–2243.
50. He, B.B.; Singh, A.P.; Thompson, J.C. A novel continuous-flow reactor using reactive distillation for biodiesel production. Trans.
ASAE 2006, 49, 107–112.
51. Thompson, J.C.; He, B.B. Biodiesel Production Using Static Mixers. Trans. ASABE 2007, 50, 161–165. [CrossRef]
52. Boonanuwat, N.; Kiatkittipong, W.; Aiouache, F.; Assabumrungrat, S. Process design of continuous biodiesel production by
reactive distillation: Comparison between homogeneous and heterogeneous catalysts. Chem. Eng. Processing 2015, 92, 33–44.
[CrossRef]
53. Agarwal, M.; Soni, S.; Singh, K.; Chaurasia, S.P.; Dohare, R.K. Biodiesel yield assestment in continuous-flow reactors using batch
reactor conditions. Int. J. Green Energy 2013, 10, 28–40. [CrossRef]
54. Khedri, B.; Mostafaei, M.; Safieddin Ardebili, S.M. A review on microwave-assisted biodiesel production. Energy Sources Part A
Recover. Util. Environ. Eff. 2019, 41, 2377–2395. [CrossRef]
55. Ding, H.; Ye, W.; Wang, Y.; Wang, X.; Li, L.; Liu, D.; Gui, J.; Song, C.; Ji, N. Process intensification of transesterification for biodiesel
production from palm oil: Microwave irradiation on transesterification reaction catalyzed by acidic imidazolium ionic liquids.
Energy 2018, 144, 957–967. [CrossRef]
56. Ali, M.A.M.; Yunus, R.M.; Cheng, C.K.; Gimbun, J. Successive optimisation of waste cooking oil transesterification in a continuous
microwave assisted reactor. RSC Adv. 2015, 5, 76743–767651. [CrossRef]
57. Barnard, T.M.; Leadbeater, N.E.; Boucher, M.B.; Stencel, L.M.; Wilhite, B.A. Continuous-Flow Preparation of Biodiesel Using
Microwave Heating. Energy Fuels 2007, 21, 1777–1781. [CrossRef]
Catalysts 2022, 12, 717 31 of 31

58. Groisman, Y.; Gedanken, A. Continuous Flow, Circulating Microwave System and Its Application in Nanoparticle Fabrication
and Biodiesel Synthesis. J. Phys. Chem. C 2008, 112, 8802–8808. [CrossRef]
59. Encinar, J.M.; González, J.F.; Martínez, G.; Sánchez, N.; Pardal, A. Soybean oil transesterification by the use of a microwave flow
system. Fuel 2012, 95, 386–393. [CrossRef]
60. Gusniah, A.; Veny, H.; Hamzah, F. Ultrasonic Assisted Enzymatic Transesterification for Biodiesel Production. Ind. Eng. Chem.
Res. 2019, 58, 581–589. [CrossRef]
61. Tan, S.X.; Lim, S.; Ong, H.C.; Pang, Y.L. State of the art review on development of ultrasound-assisted catalytic transesterification
process for biodiesel production. Fuel 2019, 235, 886–907. [CrossRef]
62. Stavarache, C.; Vinatoru, M.; Maeda, Y.; Bandow, H. Ultrasonically driven continuous process for vegetable oil transesterification.
Ultrason. Sonochem. 2007, 14, 413–417. [CrossRef]
63. Shinde, K.; Kaliaguine, S. A Comparative Study of Ultrasound Biodiesel Production Using Different Homogeneous Catalysts.
Chem. Eng. 2019, 3, 18. [CrossRef]
64. Sansawang, T.; Chimmanee, C.; Butsing, T. The Continuous Process of Biodiesel Production with Water Heater Assist. J. Sci.
Technol. MSU 2016, 35, 362–367.
65. Behzadi, S.; Farid, M.M. Production of biodiesel using a continuous gas–liquid reactor. Bioresour. Technol. 2009, 100, 683–689.
[CrossRef] [PubMed]
66. Britton, J.; Raston, C.L. Continuous flow vortex fluidic production of biodiesel. RSC Adv. 2014, 4, 49850–49854. [CrossRef]
67. He, H.; Wang, T.; Zhu, S. Continuous production of biodiesel fuel from vegetable oil using supercritical methanol process. Fuel
2007, 86, 442–447. [CrossRef]
68. Bunyakiat, K.; Makmee, S.; Sawangkeaw, R.; Ngamprasertsith, S. Continuous Production of Biodiesel via Transesterification from
Vegetable Oils in Supercritical Methanol. Energy Fuels 2006, 20, 812–817. [CrossRef]
69. Darnoko, D.; Cheryan, M. Continuous production of palm methyl esters. J. Am. Oil Chem. Soc. 2000, 77, 1269–1272. [CrossRef]
70. Noureddini, H.; Harkey, D.; Medikonduru, V. A continuous process for the conversion of vegetable oils into methyl esters of fatty
acids. J. Am. Oil Chem. Soc. 1998, 75, 1775–1783. [CrossRef]
71. Noriega, M.A.; Narváez, P.C.; Cadavid, J.G.; Habert, A.C. Modeling of biodiesel production in Liquid-Liquid Film Reactors
including mass transfer effects. Fuel Process. Technol. 2017, 167, 524–534. [CrossRef]
72. Komers, K.; Skopal, F.; Cegan, A. A continuous-flow bubble column reactor for biodiesel production by non-catalytic transesterifi-
cation. Bioresour. Technol. 2010, 101, 3772–3775. [CrossRef]
73. Peterson, C.L.; Cook, J.L.; Thompson, J.C.; Taberski, J.S. Continuous flow biodiesel production. Appl. Eng. Agric. 2002, 18, 5–11.
[CrossRef]
74. Ilmi, M.; Kloekhorst, A.; Winkelman, J.G.M.; Euverink, G.J.W.; Hidayat, C.; Heeres, H.J. Process intensification of catalytic
liquid-liquid solid processes: Continuous biodiesel production using an immobilized lipase in a centrifugal contactor separator.
Chem. Eng. J. 2017, 321, 76–85. [CrossRef]
75. Suranani, S.; Marallaa, Y.; Gaikwadb, S.M.; Sonawanea, S.H. Process intensification using corning® advanced-flowTM reactor for
continuous flow synthesis of biodiesel from fresh oil and used cooking oil. Chem. Eng. Processing 2018, 126, 62–73. [CrossRef]
76. Joelianingsih, J.; Nabetani, H.; Sagara, Y.; Tambunan, A.H.; Abdullah, K. A continuous-flow bubble column reactor for biodiesel
production by non-catalytic transesterification. Fuel 2012, 96, 595–599. [CrossRef]