FLOW CHEMISTRY

ANGELOS POLYZOIDIS, MAUD SCHWARZER, STEFAN LOEBBECKE, CALOGERO G. PISCOPO*

*Corresponding author
Fraunhofer Institute for Chemical Technology ICT, Joseph-von-Fraunhofer-Str. 7, 76327 Pfinztal, Germany

Calogero G. Piscopo

Metal Organic Frameworks (MOFs):

time for a breakthrough in material supply
Advantages and perspectives of MOF synthesis in flow

KEYWORDS: Metal-organic frameworks, Continuous flow, Scale-up, Micro-reactor technology

Abstract

Metal-organic frameworks have emerged as an attractive new class of solid material with a wide range
of potential applications. However, in order to boost their market implementation a decisive
improvement in material supply is needed. The continuous flow approach represents a promising methodology to attain the scale-up
of these materials. This paper provides a survey of the research performed in this area, and highlights challenges and opportunities.

INTRODUCTION
Scientific interest in metal-organic frameworks (MOFs) has
reached an exceptional level over the last decade (1). MOFs are
composed of organic and inorganic building units (Figures 1, 2),
and provide an infinite number of possible structures with
variable properties and potential applications. They offer
significant new scientific and technological opportunities, as
the attractive features of both building units can be
combined.
Considering the potential applications of these materials,
ranging from gas separation (2-4) to gas storage (5-6), drug
delivery (7), catalysis (8-10) sensors (11), etc., a wide
interdisciplinary technological advancement can be
expected.
One of the most attractive characteristics of MOFs is the
possibility to finely tune their chemical and physical features.
For example, the organic linkers can either be replaced or
chemically modified, leading to a theoretically infinite number
of materials with different properties.
The commercial potential of MOFs has led to an exponential
increase of both fundamental research on MOF substances
and their experimental testing in various application fields.
Several MOFs with thoroughly investigated properties have
already been commercialized (ZIF-8, HKUST-1, MIL-53) (12) and
produced by chemical companies (13). However, despite the
impressive volume of research that has already been carried
out, MOF applications are mostly confined to the academic
level. Among other issues, resistance under different chemical
and environmental conditions is of essential importance for
potential technical applications. For instance, when MOFs are

Chimica Oggi - Chemistry Today - vol. 33(3) May/June 2015

Figure 1. Structure of
ZIF-8 (grey and green
spheres represent
different sized pores
within the framework).

Figure 2. Structure of HKUST-1

(blue, red and green spheres
represent different sized pores
within the framework).

used as catalysts or gas storage media they might undergo

structural transformations and decompositions in a relatively
short time-frame, although the stability of the materials may
appear to be satisfactory according to preliminary laboratory
tests (14).
The increasing demand for MOFs can only be satisfied by
establishing robust and reproducible synthesis routes which
allow a profitable scale-up of the requested materials while
preserving their textural properties and stability. A scalable
MOF synthesis may provide a technology platform for the
further development and modification of the product, from
both a chemical and an engineering perspective. And,

65

above all, MOFs could be delivered to the market at a

substantially reduced price. Supplying MOFs in considerable
amounts and at competitive prices will obviously increase the
chance to introduce these promising materials into industrial
applications which will consequently result in an increased
demand for different MOF materials (Figure 3).
In order to boost MOF implementation in relevant industrial
processes, some important technical issues must be resolved.
In the following sections these issues will be discussed and a
promising strategy will be presented.

Figure 3. Flow chart for

market integration of MOFs.

Figure 4. i) top left:

ZIF-8 batch synthesis.
ii) top right: UiO-66
batch synthesis. iii)
bottom left: ZIF-8
continuous synthesis.
iv) bottom right:
UiO-66 continuous
synthesis.

However, the downstream processing of continuous MOF

syntheses remains challenging. The small particle sizes in fact
constitute a limitation to continuous filtration, while the
reaction slurries tend to show thixotropic behavior, clogging
and aggregation.

EXAMPLES OF CONTINUOUS MOF SYNTHESIS

THE CHALLENGES IN MOF SYNTHESIS AND SCALE-UP
The introduction of new materials into technical applications
requires robust synthesis processes, which provide both good
repeatability and reproducibility. In the case of MOFs this is an
important obstacle to overcome, since their preparation is
often quite alchemistic. Repeating the same synthesis
protocol can easily lead to different product properties
(morphology, crystal phase, density, porosity, etc.) a fact
that has led to the ironic expression my MOF is not your MOF
within the research community. The delicate process of selfassembly of a MOF crystal structure reflects the sensitivity of
these materials to the process conditions. Different synthesis
pathways are often associated with altered stability of the
crystalline network (15). There are on-going studies about
MOF crystallization mechanisms (16-17), but a general
understanding of the nucleation processes in MOF synthesis
has not yet been achieved.
In addition, a topic mostly neglected in standard batch
synthesis of MOFs is mixing. Particularly in fast reacting systems
such as ZIF-8 or HKUST-1 mixing has a significant impact on the
resulting product quality. Consequently the scale-up of these
processes is challenging. A validated MOF synthesis at a 100
mg scale might often fail even when scaled up to 5 g,
producing either an amorphous material or a MOF with poor
textural properties. Similarly, the scale-up of solvothermal MOF
syntheses is often unsuccessful due to mass and heat transport
restrictions that cannot be easily tuned with the required
precision in a classical batch reactor.
Continuous processing in micro- or milli-structured reactors is a
favourable option to overcome mass and heat transport
restrictions in MOF syntheses due to the significantly enhanced
mixing and heat exchange performance of the reactors. The
process can be ideally run under steady-state conditions with
a well-controlled residence time, leading to the generation of
small MOF particles with narrow particle size distributions.
These can be further processed either in a semi-batch
process, to promote crystal growth, or in a continuous
operation, to keep particle sizes below 100 nm (Figure 4).

66

Several examples of continuous MOF processes have been

reported and can be divided into three main categories
concerning reagent mixing and the overall synthetic
approach. In the first category reagents are premixed and
the reaction starts more or less immediately. For example,
Schoenecker et al. (18) have developed a continuous-flow
MOF crystallization reactor for the production of H2N-UiO-66
where the reagents are premixed inside a reactant mixing
tank and then fed into the reactor. Overflow from the reactor
is recirculated into the pre-mixing tank. This flow heats the
tank and acts as a source of MOF seed crystals. This synthesis
concept uses a CSTR reactor and exploits the upwarddirected axial flow of the stirrer to recirculate the smaller
crystals, while the bigger crystals are collected on the lower
part of the tank.
A different approach has been developed by Gimeno-Fabra
et al. (19) employing a custom-made tube-in-tube counter
current mixing reactor as part of a first high-throughput
method for MOF synthesis. A precursor solution containing the
metal salt and the organic ligand was mixed with a
preheated supercritical water stream, which was injected
under counter current flow conditions at high pressure. In this
way crystals of HKUST-1 and CPO-27 were instantly synthesized
by induced crystallization in various sizes and at production
rates of up to 132 g/h.
The premixing of reagents was also reported in the
mechanochemical synthesis of different MOFs (20). A number
of MOF structures were produced using single and twin-screw
extruders with unprecedented space-time yields. High
compression, shear and mixing forces combined with high
temperatures or small amounts of solvents promote the
reaction inside the extrusion barrel, leading to the preparation
of high-quality materials with increased productivity.
In the second synthetic category setups for in situ mixing have
been realized. In the first report of a continuous MOF synthesis,
De Vos and co-workers (21) successfully synthesized HKUST-1
superstructures by combining two immiscible solvents in a
T-junction. The aqueous phase, containing the metal salt, was
injected through a hollow needle into a co-flowing stream of

Chimica Oggi - Chemistry Today - vol. 33(3) May/June 2015

Figure 5. Technical scale reactor applied for the batch-synthesis of UiO-66.

the organic solution which contained the organic ligand as

well as an amine for fast deprotonation. Crystallization
occurred only at the liquid-liquid interface of the two phases,
leading to the formation of [Cu3(BTC)2] hollow spheres.
A heated tubular reactor comprising a corresponding
residence time unit was employed by Bayliss et al. (22). Two
aqueous streams of metal and terephthalate salts, mixed with
a preheated stream of water, resulted in the production of
MIL-53. The separation of the solid was also performed
continuously through the implementation of two sets of filter
and back pressure regulators installed in parallel. This method
led to a space-time yield of 1.300 kg/m3d.
The latest report in this synthetic category comes from RubioMartinez et al. (23) who describe the continuous flow production
of a series of MOFs. Separate precursor solutions are
simultaneously pumped into a T-type mixer with a corresponding
residence time unit. The scale-up capability of this flow chemistry
approach was demonstrated: production rates of 60 g/h and
space-time yields of 4.500 kg/m3d were achieved.
Microfluidic techniques - the third synthetic category - have
also been successfully implemented for the small-scale
continuous synthesis of a number of MOFs. HKUST-1, MOF-5,
IRMOF-3 and UiO-66 followed by a series of MIL-88B were
formed within minutes through segmented flow microfluidic
techniques (24-25). Additionally microreactors have been
used for the production of smaller particles of HKUST-1 and a
new lanthanide-based MOF. (26-27)
Faustini et al. (24) have announced a novel droplet-based
technique for the fast and continuous synthesis of MOF
crystals as well as MOF hetero-structures. The crystals are
prepared via a one-step synthetic method similar to the one
described by De Vos. In this case the generated microdroplets contain both reagents and act as microscopic
reactors during the heating stage. Hetero-structures have
been produced via a two-step synthesis. During the first stage
the core phase of the structure is produced inside the microdroplets and in the second step droplets containing the units
for the shell material are merged.
Paseta et al. (25) have synthesized three MIL-88B type MOFs in a
segmented flow process in order to screen the impact of
different reaction conditions on the material properties. The
authors investigated the effect of different ligands, temperatures
and residence times and found that their method produced

Chimica Oggi - Chemistry Today - vol. 33(3) May/June 2015

generally smaller particles with

narrow size distributions.
Using a continuous-flow
microreactor-assisted (CFMA)
solution-process Kim et al.
examined how the synthetic
parameters of HKUST-1 affect its
crystal size and textural properties
(26). Three different solvent
mixtures and three different
temperatures were tested and the
results were compared to the
batch synthesis. It was found that
the reaction temperature affected
Figure 6. Continuous
particle size and the products
flow system for the
synthesis of UiO-66
characteristics. In addition, it was
noted that the solvent mixtures
used affect the particle size and crystallinity.
In addition a high temperature and pressure coaxial flow
microsystem was used for the synthesis of a new Ce-MOF (27).
The main observations made concern the effect of
temperature on crystallinity and the smaller particle size
compared to the batch synthesis.
Finally, the authors of this mini-review have also developed a
highly productive microreaction synthesis procedure for ZIF-8.
It was found that by modifying the reaction and process
conditions it is possible to tailor both the microscopic (crystal
form and size) and the macroscopic morphology of the
product (28). This setup allows the production of ZIF-8 with a
STY of 210.000 kg/m3d and a calculated price about seven
times lower than that of products available on the market.

NEED FOR QUALITY CONTROL

The quality of the produced MOFs is a recurring topic. There is a
need for product quality control (XRD, TGA, particle size) during
the production of MOFs in order to monitor the product grade
during processing and prevent nonconforming production
(16-17). For instance, during the synthesis of ZIF-8 higher water
content leads to the formation of a dense zinc-imidazolate
phase, lowering the BET surface area of the product (29).
Moreover, when bringing MOFs into applications a very critical
examination of the stability of the crystal structure is necessary.
A qualitative proof of the crystal structure of a MOF product is
not sufficient since their performance decreases with reduced
crystal integrity. When investigating stability, XRD data of the
MOF before and after treatment provide information about the
qualitative persistence of the structure. For an assessment of
the degree of degradation of the examined material
additional information (for example Rietveld refinement, BET
surface area, TGA) is required. Without this accuracy of
reporting, a conclusion about the stability of the MOF during
application or modification is not possible.

OUTLOOK AND MARKET EXPLOITATION

As a result of their unique features MOFs can offer access to
advanced or new application-oriented materials and
products. The industrial interest in MOFs is already noticeable.

67

In the past few years, technical applications of metal-organic

frameworks have been validated at laboratory scale,
highlighting several market opportunities in various fields,
ranging from gas and energy storage, gas separation and
purification techniques to catalysis and sensor developments.
The commercial exploitation of these materials in the near future
is very likely. For example, BASF has stated that their MOF
materials (Basolites) will be used commercially as a methane
gas storage medium for the automotive market within the next
1-2 years (30). This potential high-volume market segment
requires mass production capacities for MOFs with a high and
consistant quality. The design and definition of specific and
reproducible synthetic and post-synthetic pathways will lead to
the manufacturing of multifunctional MOF catalysts which adapt
perfectly to tandem and cascade reactions (31), disclosing a
wide panorama of applications in the pharmaceutical and
fine-chemicals area. An increasing market acceptance is
furthermore envisaged through high-value products with
superior performance at small scales (membranes, sensors).
Consequently, targeted R&D measures are required to
overcome the issues listed above concerning the stability, scaleup and characterization of MOFs. The methodology of choice to
produce scalable, reproducible and robust materials is the
implementation and assessment of unambiguous synthesis
pathways. In this context effective progress has been made by
means of continuous flow techniques, in particular through a
micro- or millifluidic approach. Additionally, online monitoring
during continuous synthesis will certainly have a positive impact
on the production quality.
A preferential engineering concept has thus been identified;
the next step in the flow synthesis of MOFs will presumably
lead to dedicated industrial applications.

9.

10.
11.
12.

13.

14.

15.

16.

17.
18.

19.

20.

21.

ACKNOWLEDGEMENTS
This work was supported by Fraunhofer Internal Programs under
the Grant No. MAVO 824 704 MOF2Market. The authors thank
Carolyn Fisher for support on editing. AP thanks the Verband
der Chemischen Industrie for granting his Ph.D. scholarship.

22.
23.

24.

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