72
5 Gone with the Flow: Miniaturization and Safer Chemistry
process control and design are easier to implement for classical unit operations, e.g.
continuous stirred tank reactors. The availability of large empirical databases built
over years represents a comfortable choice for most companies in contrast with new
risky types of unit operations.
If we abstract ourselves for a moment, it becomes evident that even for batch
systems, flow is crucial. Not only the reactants and products in a batch reactor need
to be brought in and out of the vessel, but cooling media, electricity and data retrieved
by sensors monitoring the relevant parameters are continuously flowing. Then, we
could agree that there are many more similarities between batch and continuous
flow reactors; with the particularity that in the latter, the reactants and products
move with respect to our point of observation, and not only around a stirring axis.
Clearly, if we travel together with our reaction as it is transported, we can make
use of techniques and phenomena that its stationary batch counterpart cannot benefit
from. For example, the geometry defined by the conduct through which the fluid is
circulated brings certain advantages, e.g. provide close-to-homogeneous heat transfer
by wrapping a resistance around a tube, or couple optical fibres to monitor process
in-line.
There is ample technical information compiled over the last decades concerning
the advantages of using continuous flow. A few inflection points have marked a
modest increase on the popularity among scientists, although we have also observed
a timid corresponding time-delayed adoption by the industry. Perhaps, the strongest
impulses to the continuous flow concepts and popularity, among scientists at least,
were inspired by the Green Chemistry idea, as we shall discuss later in certain
detail (Elvira et al. 2013). Within this context, a key inflection point comes from
the adoption of microfluidics in the general chemical engineering communities, as
every argument linked to ‘small’ is invariably appealing in terms of costs and risks
(Whitesides 2006; Jensen 2017). Unfortunately, the miniaturization trend that has
occurred in parallel with the Green hype might have been difficult to understand,
and consequently, has hampered its utilization by the broad scientific community not
specialized in any of the two. Industry-paid research has logically been cautious not
to jump too early into these promising concepts and technology, in order not to get
affected by hypes or under-delivering promises of the academic colleagues. A lengthy
and tortuous increase in understanding and use of continuous flow microfluidics has
been accompanied by the use of ultrasound, and sonochemistry more specifically.
Our goal with this chapter is to provide new ideas and summarize a selection of
well-established elements for the better understanding of the advantages of using
flow, microfluidics and ultrasound in the particular contexts of organic chemistry
and synthetic chemistry. We also aim at providing a few examples while warning of
pitfalls and potential hyped promises. The discipline of continuous flow synthesis,
ranging from chemicals and pharmaceuticals to materials and biofuels, has grown
in a spectacular fashion in recent years, and the readership is referred to a wide
literature that includes numerous and excellent reviews (Yoshida et al. 2013; Wiles
and Watts 2014; Gutmann et al. 2015; Porta et al. 2016; Britton and Raston 2017).
5 Gone with the Flow: Miniaturization and Safer Chemistry
process control and design are easier to implement for classical unit operations, e.g.
continuous stirred tank reactors. The availability of large empirical databases built
over years represents a comfortable choice for most companies in contrast with new
risky types of unit operations.
If we abstract ourselves for a moment, it becomes evident that even for batch
systems, flow is crucial. Not only the reactants and products in a batch reactor need
to be brought in and out of the vessel, but cooling media, electricity and data retrieved
by sensors monitoring the relevant parameters are continuously flowing. Then, we
could agree that there are many more similarities between batch and continuous
flow reactors; with the particularity that in the latter, the reactants and products
move with respect to our point of observation, and not only around a stirring axis.
Clearly, if we travel together with our reaction as it is transported, we can make
use of techniques and phenomena that its stationary batch counterpart cannot benefit
from. For example, the geometry defined by the conduct through which the fluid is
circulated brings certain advantages, e.g. provide close-to-homogeneous heat transfer
by wrapping a resistance around a tube, or couple optical fibres to monitor process
in-line.
There is ample technical information compiled over the last decades concerning
the advantages of using continuous flow. A few inflection points have marked a
modest increase on the popularity among scientists, although we have also observed
a timid corresponding time-delayed adoption by the industry. Perhaps, the strongest
impulses to the continuous flow concepts and popularity, among scientists at least,
were inspired by the Green Chemistry idea, as we shall discuss later in certain
detail (Elvira et al. 2013). Within this context, a key inflection point comes from
the adoption of microfluidics in the general chemical engineering communities, as
every argument linked to ‘small’ is invariably appealing in terms of costs and risks
(Whitesides 2006; Jensen 2017). Unfortunately, the miniaturization trend that has
occurred in parallel with the Green hype might have been difficult to understand,
and consequently, has hampered its utilization by the broad scientific community not
specialized in any of the two. Industry-paid research has logically been cautious not
to jump too early into these promising concepts and technology, in order not to get
affected by hypes or under-delivering promises of the academic colleagues. A lengthy
and tortuous increase in understanding and use of continuous flow microfluidics has
been accompanied by the use of ultrasound, and sonochemistry more specifically.
Our goal with this chapter is to provide new ideas and summarize a selection of
well-established elements for the better understanding of the advantages of using
flow, microfluidics and ultrasound in the particular contexts of organic chemistry
and synthetic chemistry. We also aim at providing a few examples while warning of
pitfalls and potential hyped promises. The discipline of continuous flow synthesis,
ranging from chemicals and pharmaceuticals to materials and biofuels, has grown
in a spectacular fashion in recent years, and the readership is referred to a wide
literature that includes numerous and excellent reviews (Yoshida et al. 2013; Wiles
and Watts 2014; Gutmann et al. 2015; Porta et al. 2016; Britton and Raston 2017).