Key words
flow chemistry - practical chemistry - teaching resources
The expansion of flow chemistry as a means for undertaking a chemical reaction has
developed rapidly over recent years. When teaching chemistry to undergraduate students,
one aspect that has to be addressed is the core subject-knowledge required to function
as a chemist, usually taught through lectures. In addition, chemistry is a practical
subject; therefore, the laboratory-based skills that students learn and will require
upon graduation also need consideration. Traditionally, batch chemistry has dominated
the practical laboratory curriculum because, within an industrial setting, completing
a reaction using batch chemistry has been the norm. However, in recent years flow
chemistry has started to become more ubiquitous within the pharmaceutical industry
and fine chemical production,[1] therefore undergraduate programs have started to amend their practical provision
to reflect this.[2]
[3]
[4] In recent years there have been a number of practical classes designed that utilise
continuous-flow analysis and flow-injection analysis procedures,[5–16] as well as construction of inexpensive microfluidic chips[17–19] for use both within the undergraduate curriculum and to engage high school students
with chemistry.[20] However, the number of experiments that can be used upon preparative scale are much
smaller in number. Examples include Fischer esterification,[21]
[22] methylation of 2-napthol,[23] Hofmann rearrangement,[21] Knoevenagel condensation,[21] electrophilic aromatic substitution,[21] Paal–Knorr pyrrole synthesis,[21] Diels–Alder cycloaddition[21] and synthesis of azo dyes and disulfides.[24] Some examples showcasing more recently developed reactions are discussed further
in this Spotlight. This field is in its infancy; therefore, this Spotlight should
not be considered exhaustive but rather a starting point for any practical class developer
looking to include examples of flow chemistry. As this field develops, it is likely
that more reactions utilising flow chemistry that are suitable for an undergraduate
laboratory will be disclosed over the coming years.
Dr Cranwell is an Associate Professor of Organic Chemistry at the University of Reading. She
undertook her PhD studies under the supervision of Professor Steven Ley at the University
of Cambridge, and was a postdoctoral research assistant in the group of Professor
Erick Carreira at ETH Zürich. She has a keen interest in understanding how students
learn, particularly in relation to student misconceptions and how they arise, and
she has published work relating to the language used when teaching organic chemistry.
She has contributed extensively to the development of new chemistry programmes and
re-invigoration of existing programmes, and has a keen interest in ensuring that the
chemistry taught within the undergraduate curriculum remains relevant and incorporates
the latest technological and scientific developments.
Abstracts
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(A) A number of reactions using flow photochemistry suitable for an undergraduate
practical class have been disclosed,[25]
[26]
[27] but only two will be showcased here. The first is a photopinacol coupling of benzophenone
(1)[28] and the second a thiol-alkene coupling,[29] based on previous work by Tyson et al.[30]
[31] In both cases, students compared conversion into, and yields of, the desired product
between the flow and batch process.
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(B) Examples of reactions showcasing green chemistry under flow conditions include
the synthesis of 5-hydroxymethylfurfural (6) from fructose (5)[32] and the conversion of reclaimed vegetable oil into biodiesel (not shown).[33]
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(C) Oxidation reactions under flow conditions on a preparation scale have been developed
by Kairouz and Collins[34] and by the Leadbeater group[21] based on work developed by the Jamison group.[35] In both cases, a benzylic aldehyde was oxidised to a methyl ester using aqueous
NaOCl in the presence of tetrabutylammonium bromide. In the case of Kairouz and Colins,
a range of aldehydes were oxidised and students were able to compare the flow and
batch processes.
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(D) A ring-closing metathesis reaction[36]
[37] to form cyclopentene 10 from diethyl diallylmalonate (9) on preparative scale, suitable for undergraduate students under flow conditions
has been reported.[21]
[22] In this case, a short silica plug was required to separate the products from the
metathesis catalyst.
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(E) A Suzuki–Miyaura cross-coupling[21]
[22] between bromobenzene (11) and phenylboronic acid (12) on preparative scale under flow conditions, and suitable for undergraduate students,
has been achieved in high yield. To avoid clogging of the reactor system by precipitation
of the biaryl product (13), the product stream was intercepted with ethyl acetate, in which the product readily
dissolves.
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