Chemistry Reference
In-Depth Information
7.2 Reactions in aqueous acid and base
[120,121]. Inorganic salts account for the bulk of the
waste and are produced most often by neutralisation
of acidic or basic solutions [120-122]. Apart from
polluting soil and ground water, salts can lower the
pH of atmospheric moisture and may contribute to
acid-dew or acid-rain [64,123]. For cleaner produc-
tion, their minimisation is essential.
Significantly, the use of high-temperature water as
a reaction medium can lead to lower production of
salt. For reactions necessitating the addition of acid
or base, less agent usually was required for high-
temperature processes than for those at and below
100°C, and the reactions often proceeded more
selectively [102]. In some instances the requirement
was several orders of magnitude lower and was
reflected in the subsequent neutralisation.
In some instances improved yields and lower levels
of by-product can more than compensate for waste
generated if dilute acids or bases are used instead of
neat water. For example, phenylacetylene in high-
temperature water at 250°C gave acetophenone in
51% conversion after 5 days, along with significant
amounts of dimeric and trimeric by-products [118].
At 280°C in dilute aqueous acid (in a conventionally
heated autoclave), however, acetophenone was
obtained in 90% yield within 1 h [102]. In a less
clearcut case discussed above (see Scheme 17.12),
2,3-dimethylindole was obtained in 67% yield from
phenylhydrazine and butanone in water at 222°C for
30 min [9]. With 1 M H
2
SO
4
instead of water, the
yield was comparable but the reaction time was only
1 min [9].
By the literature method, the preparation of
3-methylcyclopent-2-enone from 2,5-hexanedione
employed strong aqueous base in 2-3% concentra-
tion at reflux [119]. Substantial amounts of salt were
produced in the work-up and the product was con-
taminated with polymeric and starting materials. A
method developed with microwave heating at 200°C
employed a two orders of magnitude less concen-
trated base (see Scheme 17.13). Competing reactions
were suppressed, salt formation was lowered and the
enone was obtained in conversions of over 90% and
isolated yields of about 85%. The preparation was
scaled-up readily by conversion to a continuous
process with the CMR [66].
7.4 Avoiding solvent extraction through
resin-based adsorption processes
From the above discussion, microwave heating in
pressurised systems can facilitate organic reactions in
aqueous media. However, customarily the products
would be recovered by extraction with organic
solvent. This would saturate the aqueous phase with
the solvent (and the solvent with water), thereby
complicating disposal and offsetting environmental
benefits gained through using water as the reaction
medium in the first place. To avoid solvent extrac-
tion, hydrophobic resins can be employed for
concentration and isolation of the products from
aqueous media [66]. Organics are retained on the
resin and subsequently can be desorbed with a
solvent such as ethanol, which is a useful solvent for
'green' chemistry because it is readily recyclable and
is both renewable and biodegradable [78]. It is pro-
duced fermentatively on the industrial scale and can
be readily removed and recycled. Advantages of
non-extractive processes include convenience, high
throughput and low waste, owing to ready disposal
of the spent water, recyclability of the resin and the
solvent used for desorption.
7.3 Limiting salt formation
Sheldon has estimated that the manufacture of
fine chemicals and pharmaceuticals generates of the
order of 25-100 times more waste than product
and is approximately 1000 times more profligate
than bulk chemicals production and oil refining
8 Metal-catalysed Processes
The first reports of the use of microwave heating to
accelerate Heck, Suzuki and Stille reactions on solid
phase [124] and in solution did not appear until
1996 [125]. Now, many metal-catalysed reactions
can be performed almost routinely, within minutes
Scheme 17.13
Preparation of 3-methylcyclopent-2-enone [66].
