Chemistry Reference
In-Depth Information
Another very important industrial process that
essentially gives a free ride to a reactant is that of
aromatic nitration. Aromatic nitro compounds are
used widely as intermediates for dyes, plastics and
pharmaceuticals, and for monosubstituted aromatic
substrates it is often the
para
-isomer that is the
required product. Conventional nitration technology
uses a mixture of concentrated nitric and sulfuric
acids, the latter acid often being used in considerable
molar excess. The sulfuric acid is present in order
to generate nitronium ions, which are the active
nitration species and, in principle, are still present
unchanged in the product mix. In practice, the reac-
tion mix usually is quenched with water, leading
to copious amounts of acidic waste to be disposed
of. Smith
et al
. [23] have developed a more selective
para
-alkylation procedure that does not involve the
use of sulfuric acid.
Para
-selectivity is enhanced
by the use of recoverable zeolites but more than
equimolar amounts of acetic anhydride are required
to generate the active nitrating species (CH
3
CO
2
NO
2
)
and to mop up the water formed; material usage
therefore is still high.
True catalytic nitration technology has been
developed using lanthanide(III) triflates [24]. Lan-
thanide(III) triflates are unusual in that they func-
tion as strong Lewis acids, are stable to water and
hence are recoverable from aqueous solutions. Using
ytterbium or scandium triflate at levels as low as 1
mol.% and equimolar amounts of nitric acid, nitra-
tion of a range of aromatic compounds was achieved
at around 90% conversion.
Rearrangements inherently should be atom effi-
cient processes but sometimes the 'catalyst' required
to cause the rearrangement cannot be readily re-
covered and reused. This is the case with some
production processes for ethylidene norbornene
(ENB) from vinylidene norbornene (VNB) (Fig.
2.11). The ENB is used as the 'diene' component in
ethene-propene diene monomer (EPDM) rubbers
and it is often manufactured by Diels-Alder reaction
of cyclopentadiene with butediene, followed by
rearrangement of the so-formed VNB using sodium/
potassium amalgam in liquid ammonia. Although
most of the liquid ammonia (which is also used as
a solvent) is recovered, there is significant loss of
metals. Sumitomo [25] have developed an alterna-
tive solid base catalyst (Na/NaOH on g-alumina) that
avoids waste and improves the safety aspects of the
process.
Fig. 2.11
Rearrangement of vinylidene norbornene (VNB) to
ethylidene norbornene (ENB).
4.2 Question the need for protection
Another major source of raw material wastage comes
from the use of protecting groups, frequently used in
the synthesis of pharmaceuticals; these are necessar-
ily used in stoichiometric amounts. Not only are
the raw materials wasted but their use frequently
requires an additional two process steps, involving
increased uses of solvents, lower yields, etc. Wher-
ever possible, the use of ancillary reagents such
as protecting groups should be avoided. An excellent
example of process simplification in which a three-
step route has been reduced to a single step by
a biotransformation is the manufacture of 6-
aminopenicillanic acid, an antibiotic intermediate
[26].
The original process involved protection of the car-
boxylate group in penicillin G by silylation; this reac-
tion also requires dimethyl aniline to remove the HCl
produced during silylation (Fig. 2.12). In the biocat-
alytic process, genetically engineered and immo-
bilised penicillin amidase is used to deacylate
penicillin G directly.
There are many additional green benefits to the
biocatalytic process, including:
• Avoidance of dichloromethane solvent—water is
used in the biocatalytic process
• Energy savings—reaction carried out at 30°C as
against -50°C for the protection step
• Fewer safety problems—PCl
5
also was used in the
non-biocatalytic process
4.3 Reduction of non-renewable raw
material use
The debate on when the supply of crude oil and gas
will run out will not be settled for some considerable
time. There is, however a growing consensus of
opinion that, at least as far as oil is concerned, if we
