Chemistry Reference
In-Depth Information
by-product per kilogram of product. In this context,
by-product is taken to mean everything other than
useful product, including any solvent consumed.
This concept is particularly useful for comparing
industrial processes, where the yield also can be
taken into account. Assuming a 100% yield for the
example in Fig. 2.3, we would have an E factor of
144/116 or 1.24 (the water produced could be justi-
fiably ignored, improving the E factor to 1.08).
According to Sheldon, this is typical of a bulk chemi-
cals production process, however in the fine chemi-
cals industry the E factor can be as high as 50
whereas in the pharmaceuticals sector it may be
even higher, which is striking evidence of the waste
problem faced by chemistry-based industries.
The cost and associated environmental problems
of disposing the sodium sulfite produced in the
phenol process contributed to its replacement, on
economic grounds, by the cumene process. In this
process the final step involves the acid-catalysed
decomposition of cumene hydroperoxide to phenol
and acetone (Fig. 2.4). In this case both the phenol
and acetone are wanted products, hence apart from
a very small amount of acid (used to aid decompo-
sition of the hydroperoxide) this reaction has a
100% atom efficiency and a zero E factor, indicating
a completely waste-free process (assuming 100%
yield).
Of course the atom economy concept should not
replace consideration of yield, ease of product isola-
tion, purity requirements, etc. when devising a
chemical synthesis but it should be thought of as an
additional consideration. The economics of chemical
production are changing, particularly in the fine,
speciality and pharmaceuticals sectors, where waste
generation and other environmental considerations
are becoming an increasingly significant [10] pro-
portion of the overall manufacturing cost.
3.2 Some inherently atom economic reactions
By their very nature some reaction types are likely
to produce less waste than others by virtue of being
inherently atom efficient. These reaction types are
worth considering when devising a synthetic strat-
egy. Obviously other factors also need to be taken
into account in determining the most efficient, com-
petitive and eco-friendly route. These factors
include:
• Cost and availability of raw materials
• Toxicity/hazardous nature of raw materials
• Yield
• Ease of product isolation and purification
• Solvent requirements
• Energy requirements
• Equipment requirements, cost and availability
• Process times
• Nature of waste materials
Pericyclic [11] reactions occur via a concerted
process through a cyclic transition state. These reac-
tions are typified by the Diels-Alder reaction, sig-
matropic rearrangements and cheletropic additions,
amongst others, and have theoretical atom efficien-
cies of 100% and hence should be high on the
list of considerations when designing synthetic
pathways.
Organic fungicides have played a vital role in
ensuring the plentiful supply of food and, although
many are not perfect from an environmental point
of view, they are generally more eco-friendly and
less toxic than the mercury-based fungicides that
they replaced. One of the major classes of contact
fungicides used today are the sulfenamides, typified
by Captan and the related materials Folpet and
Difoltan [12]. The starting reaction to all these ma-
terials is the Diels-Alder addition of maleic anhy-
dride to butadiene (Fig. 2.5).
Many Diels-Alder reactions are carried out in
organic solvents, and non-recoverable lewis acids
such as aluminium chloride frequently are used to
extend the range and speed up the reactions. Both
of these may detract from the 'greenness' but there
are examples where these reactions occur rapidly
without the use of catalysts or organic solvents.
2,2,5-Trisubstituted tetrahydrofurans are a novel
class of antifungal compounds; their synthesis
involves the key Diels-Alder reaction shown in Fig.
2.6. Saksena [13] found that the reaction proceeded
H
3
C
CH
3
OOH
OH
+ CH
3
COCH
3
Fig. 2.4
Cumene route to phenol.
