Business Considerations - Fundamentals of Industrial Chemistry: Pharmaceuticals, Polymers, and Business - page 80

Especially in situations where trace metals can change the chemistry, all
of the equipment needs to be considered. It is not enough to use a glass-lined
reactor if the piping feeding the reactor is made from carbon-steel.
Ben Franklin is credited with the saying, “Waste not; want not.” I don't
think that he was referring to chemical waste but chemical waste is a major
factor in scale-up. In the laboratory, waste from filtrates, unused distillation
fractions, etcetera is of inconsequential quantity but as the scale increases,
it can mean the success or failure of a project. In the laboratory, reactions
are often run in dilute solutions. On a larger scale, to minimize waste and
to be able to make more material, reactions are commonly much more con-
centrated; sometimes they are run without solvent. When a solvent is used,
it is best if it can be recycled. If the solvent must be disposed of, it adds to
the cost and is not as environmentally friendly. When there is less solvent to
act as a heat sink, heats of reaction become more pronounced. Lacking other
controls, an exothermic reaction run at 20% concentration will have a much
greater temperature rise than one run at 2%. The characterization of the waste
is also important. Whenever possible the waste should not be contaminated
with highly toxic or environmentally unfriendly chemicals.
If a reaction success is highly dependent upon agitation, it can present a
challenge in scale-up. Examples of reactions like this might include those
occurring at an organic / aqueous interface. Often agitation in the laboratory
is more effective than in a large-scale continuously stirred reactor (CSTR).
When extra agitation is needed, it can be accomplished by reactor design, but
the laboratory chemist must realize that it is important.
Time is something else that can vary on scale-up. It is easy to rapidly heat
or cool reactions. An ingredient can be added to the reaction in a second.
Typically, things take longer on a larger scale. It is important to realize this
and perhaps test the importance in the laboratory so that there are no surprises
on scale-up.
Another major decision on scale-up is batch versus continuous. If
something is to be manufactured in a batch reaction, starting materials are
added, the reaction is performed, and the product purified and isolated. If
more is needed, then a second run or a second batch is performed. Often
batch manufacturing processes run one batch after another around the clock.
Another option is to run chemical reactions on a continuous basis. In a
continuous process, starting materials are continuously fed to the reactor and
product continuously purified and isolated.
We can consider the two options by thinking about the production of ethyl
acetate. In a batch production acetic acid, ethanol, and catalyst are added
to a reactor, the mixture is heated for a period of time and then distilled.
The different distillation fractions are collected. This process is repeated as
often as necessary to meet customer demand. Each batch produced has its