Fundamentals of Medicinal Chemistry

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the reactions. The heat generated by a large scale reaction may exceed the

cooling capacity of the existing equipment with disastrous results. Conse-

quently, if they are not known, the heats of reaction for each of the stages

used in the process must be accurately determined and taken into account when

assessing the safety of the plant and its operatives.

Waste disposal and its environmental impact are becoming increasingly

important and must now be planned for as part of the development process. In

the past, solid wastes were buried in special landfill sites but now because of

potential water pollution it is regarded as undesirable unless alternative methods,

such as incineration, are not suitable. Aqueous liquids may be discharged into the

sewage system, rivers and the sea. However, this requires removal of high concen-

trations of impurities, especially metals, such as copper, zinc, mercury and cad-

mium, and organic halogen compounds, such as chloroform, which are highly

toxic to many forms of aquatic life. Solvents are usually recovered by distillation

but this is not always a practical proposition for some solvents such as dimethyl

sulphoxide and N,N-dimethylformamide. Gases can often be prevented from

entering the atmosphere by reaction with suitable absorbents in absorbent towers.

However, gases such as nitric oxide that cannot be disposed of in this manner

require special treatment, which can be very expensive. In all cases the disposal of

highly toxic waste is to be avoided, as it can require expensive special treatment.

An idea of the impact of a process on the environment may be determined

from its effluent load factor (ELF). This is defined as

ELF¼

mass of all ingredients of all the stagesmass of the product

mass of the product

(11:1)

The ELF is the amount of waste produced by the process per unit mass of the

product. It can refer to individual stages in the synthesis or the whole process. In

the ideal situation, where all the ingredients are converted into the product, the

ELF value will be zero. This does not happen in synthetic processes. In pharma-

ceutical processes, the ELF is usually of the order of 100. The process design

chemists will aim to minimize the ELF in order to reduce expense by selection of

the reactions and the operation of the plant.

11.2.3 Synthesis quality control

The efficiency of drug production will depend on being able to identify and

assess the chemical purity of the drug and also that of the intermediate com-

pounds involved at each step in the synthesis. This means that it is normally

CHEMICAL DEVELOPMENT 227

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