Applications and Occurrences of Heterocycles in Everyday Life 183rings, for example diazinon. The organophosphates are close relatives of nerve gases such as Sarin (page 172), but are
somewhat less toxic to humans, but still cause considerable concern. (The nerve gases were discovered during research
on insecticides in the 1930s.) Insecticides acting by non-cholinergic mechanisms include Fipronil (which acts at GABA
receptors in the CNS).
The key steps in an elegant synthesis of Fipronil are the condensation of the enolate of ethyl 2,3-dicyanopropanoate
with 2,6-dichloro-4-trifl uoromethylphenyl diazonium ion. Aqueous ammonia treatment of the product then initiates
a sequence leading directly to a pyrazole: hydrolysis of the ester induces ring closure, as shown. The sulfur substituent
can then be introduced via electrophilic attack at pyrazole C-4.
Some of these compounds are also used to treat animals, such as in sheep dips and ‘fl ea drops’ for cats and dogs. (Note
that cats are particularly sensitive to organophosphates and should only be given products designed for them in the
specifi ed dose; poisoning of cats is not uncommon if this is disregarded.)
Herbicides
Herbicides can be made selective for different classes of plants – broadleaf, grasses, and so on, but control of the mode
of use is also important. Herbicides can be divided into two classes – systemic, in which the compound is taken up by
the roots, and contact (e.g. paraquat), in which only the exposed portions of the plant are affected.
Atrazine is a controversial selective herbicide, very widely used in the world but banned in the EU. It has very low acute
toxicity to animals and humans but there are claims of longer term adverse endocrine effects and possible carcinogen-
esis. Its mechanism of action is interference with photosynthesis. Its selectivity in corn crops is achieved because the
compound is rapidly deactivated by endogenous compounds in the corn plant. A structurally related, but biologically
different, analogue, indazifl am, acts by inhibition of cellulose biosynthesis.