Four main series of novel heterocyclic compounds were successfully syniliesised.
Two of these series were found to be post-emergence herbicides with the activities of each
being based on a different mode of action. The (pyrazole-4-yl)alkanones are inhibitors of
protoporphyrinogen oxidase, an enzyme in chlorophyll biosynthesis, whereas alkyl 3-arylsulfonylamino-
3-methyllhio-2-(pyrimidin-2-ylcarbamoyl)acrylates and pyrimidin-2-yl 3-(2-
chlorophenyl)sulfonyl-amino-3-methylthio-2-cyanoacrylamides (collectively termed
"vinylogous sulfonylureas") are inhibitors of acetohydroxy acid synthase (AHAS). an enzyme
in branched-chain amino acid biosynthesis. Both these enzymes are established targets
for current commercial herbicides.
Studies of the utility of 2-(l-ethoxyalkylidene)-3-oxoaIkanenitriles (acrylonilriles)
in heterocycle synthesis were facilitated by the recent development of a convenient route
to these starting materials. Acrytonitriles were reacted with different hydrazines to give
(pyrazol-4-yl)alkanones and pyrazole-4-carbonitriles in varying proportions depending on
the reaction conditions and the substituents on the reactants. Although distinction between
alternative 3- and 5-substituted pyrazoles is a perennial problem in pyrazole synthesis, in
this case the products of these reactions were successfully characterised and identified using
a range of n.m.r. spectroscopy techniques. Once the herbicidal mode of action of the
(pyrazol-4-yl)alkanones had been confirmed, synthesis of a series of analogues allowed the
structural elements contributing to biological activity to be identified. The reaction of
acrylonitriles with bidetate nucleophiles such as thiourea gave novel pyrimidines. but these
compounds were not herbicidal.
The vinylogous sulfonylureas were synthesised using established procedures to
obtain novel compounds structurally related to the commercial herbicide chlorsulfuron. The
biological activity of the vinylogous sulfonylureas was found to be sensitive to apparently
minor changes in structure, but x-ray crystallographically-generated structures of an active
and an inactive member of the series revealed marked differences in conformation. Some
of the vinylogous sulfonylureas were used as synthons for pyrazole and pyrazolopyrimidine
derivatives. Although these compounds did not exhibit herbicidal activity, this synthesis
provided the basis for some interesting chemistry. Unexpected elimination of the arylsulfonylamino
group was observed when a vinylogous sulfonyurea was treated with methyl
hydrazine. In order to confirm the identity of the 3-methylthiopyrazole product, model compounds
were synthesised using alternative routes. The resulting pairs of 3- and 5-substituted
pyrazoles were characterised using n.m.r spectroscopy.
| Identifer | oai:union.ndltd.org:ADTP/219194 |
| Date | January 1992 |
| Creators | McFadden, Helen Georgina, n/a |
| Publisher | University of Canberra. Biomedical Sciences |
| Source Sets | Australiasian Digital Theses Program |
| Language | English |
| Detected Language | English |
| Rights | ), Copyright Helen Georgina McFadden |
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