4-aryl-pyrazolidin-3,5-diones

Three main areas of the 4-aryl-pyrazolidine-3,5-dione scaffold were modified during the optimization phase towards graminicidal activity and selectivity in small grain cereals. A major breakthrough with regard to the herbicidal activity was achieved as aryl moieties bearing ethyl, ethynyl or methoxy groups in the... 

Aryl-pyrazolidin-3,5-diones 10 and their esters 11 were prepared as outlined in Scheme 9.2. 

Very little data related to herbicidal activities of the ADs have been released [73, 74]. The overview given in this section reflects mainly the results based on studies with 4-aryl-pyrazolidin-3,5-diones [75], which were optimized towards activity and selectivity in small grain cereals. 

Figure 1. Summary ofthe aryl-pyrazolidine-dione optimization demonstrating key fragment contributions to activity level against grass weed species (aryl moiety) and tolerance in cereal crops (hydrazine moiety).

General access to analogs Aryl-pyrazolidine-diones, precursors of the target molecules, were primarily prepared via a thermal condensation reaction between hydrazines and aryl malonates. While scouting for a technical synthesis of pinoxaden, it was moreover discovered that aryl malonamides will react with equal efficacy (NH3 extrusion), a reaction unprecedented in the literature [8]. 

Synthesis of pinojaden A convergent synthetic route leads to the pyrazolidine-dione NO A 407854, which is esterihed in the last step with pivaloyl chloride. Pinoxaden is prepared effectively in a total of 5 (longest linear sequence) + 3 (oxadiazepane synthesis), total 8 steps. Key reachons are an efficient malononitrile arylation via cross-coupling [12] to access a sterically hindered aryl malononitrile and the unprecedented condensation of its malonamide derivative with [l,4,5]oxa-diazepane [8], This sequence fits feasibility criteria for a technical application. 

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