Ureas, Hill reaction inhibitors

Since the triazin-3-ones appear to be Hill reaction inhibitors and may be considered as a class of cyclic ureas, disubstitution of the aromatic ring would be expected to Increase activity. The 2-(3,4-dichlorophenyl)-1,2,4-triazin-3-one, however, was found to require >4 kg/ha for acceptable weed control, despite a respectable PI50 of 6.9 (Table II). This difference in weed control between the two compounds suggests the aromatic substitution pattern in this class is quite different from that of a "urea" like compound. This, apparently, is the case (Table III). 2,4-Disubstitution as well as the choice of halogen is important for activity. The most effective combination appears to be a fluorine at the 2-position of the aromatic ring with either a chlorine or bromine at the 4-position. However, it is only with the fluorine/bromine combination that some degree of crop tolerance is observed, and then only at the lowest acceptable weed control rate. 

Research had confirmed that no parent simazine residues were found in treated com plants, and additional data on the dissipation pathway of simazine needed to be developed. Research also indicated that triazines interfered with the photosynthetic process on susceptible growing weeds, as evidenced by the appearance of chlorotic leaves. Steps were undertaken to elucidate simazine s dissipation pathway and herbicidal mode of action. In Basel, Dr. Gast (1958) showed that the accumulation of starch by common coleus (Coleus blumei Benth.) plants was inhibited from treatment with 2-chloro-4,6-bis-(alkyl-amino)-triazines due to the inhibition of sugar synthesis. At the same time, Moreland et al. (1958) found weed control activity could be reduced by supplying carbohydrates to the plants through their leaves and that simazine was a strong inhibitor of the Hill reaction in photosynthesis. Exer (1958) found that triazines inhibited the Hill reaction as strongly as urea of the CMU (monuron) type. 

Diuron [3-(3,4-dichlorophenyl)-l,l-dimethylurea] is a potent PS II inhibitor causing necrosis, whereas the related urea Fluometuron (Chart I) induces albinism in growing plants. Pyrazon [5-amino-4-chloro-2-phenyl-3(2H)-pyridazinone] inhibits the Hill reaction and photosynthetic CO fixation. meta-Trifluoromethyl substitution on... 

Since the ureas, carbamates and vinylogous carbamates are all PS II inhibitors (Figure 1), it is not surprising that these compounds are also powerful PS II inhibitors. The more active compounds (Table I) were considerably more active than atrazine (Table II) in the Hill reaction assay. The Hill reaction assay frequently does not correlate with whole plant (greenhouse) activity ( 1 and 2 and references cited therein). However, vinylogous ureas do correlate fairly well (Table III). Other assays including the carotinoid biosynthesis and acetolactate synthesis (ALS) assays showed little or no activity for these compounds. 

Buthidazole and methazole possess heterocyclic rings containing a cyclized urea function, and, like the ureas, they act by inhibiting the Hill reaction in chloroplasts. It is believed that methazole is metabolized to a less lipophilic phenylurea that is the active compound, for methazole itself is a poor inhibitor of the Hill reaction and also is too lipophilic to be well transported to leaves from roots. ... 

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