Herbicidal activity, structure effects

Based on these and other compounds prepared in this series, several conclusions on the effect of structure on herbicidal activity can be drawn ... 

So we were induced to try this approach, too, and we started synthesis work in the field of s-triazines. The result of our primary working hypothesis was disappointing derivatives bearing anilino radicals showed no herbicidal effects. Surprisingly, however, the herbicidal activity reappeared in the structure 2-chloro-4,6-bis-diethylamino-s-triazine, compound G-25804 shown previously. The awareness that we were confronted with a completely new herbicidal matrix with apparently superior usefulness led us to intensive work around the s-triazine ring system. 

An interesting sidelight of the organic structural classification study was that herbicidal activity could also be predicted 6). The nitrodiphenylethers could be divided into compounds which were strong herbicides and those compounds which showed little or no herbicidal activity. Both Faradaic and capacitive responses could be used to separate these classes for over half the experimental conditions examined. As was found in the classification of structure, capacitive factorial features performed somewhat better than Faradaic factorial features. It also appeared that classifications of herbicidal activity using Faradaic factorial features could be improved considerably by working at high pH and without surfactant present. The information content of Faradaic or capacitive variable effects data could be improved by variations in % ethanol. 

Hansch analyses have shown that the surfactant Tween 80, when used in herbicidal formulations of TFMS derivatives at the 0.1% (w/v) concentration level, can produce one or more of the following effects in pre-emergence herbicidal tests, depending on the weed type and/or TFMS derivative under evaluation (a) no effect, (b) enhancement of herbicidal activity, (c) inhibition of herbicidal activity, or (d) shifting of optimum herbicidal activity from one TFMS derivative to another within each series. Mathematical equations relating structure to activity have been derived for the TFMS compounds both for the surfactant present and surfactant absent cases. 

The phenoxynicotinamides represent a novel class of promising preemergence and postemergence herbicides. The results obtained to date indicate that relatively minor variations in structure can have a significant effect on the level of herbicidal activity and spectrum of weeds controlled. 

Independent of this discovery, in 1982 scientists from the same company were working on a project aimed at preparing novel Acetyl-CoA carboxylase inhibitors, based upon the typical cyclohexanedione structure known for this class. The first targeted compound (2), prepared as shown in Fig. 4.3.1, showed some herbicidal activity and they thus attempted preparation of a phenyl analogue in a similar manner. This led not to the expected product (3), but to the triketone (4). This compound was devoid of herbicidal activity, but (luckily ) in safener screens the compound showed antidotal effects in Soya for thiocarbamate herbicides. A further round of synthesis optimization was undertaken and it was found that the compound (5) with an ortho-chloro substituent showed reasonable herbicidal activity. Furthermore, they noticed that it exhibited the same unique bleaching symptomology observed for leptospermone (1, Fig. 4.3.1) [4]. Further optimiza-... 

As a starting point for structural optimization of the second lead, we divided the core structure into three subsections, the phenyl (X), the imino group (Y), and the thiazoline nucleus (R and R ) (Figure 5 ). First, we synthesized the 2-(N-ethoxycarbonylimino)-l,3-thiazolines that possessed a variety of substituents at each position of the phenyl ring to examine the effect on herbicidal activity. Preemergence activities are summarized in Figure 6. Substitution on the phenyl moiety was preferred in the meta position and we observed a progressive... 

Figure 4 shows the synthesis of 15 in which the phenyl group in the chloro carboxamide series was replaced with a t-butyl group. Compound 15 was herbicidal at 1 Ib/acre in the greenhouse. A comparison of the herbicidal activity of compounds 5, 11 and 15 showed that 11 was two times as active as 15, and four times as active as 5 (data not shown). It was determined that the analogue that best fit the structural requirements for herbicidal activity was the 5-cyano-l-(1,1-dimethylethyl)-N-methyl-lIi-pyrazole-4-carboxamide 1. However, in contrast to the phenyl series the chlorine atom of 13 was inert towards displacement by cyanide ion under a variety of conditions, apparently due to a combination of steric and electronic effects. 

There seems to be little more evidence in the literature to allow a more coherent discussion of the effects of surfactants on herbicide activity and explanation of their intrinsic phytotoxicity. It may be that with such a diversity of plant structures the task of rationalizing the activity of surfactants (with the complex pattern of wetting effects, evaporation retardation, solubilization, particle size alteration of precipitated active ingredient, membrane permeability effects and intrinsic biological effects on enzyme systems) will be more daunting than with the relatively simple problem that must be faced with surfactant effects on the human organism. It is likely, however, that study of surfactant effects on plant cells will give useful information to help in the elimination of effects on mammalian cells. 

In order to obtain more powerful PDHc El inhibitors with effective herbicidal activity, all substituents R, R, R, R, and Yn in structure I were systemically modified. Through structural modification or optimization, more than thirty novel series of structure I including alkylphosphonates, monosalts of alkylphosphonic acids, alkylphosphinates, monosalts of alkylphosphinic acid, cycUc phosphate, and caged bicyclic phosphates were designed and synthesized (Scheme 1.20). Their herbicidal activities were evaluated. Structure-activity relationship was then established and analyzed. Enzyme inhibition, toxicities and usage of representative compounds in this group were also stodied later. 

According to the study on acylphosphonates by Baillie et al., substituent R in monosodium acylphosphonates 1 (Scheme 2.3) greatly affected both enzyme inhibitory activity andherbicide activity of compounds. Therefore, and R in structure lo were firstly modified to examine their effect on herbicidal activity. Me, Et or n-Pr as R and R was introduced into the structure lo to form IB (Scheme 2.3). In the IB series, where Me as R" was kept, further optimization was focused on the modification of R and Yj,. 

The above results showed 2,4-Cl2 as Yj, on the phenoxy-benzene ring to be most beneficial for herbicidal activity. In order to confirm the effect of R R, R, and R" in structure lo on activity, the inhibitory potency of some compounds against cucumber was examined when 2,4-Cl2 as Yj, was kept constant (Table 2.31). 

It was also very interesting to examine the effect on herbicidal activity by the introduction of pyridyl group as into the structure IC to form a new series of IJ. 

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