TFMS herbicides

Determination of Octanol/Water Partition Coefficients. Since oc-tanol/water partition coefficient data for trifluoromethanesulfonanilide (I) and its substituted derivatives have not been reported in the literature and since it was not apparent that any of the substituent tt values previously determined by Fujita et al. (11) would be directly applicable to the TFMS herbicidal system, all TFMS partition coefficients and tt values were determined experimentally. The fluoroalkanesulfonanilides are very acidic because of the electron-withdrawing power of the parent fluoro-alkanesulfonyl group (5). The parent TFMS compound (I), for example, has a pKa in water of 4.45 at 25 °C. This inherent acidity extends to all TFMS series members and requires that the usual partition coefficient measurement procedure described by Fujita et al. (11) be modified to obtain accurate values of log P and tt. 

Table VI. Effect of 0.1% Tween 80 on Octanol/Water Partitioning Characteristics of TFMS Herbicides ...

Evaluation of TFMS Herbicidal Activity. The herbicidal potency of the 15 substituted TFMS compounds was rated after a 21-day test period on a 0-100% kill scale. Herbicidal test data were collected for two grass species (Foxtail, Cheat Grass) and a broadleaf weed (Wild Mustard) in the presence and absence of 0.1% (w/v) Tween 80. Since the tests... 

Hansch Correlations of TFMS Herbicidal Activity. Stepwise regression techniques were used to correlate the pre-emergence herbicidal activity data gathered for all three weed types with one or more of the following appropriate general forms of the Hansch equation (cf. Equations 2 and 6 and Table VI). 

Separation of TFMS Herbicides into Meta- and Para-Substituted Series. In our initial correlations, herbicidal activity data from Table VII for each weed type in the presence and absence of Tween 80 were fitted to the appropriate form of Equations 7-9. A typical result is illustrated by the stepwise regression obtained for Foxtail grass in the absence of surfactant ... 

The statistical parameters in Equations 13—15 for the 4-substituted TFMS series members and Equations 16-18 for the 3-substituted compounds demonstrate that the fit of the biological data to the Hansch equation is significantly improved when the TFMS herbicides are separated into two classes (cf. Equations 10-12). Both the 3- and 4-series exhibit a strong dependence not only on o-, but also on tt. For the 4-sub-... 

Table VIII. Effect on Statistics of Hansch Correlation of Separating TFMS Herbicides into Meta- and Para-Substituted Series...

Placement of the Parent Compound. Separation of the TFMS herbicides into two classes consisting of meta- and para-substituted derivatives which were fitted separately resulted in significantly improved correlations via the Hansch equation. It was not readily apparent, however, into which of the two herbicidal categories the H-substituted parent com-... 

On the basis of the statistical data in Table IX, the parent TFMS herbicide is obviously more correctly placed with the 4-substituted series members than with the 3-TFMS compounds. Finally, Table X lists, for comparative purposes, the best-fitting equational and statistical parameters for Hansch correlations of the herbicidal data for 4-substituted series members in which the parent compound has been included. These equations should be compared with those in Table XI. 

It is evident from the statistical tabulation in Table XI that the TFMS herbicidal data for Foxtail, Cheat Grass, and Wild Mustard are well-correlated by the given Hansch relationships, both in the presence and absence of surfactant. The numbers in parentheses beneath the fit parameter coefficients in Table XI are the standard errors in those coefficients. Perusal of Table XI leads to the following observations ... 

In both the Foxtail and Wild Mustard tests, addition of 0.1% Tween 80 to TFMS herbicidal formulations results in an increase in magnitude of the tt and w2 parameter coefficients for both 3- and 4-sub-... 

Table X. Final Correlation Equations for 4-Substituted TFMS Herbicides...

For these correlations, TFMS herbicidal data obtained in the presence and absence of Tween 80 for a given species were combined and fitted simultaneously, x and x values in Table VI were used. Parent compound data were omitted. See text for details. 

Two general questions relating to the pre-emergence activity of the TFMS herbicides have been raised—namely ... 

Besides providing mathematical relationships correlating structural changes to herbicidal activity variations among TFMS series members, Hansch analyses brought to light other facts which undoubtedly would have been overlooked had the TFMS herbicides not been examined by the Hansch method. In particular, the stepwise regression procedure demonstrated that ... 

Figure 2a. Three-dimensional perspective plot of the Hansch equation describing pre-emergence activity of 4-sub stituted TFMS herbicides on Foxtail grass (no Tween 80 present)...

TFMS Herbicides in the Presence of 0.1% Tween 80. Let us now turn our attention to the effect that the addition of a small amount of Tween 80 to the TFMS herbicidal formulations has on the shape and orientation of the activity plots for Foxtail and Wild Mustard. Considering first the 4-substituted derivatives and comparing Figure 2a with 2c for Foxtail and Figure 3a with 3c for Wild Mustard, we note that the addition of surfactant in both cases has two obvious consequences ... 

In addition to the pronounced effects of surfactant on ir discussed above, addition of Tween 80 to 4-TFMS herbicidal formulations produces smaller changes in the a dependence (cf. Figures 2a and 2c for Foxtail and 3a and 3c for Wild Mustard). In Table XI, this a dependence appears as a slight decrease in the parameter coefficient p for 4-TFMS activity on Wild Mustard and as a large decrease in p for 4-TFMS activity on Foxtail when surfactant is added. Comparing Figures 2a and 2c for Foxtail, this decrease in p manifests itself as a decrease in slope of the activity surface in the positive a direction. For substituents with large positive o- values,... 

One point should be clarified with reference to the plots of Figures 2, 3, and 4 and the Hansch relationships in Table XI. The appropriate equations and plots describing TFMS herbicidal activity in the absence... 

Implications of the TFMS Correlations. Meta-TFMS Activity on Wild Mustard in the Presence of Tween 80. Table XI and Figure 3d showed that the activity of the meta-TFMS herbicides on Wild Mustard in the presence of Tween 80 was anomalous (relative to the other weed types and formulation conditions examined) in the following ways ... 

Thus, it seems that the anomalous methylthio-TFMS herbicidal activity we have observed in our structure-activity studies on grass and broadleaf weeds is attributable to in vivo conversion of the -SCH3 side chain to more highly oxidized forms (-SOCH3, -S02CH3). Alternatively, methylthio-TFMS derivatives may function herbicidally via a completely different mode of action than the other TFMS derivatives examined. In light of the arguments presented, however, this seems to be a much less likely possibility than the in vivo oxidation proposal. 

Figure 6. 7r values for para- and meta-TFMS herbicides obtained... 

Partition Coefficient. Partition coefficients of the TFMS herbicides in both the presence and absence of surfactant were determined between 1-octanol and pH 1.0 water (made acid by addition of HC104) by ultraviolet spectroscopy. The absorption spectrum of Tween 80 did not interfere with the spectra of the sulfonanilides (6). 

Structure-activity correlations were carried out using least-squares regression analysis techniques on an IBM 360 computer. As in the accompanying publication (6), the data in Tables I and II were fitted to Equation 3 in stepwise fashion. Standard statistical tests were carried out at each stage of fitting to determine the over-all goodness of fit of the x and o- data to the various equational forms examined. As in our previous study (6), the most statistically significant correlations were always obtained when activity data for meta-substituted and para-sub-stituted TFMS herbicides were divided into two discrete series and fitted separately. 

As judged from octanol/water partitioning experiments in the presence and absence of Tween 80, the principal effect of adding surfactant to the TFMS herbicides at the 0.1% (w/v) level was to alter their relative solubilities in the aqueous and lipid phases. Since the trifluoro-methanesulfonanilides are all quite hydrophobic, the addition of Tween 80 in every case increased the water solubility of the compound in question and hence decreased its octanol/water partition coefficient (6). 

When the most statistically significant relationships derived for the meta- and para-TFMS herbicides acting on Foxtail and Wild Mustard... 

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