Metolachlor, structure

Chloroacetanilides are soil-applied herbicides used for pre- and early post-emergence control of annual grasses and broadleaf weeds in crops. Representative chloroacetanilide compounds, alachlor, acetochlor, and metolachlor, are extensively used worldwide. Other chloroacetanilides with limited usages include propachlor, bu-tachlor, metazachlor, pretilachlor, and thenylchlor. Public environmental concerns and government regulatory requirements continue to prompt the need for reliable methods to determine residues of these herbicides. There now exist a variety of analytical methods to determine residues of these compounds in crops, animal products, soil, and water. The chemical structures and major crops in which these compounds are used are summarized in Table 1. 

Our previous work showed that alachlor, a compound that is structurally similar to metolachlor, could be separated from its acidic metabolites using a C-18 SPE cartridge (12). However, this procedure does not allow the separation of the OXA and the ESA. Thus, different adsorption mechanisms and solvent systems will be explored to separate the analytes into three fractions metolachlor, OXA, and ESA. This procedure is depicted in Figure 4 [not included in excerpt]. The SPE procedure will be necessary to avoid overlapping of the eight isomers of each compound in the chiral chromatographic analysis. 

Figure 15.6 Structures of metolachlor and its active (S) and inactive (7 ) isomers.

Figure 3.35 a Chemical structures of the four stereoisomers of metolachlor b 3D representation ofthe (aR, l S) isomer, showing the chiral axis and c the asymmetric imine hydrogenation step. 

With the exception of S-metolachlor, all the molecules listed under the column Final Target are used in pharmaceutical formulations. Dilitiazem is a Ca2+ antagonist, while Cilazapril is an angiotensin-converting enzyme inhibitor. Levofloxacin is an antibacterial, and cilastatin is used as an in vivo stabilizer of the antibiotic imipenem. S-metolachlor is a herbicide sold under the trade name of DUAL MAGNUM. Although the structures of the final targets are more complex than those of the intermediates, enantioselective syntheses of the intermediates are the most crucial steps in the complex synthetic schemes of these molecules. 

Figure 2.55 Preparation and structure of ferrocenyl diphosphine ligands for enantioselective Metolachlor synthesis and dependence of performance on the substituents in the ligand.

When it became clear that the two IS-enantiomers of metolachlor were responsible fijr most of the biological activity (see Fig. 1), there was the obvious challenge of finding a chemically and economically feasible production process for the active stereoisomers. Many methods allow the enantioselective synthesis of chiral molecules (that is the preferential formation of one enantiomer instead of the usual racemate). However, the selective preparation of S-metolachlor was a formidable task, due to the very special structure and properties of this molecule and also because of the extremely efficient production process for the racemic product as described above. During the course of the development efforts, the following minimal requirements evolved for a technically viable catalytic system ee S80%, substrate to catalyst ratio (s/c) >50 000 and turnover fi-equency (tof) >10 000 h" . 

So far only certain details of the biochemical mode of action of metolachlor are known. Pillai and Davis (1975) found that in 2 hours metolachlor at a concentration of 110 mole/dm reduced the photosynthesis of Chlorella pyrenoidosa by 33%. It is remarkable that the other structural analogue investigated CGA 17020, 2-chloro-N-(2-methoxyethyl)-2,6-dimethylacetanilide, does not inhibit photosynthesis at this concentration. 

Fig. 2 Structures of parent herbicides and transformation products under investigation. Structures I-X represent alachlor and its transformation products structures XI-XIX represent metolachlor and its transformation products structures XX-XXIV represent acetochlor and its transformation products structures XXV-XXVIII are those transformation products that can result from either metolachlor or acetochlor structures XXIX-XXX represent dimethenamid and its transformation product and structures XXXI-XXXV are triazine herbicides and their transformation products. Reprinted with permission from [50]...

Only hydroxyatrazine deviates from this pattern in cross reactivity. Because it has the same alkyl structure as atrazine, one would predict a cross reactivity similar to ametryn (about 0.6 ug/L as atrazine). However, hydroxyatrazine gave a response of less than 0.1 ug/L as atrazine. A possible explanation is that the hydroxyl group decreases the binding energy at the specific antibody recognition site. The didealkylatrazine was nonreactive (fig. 2). Neither alachlor nor metolachlor cross reacted with atrazine, which is consistent with results of a previous study (12). 

Figure 1. Chemical structures of (a) alachlor, (b) acetochlor, and (c) metolachlor.

Al ough alachlor is no longer used in the U.S., the three chemical compounds have very similar structural (Figure 1) and chemical properties. Alachlor degradataion data may be useful as a model for this chemical class. Caution must be used in interpolating these data however since the ESA metabolite of metolachlor is formed more slowly and at lower concentrations in soil (18). The objective of this study was to compare atrazine and alachlor sorption, mineralization, and degradation potential, processes that are major contributors to the environmental fate of pesticides, from surface soil to aquifer sediments in laboratoiy studies. In addition, ctegradation of alachlor was compared under aerobic and anaerobic conditions. 

FIGURE 39.4. Structure of metolachlor and its active and inactive stereoisomers. 

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