The Metolachlor Herbicide: An Exercise in Today's Stereochemistry

Abstract

In the ClassroomMany plants such as cereals are cultivated for the nutrition of humans and animals. The output of these crops would be considerably diminished if they were not protected against a variety of detrimental weeds. The latter compete successfully with the cultivated plants for space, sunlight, water, and nutrients in the soil. Chemicals used to selectively inactivate or kill weeds are called herbicides (1a). One of the most used representatives, (particularly in the United States) is metolachlor (Figure 1), an anilide registered for the protection of many different types of plants worldwide (2). This molecule forms stereoisomers 1 that have been analyzed separately and as a mixture for their bioactivity in reference to weed extermination. Such experiments are required because of environmental aspects (2) and the necessity to optimize the agronomic use. The compositions of stereoisomeric mixtures must also be taken into account for the industrial preparation. The present article deals with the three-dimensional structures, the syntheses, and the bioactivities of metolachlor stereoisomers.An overview of the following topics is beneficial to the comprehension of this manuscript: racemic and chiral nonracemic (3a) samples; zigzag formulas (3b); the principle of NMR and chromatography with a nonracemic auxiliary or sorbent, respectively (4); crystallization of diastereomeric derivatives (5a, 6a); and the elements of enantioselective reactions (7a). The content of this article can be integrated into a lecture on advanced organic agrochemistry. The present manuscript describes facts related to metolachlor, such as its stereoisomers or its syntheses. These specific facts are proposed as examples to illustrate general stereochemical aspects, such as axial and central chirality or enantioselective hydrogenation of achiral substrates. These topics are often taught in the third (or a later) year of university chemistry curriculum. The general aspects will be summarized in the conclusion of the article. Several Metolachlor Stereoisomers Two Elements of ChiralityMetolachlor, 1, has a stereocenter in one of the N substituents but, in addition, it exhibits a second, less usual element of chirality, the axial one (3c, 7b). Before looking at metolachlor, we shall consider a similar molecule, the model anilide 2, showing this element exclusively. We focus for a moment on formulas (M)-and (P)-2 ( Figure 2) representing the enantio mers; the descriptors (M) and (P) will be explained later. (M)-2 contains two planar π systems: the arene ring and the O=C−N fragment 1 with O=C and C−N partial double bonds. When considering rotation about the aryl-nitrogen bond, one sees that conformations with noncoplanar π systems such as (M)-2 are sterically less hindered than coplanar ones. (M)-2 shows neither an internal plane of symmetry nor a center of symmetry; thus two enantiomers must exist (6b, 8). These stereoisomers were experimentally separated and characterized (9).The descriptors (M) and (P) will be briefly explained with the e...

Enantioselective Synthesis of N–C Axially Chiral Compounds by Cu‐Catalyzed Atroposelective Aryl Amination

“…However, since several years, atropisomerism arising from a restricted rotation of a N-C bond has been attracting a growing attention, [2] with appealing applications in drug design. [3] Besides, the applications of N-C axially chiral compounds encompass also fields of agrochemistry (Metolachlore), [4] asymmetric catalysis via development of new chiral ligands [5] and material science (Figure 1). [6] The enantioselective synthesis of N-C axially chiral molecules remains however strongly underdeveloped (Figure 2).…”

“…[3] The potential of N À C axially chiral compounds also encompasses the fields of agrochemistry (e.g. the herbicide metolachlore), [4] asymmetric catalysis through the development of new chiral ligands, [5] and material science (Figure 1). [6] However, the enantioselective synthesis of NÀC axially chiral molecules remains strongly underdeveloped (Figure 2).…”

Asymmetric Synthesis of Axially Chiral C−N Atropisomers

“…Many of them are natural products or present varied biological activities [9] . For example, quinazolinone derivative methaqualone II has sedative and hypnotic properties and has also been illegally used as a recreational drug, [10] while aniline derivative metolachlor III is one of the most important grass herbicides for use in maize [11] . Other relevant representatives include ancisheynine IV , a naphthylisoquinoline alkaloid isolated from Ancistrocladus heyneanus , [12] or murrastifoline A, B and F alkaloids, extracted from the root of Murraya koenigii plants, which constitute a family of axially chiral carbazole‐derived C−N compounds, [13] whose configurational properties were studied by Bringmann in 2001 (compound V ) [14] .…”

Scientific Opinion on Evaluation of the Toxicological Relevance of Pesticide Metabolites for Dietary Risk Assessment

“…Furthermore, progress in asymmetric synthesis of pesticides led to a decrease in costs of production of enantiopure active ingredients (e.g. racemic metolachlor metolachlor-S, Mannschreck and von Angerer, 2009).…”

“…Furthermore, progress in asymmetric synthesis of pesticides led to a decrease in costs of production of enantiopure active ingredients (e.g. racemic metolachlor metolachlor-S, Mannschreck and von Angerer, 2009). For example, cypermethrin was introduced in 1968 as the unresolved isomeric mixture but subsets of isomers of this substance have their own ISO common names: alpha-cypermethrin, beta-cypermethrin, theta-cypermethring and zeta-cypermethrin are considered different active substances.…”