Halogen herbicidal activity

The biological activity of several halogenated herbicides in water is destroyed by ultraviolet irradiation (18). Irradiation seems to be a promising method for decontaminating small quantities of pesticides. The chemical similarity between the chlorinated dioxins and other chlo-rinted aromatic compounds suggested that if there were parallels in their photochemical behavior, sunlight might destroy dioxins in the environment. 

Herbicidal and chemotherapeutic activity have also been noted in other dihydropyrimidines. Certain 5,5-dihalo-6-methoxydihydropyrimidines, especially the 3-substituted derivatives such as (LXXXIll), are reported to have herbicide activity against many grasses and broad-leaf weeds [645] (herbicidal activity of some corresponding A -substituted uracils has been discussed in the preceding section). The compounds can generally be prepared by halogenation of uracil derivatives in alcohol [646, 647]. 

In the case of multiply substituted benzyl analogs, halogen is important for a high level of herbicidal activity. The relative activity for some disubstituted analogs is shown below. The most active member in this series is 2-chloro-4-fluoro analog. 

Unsubstituted aliphatic acids have no herbicidal activity. Several of the halogenated acetic acid and propionic acid derivatives, however, reveal important herbicidal properties. Today, two compounds, trichloroacetic acid and 2,2-di-chloropropionic acid are of commercial importance. 

Swithenbank et al. (1971) synthesised forty related benzamide derivatives to study the relationship between chemical structure and action. The herbicidal activity of N-alkyl-3,S-dichlorobenzamides was enhanced by, y-unsaturation, and activity was further improved by a,a-dimethyl groups. In the case of dimethylpro-pynyl nzamides, derivatives with halogen substituents on the aromatic ring are the most active, substitution in positions 3 and 5 being optimal. 

Pyridine derivatives with several halogen atom substituents show herbicidal activity. The herbicidal action of 2,3,4-trichloro-4-pyridinol (pyrichlor, 1) and of... 

Introduction of a halogen in the position Z leads to a decrease of the herbicidal activity (Fig. 9.7). 

Finally, our attention was directed toward the activity optimization at the 4-and 5-positions on the thiazoline ring (Figure 7). In the series of 4-substituted derivatives (where is methyl), introduction of various substituents, such as methyl, halogen and ester groups, resulted in diminished activity. In contrast, the excellent herbicidal activity of the 5-substituted derivatives was observed... 

Historically, the discovery of one effective herbicide has led quickly to the preparation and screening of a family of imitative chemicals (3). Herbicide developers have traditionally used combinations of experience, art-based approaches, and intuitive appHcations of classical stmcture—activity relationships to imitate, increase, or make more selective the activity of the parent compound. This trial-and-error process depends on the costs and availabiUties of appropriate starting materials, ease of synthesis of usually inactive intermediates, and alterations of parent compound chemical properties by stepwise addition of substituents that have been effective in the development of other pesticides, eg, halogens or substituted amino groups. The reason a particular imitative compound works is seldom understood, and other pesticidal appHcations are not readily predictable. Novices in this traditional, quite random, process requite several years of training and experience in order to function productively. 

Hydroxybenzaldehyde has extensive use as an intermediate in the synthesis of a variety of agricultural chemicals. Halogenation of Nhydroxybenzaldehyde, followed by conversion to the oxime, and subsequent dehydration results in the formation of 3,5-dihalo-4-hydroxybenzonitrile (2). Both the dibromo- and dhodo-compounds are commercially important contact herbicides, hromoxynil [1689-84-5] (2) where X = Br, and ioxynil [1689-83-4]( where X = I respectively (74). Several hydrazone derivatives have also been shown to be active herbicides (70). 

We can, in a qualitative way, combine the directing effects of two or more substituents. In some cases the substituents both direct to the same positions, as in the syntheses of bromoxynil and ioxynil, contact herbicides especially used in spring cereals to control weeds resistant to other weedkillers. They are both synthesized from p-hydroxybenzaldehyde by halogenation. The aldehyde directs meta and the OH group directs ortho so they both direct to the same position. The aldehyde is deactivating but the OH is activating. 

Many quinoline derivatives are important biologically active agents. 8-Hydroxyquinoline and some of its halogenated derivatives are used as antiseptics. Chloroquine 111 is one of the older but still important antimalarials. A -Alkyl-4-quinolone-3-carboxylic acid and systems derived therefrom are constituents of antibacterials (gyrase inhibitors [112]) such as nalidixic acid 112, ciprofloxazin 113 and moxifloxazin 114. The quinoline-8-carboxylic acid derivative 115 (quinmerac) is employed as a herbicide for Galium aparine and other broad-leaved weeds. Methoxatin 116, known as coenzyme PQQ is a heterotricyclic mammalian cofactor for lysyl oxidase and dopamine P-hydroxylase [113]. 

A class of Protox inhibitors that redefined the accepted SARs and QSARs of the aromatic 4 position was the substituted benzyloxyphenyl heteroaryl area. As discussed earlier, SAR and QSAR studies of the phenyl ring of Protox herbicides demonstrated the need for halogens in the 2- and 4 positions of the phenyl ring, with the exception of the 4-chlorobenzyloxy group such as that of 4-chlorobenzyloxyphenyl tetrahydrophthalimide outlier 55 (Fig. 3.15) and reported by Ohta and coworkers in 1980 [79]. Chlorine at the para position of the benzy-loxy was reported to provide optimum biological activity. 

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