Herbicides pyridazines

The pyridazin-3-ones are interesting because they include herbicides having two different modes of action, distinguished only by small changes in substitution pattern. Thus pyrazon (8) (61GEP1105232) is a photosynthesis inhibitor, while other discussed later are carotenoid biosynthesis inhibitors. The pyridazin-3-one ring is constructed by condensation of phenyl-hydrazine with 3,4-dichloro-2,5-dihydro-5-hydroxyfuran-2-one (9), in turn produced by chlorination of furan-2-carbaldehyde. Amination of (10) then occurs exclusively at the 5-position to give pyrazon (Scheme 4). 

Uses herbicide, cereals, maize, rice Trade names Lentagran (Chemie Linz) Type pyridazine... 

Synthesis and Herbicidal Activity of Pyridazines Based on 3-Chloro-4-methyl-6-[tr -(trifluoromethyl)phenyl]pyridazine... 

Greenhouse evaluation in a random herbicide screen showed that 3-chloro-4-methyl-6-[m-(trifluoro-methyl)phenyl)pyridazine was sufficiently active to serve as a lead for a synthesis project. Related 3-chloropyridazines were prepared by a sequence based on the addition of acyl anion equivalents of substituted benzaldehydes to the appropriately substituted acrylate esters. Using 3-chloro-pyridazines as key intermediates, a variety of other 3-substituted-pyridazines were prepared. The effect of altering substitution at each position of the pyridazine and phenyl rings on herbicidal activity was examined. 

The first pyridazine for which plant growth regulating activity was patented was maleic hydrazide ( 1). Since the introduction of MH in the late 1940 s, at least four other pyridazines have been developed as herbicides Pyramin by BASF in 1962, Kusakira by Sankyo in 1970, Zorial by Sandoz A. G. in 1971 and pyridate by Chemie Linz in 1976 (2). 

We first became interested in pyridazines as herbicides when a number of pyridazines synthesized in a CNS project at our Lederle division were evaluated in our primary herbicide screen. One of these compounds, AC 228,764, controlled eleven of the twelve weed species at 8 kg/ha in the preemergence test. All of the test species were bleached, emerging white from the soil. In our secondary evaluation at 4 kg/ha, AC 228,764 controlled ten out of eleven annual grass and broadleaf weed species with selectivity in cotton, soybeans and rice. This spectrum of activity and crop... 

Based on available herbicide data for related Cyanamid pyridazines and patented compounds, the following structural modifications were proposed 1) substitution of the chlorine at the 3-position 2) replacement or derivatization of the 4-methyl group 3) introduction of substituents at the 5-position 4) alternate substitution in the 6-phenyl ring as well as reduction to the corresponding cyclohexyl derivatives and replacement of the phenyl by heterocycles and 5) oxidation and quaternization of the nitrogens at positions 1 and 2. 

A number of pyridazines were selected for further deriva-tization based on their herbicidal activity. Pyridazines containing methoxy, substituted-amino, chloro, and hydrogen in the 3-position were selectively reduced using platinum oxide in tri-fluoroacetic acid to yield the corresponding 6-cyclohexyl derivatives (2.) Selected analogs were also oxidized in the 1-and/or 2-positions using meta-chloroperbenzoic acid (8) and were quater-nized with methyl iodide in refluxing acetonitrile (9) to... 

The most active pyridazine of the group was the 3-methoxy analog, AC 247,909. Like most of the active pyridazine analogs, preemergence application of AC 247,909 caused bleaching. As the most active postemergence pyridazine herbicide, AC 247,909 caused rapid necrosis, suggesting a potential use as a contact-type herbicide. As in the 3-amino series, an extension of the alkyl chain resulted in the loss of activity. Besides methyl, other substituents introduced at the 3-position included alkylsulfonyl, cyano, carboxy, and amido. These pyridazines were inactive at 1 kg/ha and in some cases at 8 kg/ha. 

Although the synthesis program did not result in any commercial herbicides, two types of pyridazines were discovered which produced unexpected results, both in the level and the type of activity. The first series, which includes the 3-methoxy- and the 3-dimethylaminopyridazines, resulted in a high level of postemergence activity not observed in the lead or in the other 3-sub-stituted-pyridazines. Secondly, based on a comparison with the N-oxides of other pyridazines, the N-oxide of the 3-hydropyridazine resulted in unexpectedly high preemergence activity, yet without phytotoxicity to cotton. 

Figure 5. Herbicidal Activity as a Function of N-Oxidation of Selected Pyridazines...

Several 3-alkoxy- 4-methyl-6-phenylpyridazines, one of which is AC 247,909, have subsequently been disclosed as selective herbicides (JX)). A patent covering novel pyridazines and pyridazine N-oxides has been assigned to American Cyanamid (11). 

Free radicals have been generated by decarboxylation of carboxylic acids in the presence of silver ion. The resulting radicals reacted with pyridazines 205 to yield 206, which are intermediates in herbicide and fungicide synthesis (86USP4628088). 

Pyridazine derivatives influence plant growth " and are effective in weed control. - Herbicidal activity of aryloxypyridazines - and other pyridazines was investigated. - Maleic hydrazide has been used extensively as a sucker-inhibiting agent in tobacco fields in the United States. ... 

Pyridazine herbicides reduce or inhibit photosynthesis and carotenoid biosynthesis, - and they interfere with the formation of polar... 

Ring contraction occurs also on irradiation of pyridazine-3(2//)-ones to give a mixture of pyrrolines 278 and 279 (minor product).576 Similarly, 3-methyl-l-phenyl-hexahydropyridazine-6-one gives 280.577 However, photolysis of 5-amino-4-chloro-2-phenylpyridazine-3(2H)-one, a selective herbicide, in sunlight gives a mixture of 281 and 282, the last compound originating from 281.578 The first photoisomerization of 3-hydroxypyrid-azinium betaines into pyrimidinones converts 283 into 284 the mechanism proposed involves valence isomerization.579... 

The herbicidal properties of the pyridazine group were described by Fischer in 1962, and the first of them, pyrazon, 5-amino-4-chloro-2-phenyl-3-pyridazone (1), was introduced in 1962 by the BASF AG under the trade name Pyramin . 

For transplanted, submerged rice 3-(2-isopropylphenoxy)- and 3-(2-/i-butyl-phenoxy)pyridazines showed a remarkable margin of selectivity, but 3-(2-methylphenoxy)pyridazine exhibited the highest herbicidal activity. 

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