Pyrimidines, herbicidal

The most commonly used pyrimidine herbicides are the uracils, e.g. bromacil and terbacil, which have the following structures... 

Application of Global Sequence Similarity to Find an Inhibitor of Acetolactate Synthase. Acetolactate synthase (ALS) Is the site of action of sulfonylurea, Imldazollnone, and trlazolo pyrimidine herbicides (10-14). Their mode of Inhibition and binding sites on ALS were ambiguous, because (1) these herbicides bear no obvious similarity In their chemical structures to those of ALS substrates (pyruvate and acetolactate), cofactors (thiamine pyrophosphate, FAD, and Mg ) and effectors (valine, Isoleuclne, and leucine) and (2) they Inhibit ALS In a mode too complex to be analyzed. 

Pyrimido[4,5-d]pyrimidin-4(3H)-one, 2,5,7-trialkyl-herbicidal activity, 3, 368 Pyrimido[ 1,2-a ]pyrimidin-2-ones hydrobromide H NMR, 3, 337 UV spectra, 3, 338 Pyrimido[ 1,2-a]pyrimidin-4-ones... 

As sulfones are known to be readily displaced from electron deficient nitrogen-containing heterocycles, Bessard noted significant rate enhancements as well as improved yields in the displacement of the chloride on pyrimidine 49 by alcohols, through the use of sodium methylsulfinate as a catalyst <00T4739>. The production of trialkoxypyrimidines 51 as potential herbicides, presumably formed from the displacement of methysulfinate from intermediate 50 by the various alcohols, required a less than a stoichiometric amount of sodium methylsulfinate (typically 0.10-0.25 equivalents). 

The uracils with herbicidal activity do not necessarily contain 5-halo substituents. 3-Cyclohexyl-5-methyluracil [354] (XLIV), l,3-di-isopropyl-6-methyl-uracil [352] (XLV) and 3-s-butyl-5-thiocyanato-6-methyluracil [353] (XLVI), for example, are cited as having this type of activity. 3-Butyl-6-methyluracil (XLlllc) possesses interesting selective activities. For instance, this pyrimidine kills many annual weed species without damage to peas and peanuts, even when applied at twice the concentration needed to kill the weeds [346]. On the other hand, the related 5-bromo derivatives, such as (XLlIlb), are useful as industrial herbicides where it is desirable to kill all plants [346]. 

In summary, the sulfonylureas are new herbicides which exhibit activity at extremely low rates of application and show very low mammalian toxicity. Exceptionally high activity is shown by compounds containing a benzene ring substituted in the ortho position, an unsubstituted sulfonylurea bridge, and a pyrimidine or triazine heterocycle substituted with methyl or methoxy groups. 

There are several commercially available sulfonylurea herbicides that contain a 2-pyrimidine group <2006H(68)561>. These compounds, which function by inhibition of acetolactate synthase (ALS), an enzyme involved in the early stage of branched-chain amino acid synthesis, include sulfometuron-methyl 1095, primisulfuron-methyl 1096, chlorimuron-ethyl 1097, bensulfuron-methyl 1098, ethoxysulfuron 1099, nicosulfuron 1100, and pyrazosulfuron-ethyl 1101. Related nonsulfonylureas include the sulfide pyrftalid 1102 and the ether pyriminobac-methyl 1103. 

Similar to pyrazolo[l,5-a]pyrimidines certain pyrazolo[3,4-4]pyrimidines exhibit phosphodiesterase inhibitory action (68MI1). Herbicidal activity of pyrazolo[3,4-4]pyrimidines has also been observed (79MIP354186). 

As active transport uses a carrier system, it is normally specific for a particular substance or group of substances. Thus, the chemical structure of the compound and possibly even the spatial orientation are important. This type of transport is normally reserved for endogenous molecules such as amino acids, required nutrients, precursors, or analogues. For example, the anticancer drug 5-fluorouracil (Fig. 3.6), an analogue of uracil, is carried by the pyrimidine transport system. The toxic metal lead is actively absorbed from the gut via the calcium transport system. Active uptake of the toxic herbicide paraquat into the lung is a crucial part of its toxicity to that organ (see chap. 7). Polar and nonionized molecules as well as lipophilic molecules may be transported. As active transport may be saturated, it is a zero-order rate process in contrast to passive diffusion (Fig. 3.3). 

Compounds 272 are useful as herbicides and inhibitors of nitrification of amino nitrogen in soil, and they are used for the control of Echinochioa crusgalli without damage to rice. 5-Fluoromethyl-7-methoxy-l,2,4-triazolo-[l,5-a]pyrimidine-2-sulfonamides are useful for the control of pigweed (85USP4818273). 

Dialkyl- and 2,5,7-trialkyl-pyrimido[4,5-d]pyrimidin-4(3H)-ones have been found to possess pre- and post-emergence herbicidal activity (74USP3830812). 2,4,7-Triamino-5-phenylpyrimido[4,5-if]pyrimidine has diuretic activity similar to triamterene (6-phenyl-2,4,7-pteridinetriamine) (68JMC573). 

A number of 1,2,4-triazines are of interest owing to their biological activity. 1,2,4-Triazine-3,5-diones (6) represent aza analogues of pyrimidine nucleic acid bases, a number of natural antibiotics are derivatives of pyrimido[5,4-e][l,2,4]triazine (7), and 4-amino-6-r-butyl-3-methylthio-l,2,4-triazin-5-one (8) and 4-amino-3-methyl-6-phenyl-l,2,4-triazin-5-one (9) are used as herbicides. 

Dichloroacetyl)-3,3,9a-trimethylperhydropyrido[ 1,2-u]pyrimidin-6-one was applied in herbicidal compositions as a sefaner (99EUP901752). 

Indolin-2-on-3yl)hydrazino-5,6,7,8-tetrahydrobenzo[fe]thieno[2,3-d]-pyrimidine 185 showed 10-20% herbicidal activity against pigweed, velvet leaf, red millet, green foxtail, and soya bean (81JHC1277). 

ALS herbicides. Two classes of ALS-inhibiting herbicides are the sulfonylurea herbicides, discussed in Sections 2.1.2.1 and 2.2.3.1, and the imidazolinone herbicides. A third class of ALS-inhibiting herbicides is the 1,2,4-triazolo [1,5-a]pyrimidine-2-sulfonanilides. The triazolopyrimidine sulfonanilides act by disrupting the biosynthesis of branched chain amino acids in plants. Representatives of this class of herbicides include florasulam (Boxer , Nikos ) [151], initially introduced in Belgium in 1999 and used for the postemergence control of broadleaf weeds in cereals and corn, and flumetsulam (Broadstrike ) [152], used alone or in combination with other herbicides for the control of broadleaf weeds in soybean and corn. 

The point arose as to the actual site of action of moniliformin in plants. Earlier, it had been stated that the geometrical criteria of hydrogen bond formation suggested that MH could be regarded as either a purine or pyrimidine analogue and, therefore, could substitute as one of the base pairs in nucleic acid.11 And the fact that it had shown plant growth regulatory activity had led an industrial company to become interested in the product as a potential herbicide. 

In every study, light was required for the effects of the inhibitors to become apparent. Chloroplasts of herbicide-treated plants kept in the dark resembled, in all respects, chloroplasts of the dark-control plants. The modifications produced in chloroplasts are not unique to herbicides. Mineral and vitamin deficiencies, antibiotics, unnatural pyrimidines, and genetic alterations all cause similar aberrant ultrastruetural changes in chloroplasts however, the extent of the disruptions produced by herbicides is more extreme. The changes induced by herbicides are similar in many respects to those that occur in normal senescence, reflecting the characteristic pattern associated with degeneration and death of a cell. 

A group of 3-oxoisothiazolopyrimidines (164) have been patented for their ability to inhibit human blood platelet aggregation (77GEP2718707). 3,6-Dialkylisothiazolo[3,4-d]pyrimidin-4(5H)-ones (165) show useful herbicidal activity (73GEP2249099). 

Uses herbicide, soyabeans, maize Trade names Broadstrike, (DowElanco) Type pyrimidine, triazole, sulfonamide... 

SU and IM (Figure 1), are proprietary chemistry of DuPont (2.3) and American Cyanamid (4), respectively. The substituted 1,2,4-tria-zolo[l,5-a]pyrimidines (TP, Figure 1) are a new class of herbicides under development at Dow Chemical Co. (5). A number of reviews have already appeared on the biology and biochemistry of SU (6-10) and IM (1LJL2). Hence, the focus of this article has been on the work done at our premises on TP. Wherever appropriate, our results have been compared with those of SU and IM. 

Radiolabelled derivatives of the herbicide florasulam (N-(2,6-difluo-rophenyl)-5-methoxy-8-fluoro(l,2,4)-triazolo-[l,5-c]-pyrimidine-2-sulphon-amide) (VII) were exposed to natural sunlight in a sterile pH 5 buffer water and in a natural lake water collected from 20 to 30 cm below the surface [70]. The photo degradation was much faster in the natural water system, with a half-life of 3.3 days against 73 days in the buffered aqueous medium. Moreover, the photoproducts produced in the distilled and natural waters were found to be different. Direct photolysis led to the cleavage of the N - S bond with formation of the sulphonic acid derivative (Vila) after 10% of conversion (see Scheme 7). 

Similar to their [4,3-c] isomers [99AHC(75)243], 1,2,4-triazolo [l,5-c]pyrimidines displayed numerous biological and medicinal activities. In addition, the [1,5-c] isomers found useful agrochemical applications as herbicides. 

These two herbicides have been prepared177 by condensation of 14C-labelled heterocycles 179 and 180 with methyl 2-(sulphonylisocyanate)benzoate 178 (equations 65 and 66). [2-14C] 2-Amino-4,6-dimethyl pyrimidine 179 has been obtained from [14C]guani-... 

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