Sulfonylureas degradation

SPE LC/MS/MS methods have been developed for the determination of polar pesticides (as propanyl, thiobencarb, diuron, simazine, bentazone etc.) and of their degradation products in waters with LOQ aronnd 25 ng L (Figure 18.1) [73], for the determination of chloroacetamide herbicides (LOD=25ng L ) [74], of sulfonylureas, bentazone, and phenoxyacids in river and drainage waters (LOD of the order of few ng L" ) [9]. 

An example of an API containing the sulfonylurea functionality is glibenclamide (Fig. 65) (107). Acid degradation produces the corresponding sulfonamide, amine, and carbon dioxide. 

Agrochemical Products. The principal thiophene derivative in herbicidal protection, one of a range of sulfonylurea herbicides, is Harmony [79277-27-3] (Du Pont) (60), based on the intermediate methyl 3-aminothiophene-2-carboxylate (9). The product is characterized by a rapid bio degradability in the soil. Many other thiophene derivatives have been shown to have agrochemical activity, but few of these have been developed to the commercial level. 

DineUi G., Di Martino E., and Vicari A. (1998) Influence of soil moisture and temperature on degradation of three sulfonylurea herbicides in soil. Agrochimica 42(1—2), 50-58. 

A multiple compartment system would probably be necessary to obtain a rate constant for metabolism, distribution rate constant, rate constant for absorption, etc. Sulfonylurea drugs may lower blood sugar by stimulating the beta cells of the pancreatic islets to release endogenous insulin. Also, it has been reported that the sulfonylureas block the degradation of insulin by the enzyme insulinase13. 

The last ten years have seen important developments in this respect in the three most important families of pesticides fungicides of the triazole group applied at about 100 g/ha, insecticides of the synthetic pyrethroid type at 20 g/ha and herbicides of the sulfonylurea type at 30 and even as little as 5 g/ha exert an effect which could be achieved with the pesticides of 15-20 years earlier only at rates of a few kilograms per hectare. These modern highly efficient preparations form only a small part of the selection of pesticides available today, but a rapid increase in their share of the total is to be expected as a result of purposeful research work. Another approach toward diminishing environmental contamination by chemicals is the development of new active substances which are less volatile, are degraded more rapidly or are more readily adsorbed by soil particles. 

Bossi, R., Vejrup, K., and Jacobsen, C. S., Determination of sulfonylurea degradation products in soil by liquid chromatography-ultraviolet detection followed by confirmatory liquid chromatography-tandem mass spectrometry, J. Chromatogr. A, 855, 575-582, 1999. 

Sulfonylurea herbicides (SUHs) are relatively new herbicides, introduced in the 1980s. Chlorsulfuron was the first sulfonylurea marketed in the United States, in 1982. World-wide, 19 sulfonylureas had been commercialized by 1994, and five more are being developed. This rapid increase is due to their very high and specific herbicidal activity, which results in extremely low application rates of 10 to 40 g/ha. Furthermore, as compared to other herbicides, sulfonylureas are less toxic and degrade more rapidly. Chemical structures of some representative sulfonylureas are presented in Figure 25.2. From a chemical point of view, these herbicides are labile and weakly acidic compounds. The common names, chemical formulas, water solubility, pKa, half-life in soil, and leaching potential through the soil (when available) of the most representative sulfonylureas are reported in Table 25.2. 

Sulfonylureas are systemic herbicides absorbed by the foliage and roots. They act by inhibiting acetolactate synthase, a key enzyme in the biosynthesis of branched chain aminoacids." This results in stopping cell division and plant growth. The most important degradation pathways of sulfonylureas are chemical hydrolysis and microbial degradation. 

Microsomes isolated from shoot tissues of etiolated wheat seedlings (Tritkum aestivum L. var. Olaf) oxidized the sulfonylurea herbicide prosulfuron (CGA 152005). Identification of the major oxidation product as l-(4-methoxy-6-methyl-l,3,5-triazin-2-yl)-3-[2-(3,3,3-trifluoropropyl)-5-hydroxyphenylsulfonyl]-urea 28 was confirmed by proton NMR spectroscopy (Figure 15). Proton NMR spectra of isolated minor oxidation products were not obtained because of insufficient sample size for analysis. However, these products were identified tentatively as l-[4-(hydroxymethyl)-6-methoxy-l,3,5-triazin-2-yl]-3-[2-(3,3,3-trifluoropropyl)phenylsulfonyl] urea 29 and an intermediate oxidation product l-[4-[(hydroxymethyl)oxy]-6-methyl]-l,3,5-triazin-2-yl]-3-[2-(3,3,3-trifluoropropyl)phenylsulfonyl]urea 30, that degraded to l-(4-hydroxy-6-methyl-l,3,5-triazin-2-yl)-3-[2-(3,3,3-trifluoropropyl)phenylsulfonyl]urea 31 <19%JFA3658>. 

The basis of selectivity of foramsulfuron in the presence of the safener isoxadifen-ethyl is a more rapid rate of metabolic detoxification in maize compared with target weeds, in which little or no degradation of the parent sulfonylurea occurs [51]. Three main routes of metabolism have been established in maize - a hydrolytic cleavage of the sulfonylurea bridge, a deformylation of the amino group and oxidative metabolism of the dimethoxypyrimidine ring. 

In the soil, there are two major pathways of sulfonylurea degradation [58] (a) chemical hydrolysis and (b) microbial degradation. The breakdown of sulfony-lureas in sterile soils is solely attributable to chemical hydrolysis, whereas breakdown in non-sterile soils is a combination of both microbial degradation and... 

The main soil degradation pathways of sulfonylurea herbicides are cleavage of the sulfonylurea bridge, O- and N-dealkylation reactions, aryl and aliphatic hydroxylation reactions, dehalogenation and ester hydrolysis. It is not within the scope of this chapter to discuss each of these in detail for all of the above-mentioned new sulfonylureas. Instead mesosulfuron-methyl is taken below as a general illustration of commonly found soil degradation pathways established within the sulfonylurea family. 

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