Air & Water Reactions

Insoluble in water.

Reactivity Profile

Triadimefon is incompatible with strong oxidizing agents and acids. Reacts with acid halides and anhydrides. Also reacts with most active hydrogen compounds .

Fire Hazard

Flash point data for Triadimefon are not available; however, Triadimefon is probably combustible.

Trade name

ACCOST?; ACIZOL?; AMIRAL?; BAY? 6681-F; BAYLETON?; BAY?-MEB-6447; BAYER? 6681-F; BAYER? MEB-6447; MEB 6447?; PRO-TEK?; ROFON?

Pharmacology

Triadimefon (36) and its alcohol analog triadimenol (37) have been intensively investigated to determine the influence of their enantiomeric difference on fungicidal activity. Between stereoisomeric triadimefon, no significant difference is observed in their fungicidal activity. However, triadimenol, which shows a much higher fungicidal activity than triadimefon, exhibits a clear stereochemistry-dependent activity difference. Greater fungicidal activity is possessed by the (1S, 2R)-isomer (28).

Safety Profile

Poison by ingestion. Mutation data reported. When heated to decomposition it emits very toxic fumes of Cland NOx. See also KETONES.

Environmental Fate

Soil. In a culture study, the microorganism Aspergillus niger degraded 32% of tri- adimefon to triadimenol after 5 days (Clark et al., 1978).Plant. In soils and plants, triadimefon degrades to triadimenol (Clark et al., 1978; Rouchaud et al., 1981). In barley plants, triadimefon was metabolized to triadimenol and p-chlorophenol (Rouchaud et al., 1981; Rouchaud, 1982). In the grains anPhotolytic. When triadimefon was subjected to UV light for one week, p-chlorophenol, 4-chlorophenyl methyl carbamate and a 1,2,4-triazole formed as products (Clark et al., 1978).

Metabolic pathway

Enzymic reduction of triadimefon is an important pathway in plants, soils and fungi and may be regarded as an activation process, which produces fungicidally active triadimenol. Two diastereoisomers of triadimenol, A and B [( 1RS,2SR)-l-(4-chlorophenoxy)-3,3-dimethyl-1-(1H-1,2,4-triazol-1-yl) butan-2-ol is referred to as diastereoisomer A; 1RS,2RS- is referred to as diastereoisomer β], are produced in different amounts by plants and fungi and the proportions may differ within the plant. Similar metabolic pathways are followed in mammals where reduction of the keto group yields triadimenol as the principal metabolite and oxidation of the butyl group gives alcohol and carboxylic acid derivatives.

Degradation

Triadimefon is stable to hydrolysis with a DT50 of more than 1 year at pH 3,6 and 9 (22 °C). On photolysis in methanol in borosilicate glass apparatus using a medium pressure mercury lamp, triadimefon undergoes cleavage of the C-1-N bond giving 1,2,4-triazole (2), 4-chlorophenyl methyl carbonate (3) and 4-chlorophenol(4) (Clark et al., 1978) (Scheme 1). Sensitised photolysis of triadimefon irradiated by light from a highpressure mercury lamp, with a Pyrex filter to exclude wavelengths below 290 nm, in the presence of fulvic acid and humic acid gave a variety of products. In water, the products formed were 4 and a dihydroxychlorobenzene (5). Although there are some ambiguities in the report concerning the allocation of structures to the compounds obtained, these included a dihydroxybenzaldehyde (6) and 5-chlorosalicylaldehyde (7). Major products in the presence of fulvic acid were 4 and a dihydroxychlorobenzene (5). In the presence of humic acid 4,5, a dihydroxybenzaldehyde (6) and 1-phenoxy-33-dimethyl-1- ( 1H-1,2,4-triazol-l- yl) -2-butanone (8) were formed (Moza et al., 1995).

Toxicity evaluation

Triadimefon inhibits the lanosterol demethylase, thereby interfering with ergosterol synthesis that is necessary for the integrity of fungal cell walls. This action confers specificity for fungi over vertebrates; however, by a similar mechanism triazoles have been reported to disrupt steroid and cholesterol metabolism in mammals. Perturbations of fatty acid, steroid, and xenobiotic metabolism pathways in liver through specific nuclear signaling pathways (constitutive androstane receptor (CAR) and pregnane X receptor (PXR)) have been suggested to contribute to the observed reproductive and hepatic toxicities. Triadimefon also both inhibits and induces specific hepatic cytochrome P-450 enzymes. A series of studies comparing triadimefon with other two conazoles (propiconazole and myclobutanil) have shown different modes of action in terms of carcinogenicity, hepatotoxicity, and developmental and reproductive toxicities. Studies in several species have shown that neurotoxicity is the endpoint of concern with both acute and repeated exposures to triadimefon and triadimenol. Triadimefon causes accumulation of synaptic dopamine, both in vivo and in vitro. Pharmacological challenges and neurochemical studies have shown that triadimefon blocks dopamine reuptake by binding to the dopamine transporter in a manner similar to other indirect dopamine agonists, such as cocaine and d-amphetamine.

General Description

Colorless to pale yellow crystalline solid with a slight odor.

Agricultural Uses

Fungicide: Triadimefon is a systemic fungicide that is used to control powdery mildews, rusts, and other fungi on coffee, seed grasses, cereals, fruits, grapes, vegetables, vines, pineapple, sugar cane, sugar beets, turf, shrubs, and trees. Not approved for use in EU countries. Registered for use in the U.S. U.S. Maximum Allowable Residue Levels for Triadimefon