Triadimefon

Description

Triadimefon has been a widely used fungicide on crops and nonfood products since the early 1970s. The metabolite triadimenol is also active and is registered separately for use as seed treatment. Triadimenol has a broad regulatory toxicology database, but its toxicity is considered to be encompassed in that of triadimefon and therefore the same study was used by the United States Environmental Protection Agency (US EPA) in establishing regulatory levels for both pesticides. In nontarget species, dopaminergic neurotoxicity is the primary effect, but with chronic exposures its toxicities include hepatic, carcinogenic, developmental, and reproductive effects.

Chemical Properties

Colorless crystal. Solubility in water is 260mg/L at 20°C. Easily soluble in cyclohexanone, dichloromethane, soluble in isopropanol, toluene. Stable under acidic and alkaline conditions.

Uses

Systemic fungicide used to control mildews and rusts that attack coffee, cereals, stone fruit, grapes and ornamentals.

Uses

Triadimefon is used for the control of powdery mildews in cereals, pome fruit, stone fruit, berry fruit, vines, hops, cucurbits, tomatoes, vegetables, sugar beet, mangoes, ornamentals, turf, flowers, shrubs and trees, Monilinia spp. in stone fruit, black rot of grapes, leaf blotch, leaf spot and snow mould in cereals, pineapple disease butt rot in pineapples and sugar cane, leaf spots and flower blight in flowers, shrubs and trees and many other diseases of turf.

Uses

antifungal, P450 inhibitor

Uses

Triadimefon is an triazole fungicide is used for the management of mango powdery mildew in South Gujarat.

Uses

Systemic agricultural fungicide.

Definition

ChEBI: 1-(4-chlorophenoxy)-3,3-dimethyl-1-(1,2,4-triazol-1-yl)butan-2-one is a member of the class of triazoles that is 1-hydroxy-3,3-dimethyl-1-(1,2,4-triazol-1-yl)butan-2-one in which the hydroxyl hydrogen is replaced by a 4-chlorophenyl group. It is a member of triazoles, a member of monochlorobenzenes, an aromatic ether, a ketone and a hemiaminal ether.

General Description

Colorless to pale yellow crystalline solid with a slight odor.

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.

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

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.

Synthesis

A, ammonium formate and hydrazine hydrate into the condensation kettle, warming, when the temperature is 140 , dropwise addition of hydrazine hydrate, dropwise addition of the end of the temperature, warming to 160 , holding reaction for 3 hours, dehydration for 1 hour, after the end of the reaction, the ammonia generated by the tertiary absorption of water, crystal centrifugation, the solid is a triazole;

B, will be p-chlorophenol, potassium carbonate dissolved in dichloromethane, to get a mixed System, warming to 100 to the mixed system dropwise addition of monochloropinacolone, holding time 4h, to get intermediate 1;

C, thionyl chloride drops added to intermediate 1 dichloromethane solution (thionyl chloride and intermediate 1 of the molar ratio of 1.5:1), and then at 50 holding time of 3 hours, sampling qualitatively qualified, the use of water circulating vacuum pump with a negative pressure, slowly warm up, pumping the exhaust to the tertiary water absorption, and then into the tertiary alkali absorption. Then enter the three-stage alkali absorption. Decrease the temperature to 50 , transfer to the condensation kettle;

D, triazole added to the mixed system of step C, and then warmed to 100 insulation for 3 hours, the end of the insulation, cooled down to less than 100 , add water stirring for 30 minutes, static separation of the water layer, put the material into the filtration, filtration of toluene solution into the distillation kettle, the product centrifugal drying and then drying to get triazolone.

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 an
Photolytic. 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.