124495-18-7

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Agricultural fungicide.

Quinoxyfen is under development for the control of powdery mildew in cereals and grapes.

ChEBI: A member of the class of quinolines carrying two chloro substituents at positions 5 and 7 together with a 4-fluorophenoxy substituent at position 4. A fungicide used mainly to control powdery mildew in cereals.

Quinoxyfen is commercially produced through a multi-step synthesis starting with the Skraup reaction of 4-fluoroaniline with glycerol and an oxidizing agent to form 6-fluoroquinoline, followed by nitration to introduce a nitro group at the 5-position, reduction to the corresponding amine, and Sandmeyer reaction with copper(I) chloride to yield 5-chloro-6-fluoroquinoline. This intermediate undergoes nucleophilic aromatic substitution with 4-chlorophenoxide (generated from 4-chlorophenol under basic conditions) at the 2-position to form the active substance.

Systemic with protective properties, translocates and inhibits appressoria development stopping infections. Signal transduction

The stability of quinoxyfen in the soil has been shown to vary depending on soil type and source. DT₅₀ values obtained in the field varied from 5 to 454 days for a range of soil types. The strong adsorptive properties of quinoxyfen reduce its soil dissipation rate, but result in no leaching potential of this fungicide into waterways or groundwater. The primary metabolite formed in the soil is 3-hydroxyquinoxyfen . A secondary soil metabolite is 5,7-dichloro-4-hydroxyquinoline (DCHQ). DCHQ was also found not to leach, even in sandy soils. Under acidic aqueous conditions, DCHQ was the primary metabolite found, and this was produced in greater quantities at acidic pHs. An additional metabolite was isolated from both water and the sediment in an aqueous clay loam system. Although not positively identified, it is suspected to be 6-hydroxyquinoxyfen.
A similar hydrolysis profile is observed in water as in soil (3). The primary product produced under acidic conditions in the absence of light was DCHQ. However, in the presence of light, photolysis was greatly increased and dose dependent on the amount of sunlight received. The primary photolysis product was 2-chloro-10- fluoro[1]benzopyrano[2,3,4-de]quinoline (CFBPQ).

Quinoxyfen is a novel fungicide for the control of powdery mildew in cereals. Its mode of action is unknown but it appears to differ from those of current fungicides and thus may be novel (Longhurst et al., 1996). Quinoxyfen is tightly bound to soil components and is somewhat persistent in this medium but in aqueous solution it is subject to rapid photodecomposition. Photodegradation is therefore likely to be an important process in its immediate removal from the environment. Plant metabolites have not been reported but unchanged quinoxyfen has been confirmed as the major residue.
The compound is rapidly metabolised and eliminated following ingestion by rats and goats. Metabolism involves mainly hydroxylation of the intact quinoxyfen, cleavage at the ether bond and conjugation of the resulting metabolites. The information presented below was obtained from two sources (DowElanco, 1996; Reeves et al., 1996).

Quinoxyfen is stable in the dark at 25 °C and it is stable in aqueous solution at pH 7 and 9. Its DT₅₀ at pH 4 was 16 days (40°C) but it was degraded more rapidly than this in light. Aqueous photolysis of dilute solutions occurs with DT₅₀ values of 1.7 and 22.8 hours in June and December (Europe), respectively. The main degradation product was 2-chloro-10-fluoro[1]benzopyrano[2,3,4-de]quinoline (2, up to 30%); a second product (up to 11%) was probably 5,7-dichloro-4-hydroxyquinoline (3) (see Scheme 1).

The specificity of quinoxyfen to fungi may account for its relatively safe toxicological profile. Quinoxyfen has no demonstrable effect in any genotoxicity tests, and the rat oral LD₅₀ is >5000 mg/kg. Quinoxyfen was not shown to cause skin irritation, but studies with rabbit indicated it might cause mild eye irritation and it has the potential to cause skin sensitization, as shown in guinea pigs with repeated exposure. A NOEL of 20 mg/kg bw/day was established through 1-year and 2-year rat chronic feeding studies. The aquatic precautions with quinoxyfen may be due to its high logP. The rainbow trout LD₅₀ is 0.27 mg/L; however, this is well above its water solubility of 0.116 mg/L. In addition, the Daphnia 48h EC50 is 0.08 mg/kg and the Selenastrum capricornutum 72 h EbC50 is 0.03 mg/kg. With the exception of some aquatic species, quinoxyfen has a very desirable toxicological profile toward nontarget species in the environment. Its toxicity toward birds, honeybees, and earthworms is low.

Fungicide