Fluazifop

Fluazifop
	; Fluazifop-P (R isomer)
Names
	IUPAC name (2R)-2-(4-([5-(trifluoromethyl)-2-pyridyl]oxy)phenoxy)propanoic acid
	Preferred IUPAC name (2R)-2-(4-([5-(trifluoromethyl)pyridin-2-yl]oxy)phenoxy)propanoic acid
	Other names PP005, SL118
Identifiers
	Compounds; (RS): Fluazifop; (R): Fluazifop-P; (R) butyl ester: Fluazifop-P butyl ester;
CAS Number	(RS): 69335-91-7 ; (R): 83066-88-0 ; (R) butyl ester: 79241-46-6 ;
3D model (JSmol)	(R): Interactive image ;
ChEBI	(RS): CHEBI:83598 ; (R) butyl ester: CHEBI:132964 ;
ChEMBL	(RS): ChEMBL376218 ;
ChemSpider	(RS): 82803 ; (R): 82832 ; (R) butyl ester: 2298297 ;
ECHA InfoCard	100.130.325
EC Number	(RS):614-949-9; (R) butyl ester:616-669-2;
PubChem CID	(RS): 91701 ; (R): 91733 ; (R) butyl ester: 3033674 ;
UNII	(RS): 8JD49YW45K ;
CompTox Dashboard (EPA)	(RS): DTXSID3058163 ;
	InChI (RS):InChI=1S/C15H12F3NO4/c1-9(14(20)21)22-11-3-5-12(6-4-11)23-13-7-2-10(8-19-13)15(16,17)18/h2-9H,1H3,(H,20,21) Key: YUVKUEAFAVKILW-UHFFFAOYSA-N; (R):InChI=1S/C15H12F3NO4/c1-9(14(20)21)22-11-3-5-12(6-4-11)23-13-7-2-10(8-19-13)15(16,17)18/h2-9H,1H3,(H,20,21)/t9-/m1/s1 Key: YUVKUEAFAVKILW-SECBINFHSA-N; (R) butyl ester:Key: VAIZTNZGPYBOGF-CYBMUJFWSA-N;
	SMILES (R):C[C@H](C(=O)O)Oc1ccc(cc1)Oc2ccc(cn2)C(F)(F)F;
Properties
Chemical formula	C15H12F3NO4
Molar mass	327.259 g·mol−1
Solubility in water	40.5 mg/L (20 °C)
log P	3.18
Acidity (pKa)	3.12
Hazards
	GHS labelling:
Pictograms
Signal word	Warning
Hazard statements	H361, H410
Precautionary statements	P201, P202, P273, P281, P308+P313, P391, P405, P501
Flash point	225 °C (437 °F; 498 K)
	Except where otherwise noted, data are given for materials in their standard state (at 25 °C [77 °F], 100 kPa). Infobox references

Last updated July 25, 2023

Fluazifop is the common name used by the ISO ^[3] for an organic compound that is used as a selective herbicide.^[4] The active ingredient is the 2R enantiomer at its chiral centre and this material is known as fluazifop-P when used in that form. More commonly, it is sold as its butyl ester, fluazifop-P butyl with the brand name Fusilade.

History

In the 1970s, a number of agrochemical companies were working to develop new herbicides to be complementary to the auxin phenoxyacetic acid types such as 2,4-D, which had activity on broad-leaved weeds but were safe to grass crops such as the cereals. Thus the aim was to find materials which would selectively control grass weeds in broad-leaved crops such as cotton and soybean.

Diclofop: X = CH, R = R = Cl Chlorazifop: X = N, R = R = Cl Fluazifop: X = N, R = CF3, R = H Haloxyfop: X = N, R = CF3, R = Cl Aryloxyphenoxypropionate.svg — Diclofop: X = CH, R = R = Cl Chlorazifop: X = N, R = R = Cl Fluazifop: X = N, R = CF₃, R = H Haloxyfop: X = N, R = CF₃, R = Cl

In 1973, Hoechst AG filed patents on a new class of compound, the aryloxphenoxypropionates, which showed such selectivity and led to the commercialisation of diclofop. Then the Japanese company Ishihara Sangyo Kaisha (ISK) found improved biological activity in an analogue, chlorazifop, which replaced the aryloxy portion of diclofop with a pyridine ring containing the same two chlorine substituents. This area of research became very competitive and within three weeks of one another in 1977 ISK, Dow Chemicals and Imperial Chemical Industries (ICI) all filed patents covering another group of analogues, with a trifluoromethyl (CF₃) group in place of one of the chlorine atoms in the pyridine. Subsequently, ISK and ICI cross-licensed their intellectual property and first marketed fluazifop as its butyl ester in 1981 under the brand name Fusilade^[1] while Dow marketed haloxyfop as its methyl ester.^[5] All these compounds have an additional oxygen-linked aromatic group in the para position of the phenyl ring with its OCH(CH₃)COOH group and as a class are called "fops", referring to their common fenoxy-phenoxy [sic] feature.^[6] (In other words, fops are a subtype of ACCase herbicides, specifically the aryloxyphenoxypropionates.)^[7]^[8]^[9]

Synthesis

The preparation of fluazifop butyl ester as a racemate was disclosed in patents filed by ICI^[10] and ISK.^[11] Hydroquinone is combined to form ethers with 2-chloro-5-trifluoromethyl pyridine and the butyl ester of 2-bromopropionic acid: these nucleophilic substitution reactions can be performed in either order. The compound is now sold in its single-enantiomer form by Syngenta and other manufacturers.^[12] It is produced from chiral starting materials such as alanine and lactic acid.^[13]

Mechanism of action

Fluazifop and other similar herbicides act by inhibiting plant acetyl-CoA carboxylase (ACCase).^[14]^[15]^[6] Their selectivity for grasses arises because they target the plastid isoform of the enzyme present only in these species, making them ineffective on broad-leaved weeds and other organisms including mammals.^[16] When applied as an ester, metabolism in the target plant leads to the parent acid which is responsible for the herbicidal action.^[5]

Usage

The estimated annual use of fluazifop in US agriculture is mapped by the US Geological Service and shows that in 2018, approximately 200,000 pounds (91,000 kg) were applied — almost exclusively in soyabean. The earlier much higher figure is partly because the compound was initially used as its racemate.^[17] The herbicide is also registered for use in the European Union under EC Regulation 1107/2009.^[1]^[18]

Human safety

The LD₅₀ of fluazifop-P butyl is 2451 mg/kg (rats, oral), which means that it has low toxicity by oral ingestion. It metabolises in plants and soil to the parent acid, fluazifop-P.^[1] The World Health Organization (WHO) and Food and Agriculture Organization (FAO) joint meeting on pesticide residues has determined that the acceptable daily intake for fluazifop is 0-0.004 mg/kg bodyweight.^[19] The Codex Alimentarius database maintained by the FAO lists the maximum residue limits for fluazifop in various food products, some of which are set at its 0.01 mg/kg limit of detection while others are much higher, including soyabean at 15 mg/kg.^[20]

Effects on the environment

The environmental fate and ecotoxicology of fluazifop-P are summarised in the Pesticide Properties database^[1] and a very extensive risk assessment of the compound was made by the USDA Forest Service.^[21]

Resistance Management

There are many reports of individual weed species becoming resistant to fluazifop^[22]^[23] and other ACCase inhibitors.^[8]^[9] These are monitored by manufacturers, regulatory bodies such as the EPA and the Herbicides Resistance Action Committee (HRAC).^[24] In some cases, the risks of resistance developing can be reduced by using a mixture of two or more herbicides which each have activity on relevant weeds but with unrelated mechanisms of action. HRAC assigns active ingredients into classes so as to facilitate this.

Related Research Articles

Herbicides, also commonly known as weed killers, are substances used to control undesired plants, also known as weeds. Selective herbicides control specific weed species while leaving the desired crop relatively unharmed, while non-selective herbicides can be used to clear waste ground, industrial and construction sites, railways and railway embankments as they kill all plant material with which they come into contact. Apart from selective/non-selective, other important distinctions include persistence, means of uptake, and mechanism of action. Historically, products such as common salt and other metal salts were used as herbicides, however, these have gradually fallen out of favor, and in some countries, a number of these are banned due to their persistence in soil, and toxicity and groundwater contamination concerns. Herbicides have also been used in warfare and conflict.

<span class="mw-page-title-main">Triclopyr</span> Chemical compound used as a herbicide

Triclopyr is an organic compound in the pyridine group that is used as a systemic foliar herbicide and fungicide.

MCPA is a powerful, selective, widely used phenoxy herbicide. The pure compound is a brown-colored powder. MCPA has been extensively used in agriculture to control broad-leaf weeds as a growth regulator primarily in pasture and cereal crop fields since 1945. The mode of action of MCPA is as an auxin, which are growth hormones that naturally exist in plants. Overdose application of MCPA acts as an herbicide and results in abnormal growth.

Diquat is the ISO common name for an organic dication that, as a salt with counterions such as bromide or chloride is used as a contact herbicide that produces desiccation and defoliation. Diquat is no longer approved for use in the European Union, although its registration in many other countries including the USA is still valid.

<span class="mw-page-title-main">Phenoxy herbicide</span> Class of herbicide

Phenoxy herbicides are two families of chemicals that have been developed as commercially important herbicides, widely used in agriculture. They share the part structure of phenoxyacetic acid.

Glufosinate is a naturally occurring broad-spectrum herbicide produced by several species of Streptomyces soil bacteria. Glufosinate is a non-selective, contact herbicide, with some systemic action. Plants may also metabolize bialaphos and phosalacine, other naturally occurring herbicides, directly into glufosinate. The compound irreversibly inhibits glutamine synthetase, an enzyme necessary for the production of glutamine and for ammonia detoxification, giving it antibacterial, antifungal and herbicidal properties. Application of glufosinate to plants leads to reduced glutamine and elevated ammonia levels in tissues, halting photosynthesis and resulting in plant death.

<span class="mw-page-title-main">Sulfentrazone</span> Chemical compound

Sulfentrazone is the ISO common name for an organic compound used as a broad-spectrum herbicide. It acts by inhibiting the enzyme protoporphyrinogen oxidase. It was first marketed in the US in 1997 by FMC Corporation with the brand name Authority.

<span class="mw-page-title-main">Saflufenacil</span> Chemical compound

Saflufenacil is the ISO common name for an organic compound of the pyrimidinedione chemical class used as an herbicide. It acts by inhibiting the enzyme protoporphyrinogen oxidase to control broadleaf weeds in crops including soybeans and corn.

Dimethyl tetrachloroterephthalate (DCPA, with the main trade name Dacthal) is an organic compound with the formula C₆Cl₄(CO₂CH₃)₂. It is the dimethyl ester of tetrachloroterephthalic acid, used as a preemergent herbicide with the ISO common name chlorthal-dimethyl. It kills annual grasses and many common weeds without killing sensitive plants such as turf grasses, flowers, fruits, vegetables, and cotton.

<span class="mw-page-title-main">Mesotrione</span> Chemical compound used as an herbicide

Mesotrione is the ISO common name for an organic compound that is used as a selective herbicide, especially in maize. A synthetic inspired by the natural substance leptospermone, it inhibits the enzyme 4-hydroxyphenylpyruvate dioxygenase (HPPD) and is sold under brand names including Callisto and Tenacity. It was first marketed by Syngenta in 2001.

2,4-Dichlorophenoxyacetic acid is an organic compound with the chemical formula C₈H₆Cl₂O₃ which is usually referred to by its ISO common name 2,4-D. It is a systemic herbicide which kills most broadleaf weeds by causing uncontrolled growth in them but most grasses such as cereals, lawn turf, and grassland are relatively unaffected.

Acifluorfen is the ISO common name for an organic compound used as an herbicide. It acts by inhibiting the enzyme protoporphyrinogen oxidase which is necessary for chlorophyll synthesis. Soybeans naturally have a high tolerance to acifluorfen and its salts, via metabolic disposal by glutathione S-transferase. It is effective against broadleaf weeds and grasses and is used agriculturally on fields growing soybeans, peanuts, peas, and rice.

4-Hydroxyphenylpyruvate dioxygenase (HPPD) inhibitors are a class of herbicides that prevent growth in plants by blocking 4-Hydroxyphenylpyruvate dioxygenase, an enzyme in plants that breaks down the amino acid tyrosine into molecules that are then used by plants to create other molecules that plants need. This process of breakdown, or catabolism, and making new molecules from the results, or biosynthesis, is something all living things do. HPPD inhibitors were first brought to market in 1980, although their mechanism of action was not understood until the late 1990s. They were originally used primarily in Japan in rice production, but since the late 1990s have been used in Europe and North America for corn, soybeans, and cereals, and since the 2000s have become more important as weeds have become resistant to glyphosate and other herbicides. Genetically modified crops are under development that include resistance to HPPD inhibitors. There is a pharmaceutical drug on the market, nitisinone, that was originally under development as an herbicide as a member of this class, and is used to treat an orphan disease, type I tyrosinemia.

<span class="mw-page-title-main">Imazaquin</span> Chemical compound

Imazaquin is an imidazolinone herbicide, so named because it contains an imidazolinone core. This organic compound is used to control a broad spectrum of weed species. It is a colorless or white solid, although commercial samples can appear brown or tan.

<span class="mw-page-title-main">Bifenox</span> Chemical compound

Bifenox is the ISO common name for an organic compound used as an herbicide. It acts by inhibiting the enzyme protoporphyrinogen oxidase which is necessary for chlorophyll synthesis.

<span class="mw-page-title-main">Fomesafen</span> PPOi herbicide

Fomesafen is the ISO common name for an organic compound used as an herbicide. It acts by inhibiting the enzyme protoporphyrinogen oxidase (PPO) which is necessary for chlorophyll synthesis. Soybeans naturally have a high tolerance to fomesafen, via metabolic disposal by glutathione S-transferase. As a result, soy is the most common crop treated with fomesafen, followed by other beans and a few other crop types. It is not safe for maize/corn or other Poaceae.

<span class="mw-page-title-main">Indaziflam</span> Preemergent herbicide discovered in 2009

Indaziflam is a preemergent herbicide especially for grass control in tree and bush crops.

<span class="mw-page-title-main">Butafenacil</span> Chemical compound

Butafenacil is the ISO common name for an organic compound of the pyrimidinedione chemical class used as an herbicide. It acts by inhibiting the enzyme protoporphyrinogen oxidase to control broadleaf and some grass weeds in crops including cereals and canola.

<span class="mw-page-title-main">Aclonifen</span> Chemical compound

Aclonifen is a diphenyl ether herbicide which has been used in agriculture since the 1980s. Its mode of action has been uncertain, with evidence suggesting it might interfere with carotenoid biosynthesis or inhibit the enzyme protoporphyrinogen oxidase (PPO). Both mechanisms could result in the observed whole-plant effect of bleaching and the compound includes chemical features that are known to result in PPO effects, as seen with acifluorfen, for example. In 2020, further research revealed that aclonifen has a different and novel mode of action, targeting solanesyl diphosphate synthase which would also cause bleaching.

Tribenuron in the form of tribenuron-methyl is a sulfonylurea herbicide. Its mode of action is the inhibition of acetolactate synthase, group 2 of the Herbicide Resistance Action Committee's classification scheme.

References

1 2 3 4 5 Pesticide Properties Database. "Fluazifop-P". University of Hertfordshire . Retrieved 2021-02-25.
↑ PubChem Database. "Fluazifop" . Retrieved 2021-02-25.
↑ "Compendium of Pesticide Common Names: fluazifop". British Crop Production Council (BCPC).
↑ Pesticide Properties Database. "Fluazifop-P butyl". University of Hertfordshire. Retrieved 2021-02-25.
1 2 Evans, D. (1992). "Designing more efficient herbicides" (PDF). Proceeding of the First International Weed Control Congress , Melbourne. pp. 37–38. Retrieved 2021-02-27.
1 2 Rani, Priyanka; Kumari, Juli; Agarwal, Shikha; Singh, Durg Vijay (2019). "Binding mode of aryloxyphenoxypropionate (FOP) and cyclohexanedione (DIM) groups of herbicides at the carboxyl transferase (CT) domain of Acetyl-CoA carboxylase of Phalaris minor". Network Modeling Analysis in Health Informatics and Bioinformatics. 8. doi:10.1007/s13721-019-0190-8. S2CID 152283206.
↑ "aryloxyphenoxypropionic herbicides". alanwood.net. Retrieved 2021-02-27.
1 2 Collavo, A.; Panozzo, S.; Lucchesi, G.; Scarabel, L.; Sattin, M. (2011). "Characterisation and management of Phalaris paradoxa resistant to ACCase-inhibitors". Crop Protection . 30 (3): 293–299. doi:10.1016/j.cropro.2010.11.011. S2CID 84631177.
1 2 Kaundun, Shiv S (2014-05-06). "Resistance to acetyl-CoA carboxylase-inhibiting herbicides". Pest Management Science . 70 (9): 1405–1417. doi:10.1002/ps.3790. PMID 24700409. S2CID 42537130.
↑ WOpatent 7900094,Cartwright D.,"Herbicidal pyridine compounds", assigned to ICI Ltd.
↑ GBpatent 1599126,Ishihara Sangyo Kaisha Ltd,"An α-[4-(5-fluoromethyl-2-pyridyloxy)phenoxy]alkanecarboxylic acid derivative and its use as a herbicide", assigned to ISK Ltd.
↑ Syngenta. "Fusilade DX" . Retrieved 2021-02-27.
↑ Fleer, Michel P. M.; Verkuijl, Bastiaan J. V. (2014). "Optimization of the use of a chiral bio-based building block for the manufacture of DHPPA, a key intermediate for propionate herbicides". Green Chemistry. 16 (8): 3993. doi:10.1039/C4GC00797B.
↑ Walker, K. A.; Ridley, S. M.; Lewis, T.; Harwood, J. L. (1988). "Fluazifop, a grass-selective herbicide which inhibits acetyl-CoA carboxylase in sensitive plant species". Biochemical Journal. 254 (1): 307–310. doi:10.1042/bj2540307. PMC 1135074 . PMID 2902848.
↑ Lichtenthaler, Hartmut K. (1990). "Mode of Action of Herbicides Affecting Acetyl-CoA Carboxylase and Fatty Acid Biosynthesis". Zeitschrift für Naturforschung C. 45 (5): 521–528. doi: 10.1515/znc-1990-0538 . S2CID 27124700.
↑ Price, Lindsey J.; Herbert, Derek; Moss, Stephen R.; Cole, David J.; Harwood, John L. (2003). "Graminicide insensitivity correlates with herbicide-binding co-operativity on acetyl-CoA carboxylase isoforms". Biochemical Journal. 375 (2): 415–423. doi:10.1042/bj20030665. PMC 1223688 . PMID 12859251.
↑ US Geological Survey (2021-10-12). "Estimated Agricultural Use for Fluazifop, 2018" . Retrieved 2021-12-27.
↑ "Substance Infocard, fluazifop-P-butyl". echa.europa.eu. Retrieved 2021-02-27.
↑ FAO / WHO (2020). Pesticide Residues in Food 2019 (pdf). pp. 179–182. ISBN 9789251320860.
↑ FAO / WHO. "Fluazifop-P butyl".
↑ Durkin, Patrick R. (2014-07-21). "Scoping/Screening Level Risk Assessment on Fluazifop-P-butyl" (PDF). fs.fed.us. p. 275. Retrieved 2021-02-27.
↑ Hidayat, Imam; Preston, Christopher (1997). "Enhanced Metabolism of Fluazifop Acid in a Biotype of Digitaria sanguinalis Resistant to the Herbicide Fluazifop-P-Butyl". Pesticide Biochemistry and Physiology. 57 (2): 137–146. doi:10.1006/pest.1997.2265.
↑ Jalaludin, A.; Yu, Q.; Powles, S. B. (2015). "Multiple resistance across glufosinate, glyphosate, paraquat and ACCase-inhibiting herbicides in an Eleusine indica population" (PDF). Weed Research. 55: 82–89. doi:10.1111/wre.12118.
↑ "Herbicides Resistance Action Committee website".