Fomesafen
Names
Preferred IUPAC name
5-[2-Chloro-4-(trifluoromethyl)phenoxy]-N-(methanesulfonyl)-2-nitrobenzamide
Identifiers
3D model (JSmol)
ChEBI
ChEMBL
ChemSpider
ECHA InfoCard 100.069.470 Edit this at Wikidata
EC Number
  • 276-439-9
KEGG
UNII
  • InChI=1S/C15H10ClF3N2O6S/c1-28(25,26)20-14(22)10-7-9(3-4-12(10)21(23)24)27-13-5-2-8(6-11(13)16)15(17,18)19/h2-7H,1H3,(H,20,22)
    Key: BGZZWXTVIYUUEY-UHFFFAOYSA-N
  • CS(=O)(=O)NC(=O)C1=C(C=CC(=C1)OC2=C(C=C(C=C2)C(F)(F)F)Cl)[N+](=O)[O-]
Properties[1]
C15H10ClF3N2O6S
Molar mass 438.76 g·mol−1
50 mg/L (20 °C)
log P -1.2 (20 °C)
Acidity (pKa) 2.83
Hazards
GHS labelling:
GHS07: Exclamation mark
Warning
H302
P264, P270, P301+P312, P330, P501
Except where otherwise noted, data are given for materials in their standard state (at 25 °C [77 °F], 100 kPa).

Fomesafen is the ISO common name[2] for an organic compound used as an herbicide. It acts by inhibiting the enzyme protoporphyrinogen oxidase (PPO)[3] which is necessary for chlorophyll synthesis. Soybeans naturally have a high tolerance to fomesafen,[3][4] via metabolic disposal by glutathione S-transferase.[3][4] As a result, soy is the most common crop treated with fomesafen, followed by other beans and a few other crop types.[5] It is not safe for maize/corn[6] or other Poaceae.[4]

History

The nitrophenyl ethers are a well-known class of herbicides, the oldest member of which was nitrofen, invented by Rohm & Haas and first registered for sale in 1964.[7] This area of chemistry became very competitive, with the Mobil Oil Corporation's filing in 1969 and grant in 1974 of a patent to the structural analog with a COOCH3 group adjacent to the nitro group of nitrofen.[8] This product, bifenox, was launched with the brand name Mowdown in 1981. Meanwhile Rohm & Haas introduced acifluorfen (as its sodium salt with brand name Blazer) in 1980, having developed it under the code number RH-6201.[9] It had much improved properties including a wider spectrum of herbicidal effect and good safety to soybean crops. The first patent for the material was published in December 1975,[10] although an earlier Belgian patent published in September 1973 had described related chemistry.[11]

Chemists at the Imperial Chemical Industries (ICI) research site at Jealott's Hill, UK, investigated this area to attempt to find their own intellectual property and develop a proprietary material that could compete in the market. The idea which proved successful was to replace the carboxylic acid in acifluorfen with a group that could mimic it (by having similar pKa and overall solubility, for example) but could not metabolise to acifluorfen and potentially infringe the competitor's patents. Patent filings on this invention, where the replacement for COOH was a CONHSO2CH3 group were made in January 1978.[12] Fomesafen was developed under the code number PP021 and first sales were in Argentina in 1983, with the brand name Flex.[1]

Synthesis

As described in the ICI patent,[12] fomesafen can be made from acifluorfen by reaction with thionyl chloride to form the acid chloride and then with methanesulfonamide, in pyridine as solvent.

Ar-COOH + SOCl2 → ArCOCl
Ar-COCl + CH3SO2NH2 → ArCONHSO2CH3

Mechanism of action

The detailed mechanism of action for fomesafen and related nitrophenyl ether herbicides was unknown at the time they were invented. The effects visible on whole plants are chlorosis and desiccation: several hypotheses were advanced regarding the molecular-level interactions which might explain these symptoms.[13] The now-accepted explanation for the damage is that these compounds inhibit the enzyme protoporphyrinogen oxidase, which leads to an accumulation of protoporphyrin IX in the plant cells. This is a potent photosensitizer which activates oxygen, leading to lipid peroxidation. Both light and oxygen are required for this process to kill the plant.[14][15]

Usage

In the United States, the Environmental Protection Agency (EPA) is responsible for regulating pesticides under the Federal Insecticide, Fungicide, and Rodenticide Act (FIFRA), the Food Quality Protection Act (FQPA) and the Pesticide Registration Improvement Act (PRIA). A pesticide can only be used legally according to the directions on the label that is included at the time of the sale of the pesticide. The purpose of the label is "to provide clear directions for effective product performance while minimizing risks to human health and the environment". A label is a legally binding document that mandates how the pesticide can and must be used and failure to follow the label as written when using the pesticide is a federal offence.[16][17]

Fomesafen is normally applied postemergence (when weeds are visible in the crop) but may also be used preemergence. It controls or suppresses broadleaf weeds, grasses and sedges in soybeans and is effective on a very wide range of weed species including Abutilon theophrasti, Acalypha ostryifolia, Acanthospermum hispidum, Amaranthus palmeri, Ambrosia artemisiifolia, Anoda cristata, Barbarea vulgaris, Brassica kaber, Calystegia sepium, Cannabis sativa, Cardiospermum halicacabum, Cassia obtusifolia, Chenopodium album, Citrullus vulgaris, Convolvulus arvensis, Croton glandulosus, Cucumis melo, Cyperus esculentus, Datura stramonium, Digitaria, Echinochloa crus-galli, Eleusine indica, Euphorbia heterophylla, Helianthus annuus, Hibiscus trionum, Ipomoea quamoclit, Melochia corchorifolia, Mollugo verticillata, Polygonum pensylvanicum, Portulaca oleracea, Richardia scabra, Sesbania exaltata, Setaria faberi, Solanum carolinense, Sorghum halepense, Striga asiatica and Xanthium strumarium. The product is typically used at application rates of 0.3 lb a.i. per acre.[17]

US Geological Survey estimate of fomesafen use in the USA to 2018

The estimated annual use of fomesafen in US agriculture is mapped by the US Geological Service and shows that in 2018, the latest date for which figures are available, approximately 6,000,000 pounds (2,700,000 kg) were applied — mainly in soybean.[18] The compound is not registered for use in the European Union, although a closely related nitrophenyl ether, bifenox, is available there.[19]

Human safety

The LD50 of fomesafen is 1250 mg/kg (rats, oral), which means that it is moderately toxic by oral ingestion.[1] The US Code of Federal Regulations records the maximum residue tolerances for fomesafen in various food products.[20]

Effects on the environment

The environmental fate and ecotoxicology of fomesafen are summarised in the Pesticide Properties database[1] The compound was used in a case study that developed methods for conducting nationwide endangered species assessments in the USA.[21]

Resistance

Resistance to fomesafen has developed including in Amaranthus retroflexus in Northeast China,[22] Amaranthus palmeri in Arkansas,[23] and Euphorbia heterophylla in Brazil.[24]

References

  1. ^ a b c d Pesticide Properties Database. "Fomesafen". University of Hertfordshire. Retrieved 2021-03-03.
  2. ^ "Compendium of Pesticide Common Names: fomesafen". BCPC.
  3. ^ a b c "fomesafen". Weed Ecology and Management Laboratory at Cornell University. Retrieved 2020-11-22.
  4. ^ a b c Andrews, Christopher J.; Skipsey, Mark; Townson, Jane K.; Morris, Carol; Jepson, Ian; Edwards, Robert (1997). "Glutathione transferase activities toward herbicides used selectively in soybean". Pesticide Science. 51 (2). Wiley: 213–222. doi:10.1002/(sici)1096-9063(199710)51:2<213::aid-ps622>3.0.co;2-l. ISSN 0031-613X.
  5. ^ "Registration Review Label Mitigation for Fomesafen" (PDF). United States Environmental Protection Agency.
  6. ^ "Fomesafen Carryover Injury to Corn". Iowa State University. 2014-06-03. Retrieved 2020-11-22.
  7. ^ Pesticide Properties Database. "Nitrofen". University of Hertfordshire. Retrieved 2021-03-03.
  8. ^ US patent 3784635, Theissen R.J., "Herbicidal 4-trifluoromethyl-4'-nitrodiphenyl ethers", issued 1974-01-08, assigned to Mobil Oil Corporation 
  9. ^ Pesticide Properties Database. "Acifluorfen-sodium". University of Hertfordshire. Retrieved 2021-03-03.
  10. ^ US patent 3928416, Bayer H. O.; Swithenbank C. & Yih R. Y., "Herbicidal 4-trifluoromethyl-4'-nitrodiphenyl ethers", issued 1975-12-23, assigned to Rohm & Haas 
  11. ^ BE patent 796677, Bayer H. O.; Swithenbank C. & Yih R. Y., "Nouveaux ethers 4-trifluoromethyl-4'-nitro-diphenyliques herbicides et leur application a la lutte contre les mauvaises herbes", issued 1973-09-13, assigned to Rohm & Haas 
  12. ^ a b EP patent 0003416, Cartwright D. & Collins D. J., "Diphenyl ether compounds useful as herbicides; methods of using them, processes for preparing them, and herbicidal compositions containing them.", issued 1981-08-26, assigned to ICI Ltd. 
  13. ^ Ridley, Stuart M. (1983). "Interaction of Chloroplasts with Inhibitors". Plant Physiology. 72 (2): 461–468. doi:10.1104/pp.72.2.461. PMC 1066256. PMID 16663025.
  14. ^ Dayan, Franck E.; Reddy, Krishna N.; Duke, Stephen O. (1999). "Structure-Activity Relationships of Diphenyl Ethers and Other Oxygen-Bridged Protoporphyrinogen Oxidase Inhibitors". Peroxidizing Herbicides. pp. 141–161. doi:10.1007/978-3-642-58633-0_5. ISBN 978-3-642-63674-5.
  15. ^ Nagano, Eiki (1999). "Herbicidal Efficacy of Protoporphyrinogen Oxidase Inhibitors". Peroxidizing Herbicides. pp. 293–302. doi:10.1007/978-3-642-58633-0_11. ISBN 978-3-642-63674-5.
  16. ^ "About Pesticide Registration". US EPA. 27 February 2013. Retrieved 2021-02-27.
  17. ^ a b Syngenta US. "Flexstar". syngenta-us.com. Retrieved 2021-03-02.
  18. ^ US Geological Survey (2021-10-12). "Estimated Agricultural Use for Fomesafen, 2018". Retrieved 2022-01-17.
  19. ^ Pesticide Properties Database. "Bifenox". University of Hertfordshire. Retrieved 2021-03-03.
  20. ^ "Fomesafen; tolerances for residues". ecfr.federalregister.gov. 2018-02-07. Retrieved 2021-03-05.
  21. ^ Campbell, Dan; Overmyer, Jay; Bang, Jisu; Perine, Jeff; Brain, Richard (2012). "Endangered Species Assessments Conducted Under Registration Review: Fomesafen Case Study". Pesticide Regulation and the Endangered Species Act. ACS Symposium Series. Vol. 1111. pp. 119–137. doi:10.1021/bk-2012-1111.ch009. ISBN 978-0-8412-2703-3.
  22. ^ Huang, Zhaofeng; Cui, Hailan; Wang, Chunyu; Wu, Tong; Zhang, Chaoxian; Huang, Hongjuan; Wei, Shouhui (2020). "Investigation of resistance mechanism to fomesafen in Amaranthus retroflexus L.". Pesticide Biochemistry and Physiology. 165. Elsevier: 104560. doi:10.1016/j.pestbp.2020.104560. ISSN 0048-3575. PMID 32359536. S2CID 216246076.
  23. ^ Salas, Reiofeli A; Burgos, Nilda R; Tranel, Patrick J; Singh, Shilpa; Glasgow, Les; Scott, Robert C; Nichols, Robert L (2016). "Resistance to PPO-inhibiting herbicide in Palmer amaranth from Arkansas". Pest Management Science. 72 (5). Wiley-Blackwell: 864–869. doi:10.1002/ps.4241. ISSN 1526-498X. PMC 5069602. PMID 26817647.
  24. ^ Brusamarello, Antonio P.; Oliveira, Paulo H.; Trezzi, Michelangelo M.; Finatto, Taciane; Pagnoncelli, Fortunato D. B.; Vidal, Ribas A. (2020). "Inheritance of fomesafen and imazethapyr resistance in a multiple herbicide-resistant Euphorbia heterophylla population". Weed Research. 60 (4). Wiley: 278–286. Bibcode:2020WeedR..60..278B. doi:10.1111/wre.12425. ISSN 0043-1737. S2CID 219415301.

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