fomesafen

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.{{cite web |url=http://sitem.herts.ac.uk/aeru/ppdb/en/Reports/1422.htm |title=Nitrofen |publisher=University of Hertfordshire |author=Pesticide Properties Database |access-date=2021-03-03}} 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.{{cite patent |country=US |number=3784635 |status=patent |gdate=1974-01-08 |fdate=1969-04-25 |pridate=1969-04-25 |invent1 =Theissen R.J. |title=Herbicidal 4-trifluoromethyl-4'-nitrodiphenyl ethers |assign1=Mobil Oil Corporation}} 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.{{cite web |url=http://sitem.herts.ac.uk/aeru/ppdb/en/Reports/14.htm |title=Acifluorfen-sodium |publisher=University of Hertfordshire |author=Pesticide Properties Database |access-date=2021-03-03}} 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,{{cite patent |country=US |number=3928416 |status=patent |gdate=1975-12-23 |fdate=1973-02-12 |pridate=1972-03-14 |invent1 =Bayer H. O. |invent2=Swithenbank C. |invent3=Yih R. Y. |title=Herbicidal 4-trifluoromethyl-4'-nitrodiphenyl ethers |assign1=Rohm & Haas}} although an earlier Belgian patent published in September 1973 had described related chemistry.{{cite patent |country=BE |number=796677 |status=patent |gdate=1973-09-13 |fdate= |pridate=1972-03-14 |invent1 =Bayer H. O. |invent2=Swithenbank C. |invent3=Yih R. Y. |title=Nouveaux ethers 4-trifluoromethyl-4'-nitro-diphenyliques herbicides et leur application a la lutte contre les mauvaises herbes |assign1=Rohm & Haas}}

File:Nitrofen.svg|Nitrofen

File:Bifenox-flip.svg|Bifenox

File:Acifluorfen structure.svg|Acifluorfen

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 pK_a 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.{{cite patent |country=EP |number=0003416 |status=patent |gdate=1981-08-26 |fdate= |pridate=1978-01-19 |invent1 =Cartwright D. |invent2=Collins D. J. |title=Diphenyl ether compounds useful as herbicides; methods of using them, processes for preparing them, and herbicidal compositions containing them. |assign1=ICI Ltd.}} Fomesafen was developed under the code number PP021 and first sales were in Argentina in 1983, with the brand name Flex.

As described in the ICI patent, 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

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.{{cite journal |doi=10.1104/pp.72.2.461 |title=Interaction of Chloroplasts with Inhibitors |year=1983 |last1=Ridley |first1=Stuart M. |journal=Plant Physiology |volume=72 |issue=2 |pages=461–468 |pmid=16663025 |pmc=1066256 }} 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.{{cite book |doi=10.1007/978-3-642-58633-0_5 |chapter=Structure-Activity Relationships of Diphenyl Ethers and Other Oxygen-Bridged Protoporphyrinogen Oxidase Inhibitors |title=Peroxidizing Herbicides |year=1999 |last1=Dayan |first1=Franck E. |last2=Reddy |first2=Krishna N. |last3=Duke |first3=Stephen O. |pages=141–161 |isbn=978-3-642-63674-5 }}{{cite book |doi=10.1007/978-3-642-58633-0_11 |chapter=Herbicidal Efficacy of Protoporphyrinogen Oxidase Inhibitors |title=Peroxidizing Herbicides |year=1999 |last1=Nagano |first1=Eiki |pages=293–302 |isbn=978-3-642-63674-5 }}

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.{{cite web|url=https://www.epa.gov/pesticide-registration/about-pesticide-registration |title=About Pesticide Registration |date=27 February 2013 |publisher=US EPA |access-date=2021-02-27 }}{{cite web|url=https://www.syngenta-us.com/current-label/flexstar |author=Syngenta US|website=syngenta-us.com|title=Flexstar |access-date=2021-03-02}}

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.

File:Fomesafen use USA.png

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 {{convert|6000000|lb|kg}} were applied — mainly in soybean.{{cite web |url=https://water.usgs.gov/nawqa/pnsp/usage/maps/show_map.php?year=2018&map=FOMESAFEN&hilo=L&disp=Fomesafen |title=Estimated Agricultural Use for Fomesafen, 2018 |date=2021-10-12 |author=US Geological Survey |access-date=2022-01-17 }} The compound is not registered for use in the European Union, although a closely related nitrophenyl ether, bifenox, is available there.{{cite web |url=http://sitem.herts.ac.uk/aeru/ppdb/en/Reports/77.htm |title=Bifenox |publisher=University of Hertfordshire |author=Pesticide Properties Database |access-date=2021-03-03}}

The LD₅₀ of fomesafen is 1250 mg/kg (rats, oral), which means that it is moderately toxic by oral ingestion. The US Code of Federal Regulations records the maximum residue tolerances for fomesafen in various food products.{{cite web|url=https://ecfr.federalregister.gov/on/2021-03-05/title-40/chapter-I/subchapter-E/part-180/subpart-C/section-180.433|title=Fomesafen; tolerances for residues|website=ecfr.federalregister.gov|date=2018-02-07|access-date=2021-03-05}}

The environmental fate and ecotoxicology of fomesafen are summarised in the Pesticide Properties database The compound was used in a case study that developed methods for conducting nationwide endangered species assessments in the USA.{{cite book |doi=10.1021/bk-2012-1111.ch009 |chapter=Endangered Species Assessments Conducted Under Registration Review: Fomesafen Case Study |title=Pesticide Regulation and the Endangered Species Act |series=ACS Symposium Series |year=2012 |last1=Campbell |first1=Dan |last2=Overmyer |first2=Jay |last3=Bang |first3=Jisu |last4=Perine |first4=Jeff |last5=Brain |first5=Richard |volume=1111 |pages=119–137 |isbn=978-0-8412-2703-3 }}

Resistance to fomesafen has developed including in Amaranthus retroflexus in Northeast China,{{cite journal|last1=Huang|first1=Zhaofeng|last2=Cui|first2=Hailan|last3=Wang|first3=Chunyu|last4=Wu|first4=Tong|last5=Zhang|first5=Chaoxian|last6=Huang|first6=Hongjuan|last7=Wei|first7=Shouhui|title=Investigation of resistance mechanism to fomesafen in Amaranthus retroflexus L.|journal=Pesticide Biochemistry and Physiology|volume=165|year=2020|pages=104560|issn=0048-3575|doi=10.1016/j.pestbp.2020.104560|publisher=Elsevier|pmid=32359536|s2cid=216246076 }} Amaranthus palmeri in Arkansas,{{cite journal|last1=Salas|first1=Reiofeli A|last2=Burgos|first2=Nilda R|last3=Tranel|first3=Patrick J|last4=Singh|first4=Shilpa|last5=Glasgow|first5=Les|last6=Scott|first6=Robert C|last7=Nichols|first7=Robert L|title=Resistance to PPO-inhibiting herbicide in Palmer amaranth from Arkansas|journal=Pest Management Science|volume=72|issue=5|year=2016|pages=864–869|issn=1526-498X|doi=10.1002/ps.4241|pmc=5069602|pmid=26817647|publisher=Wiley-Blackwell}} and Euphorbia heterophylla in Brazil.{{cite journal|last1=Brusamarello|first1=Antonio P.|last2=Oliveira|first2=Paulo H.|last3=Trezzi|first3=Michelangelo M.|last4=Finatto|first4=Taciane|last5=Pagnoncelli|first5=Fortunato D. B.|last6=Vidal|first6=Ribas A.|title=Inheritance of fomesafen and imazethapyr resistance in a multiple herbicide-resistant Euphorbia heterophylla population|journal=Weed Research|volume=60|issue=4|year=2020|pages=278–286|issn=0043-1737|doi=10.1111/wre.12425|publisher=Wiley|bibcode=2020WeedR..60..278B |s2cid=219415301 }}

{{reflist}}

• {{PPDB|355}}

Category:PPO herbicides

Category:Benzamides

Category:Trifluoromethyl compounds

Category:Diphenyl ethers

Category:Sulfonamides

Category:Group 14 herbicides