bifenox

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=Substituted Phenoxybenzoic Acids and Esters thereof |assign1=Mobil Oil Corporation}} Bifenox was launched with the brand name Mowdown in 1981. Meanwhile Rohm & Haas had patented{{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}} and developed acifluorfen (as its sodium salt with brand name Blazer) in 1980.{{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}} Both compounds had much improved properties including a wider spectrum of herbicidal effect and good safety to some crops, including soybean.

Bifenox was first synthesized by R.J. Theissen of the agricultural research section of Mobil Chemical's Central Research Laboratory in 1969 .File:Bifenox synthesis.svg

The preparation of bifenox first described in the Mobil patent includes as its final step an Ullmann condensation between the potassium salt of 2,4-dichlorophenol and methyl 2-nitro-5-chlorobenzoic acid.{{cite web|url=https://nepis.epa.gov/Exe/ZyPDF.cgi/9100P8OL.PDF?Dockey=9100P8OL.PDF|date=December 1981|title=Bifenox: Pesticide Registration Standard|publisher=EPA|access-date=2021-03-07}}{{rp|43}}

The methyl 2-nitro-5-chlorobenzoic acid was made starting from Toluene/Chlorine/benzoic acid/Methanol/nitric acid/  in a 5 steps synthesis http://www.microchem.fr/patent_alas/process_info/bifenox/bifenox.html

The detailed mechanism of action for nitrofen, acifluorfen and related diphenyl 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 }}

Bifenox is not currently used in the United States{{cite web|url=https://pubchem.ncbi.nlm.nih.gov/source/hsdb/6567#section=Manufacturing-Use-Information|title=Bifenox: Uses|website=pubchem.ncbi.nlm.nih.gov|access-date=2021-03-08}} although in 1981 it had been subject to a full regulatory review, under the then-new "Registration Standard" process. Within the European Union, a 2-tiered approach is used for the approval and authorisation of pesticides. Firstly, before a formulated product can be developed for market, the active substance must be approved for the European Union. After this has been achieved, authorisation for the specific product must be sought from every Member State that the applicant wants to sell it to. Afterwards, there is a monitoring programme to make sure the pesticide residues in food are below the limits set by the European Food Safety Authority. Bifenox is registered for use against weeds in crops including cereals, soybeans, sugarbeet and rice.{{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=2021-03-08}}{{cite journal |doi=10.2903/j.efsa.2008.119r |title=Conclusion regarding the peer review of the pesticide risk assessment of the active substance bifenox|doi-access=free |journal=EFSA Journal |year=2008 |volume=6 |issue=2 |pages=119r }} In Switzerland, some of its formulations can be used in lawns and orchards.{{cn|date=March 2021}}

Bifenox is normally applied postemergence (when weeds are visible in the crop). It controls or suppresses a wide range of species including Capsella bursa-pastoris, Galium aparine, Lamium purpureum, Myosotis arvensis, Papaver rhoeas, Veronica hederifolia, Veronica persica and Viola arvensis. The product is typically used at application rates of 720 g a.i. per hectare.{{cite web|url=https://www.adama.com/documents/268722/268805/fox-label_tcm105-33064.pdf|website=Adama.com|access-date=2021-03-08|title=Fox: MAPP 11981|date=August 2019|archive-date=2021-02-27|archive-url=https://web.archive.org/web/20210227162058/http://www.adama.com/documents/268722/268805/fox-label_tcm105-33064.pdf|url-status=dead}}

{{reflist}}

• {{PPDB|77}}
• Bifenox synthesis : https://www.microchem.fr/patent_alas/process_info/bifenox/bifenox.html

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Category:PPO herbicides

Category:Nitrobenzene derivatives

Category:Methyl esters

Category:Chlorobenzene derivatives

Category:Group 14 herbicides