Fomesafen is the

ISO The International Organization for Standardization (ISO ; ; ) is an independent, non-governmental, international standard development organization composed of representatives from the national standards organizations of member countries. Me ...

common name In biology, a common name of a taxon or organism (also known as a vernacular name, English name, colloquial name, country name, popular name, or farmer's name) is a name that is based on the normal language of everyday life; and is often con ...

for an

organic compound Some chemical authorities define an organic compound as a chemical compound that contains a carbon–hydrogen or carbon–carbon bond; others consider an organic compound to be any chemical compound that contains carbon. For example, carbon-co ...

used as an

herbicide Herbicides (, ), also commonly known as weed killers, are substances used to control undesired plants, also known as weeds.EPA. February 201Pesticides Industry. Sales and Usage 2006 and 2007: Market Estimates. Summary in press releasMain page f ...

. It acts by inhibiting the enzyme protoporphyrinogen oxidase (PPO) which is necessary for

chlorophyll Chlorophyll is any of several related green pigments found in cyanobacteria and in the chloroplasts of algae and plants. Its name is derived from the Greek words (, "pale green") and (, "leaf"). Chlorophyll allows plants to absorb energy ...

synthesis Synthesis or synthesize may refer to: Science Chemistry and biochemistry *Chemical synthesis, the execution of chemical reactions to form a more complex molecule from chemical precursors **Organic synthesis, the chemical synthesis of organi ...

Soybean The soybean, soy bean, or soya bean (''Glycine max'') is a species of legume native to East Asia, widely grown for its edible bean. Soy is a staple crop, the world's most grown legume, and an important animal feed. Soy is a key source o ...

s 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

bean A bean is the seed of some plants in the legume family (Fabaceae) used as a vegetable for human consumption or animal feed. The seeds are often preserved through drying (a ''pulse''), but fresh beans are also sold. Dried beans are traditi ...

s and a few other crop types. It is not safe for maize/corn or other

Poaceae Poaceae ( ), also called Gramineae ( ), is a large and nearly ubiquitous family of monocotyledonous flowering plants commonly known as grasses. It includes the cereal grasses, bamboos, the grasses of natural grassland and species cultivate ...

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. 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 A structural analog, also known as a chemical analog or simply an analog, is a chemical compound, compound having a chemical structure, structure similar to that of another compound, but differing from it in respect to a certain component. It can ...

with a COOCH₃ group adjacent to the nitro group of nitrofen. This product, bifenox, was launched with the

brand name A brand is a name, term, design, symbol or any other feature that distinguishes one seller's goods or service from those of other sellers. Brands are used in business, marketing, and advertising for recognition and, importantly, to create and ...

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. 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, although an earlier Belgian patent published in September 1973 had described related chemistry. File:Nitrofen.svg, Nitrofen File:Bifenox-flip.svg, Bifenox File:Acifluorfen structure.svg, Acifluorfen Chemists at the

Imperial Chemical Industries Imperial Chemical Industries (ICI) was a British Chemical industry, chemical company. It was, for much of its history, the largest manufacturer in Britain. Its headquarters were at Millbank in London. ICI was listed on the London Stock Exchange ...

(ICI) research site at

Jealott's Hill Jealott's Hill is a village in the county of Berkshire, England, within the civil parish of Warfield. The settlement is on the A3095 road approximately north of Bracknell. The nearest railway station is in . History The name of the hill is re ...

, UK, investigated this area to attempt to find their own

intellectual property Intellectual property (IP) is a category of property that includes intangible creations of the human intellect. There are many types of intellectual property, and some countries recognize more than others. The best-known types are patents, co ...

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 A group is a number of persons or things that are located, gathered, or classed together. Groups of people * Cultural group, a group whose members share the same cultural identity * Ethnic group, a group whose members share the same ethnic iden ...

that could mimic it (by having similar pK_a and overall solubility, for example) but could not

metabolise Metabolism (, from ''metabolē'', "change") is the set of life-sustaining chemical reactions in organisms. The three main functions of metabolism are: the conversion of the energy in food to energy available to run cellular processes; the co ...

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. Fomesafen was developed under the code number PP021 and first sales were in Argentina in 1983, with the brand name Flex.

Synthesis

As described in the ICI patent, fomesafen can be made from acifluorfen by reaction with

thionyl chloride Thionyl chloride is an inorganic compound with the chemical formula . It is a moderately Volatility (chemistry), volatile, colourless liquid with an unpleasant acrid odour. Thionyl chloride is primarily used as a Halogenation, chlorinating reagen ...

to form the

acid chloride In organic chemistry, an acyl chloride (or acid chloride) is an organic compound with the functional group . Their formula is usually written , where R is a side chain. They are reactive derivatives of carboxylic acids (). A specific example o ...

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 In botany, chlorosis is a condition in which leaves produce insufficient chlorophyll. As chlorophyll is responsible for the green color of leaves, chlorotic leaves are pale, yellow, or yellow-white. The affected plant has little or no ability to ...

and

desiccation Desiccation is the state of extreme dryness, or the process of extreme drying. A desiccant is a hygroscopic (attracts and holds water) substance that induces or sustains such a state in its local vicinity in a moderately sealed container. The ...

: several hypotheses were advanced regarding the molecular-level interactions which might explain these symptoms. The now-accepted explanation for the damage is that these compounds inhibit the enzyme protoporphyrinogen oxidase, which leads to an accumulation of

protoporphyrin IX Protoporphyrin IX is an organic compound, classified as a porphyrin, that plays an important role in living organisms as a precursor to other critical compounds like heme (hemoglobin) and chlorophyll. It is a deeply colored solid that is not sol ...

in the plant cells. This is a potent

photosensitizer Photosensitizers are light absorbers that alter the course of a photochemical reaction. They usually are catalysts. They can function by many mechanisms; sometimes they abstract an electron from the substrate, and sometimes they abstract a hydro ...

which activates oxygen, leading to

lipid peroxidation Lipid peroxidation, or lipid oxidation, is a complex chemical process that leads to oxidative degradation of lipids, resulting in the formation of peroxide and hydroperoxide derivatives.{{Cite journal , last1=Ayala , first1=Antonio , last2=Muñoz ...

. Both light and oxygen are required for this process to kill the plant.

Usage

In the

United States The United States of America (USA), also known as the United States (U.S.) or America, is a country primarily located in North America. It is a federal republic of 50 U.S. state, states and a federal capital district, Washington, D.C. The 48 ...

, the

Environmental Protection Agency Environmental Protection Agency may refer to the following government organizations: * Environmental Protection Agency (Queensland), Australia * Environmental Protection Agency (Ghana) * Environmental Protection Agency (Ireland) * Environmenta ...

(EPA) is responsible for regulating pesticides under the

Federal Insecticide, Fungicide, and Rodenticide Act The Federal Insecticide, Fungicide, and Rodenticide Act (FIFRA) is a United States federal law that set up the basic U.S. system of pesticide regulation to protect applicators, consumers, and the environment. It is administered and regulated by t ...

(FIFRA), the

Food Quality Protection Act The Food Quality Protection Act (FQPA), or H.R.1627, was passed unanimously by Congress in 1996 and was signed into law by President Bill Clinton on August 3, 1996. The FQPA standardized the way the Environmental Protection Agency (EPA) would ...

(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. 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 ''Abutilon theophrasti,'' also known as velvetleaf, velvet plant, velvetweed and the Chinese jute is an annual plant in the Family (biology), family Malvaceae that is native to South Asia, southern Asia and it serves as a type species of the genu ...

'', '' Acalypha ostryifolia'', ''

Acanthospermum hispidum ''Acanthospermum hispidum'' (bristly starbur, goat's head, hispid starburr, starbur) is an annual plant in the family Asteraceae, which is native to Central and South America. This plant is cited as a weed in cotton culture in Brazil, and it is ...

'', ''

Amaranthus palmeri ''Amaranthus palmeri'' is a species of edible flowering plant in the amaranth genus. It has several common names, including carelessweed, dioecious amaranth, Palmer's amaranth, Palmer amaranth, and Palmer's pigweed. It is native to most of the s ...

'', ''

Ambrosia artemisiifolia ''Ambrosia artemisiifolia'', with the common names common ragweed, annual ragweed, and low ragweed, is a species of the genus ''Ambrosia'' native to regions of the Americas. Taxonomy The species name, ''artemisiifolia'', is given because the lea ...

'', ''

Anoda cristata ''Anoda cristata'' is a species of flowering plant in the Malvaceae, mallow family known by many common names, including spurred anoda, crested anoda, and violettas. It is native to North and South America. It is known throughout the rest of th ...

'', ''

Barbarea vulgaris ''Barbarea vulgaris'', also called wintercress (usual common name), or alternatively winter rocket, rocketcress, yellow rocketcress, yellow rocket, wound rocket, herb barbara, creases, or creasy greens, is a Biennial plant, biennial herb of the ...

'', '' Brassica kaber'', ''

Calystegia sepium ''Calystegia sepium'' (hedge bindweed, Rutland beauty, bugle vine, heavenly trumpets, bellbind, granny-pop-out-of-bed and many others) is a species of flowering plant in the family Convolvulaceae. It has a cosmopolitan distribution, subcosmopolit ...

'', ''

Cannabis sativa ''Cannabis sativa'' is an annual Herbaceous plant, herbaceous flowering plant. The species was first classified by Carl Linnaeus in 1753. The specific epithet ''Sativum, sativa'' means 'cultivated'. Indigenous to East Asia, Eastern Asia, the pla ...

'', ''

Cardiospermum halicacabum ''Cardiospermum halicacabum'', known as the lesser balloon vine, balloon plant or love in a puff, is a climbing plant widely distributed across tropical and subtropical areas of Africa, Australia, South Asia and North America that is often found ...

'', '' Cassia obtusifolia'', ''

Chenopodium album ''Chenopodium album'' is a fast-growing annual plant in the flowering plant family Amaranthaceae. Though cultivated in some regions, the plant is elsewhere considered a weed. Common names include lamb's quarters, melde, goosefoot, wild spinach a ...

'', '' Citrullus vulgaris'', ''

Convolvulus arvensis ''Convolvulus arvensis'', or field bindweed, is a species of bindweed in the Convolvulaceae native to Europe and Asia. It is a rhizomatous and climbing or creeping herbaceous perennial plant with stems growing to in length. It is usually found a ...

'', '' Croton glandulosus'', ''

Cucumis melo ''Cucumis melo'', also known as melon, is a species of ''Cucumis'' that has been developed into many cultivated varieties. The fruit is a pepo. The flesh is either sweet or bland, with or without an aroma, and the rind can be smooth (such as ho ...

'', ''

Cyperus esculentus ''Cyperus esculentus'' (also called chufa, tiger nut, atadwe, yellow nutsedge, earth almond, and in Chishona, pfende) is a species of plant in the sedge family widespread across much of the world. It is found in most of the Eastern Hemisphere, i ...

'', ''

Datura stramonium ''Datura stramonium'', known by the common names thornapple, jimsonweed (jimson weed), or devil's trumpet, is a poisonous flowering plant in the ''Datureae, Daturae'' Tribe (botany), tribe of the nightshade family Solanaceae. Its likely origi ...

'', ''

Digitaria ''Digitaria'' is a genus of plants in the grass family native to tropical and warm temperate regions but can occur in tropical, subtropical, and cooler temperate regions as well. Common names include crabgrass, finger-grass, and fonio. They ar ...

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Echinochloa crus-galli ''Echinochloa crus-galli'' is a type of wild grass originating from tropical Asia that was formerly classified as a type of panicum grass. It is commonly known as cockspur (or cockspur grass), barnyard millet, Japanese millet, water grass, commo ...

'', ''

Eleusine indica ''Eleusine indica'', the Indian goosegrass, yard-grass, goosegrass, wiregrass, or crowfootgrass, is a species of grass in the family Poaceae. It is a small annual grass distributed throughout the warmer areas of the world to about 50 degrees lati ...

'', ''

Euphorbia heterophylla ''Euphorbia heterophylla'', also known under the common names of Mexican fireplant, painted euphorbia, Japanese poinsettia, paintedleaf, painted spurge and milkweed, is a plant belonging to the Euphorbiaceae or spurge family. Distribution ''Euph ...

'', ''

Helianthus annuus The common sunflower (''Helianthus annuus'') is a species of large annual forb of the daisy family Asteraceae. The common sunflower is harvested for its edible oily seeds, which are often eaten as a snack food. They are also used in the pro ...

'', ''

Hibiscus trionum ''Hibiscus trionum'', commonly called flower-of-an-hour, bladder hibiscus, bladder ketmia, bladder weed, puarangi and venice mallow, is an annual plant native to the Old World tropics and subtropics. It has spread throughout southern Europe bot ...

'', '' Ipomoea quamoclit'', ''

Melochia corchorifolia ''Melochia corchorifolia'', the chocolateweed, is a weedy tropical plant that is typically seen in the wastelands. It has been most frequently observed to grow in open areas, such as highways.Mohlenbrock, R. (1982) The Illustrated Flora of Illino ...

'', '' Mollugo verticillata'', ''

Polygonum pensylvanicum ''Persicaria pensylvanica'' (syn. ''Polygonum pensylvanicum'') is a species of flowering plant in the buckwheat family, Polygonaceae. It is native to parts of North America, where it is widespread in Canada and the United States. It has also been ...

'', ''

Portulaca oleracea ''Portulaca oleracea'' (common purslane, also known as little hogweed, or pursley) is a succulent plant in the family Portulacaceae. Description The plant may reach in height. It has smooth, reddish, mostly prostrate stems, and the leaves, w ...

'', '' Richardia scabra'', '' Sesbania exaltata'', '' Setaria faberi'', ''

Solanum carolinense ''Solanum carolinense'', the Carolina horsenettle, is not a true nettle, but a member of the Solanaceae, or nightshade family. It is a perennial herbaceous plant, native to the southeastern United States, though its range has expanded throughou ...

'', ''

Sorghum halepense Johnson grass or Johnsongrass, ''Sorghum halepense'', is a plant in the grass family, Poaceae, native to Asia and northern Africa. The plant has been introduced to all continents except Antarctica, and most larger islands and archipelagos. It re ...

'', ''

Striga asiatica ''Striga asiatica'', the Asiatic witchweed or the red witchweed, is a hemiparasitic plant in the family Orobanchaceae. It is native to Asia and sub-Saharan Africa, but has been introduced into other parts of the world including Australia and th ...

'' and ''

Xanthium strumarium ''Xanthium strumarium'' (rough cocklebur, Noogoora burr, clotbur, common cocklebur, large cocklebur, woolgarie bur) is a species of annual plants of the family Asteraceae. Some sources claim it originates in southern Europe and Asia, but has been ...

''. The product is typically used at application rates of 0.3 lb a.i. per acre. Fomesafen use USA

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 were applied — mainly in soybean. The compound is not registered for use in the

European Union The European Union (EU) is a supranational union, supranational political union, political and economic union of Member state of the European Union, member states that are Geography of the European Union, located primarily in Europe. The u ...

, although a closely related nitrophenyl ether, bifenox, is available there.

Human safety

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.

Effects on the environment

The environmental fate and

ecotoxicology Ecotoxicology is the study of the effects of toxic chemicals on biological organisms, especially at the population biology, population, biological community, community, ecosystem, and biosphere levels. Ecotoxicology is a multidisciplinary field, ...

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.

Resistance

Resistance to fomesafen has developed including in ''

Amaranthus retroflexus ''Amaranthus retroflexus'' is a species of flowering plant in the family Amaranthaceae with several common names, including red-root amaranth, redroot pigweed, red-rooted pigweed, common amaranth, pigweed amaranth, and common tumbleweed. Outside ...

'' in

Northeast China Northeast China () is a geographical region of China, consisting officially of three provinces Liaoning, Jilin and Heilongjiang. The heartland of the region is the Northeast China Plain, the largest plain in China with an area of over . The regi ...

, ''Amaranthus palmeri'' in

Arkansas Arkansas ( ) is a landlocked state in the West South Central region of the Southern United States. It borders Missouri to the north, Tennessee and Mississippi to the east, Louisiana to the south, Texas to the southwest, and Oklahoma ...

, and ''Euphorbia heterophylla'' in

Brazil Brazil, officially the Federative Republic of Brazil, is the largest country in South America. It is the world's List of countries and dependencies by area, fifth-largest country by area and the List of countries and dependencies by population ...

References

External links

* {{PPDB, 355 PPO herbicides Benzamides Trifluoromethyl compounds Diphenyl ethers Sulfonamides Group 14 herbicides