Sedaxane

Last updated
Sedaxane
Sedaxane.svg
Names
Preferred IUPAC name
N-[2-([1,1′-Bi(cyclopropan)]-2-yl)phenyl]-3-(difluoromethyl)-1-methyl-1H-pyrazole-4-carboxamide
Other names
SYN524464
Identifiers
3D model (JSmol)
ChemSpider
ECHA InfoCard 100.214.982 OOjs UI icon edit-ltr-progressive.svg
PubChem CID
UNII
  • InChI=1S/C18H19F2N3O/c1-23-9-14(16(22-23)17(19)20)18(24)21-15-5-3-2-4-11(15)13-8-12(13)10-6-7-10/h2-5,9-10,12-13,17H,6-8H2,1H3,(H,21,24)
    Key: XQJQCBDIXRIYRP-UHFFFAOYSA-N
  • CN1C=C(C(=N1)C(F)F)C(=O)NC2=CC=CC=C2C3CC3C4CC4
Properties [1]
C18H19F2N3O
Molar mass 331.367 g·mol−1
AppearanceWhite powder
Odor Odorless
Density 1.23 g/cm3 (26 °C)
Melting point 121.4 °C (250.5 °F; 394.5 K)
Very slightly soluble (0.67 g/L, 20 °C)
Solubility in other solventsSlightly soluble in acetone (410 g/L) and dichloromethane (500 g/L)
Except where otherwise noted, data are given for materials in their standard state (at 25 °C [77 °F], 100 kPa).

Sedaxane is a broad spectrum fungicide used as a seed treatment in agriculture to protect crops from fungal diseases. It was first marketed by Syngenta in 2011 using their brand name Vibrance. The compound is an amide which combines a pyrazole acid with an aryl amine to give an inhibitor of succinate dehydrogenase. [1] [2]

Contents

The compound is widely registered for use, including in Australia, the EU, UK and US.

History

Inhibition of succinate dehydrogenase, the complex II in the mitochondrial respiration chain, has been known as a fungicidal mechanism of action since the first examples were marketed in the 1960s. The first compound in this class was carboxin, which had a narrow spectrum of useful biological activity, mainly on basidiomycetes and was used as a seed treatment. [3] [4] By 2016, at least 17 further examples of this mechanism of action were developed by crop protection companies, with the market leader being boscalid, owing to its broader spectrum of fungal species controlled. However, it lacked full control of important cereal diseases, especially septoria leaf blotch Zymoseptoria tritici . [3]

Pyrazole intermediate Pyrazole SDHI intermediate.svg
Pyrazole intermediate

A group of compounds which did control septoria were amides of 3-(difluoromethyl)-1-methyl-1H-pyrazole-4-carboxylic acid. These included fluxapyroxad and pydiflumetofen as well as sedaxane. [5] [6]

Synthesis

Sedaxane combines the acid chloride of the pyrazole carboxylic acid with a novel amine derivative which was made from 2-chlorobenzaldehyde.

Sedaxane synthesis.svg

A base-catalysed aldol condensation between the aldehyde and cyclopropyl methyl ketone forms an α,β-unsaturated carbonyl compound which, when combined with hydrazine gives a dihydropyrazole derivative. Further treatment with potassium hydroxide forms the second cyclopropyl ring and this material is converted to the aniline required for sedaxane formation by Buchwald–Hartwig amination using benzophenone imine in the presence of a palladium catalyst, followed by hydroxylamine. [3] : 413–4  [7]

Owing to a lack of stereoselectivity in the formation of the second cyclopropane ring, sedaxane consists of two diastereomers: two pairs of enantiomers which are cis–trans isomers. [1] : 1828  [3] : 414  The commercial product consists of >80% of the trans isomers. [8]

Mechanism of action

SDHI of this type act by binding at the quinone reduction site of the enzyme complex, preventing ubiquinone from doing so. As a consequence, the tricarboxylic acid cycle and electron transport chain cannot function. [9] [10]

Usage

Sedaxane is used as a seed treatment to control, for example, common bunt, Rhizoctonia species and Ustilago species (smuts). As a result, it has potential use in crops including cereals, cotton, potato and soybean. As of 2023 it is registered for use in Argentina, Australia, Canada, Chile, China, the EU, Mexico, the UK, Uruguay and the US. [8]

Human safety

Sedaxane has low toxicity [8] and its use was found to leave no residues in human food: [1] however the Codex Alimentarius database maintained by the FAO lists the maximum residue limits for it in various food products. [11]

Resistance management

Fungal populations have the ability to develop resistance to SDHI inhibitors. This potential can be mitigated by careful management. Reports of individual pest species becoming resistant [8] are monitored by manufacturers, regulatory bodies such as the EPA and the Fungicides Resistance Action Committee (FRAC). [12] The risks of resistance developing can be reduced by using a mixture of two or more fungicides which each have activity on relevant pests but with unrelated mechanisms of action. FRAC assigns fungicides into classes so as to facilitate this and sedaxane is frequently used in combination with other active ingredients as seed treatments. [13] [14]

Brands

Sedaxane is the ISO common name [15] for the active ingredient which is formulated into the branded product sold to end-users. Vibrance is the brand name for Syngenta's suspension concentrate. [14]

Related Research Articles

Q<sub>o</sub>I Kind of chemicals used to kill fungus

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Fungicides are pesticides used to kill parasitic fungi or their spores. They are most commonly chemical compounds, but may include biocontrols and fungistatics. Fungi can cause serious damage in agriculture, resulting in critical losses of yield, quality, and profit. Fungicides are used both in agriculture and to fight fungal infections in animals. Fungicides are also used to control oomycetes, which are not taxonomically/genetically fungi, although sharing similar methods of infecting plants. Fungicides can either be contact, translaminar or systemic. Contact fungicides are not taken up into the plant tissue and protect only the plant where the spray is deposited. Translaminar fungicides redistribute the fungicide from the upper, sprayed leaf surface to the lower, unsprayed surface. Systemic fungicides are taken up and redistributed through the xylem vessels. Few fungicides move to all parts of a plant. Some are locally systemic, and some move upward.

<span class="mw-page-title-main">Succinate dehydrogenase</span> Enzyme

Succinate dehydrogenase (SDH) or succinate-coenzyme Q reductase (SQR) or respiratory complex II is an enzyme complex, found in many bacterial cells and in the inner mitochondrial membrane of eukaryotes. It is the only enzyme that participates in both the citric acid cycle and the electron transport chain. Histochemical analysis showing high succinate dehydrogenase in muscle demonstrates high mitochondrial content and high oxidative potential.

A biopesticide is a biological substance or organism that damages, kills, or repels organisms seen as pests. Biological pest management intervention involves predatory, parasitic, or chemical relationships.

Pyrazole is an organic compound of azole group with the formula C3H3N2H. It is a heterocycle characterized by a 5-membered ring of three carbon atoms and two adjacent nitrogen atoms, which are in ortho-substitution. Pyrazole is a weak base, with pKb 11.5 (pKa of the conjugate acid 2.49 at 25 °C). Pyrazoles are also a class of compounds that have the ring C3N2 with adjacent nitrogen atoms. Notable drugs containing a pyrazole ring are celecoxib (celebrex) and the anabolic steroid stanozolol.

The cereal grain wheat is subject to numerous wheat diseases, including bacterial, viral and fungal diseases, as well as parasitic infestations.

Acibenzolar-<i>S</i>-methyl Chemical compound

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

Azoxystrobin is a broad spectrum systemic fungicide widely used in agriculture to protect crops from fungal diseases. It was first marketed in 1996 using the brand name Amistar and by 1999 it had been registered in 48 countries on more than 50 crops. In the year 2000 it was announced that it had been granted UK Millennium product status.

<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.

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

Fluxapyroxad is a broad-spectrum pyrazole-carboxamide fungicide used on a large variety of commercial crops. It stunts fungus growth by inhibiting the succinate dehydrogenase (SQR) enzyme. Application of fluxapyroxad helps prevent many wilts and other fungal infections from taking hold. As with other systemic pesticides that have a long chemical half-life, there are concerns about keeping fluxapyroxad out of the groundwater, especially when combined with pyraclostrobin. There is also concern that some fungi may develop resistance to fluxapyroxad.

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

Cyproconazole is an agricultural fungicide of the class of azoles, used on cereal crops, coffee, sugar beet, fruit trees and grapes, on sod farms and golf courses and on wood as a preservative. It was introduced to the market by then Sandoz in 1994.

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

Fluopyram is a fungicide and nematicide used in agriculture. It is used to control fungal diseases such as gray mold, powdery mildew, apple scab, Alternaria, Sclerotinia, and Monilinia. It is an inhibitor of succinate dehydrogenase.

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

Oxycarboxin is an organic chemical used in agriculture to protect crops from fungal diseases. It was first marketed by Uniroyal in 1969 using their brand name Plantvax. The compound is an anilide which combines a heterocyclic acid with aniline to give an inhibitor of succinate dehydrogenase (SDHI).

<span class="mw-page-title-main">Carboxin</span> Chemical compound used to kill fungi

Carboxin is a narrow-spectrum fungicide used as a seed treatment in agriculture to protect crops from fungal diseases. It was first marketed by Uniroyal in 1969 using their brand name Vitavax. The compound is an anilide which combines a heterocyclic acid with aniline to give an inhibitor of succinate dehydrogenase (SDHI).

<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">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">Boscalid</span> Chemical compound used to kill fungi

Boscalid is a broad spectrum fungicide used in agriculture to protect crops from fungal diseases. It was first marketed by BASF in 2002 using their brand name Endura. The compound is an biphenyl amide derived inhibitor of succinate dehydrogenase.

<span class="mw-page-title-main">Pydiflumetofen</span> Chemical compound used to kill fungi

Pydiflumetofen is a broad spectrum fungicide used in agriculture to protect crops from fungal diseases. It was first marketed by Syngenta in 2016 using their brand name Miravis. The compound is an amide which combines a pyrazole acid with a substituted phenethylamine to give an inhibitor of succinate dehydrogenase.

3-(Difluoromethyl)-1-methyl-1<i>H</i>-pyrazole-4-carboxylic acid Chemical compound

3-(Difluoromethyl)-1-methyl-1H-pyrazole-4-carboxylic acid is a chemical compound which is used commercially as an intermediate to seven fungicides which act by inhibition of succinate dehydrogenase (SDHI). It consists of a pyrazole ring with difluoromethyl, methyl and carboxylic acid groups attached in specific positions.

References

  1. 1 2 3 4 William Donovan. "Sedaxane" (PDF). United States Environmental Protection Agency.
  2. ↑ Ronald Zeun, Gabriel Scalliet and Michael Oostendorp (2013). "Biological activity of sedaxane - a novel broad-spectrum fungicide for seed treatment". Pest Management Science. 69 (4): 527–534. doi: 10.1002/ps.3405 . PMID   23044852.
  3. 1 2 3 4 Walter, Harald (2016). "Fungicidal Succinate-Dehydrogenase-Inhibiting Carboxamides". In Lamberth, Clemens; Dinges, Jürgen (eds.). Bioactive Carboxylic Compound Classes: Pharmaceuticals and Agrochemicals. Wiley. pp. 405–425. doi:10.1002/9783527693931.ch31. ISBN   9783527339471.
  4. ↑ "History of SDHI-fungicides". frac.info. Retrieved 2023-07-26.
  5. ↑ "Pyrazolecarboxamide fungicides". BCPC . Retrieved 2023-07-27.
  6. ↑ Walter, Harald; Lamberth, Clemens; Corsi, Camilla (2018). "Synthesis of fungicidally active succinate dehydrogenase inhibitors with novel difluoromethylated heterocyclic acid moieties". Monatshefte für Chemie - Chemical Monthly. 149 (4): 791–799. doi:10.1007/s00706-017-2101-y. S2CID   103548298.
  7. ↑ WOpatent 2003074491,Ehrenfreund, J; Tobler, H& Walter, H,"O-cyclopropyl-carboxanilides and their use as fungicides",published 2003-09-12, assigned to Syngenta
  8. 1 2 3 4 Pesticide Properties Database (2023-08-01). "Sedaxane". University of Hertfordshire. Retrieved 2023-08-03.
  9. ↑ Oyedotun, Kayode S.; Lemire, Bernard D. (2004). "The Quaternary Structure of the Saccharomyces cerevisiae Succinate Dehydrogenase". Journal of Biological Chemistry. 279 (10): 9424–9431. doi: 10.1074/jbc.M311876200 . PMID   14672929.
  10. ↑ Avenot, Hervé F.; Michailides, Themis J. (2010). "Progress in understanding molecular mechanisms and evolution of resistance to succinate dehydrogenase inhibiting (SDHI) fungicides in phytopathogenic fungi". Crop Protection. 29 (7): 643–651. doi:10.1016/j.cropro.2010.02.019.
  11. ↑ FAO / WHO. "Sedaxane" . Retrieved 2023-08-03.
  12. ↑ "Fungicides Resistance Action Committee website".
  13. ↑ "Search Fungicides to find FRAC Recommendations". Fungicides Resistance Action Committee. Retrieved 2023-08-03.
  14. 1 2 "Vibrance". Syngenta Australia. 2023. Retrieved 2023-08-03.
  15. ↑ "Compendium of Pesticide Common Names: Sedaxane". BCPC. Retrieved 2023-08-03.
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