Metolachlor
{{chembox
| Verifiedfields = changed
| Watchedfields = changed
| verifiedrevid = 477170024
| Reference = [http://extoxnet.orst.edu/pips/metolach.htm Extoxnet], Oregon State University
| ImageFile = Metolachlor.png
| ImageSize =
| IUPACName = (RS)-2-Chloro-N-(2-ethyl-6-methyl-phenyl)-N-(1-methoxypropan-2-yl)acetamide
| OtherNames = Dual, Pimagram, Bicep, CGA-24705, Pennant.
|Section1={{Chembox Identifiers
| ChemSpiderID_Ref = {{chemspidercite|correct|chemspider}}
| ChemSpiderID = 4025
| KEGG_Ref = {{keggcite|correct|kegg}}
| KEGG = C10953
| ChEBI_Ref = {{ebicite|changed|EBI}}
| ChEBI = 6902
| ChEMBL_Ref = {{ebicite|changed|EBI}}
| ChEMBL = 1884974
| InChI = 1/C15H22ClNO2/c1-5-13-8-6-7-11(2)15(13)17(14(18)9-16)12(3)10-19-4/h6-8,12H,5,9-10H2,1-4H3
| InChIKey = WVQBLGZPHOPPFO-UHFFFAOYAS
| StdInChI_Ref = {{stdinchicite|correct|chemspider}}
| StdInChI = 1S/C15H22ClNO2/c1-5-13-8-6-7-11(2)15(13)17(14(18)9-16)12(3)10-19-4/h6-8,12H,5,9-10H2,1-4H3
| StdInChIKey_Ref = {{stdinchicite|correct|chemspider}}
| StdInChIKey = WVQBLGZPHOPPFO-UHFFFAOYSA-N
| CASNo_Ref = {{cascite|correct|CAS}}
| CASNo = 51218-45-2
| UNII_Ref = {{fdacite|correct|FDA}}
| UNII = X0I01K05X2
| PubChem = 4169
| SMILES = CCc1cccc(c1N(C(C)COC)C(=O)CCl)C
}}
|Section2={{Chembox Properties
| C=15 | H=22 | Cl=1 | N=1 | O=2
| Appearance = Off-white to colorless liquid
| Density = 1.1 g/mL
| MeltingPt =
| BoilingPtC = 100
| BoilingPt_notes = at 0.001 mmHg
| Solubility = 530 ppm at 20 °C
}}
|Section3={{Chembox Hazards
| MainHazards = {{cite web|url=http://extoxnet.orst.edu/pips/metolach.htm|title=EXTOXNET PIP - METOLACHLOR|work=orst.edu|accessdate=17 May 2015}}
| FlashPt =
| AutoignitionPt =
}}
}}
Metolachlor is an organic compound that is widely used as an herbicide. It is a derivative of aniline and is a member of the chloroacetanilide family of herbicides. It is highly effective toward grasses.
Agricultural use
Metolachlor was developed by Ciba-Geigy. Its acts by inhibition of elongases and of the geranylgeranyl pyrophosphate (GGPP) cyclases, which are part of the gibberellin pathway. It is used for grass and broadleaf weed control in corn, soybean, peanuts, sorghum, and cotton. It is also used in combination with other herbicides.
Metolachlor is a popular herbicide in the United States.Kiely, T., D. Donaldson, and A. Grube. 2004. Pesticide industry sales and usage: 2000 and 2001 market estimates. US Environmental Protection Agency, Office of Pesticides Programs, Washington, DC As originally formulated metolachlor was applied as a racemate, a 1:1 mixture of the (S)- and (R)-stereoisomers. The (R)-enantiomer is less active, and modern production methods afford a higher concentration of S-metolachlor, thus current application rates are far lower than original formulations.
Production and basic structure
Metolachlor is produced from 2-ethyl-6-methylaniline (MEA) via condensation with methoxyacetone. The resulting imine is hydrogenated to give primarily the S-stereoisomeric amine. This secondary amine is acetylated with chloroacetylchloride. Because of the steric effects of the 2,6-disubstituted aniline, rotation about the aryl-C to N bond is restricted. Thus, both the (R)- and the (S)-enantiomers exist as atropisomers. Both atropisomers of (S)-metolachlor exhibit the same biological activity.{{cite journal | author = H.U.-Blaser | title = The Chiral Switch of (S)-Metolachlor: A Personal Account of an Industrial Odyssey in Asymmetric Catalysis | journal = Advanced Synthesis and Catalysis | year = 2002 | volume = 344 | pages = 17–31 | doi = 10.1002/1615-4169(200201)344:1<17::AID-ADSC17>3.0.CO;2-8}}
File:Metolachlor four stereoisomers V.1.svg{{clear left}}
Safety and ecological effects
The European Chemicals Agency classified metolachlor as a suspected human carcinogen (Carcinogen category 2) in 2022.{{cite journal |last1=Alvarez |first1=Fernando |last2=Arena |first2=Maria |last3=Auteri |first3=Domenica |last4=Binaglia |first4=Marco |last5=Castoldi |first5=Anna Federica |last6=Chiusolo |first6=Arianna |last7=Colagiorgi |first7=Angelo |last8=Colas |first8=Mathilde |last9=Crivellente |first9=Federica |last10=De Lentdecker |first10=Chloe |last11=De Magistris |first11=Isabella |last12=Egsmose |first12=Mark |last13=Fait |first13=Gabriella |last14=Ferilli |first14=Franco |last15=Gouliarmou |first15=Varvara |last16=Nogareda |first16=Laia Herrero |last17=Ippolito |first17=Alessio |last18=Istace |first18=Frederique |last19=Jarrah |first19=Samira |last20=Kardassi |first20=Dimitra |last21=Kienzler |first21=Aude |last22=Lanzoni |first22=Anna |last23=Lava |first23=Roberto |last24=Leuschner |first24=Renata |last25=Linguadoca |first25=Alberto |last26=Lythgo |first26=Christopher |last27=Magrans |first27=Oriol |last28=Mangas |first28=Iris |last29=Miron |first29=Ileana |last30=Molnar |first30=Tunde |last31=Padovani |first31=Laura |last32=Panzarea |first32=Martina |last33=Parra Morte |first33=Juan Manuel |last34=Rizzuto |first34=Simone |last35=Serafimova |first35=Rositsa |last36=Sharp |first36=Rachel |last37=Szentes |first37=Csaba |last38=Szoradi |first38=Andras |last39=Terron |first39=Andrea |last40=Theobald |first40=Anne |last41=Tiramani |first41=Manuela |last42=Vianello |first42=Giorgia |last43=Villamar‐Bouza |first43=Laura |title=Peer review of the pesticide risk assessment of the active substance S‐metolachlor excluding the assessment of the endocrine disrupting properties |journal=EFSA Journal |date=February 2023 |volume=21 |issue=2 |doi=10.2903/j.efsa.2023.7852|pmc=9972551 }} The United States Environmental Protection Agency (US EPA) has classified Metolachlor as a Group C, possible human carcinogen, based on liver tumors in rats at the highest dose tested (HDT).{{cite web |title=S-metolachlor; Pesticide Tolerance |url=https://www.federalregister.gov/documents/2006/08/30/E6-14443/s-metolachlor-pesticide-tolerance |website=Federal Register |publisher=US EPA |access-date=15 October 2024 |date=August 30, 2006}}USEPA,1987. Metolachlor Pesticide Registration Standard. Springfield, IL: Natl. Tech. Info. Serv. Evidence of the bioaccumulation of metolachlor in edible species of fish as well as its adverse effect on the growth and development has raised concerns on its effects on human and environmental health. For example, products with this active ingredient are restricted to professional licensed applicators in the U.S. state of Massachusetts.{{cite web |author1=Massachusetts Department of Agricultural Resources |title=Groundwater Protection List |url=https://www.mass.gov/info-details/groundwater-protection-list |publisher=Commonwealth of Massachusetts |access-date=15 October 2024}} Though there is no set maximum concentration (maximum contaminant level, MCL) for metolachlor that is allowed in drinking water, the US EPA does have a health advisory level (HAL) of 0.525 mg/L. Metolachlor has been detected in ground and surface waters in concentrations ranging from 0.08 to 4.5 parts per billion (ppb) throughout the U.S.{{cite journal | author = Pothuluri, J.V., Evans, F.E., Doerge, D.R., Churchwell, M.I.,Cerniglia, C.E. | year = 1997 | title = Metabolism of metolachlor by the fungus Cunninghamella elegans | journal = Arch. Environ. Contam. Toxicol. | volume = 32 | pages = 117–125 | doi = 10.1007/s002449900163 | pmid = 9069185 | issue = 2| s2cid = 20614148 }}
Metolachlor induces cytotoxic and genotoxic effects in human lymphocytes.{{cite journal | author = Rollof, B., Belluck, D., Meiser, L. | year = 1992 | title = Cytogenic effects of cyanazine and metolachlor on human lymphocytes exposed in vitro | journal = Mutat. Res. Lett. | volume = 281 | pages = 295–298 | doi = 10.1016/0165-7992(92)90024-C | pmid = 1373225 | issue = 4| doi-access = free }} Genotoxic effects have also been observed in tadpoles exposed to metolachlor.{{cite journal | author = Clements, C., Ralph, S.,Petras, M. | year = 1997 | title = Genotoxicity of select herbicides on Rana catesbeiana tadpoles using alkaline single-cell gel DNA electrophoresis (Comet) assay | journal = Env. Mol. Mut. | volume = 29 | pages = 277–288 | doi = 10.1002/(SICI)1098-2280(1997)29:3<277::AID-EM8>3.0.CO;2-9 | issue = 3| pmid = 9142171 | s2cid = 27619855 }} Evidence also reveals that metolachlor affects cell growth. Cell division in yeast was reduced,Echeverrigaray,S., Gomes,L.H., Taveres, F.C.A.(1999). Isolation and characterization of metolachlor resistant mutants of Saccharomyces cerevisiae. World Journal of Micro and Biotech. 15: 679–681. and chicken embryos exposed to metolchlor showed a significant decrease in the average body mass compared to the control.Varnargy,L., Budai, P., Fejes, S., Susan, M., Francsi, T., Keseru, M., Szabo, R.(2003). Toxicity and degradation of metolachlor (Dual 960EC) in chicken embryos. Commun. Agric. Appl. Biol. Sci.68:807–11.
See also
References
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