57837-19-1 Usage
References
Kerkenaar, A. "On the antifungal mode of action of metalaxyl, an inhibitor of nucleic acid synthesis in Pythium splendens." Pesticide Biochemistry & Physiology 16.1(1981):1-13.
Fisher, David J., and A. L. Hayes. "Mode of action of the systemic fungicides furalaxyl, metalaxyl and ofurace." Pest Management Science13.3(2010):330-339.
Davidse, L. C., et al. "A comparison between the antifungal mode of action of metalaxyl, cyprofuram, benalaxyl and oxadixyl in phenylamide-sensitivity and -resistant strains. " Crop Protection 7.6(1988):347-355.
Metalaxyl showed the highest activity amongst the four fungicides against mycelial growth of sensitive strains on agar media.
Hazard
Moderately toxic by ingestion.
Trade name
AGROX? PREMIERE; ALLEGIENCE?;
APRON?; CG 117?; CGA-48988?; CHLORAXYL?;
COTGUARD?; EPERON?; DELTA-COAT; FOLIO?
GOLD; GAUCHO?; KODIAK?; METALAXIL?;
METAXANIN?; PACE?; PREVAIL?; RAXIL? (tebu-
conazole + metalaxyl); RIDOMIL? GOLD/BRAVO?;
RIDOMIL?; RIDOMIL 2E?; SUBDUE?
Pharmacology
In mycelium of Phytophthora
megasperma,metalaxyl affected primarily rRNA synthesis
(polymerase I), whereas mRNA was much less sensitive;
therefore, inhibition of rRNA synthesis is considered as
the primary site of action of PAFs (23).
The PAFs exhibit strong preventive and curative
activity. They affect especially hyphal growth (inside and
outside the plant tissue) as well as haustorium and spore
formation (15). Although not fully utilized for resistance
management reasons, PAFs also exhibit strong eradicative
and antisporulant activity in the disease cycle of target
pathogens. On the other hand, PAFs do not inhibit the
early stages in the disease cycle like zoospore release,
spore germination, and penetration of the host tissue (15).
Because spores contain many ribosomes to support early
growth stages, RNA synthesis is fully operating only
after spore germination; later development stages are
therefore most sensitive to PAFs (23). As a consequence
of RNA inhibition, the precursors of RNA synthesis (i.e.,
nucleoside triphosphates) are accumulated; they activate
β-1,3-glucansynthetases, which are involved in cell wall
formation (23). Metalaxyl-treated hyphae often produce
thicker cell walls than do untreated ones.
Safety Profile
Moderately toxic by
ingestion. When heated to decomposition it
emits toxic fumes of NOx.
Potential Exposure
Metalaxyl is phenylamide systemic
fungicide used on a variety of food and nonfood crops
including tobacco, turf and conifers, and ornamentals. Used
in combination with fungicides of different mode of action
as a foliar spray on tropical and subtropical crops; as a seed
treatment to control downy mildew; and as a soil fumigant
to control soil-borne pathogens. Banned for use in EU.
Environmental Fate
Soil. Little information is available on the degradation of metalaxyl in soil; however,
Sharom and Edgington (1986) reported metalaxyl acid as a possible metabolite. Repeated
applications of metalaxyl decreases its persistence. Following an initial application, the
average half-life was 28 days. After repeated applications, the half-life decreased to 14
days (Bailey and Coffey, 1985).Carsel et al. (1986) studied the persistence of metalaxyl in various soil types. The
application rate was 2.2 kg/ha. In a fine sand, metalaxyl concentrations at soil depths of
15, 20, 45 and 60 cm were 100, 150, 100 and 75 ppb, respectively, 55 days afterPlant. In plants, metalaxyl undergoes ring oxidation, methyl ester hydrolysis, ether
cleavage, ring methyl hydroxylation and N-dealkylation (Owen and Donzel, 1986). Metalaxyl
acid was identified as a hydrolysis product in both sunflower leaves anIn pigeon peas, metalaxyl may persist up to 12 days (Indira et al., 1981; Chaube et
al., 1984).
Metabolic pathway
O-Demethylation is one of the major routes of
metalaxyl degradation in the plant cell suspension
culture. Although hydroxylation of methyl groups in the
phenyl ring predominates in both lettuce and grapes,
species differences are evident in grapes, whereas
N-dealkylation and aryl hydroxylation are less
important in lettuce. Two isomeric metabolites of
methyl hydroxylation and the hydroxylated metabolite
of the phenyl ring are identified as fungus metabolites.
By UV irradiation of metalaxyl in aqueous solution, two
rearrangement products of the N-acyl group to the
4-position on the phenyl ring are identified.
Metabolism
The degradation pathways of pesticides are published
in the "FAO Plant Production and Protection Papers."
Because the degradation pathways are similar for all
PAF). In plants, metalaxyl is metabolized by
four types of phase I reaction to form eight metabolites; at
phase II, most of the metabolites are sugar-conjugated.
The types of reaction in phase I are hydroxylation at
the phenyl ring, oxidation of one of
the tolylic methyl groups (Formula d), hydrolysis of the
methyl ester (Formula e), and ether cleavage (Formula b).
In phases II and III, there is also a dealkylation of the
nitrogen (Formula l), in addition to the combination of the
above-mentioned reaction types forming the compounds
of Formulas f, h, and m. In mammals, following oral
administration, metalaxyl is rapidly absorbed and rapidly
and almost completely eliminated with urine and feces.
Metabolism proceeds via the same degradation pathways
as in plants, leading to products containing an oxidized
tolylic methyl group with or without the hydrolyzed ester function (Formulas d, h, and i, respectively) containing a
dealkylated nitrogen and a hydroxy group formed by ether
cleavage (Formula l via b or e/f), containing an oxalyl
function formed by ether cleavage followed by oxidation
of the generated alcohol (Formula c), and containing
the hydroxylated phenyl ring (Formula a). Residues in
tissues were generally low, and there was no evidence for
accumulation or retention of metalaxyl or its metabolites.
In soil, similar degradation products are found as in
plants and animals with the exception of three additional
products of Formulas k, n, and g.
Shipping
UN3077 Environmentally hazardous substances,
solid, n.o.s., Hazard class: 9; Labels: 9-Miscellaneous hazardous
material, Technical Name Required.
Toxicity evaluation
If used according to label recommendations, PAFs
are considered to be safe to humans, animals, and
the environment. The active ingredients
represent only low-to-moderate acute oral and dermal
hazard to rats, mice, and rabbits. The compounds do not
exhibit mutagenic, oncogenic, and teratogenic hazards. No
or only weak (furalaxyl, ofurace) skin irritant potential
exists in rabbits and no skin sensitization is present in
guinea pigs, whereas some compounds are weak to serious
eye irritants in rabbits (except benalaxyl and oxadixyl). In long-term toxicity studies, the "no-observableeffect
level" (NOEL) in rats is 2.5 mg/kg body weight/day
for metalaxyl, metalaxyl-M, and ofurace; 5 mg/kg for
benalaxyl; and 11 mg/kg for oxadixyl, whereas in dogs,
the NOEL is 8.0 mg/kg body weight/day for metalaxyl
and metalaxyl-M, 7 mg/kg for benalaxyl, and 12 mg/kg for
oxadixyl. Using a safety factor of 100, the "acceptable daily intake" (ADI) for PAFs ranges from 0.025 to 0.11 mg/kg. The PAFs are unlikely to pose any toxicological
risk to birds (bobwhite quail, mallard ducks), fish (rainbow
trout, carp), honeybees, earthworms, Daphnia, and algae.
The observed LD50 (LC, EC) values are very favorable for
all PAFs; only benalaxyl shows lower figures in respect to
earthworm, Daphnia, and algae.
Degradation
Metalaxyl is very stable in neutral and acidic media at room temperature
and it is reasonably stable to aqueous photolysis. Its calculated
half-lives in buffers at 25 °C below pH 7 are <3 years and at pH 9, 12
weeks. Only at pH 11 was measurable hydrolysis seen (half-life 1.6
days) (Melkebeke et al., 1986). Thus environmental degradation can be
expected to be slow.
[14C-phenyl]Metalaxy1ir radiated in aqueous solution with UV light at
30 °C was degraded with a half-life of 2-3 days at four pH values between
2.8 and 8.8. Acetone (1%) accelerated the rate of decomposition. Two
rearrangement products (2 and 3) were isolated at pH 6.8; these accounted
for 3 and 6% of the radioactivity, respectively. Irradiation of 2 showed that
it was a precursor of compound 3 (Yao et al., 1989). Though these products
appear to be unusual, there is a precedent for such reactions and the
structures were determined by 1H and 13C NMR spectroscopy.
Decomposition under simulated sunlight was slower with a half-life of
297 days (Pirisi et al., 1996). Amide bond cleavage and N-dealkylation to
compounds 4 and 5 was reported. The dimethylaniline (6) was a putative
product but a separate experiment showed that it was degraded at a
higher rate than the parent and so was not observed from metalaxyl. The
products are shown in Scheme 1.
Incompatibilities
Incompatible with alkaline materials,
strong acids, oxidizers (chlorates, nitrates, peroxides, permanganates,
perchlorates, chlorine, bromine, fluorine, etc.);
contact may cause fires or explosions. Compounds of the
carboxyl group react with all bases, both inorganic and
organic (i.e., amines) releasing substantial heat, water and a
salt that may be harmful. Incompatible with arsenic compounds
(releases hydrogen cyanide gas), diazo compounds,
dithiocarbamates, isocyanates, mercaptans, nitrides, and
sulfides (releasing heat, toxic, and possibly flammable
gases), thiosulfates and dithionites (releasing hydrogen sulfate
and oxides of sulfur).
Waste Disposal
Small amounts may be
destroyed by alkaline hydrolysis. Admixture with alkali
can be followed by soil burial. Larger quantities can be
disposed of by incineration in admixture with acetone or
xylene and using effluent gas scrubbing. Do not reuse
empty container; proper disposal required.
Check Digit Verification of cas no
The CAS Registry Mumber 57837-19-1 includes 8 digits separated into 3 groups by hyphens. The first part of the number,starting from the left, has 5 digits, 5,7,8,3 and 7 respectively; the second part has 2 digits, 1 and 9 respectively.
Calculate Digit Verification of CAS Registry Number 57837-19:
(7*5)+(6*7)+(5*8)+(4*3)+(3*7)+(2*1)+(1*9)=161
161 % 10 = 1
So 57837-19-1 is a valid CAS Registry Number.
InChI:InChI=1/C15H21NO4/c1-10-7-6-8-11(2)14(10)16(13(17)9-19-4)12(3)15(18)20-5/h6-8,12H,9H2,1-5H3
57837-19-1Relevant articles and documents
METHOD FOR SYNTHESIZING COMPOUND
-
Paragraph 0095-0103, (2021/03/23)
The compound of Chemical Formula 1 and the compound of Formula 2 are used to prepare the compound of Formula 3 (a). The present invention relates to a method for preparing a compound of Formula 3, comprising preparing a compound of Formula ROH and 4 (b) in (a) and Formula 4 obtained in the above step.
Synthesis method of optically active metalaxyl
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Paragraph 0031; 0036; 0037; 0041; 0046; 0047; 0051; 0056, (2019/01/21)
The invention discloses a synthesis method of optically active metalaxyl. The optically active metalaxyl is synthesized by performing methoxylation and acylating chlorination on chloroacetic acid to obtain methoxyacetyl chloride and then reacting Methoxyacetyl chloride with D-N-(2,6-dimethylphenyl) alanine methyl ester; a one-pot method operation is adopted for the synthesis; the two-step reactionof methoxylation and acylating chlorination is directly used for a next-step reaction without post-treatment. According to the process of the optically active metalaxyl, by adopting the one-pot method operation, the operation steps are simplified, the production of three wastes is decreased, the synthesis cost is reduced, the obtained product is stable in quality and relatively high in output andyield, and the synthesis method is suitable for large-scale production.
Synthesis of magnetic multiwall carbon nanotubes for enantioseparation of three pesticide residues in fruits and vegetables by chiral liquid chromatography
Lei, Shuo,Li, Xianhui,Wang, Yang,Sun, Lirong,Liu, Hao,Zhao, Longshan
, p. 1321 - 1329 (2018/11/03)
In this study, magnetic multiwalled carbon nanotubes (MMWCNTs) were synthesized and used as adsorbent for preconcentration of chiral pesticide residues (including epoxiconazole, tebuconazole, and metalaxyl) in lettuce, cabbage, and apple. Several parameters affecting the treatment efficiency were investigated, including extraction solvent and absorption solvent. Under the optimal conditions, all three chiral pesticides showed decent enantiomeric separation (Rs?>?1.48). The linearity of each target was good with the correlation coefficient (r2) being greater than 0.9923. The average recoveries of the three spiked levels were 73.4% to 110.9% with repeatability (RSDr) less than 7.6%, and the limit of quantification of the method was 0.10 to 0.25?mg·kg?1. The results indicated that MMWCNTs had a good purifying effect, which can be applied as an effective pretreatment tool for the determination of residual chiral pesticides in fruits and vegetables.
Nanocellulose derivative/silica hybrid core-shell chiral stationary phase: Preparation and enantioseparation performance
Zhang, Xiaoli,Wang, Litao,Dong, Shuqing,Zhang, Xia,Wu, Qi,Zhao, Liang,Shi, Yanping
, (2016/06/15)
Core-shell silica microspheres with a nanocellulose derivative in the hybrid shell were successfully prepared as a chiral stationary phase by a layer-by-layer self-assembly method. The hybrid shell assembled on the silica core was formed using a surfactant as template by the copolymerization reaction of tetraethyl orthosilicate and the nanocellulose derivative bearing triethoxysilyl and 3,5-dimethylphenyl groups. The resulting nanocellulose hybrid core-shell chiral packing materials (CPMs) were characterized and packed into columns, and their enantioseparation performance was evaluated by high performance liquid chromatography. The results showed that CPMs exhibited uniform surface morphology and core-shell structures. Various types of chiral compounds were efficiently separated under normal and reversed phase mode. Moreover, chloroform and tetrahydrofuran as mobile phase additives could obviously improve the resolution during the chiral separation processes. CPMs still have good chiral separation property when eluted with solvent systems with a high content of tetrahydrofuran and chloroform, which proved the high solvent resistance of this new material.
Chiral phosphine-phosphoramidite ligands for highly enantioselective hydrogenation of N-arylimines
Li, Qing,Hou, Chuan-Jin,Liu, Xiao-Ning,Huang, De-Zhi,Liu, Yan-Jun,Yang, Rui-Feng,Hu, Xiang-Ping
, p. 13702 - 13708 (2015/02/19)
The asymmetric hydrogenation of N-arylimines with the chiral phosphine-phosphoramidite ligand, (Sc,Sa)-PEAPhos 2b, has been developed. The results revealed that the presence of the substituents on the 3,3′-positions of the binaphthyl backbone significantly improved the enantioselectivity. The utility of this methodology was demonstrated in the synthesis of the chiral fungicide (R)-metalaxyl. This journal is
Enantiomerization and enantioselective bioaccumulation of metalaxyl in tenebrio molitor larvae
Gao, Yongxin,Wang, Huili,Qin, Fang,Xu, Peng,Lv, Xiaotian,Li, Jianzhong,Guo, Baoyuan
supporting information, p. 88 - 94 (2014/03/21)
The enantiomerization and enantioselective bioaccumulation of metalaxyl by a single dose of exposure to Tenebrio molitor larvae under laboratory condition were studied by high-performance liquid chromatography tandem mass spectroscopy (HPLC-MS/MS) based on a ChiralcelOD-3R [cellulosetris-tris-(3, 5-dichlorophenyl-carbamate)] column. Exposure of enantiopure R-metalaxyl and S-metalaxyl in Tenebrio molitor larvae exhibited significant enantiomerization, with formation of the R enantiomers from the S enantiomers, and vice versa, which might be attributed to the chiral pesticide catalyzed by a certain enzyme in Tenebrio molitor larvae. Enantiomerization was not observed in wheat bran during the period of 21 d. In addition, bioaccumulation of rac-metalaxyl in Tenebrio molitor larvae was enantioselective with a preferential accumulation of S-metalaxyl. These results showed that enantioselectivity was caused not only by actual degradation and metabolism but also by enantiomerization, which was an important process in the environmental fate and behavior of metalaxyl enantiomers.
Trifluoromethylation of arenediazonium salts with fluoroform-derived CuCF3 in aqueous media
Lishchynskyi, Anton,Berthon, Guillaume,Grushin, Vladimir V.
supporting information, p. 10237 - 10240 (2014/08/18)
A new protocol has been developed for trifluoromethylation of arenediazonium salts with moisture-sensitive CuCF3 (from fluoroform) in aqueous media. The reaction is governed by a radical mechanism, tolerates a broad variety of functional groups, and is applicable to the synthesis of complex, polyfunctionalized molecules. This journal is the Partner Organisations 2014.
PROCESSES FOR THE PREPARATION OF SUBSTITUTED ANILINES
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Page/Page column 8-10, (2011/06/11)
The invention relates to a process for the preparation of compounds of formula (III) wherein R1, R2, R3, R4 and R5 are independently selected from C1-6 alkyl or hydrogen, comprising reacting an aniline of formula (IV) with a carboxylic acid of formula (V) in the presence of a catalyst comprising silica.
Enzyme-catalyzed preparation of methyl (R)-N-(2,6-dimethylphenyl)alaninate: A key intermediate for (R)-metalaxyl
Park, Oh-Jin,Lee, Sang-Hyun,Park, Tae-Yoon,Lee, Sang-Who,Cho, Koon-Ho
, p. 1221 - 1225 (2007/10/03)
A biocatalytic approach for the production of (R)-metalaxyl, mefenoxam, has been developed. A practical synthesis of methyl (R)-N-(2,6-dimethylphenyl) alaninate, a key intermediate for (R)-metalaxyl, has been developed by the use of lipase-catalyzed hydrolytic kinetic resolution and chemical racemization of the remaining ester. At high concentrations in aqueous media (300 g/L) lipases were stable and gave moderate to good conversions and excellent enantioselectivities (>98% ee). A simple extraction procedure was used to separate the acid product from the remaining ester and the acid was esterified with methanol to give methyl (R)-N-(2,6-dimethylphenyl)alaninate without any reduction in enantiomeric excess (>98% ee). Subsequent chemical coupling with methoxyacetyl chloride provided enantiomerically pure (R)-metalaxyl (>98% ee) without racemization.
Chiral ligands, transition-metal complexes thereof and uses thereof in asymmetric reactions
-
, (2008/06/13)
Chiral ligands and transition metal complexes based on such chiral ligands useful in asymmetric catalysis are disclosed. The chiral ligands include phospholanes, P,N ligands, N,N ligands, biphenols, and chelating phosphines. The ferrocene-based irridium (R,R)-f-binaphane complex reduces imines to the corresponding amines with 95-99.6% enantioselectivity and reduces β-substituted-α-arylenamides with 95% enantioselectivity. The transition metal complexes of the chiral ligands are useful in asymmetric reactions such as asymmetric hydrogenation of imines, asymmetric hydride transfer reactions, hydrosilylation, hydroboration, hydrovinylation, hydroformylation, allylic alkylation, cyclopropanation, Diels-Alder reaction, Heck reaction, isomerization, Aldol reaction, Michael addition and epoxidation reactions.
