66230-04-4

Basic information

• Product Name: Esfenvalerate
• Synonyms: ASANA;ASANA (TM);HALLMARK;FERTIALPHA;FORALPHA;ESFENVALERATE;Cyano-3-phenoxybenzyl (S)-2-(4-chlorophenyl)-3-methylbutyrate;AMICIDIN SUPER
• CAS NO: 66230-04-4
• Molecular Formula: C₂₅H₂₂ClNO₃
• Molecular Weight: 419.9
• Product Categories: Insecticide;EQ - EZMethod Specific;PesticidesPesticides;Alpha sort;E;E-GMethod Specific;Endocrine Disruptors (Draft)Alphabetic;EPA;Insecticides;Oeko-Tex Standard 100;Pesticides&Metabolites;Pyrethroids
• Mol File: 66230-04-4.mol

Chemical Properties

• Melting Point: 59°C
• Boiling Point: 151-167°C
• Flash Point: 279.7 °C
• Appearance: White crystalline solid
• Density: d2323 1.163
• Vapor Pressure: 1.11E-11mmHg at 25°C
• Refractive Index: 1.6500 (estimate)
• Storage Temp.: 0-6°C
• Water Solubility: 0.002 mg l-1 (25 °C)
• BRN: 4275674
• CAS DataBase Reference: Esfenvalerate(CAS DataBase Reference)
• NIST Chemistry Reference: Esfenvalerate(66230-04-4)
• EPA Substance Registry System: Esfenvalerate(66230-04-4)

Safety Data

• Hazard Codes: T;N,N,T
• Statements: 23/25-43-50/53
• Safety Statements: 24-36/37/39-45-60-61
• RIDADR: UN 2811
• WGK Germany: 3
• RTECS: CY1576367
• HazardClass: 6.1(b)
• PackingGroup: III
• Hazardous Substances Data: 66230-04-4(Hazardous Substances Data)

Usage

Sources

http://pmep.cce.cornell.edu/profiles/extoxnet/dienochlor-glyphosate/esfenvalerate-ext.html https://en.wikipedia.org/wiki/Esfenvalerate https://www.domyown.com/esfenvalerate-c-114_374.html https://en.wikipedia.org/wiki/Pyrethroid https://www.sciencedirect.com/topics/agricultural-and-biological-sciences/esfenvalerate https://sitem.herts.ac.uk/aeru/ppdb/en/Reports/269.htm

Trade name

AMERICARE?; ASANA?; ASANA-XL?; ASANA? DPX-YB656-84; ENFORCER?; EVERCIDE?; HALMARK?; OMS-3023?; S-1844?; S-5602 ALPHA?; SUMI-ALFA?; SUMI-ALPHA?; SS-PYDRIN?; SUMICIDIN A-ALPHA?

Potential Exposure

Esfenvalerate is a synthetic pyrethroid Insecticide used to control wide range of pests such as moths, flies, beetles, and other insects. It is used on vegetable crops (soya beans, sugar cane), tree fruit, cotton, maize, sorghum and nut crops, and noncrop lands. It also isused on a wide variety of household pests. It is usually mixed with a wide variety of other types of pesticides such as carbamate compounds or organophosphates and has the naturally occurring compound fenvalerate for use in the United States Esfenvalerate is almost identical to fenvalerate. Much of the data for fenvalerate is applicable to the pesticide esfenvalerate (E:0207) because the two compounds contain the same components. The only differences in the two products are the relative proportions of the four separate constituents (isomers). Esfenvalerate has become the preferred compound because it requires lower applications rates than fenvalerate, is less chronically toxic, and is a more powerful insecticide. A United States Environmental Protection Agency Restricted Use Pesticide (RUP). Incompatibilities: Oxidizers (chlorates, nitrates, peroxides, permanganates, perchlorates, chlorine, bromine, fluorine, etc.); strong acids. Moisture may cause hydrolysis/ decomposition.

Environmental Fate

Chemical/Physical. May hydrolyze in aqueous solutions forming acetic acid and other compounds.

Metabolic pathway

Esfenvalerate is the 2SαS-isomer of fenvalerate (which is racemic). It possesses some small differences in physical properties when compared with the racemate. Overall, the degradation and metabolism of the two compounds are very similar. Reference should be made to the fenvalerate entry. An important exception, which is discussed fully in the latter entry, is that esfenvalerate does not form the cholesterol ester conjugate that has been shown to be responsible for granulomatous changes in several tissues on repeated dosing of fenvalerate.

Shipping

UN3349 Pyrethroid pesticide, solid toxic, Hazard Class: 6.1; Labels: 6.1-Poisonous material. UN3352 Pyrethroid pesticide, liquid toxic, Hazard Class: 6.1; Labels: 6.1-Poisonous materials

Degradation

Esfenvalerate is hydrolysed in aqueous alkali to its constituent acid and alcohol; the latter decomposes to 3-phenoxybenzaldehyde and cyanide ion as described for fenvalerate and cypermethrin. Photodecomposition occurs as for fenvalerate.

Incompatibilities

Oxidizers (chlorates, nitrates, peroxides, permanganates, perchlorates, chlorine, bromine, fluorine, etc.); strong acids. Moisture may cause hydrolysis/ decomposition.

InChI:InChI=1/C25H22ClNO3/c1-17(2)24(18-11-13-20(26)14-12-18)25(28)30-23(16-27)19-7-6-10-22(15-19)29-21-8-4-3-5-9-21/h3-15,17,23-24H,1-2H3/t23-,24+/m1/s1

Synthetic route

sodium cyanide (143-33-9) + S-(+)-2-(4-chlorophenyl)isovaleryl chloride (66230-05-5) + 3-Phenoxybenzaldehyde (39515-51-0) → esfenvalerate (66230-04-4)

Conditions	Yield
With N-butyl-N,N-dimethyl-(α-phenyl)ethylammonium bromide In water; 1,2-dichloro-ethane at 0 - 5℃; for 2.25h;	36%

α-cyano-3-phenoxybenzyl S-(+)-2-(4-chlorophenyl)isovalerate (956498-38-7) → (R)-α-cyano-3-phenoxybenzyl (S)-2-(4-chlorophenyl)-3-methylbutyrate (67614-32-8) + esfenvalerate (66230-04-4)

Conditions	Yield
With ammonia In methanol at -19 - 17℃; for 17 - 260h; Purification / work up; Resolution of racemate;	A n/a B 23%
Stage #1: α-cyano-3-phenoxybenzyl S-(+)-2-(4-chlorophenyl)isovalerate In n-heptane; toluene for 2h; Heating / reflux; Resolution of racemate; Stage #2: In methanol at -16 - 0℃; for 65 - 240h; Purification / work up;
iron rust In methanol at -5 - 12℃; for 30h; Purification / work up; Resolution of racemate;

S-(+)-2-(4-chlorophenyl)isovaleryl chloride (66230-05-5) + (S)-m-phenoxybenzaldehyde cyanohydrin (39515-47-4, 52315-06-7, 61826-76-4, 71962-66-8) → esfenvalerate (66230-04-4)

Conditions	Yield
With pyridine

S-(+)-2-(4-chlorophenyl)isovaleryl chloride (66230-05-5) + (S)-m-phenoxybenzaldehyde cyanohydrin (39515-47-4, 52315-06-7, 61826-76-4, 71962-66-8) → esfenvalerate (66230-04-4) + [R]-alpha-cyano-3-phenoxybenzyl [S]-2-(4-chlorophenyl)-2-isopropyl-acetate (66267-77-4)

Conditions	Yield
With pyridine In dichloromethane a) 0 deg C 1 h, b) r.t., overnight; Yield given. Title compound not separated from byproducts;

2-hydroxy-2-(3-phenoxyphenyl)acetonitrile (39515-47-4) + S-(+)-2-(4-chlorophenyl)isovaleryl chloride (66230-05-5) → esfenvalerate (66230-04-4) + [R]-alpha-cyano-3-phenoxybenzyl [S]-2-(4-chlorophenyl)-2-isopropyl-acetate (66267-77-4)

Conditions	Yield
With pyridine In dichloromethane for 0.5h; Acylation;	A 495 mg B 645 mg

2-(4-chlorophenyl)-3-methyl-(2SR)-butanoyl chloride (51631-50-6) + (S)-m-phenoxybenzaldehyde cyanohydrin (39515-47-4, 52315-06-7, 61826-76-4, 71962-66-8) → (R)-α-cyano-3-phenoxybenzyl (S)-2-(4-chlorophenyl)-3-methylbutyrate (67614-32-8) + esfenvalerate (66230-04-4)

Conditions	Yield
With pyridine In hexane; acetate buffer at 0℃; pH=4.5; Title compound not separated from byproducts;

(S)-(+)-cyano(3-phenoxyphenyl)methyl butyrate (298702-31-5) → esfenvalerate (66230-04-4)

Conditions	Yield
Multi-step reaction with 2 steps 1: Pseudomonas cepacia lipase gelozyme; AcOH; 1-butanol / hexane / 3 h / 20 °C / Enzymatic reaction 2: pyridine / acetate buffer; hexane / 0 °C / pH 4.5 View Scheme

2-(4-chlorophenyl)-3-methylbutyric acid (2012-74-0, 55291-27-5, 55332-38-2, 63640-09-5) → esfenvalerate (66230-04-4)

Conditions	Yield
Multi-step reaction with 3 steps 1: via (S)-(-)-α-methylbenzylamine salt 2: SOCl2; DMF / CHCl3 / 1 h / 60 °C 3: 495 mg / pyridine / CH2Cl2 / 0.5 h View Scheme

S-isopropyl-4-chlorophenylacetic acid (55332-38-2) → esfenvalerate (66230-04-4)

Conditions	Yield
Multi-step reaction with 2 steps 1: SOCl2; DMF / CHCl3 / 1 h / 60 °C 2: 495 mg / pyridine / CH2Cl2 / 0.5 h View Scheme

3-Phenoxybenzaldehyde (39515-51-0) → esfenvalerate (66230-04-4)

Conditions	Yield
Multi-step reaction with 2 steps 1: HCl / tetrahydrofuran; H2O / 0.5 h / 20 °C 2: 495 mg / pyridine / CH2Cl2 / 0.5 h View Scheme
Multi-step reaction with 3 steps 2: Candida cylindracea lipase / H2O / 23 h / 30 °C / pH 5 3: pyridine View Scheme
Multi-step reaction with 3 steps 2: 49 percent / Arthrobacter lipase / H2O / 23 h / 40 °C / further lipases and immobilized Arthrobacter lipase; effect of pH, temperature and (S)/(R) mixture of the acetate 3: pyridine View Scheme

O-acetyl-(S)-2-hydroxy-2-(3-phenoxyphenyl)acetonitrile (113301-28-3) → esfenvalerate (66230-04-4)

Conditions	Yield
Multi-step reaction with 2 steps 1: 92 percent / ethanol / diisopropyl ether / 6 h / 25 °C / lipase from Pseudomonas cepacia (Amano) 2: pyridine / CH2Cl2 / a) 0 deg C 1 h, b) r.t., overnight View Scheme

alpha-cyano-3-phenoxybenzyl acetate (61066-87-3) → esfenvalerate (66230-04-4)

Conditions	Yield
Multi-step reaction with 2 steps 1: Candida cylindracea lipase / H2O / 23 h / 30 °C / pH 5 2: pyridine View Scheme
Multi-step reaction with 2 steps 1: 49 percent / Arthrobacter lipase / H2O / 23 h / 40 °C / further lipases and immobilized Arthrobacter lipase; effect of pH, temperature and (S)/(R) mixture of the acetate 2: pyridine View Scheme

cyclo(D-phenylalanyl-D-histidine) + 2-hydroxy-2-(3-phenoxyphenyl)acetonitrile (39515-47-4) + (p-chlorophenyl)isopropylketene (92742-11-5) → esfenvalerate (66230-04-4)

racemic alpha-isopropyl-p-chlorophenylacetyl chloride + (S)-m-phenoxybenzaldehyde cyanohydrin (39515-47-4, 52315-06-7, 61826-76-4, 71962-66-8) → esfenvalerate (66230-04-4)

Conditions	Yield
With pyridine In methanol; hexane; toluene

esfenvalerate (66230-04-4) → 1-allyl-4-chlorobenzene (1745-18-2) + 4-chloro(ethylbenzene) (622-98-0) + 2-(4-Chlorophenyl)ethanol (1875-88-3) + 2-(4-chlorophenyl)-3-methylbutyric acid (2012-74-0, 55291-27-5, 55332-38-2, 63640-09-5) + 1-chloro-4-(1-methylprop-2-en-1-yl)benzene (23853-78-3) + 3-phenoxybenzoic acid (3739-38-6) + 2-(4-Chloro-phenyl)-propionic acid (938-95-4) + 3-Phenoxybenzaldehyde (39515-51-0) + para-Chlorobenzyl alcohol (873-76-7) + methyl N-hydroxybenzene carboximidoate

Conditions	Yield
With dihydrogen peroxide In methanol; water at 25℃; for 4h; pH=10.95;

...Expand

Upstream product

• 66230-05-5 S-(+)-2-(4-chlorophenyl)isovaleryl chloride 
• 39515-47-4 (S)-m-phenoxybenzaldehyde cyanohydrin 
• 39515-47-4 2-hydroxy-2-(3-phenoxyphenyl)acetonitrile 
• 51631-50-6 2-(4-chlorophenyl)-3-methyl-(2SR)-butanoyl chloride 
• 143-33-9 sodium cyanide 
• 39515-51-0 3-Phenoxybenzaldehyde 
• 298702-31-5 (S)-(+)-cyano(3-phenoxyphenyl)methyl butyrate 
• 2012-74-0 2-(4-chlorophenyl)-3-methylbutyric acid 
• 55332-38-2 S-isopropyl-4-chlorophenylacetic acid 
• 113301-28-3 O-acetyl-(S)-2-hydroxy-2-(3-phenoxyphenyl)acetonitrile 
• 61066-87-3 alpha-cyano-3-phenoxybenzyl acetate 
• 956498-38-7 α-cyano-3-phenoxybenzyl S-(+)-2-(4-chlorophenyl)isovalerate 
• 92742-11-5 p-chlorophenyl isopropyl ketene 

Downstream Products

• 1745-18-2 1-allyl-4-chlorobenzene 
• 622-98-0 4-chloro(ethylbenzene) 
• 1875-88-3 2-(4-Chlorophenyl)ethanol 
• 2012-74-0 2-(4-chlorophenyl)-3-methylbutyric acid 
• 23853-78-3 1-chloro-4-(1-methylprop-2-en-1-yl)benzene 
• 3739-38-6 3-phenoxybenzoic acid 
• 938-95-4 2-(4-Chloro-phenyl)-propionic acid 
• 39515-51-0 3-Phenoxybenzaldehyde 
• 873-76-7 para-Chlorobenzyl alcohol 

Relevant articles and documents

Process for preparing (S)- alpha-cyano-3-phenoxybenzyl-(S)-2-(4-chlorophenyl)-isovalerate

The present invention relates to an environmentally benign process for the preparation of (S)-α-cyano-3-phenoxybenzyl-(S)-2-(4-chlorophenyl)isovalerate from its diastereomeric mixture (RS)-α-cyano-3-phenoxybenzyl-(S)-2-(4-chlorophenyl) isovalerate.

A new phase transfer catalyst and its applications in organic transformations

A new quaternary ammonium bromide salt has been used for the first time in phase transfer catalysis (PTC) reactions such as oxidation of alcohols to carbonyl compounds, alkylation and esterification reactions. Improved yields and reduced reaction times have been achieved by this procedure.

'Gelozymes' in organic synthesis. Part 2: Candida rugosa lipase mediated synthesis of enantiomerically pure (S)-cyano(3-phenoxyphenyl)methyl butyrate

Significant changes in enantioselectivity (E) have been observed when the butanoate ester of (±)-1-hydroxy-1-(3-phenoxyphenyl)acetonitrile was subjected to hydrolysis in acetate buffer (pH 4.5, E = 6.4) and alcoholysis with 1-butanol in hexane catalysed by Candida rugosa lipase (E = 45). Enantiomerically pure (S)-butanoate ester so obtained (e.e. 98.4%) was converted to the corresponding (S)-cyanohydrin using Pseudomonas cepacia (Amano Ps) gelozyme. This strategy overcomes the problem of separation of the unwanted (R)-ester from the (S)-cyanohydrin.

Development of an immunoassay for the pyrethroid insecticide esfenvalerate

A competitive enzyme-linked immunosorbent assay was developed for the detection of the pyrethroid insecticide esfenvalerate. Two haptens containing amine or propanoic acid groups on the terminal aromatic ring of the fenvalerate molecule were synthesized and coupled to carrier proteins as immunogens. Five antisera were produced and screened against eight different coating antigens. The assay that had the least interference and was the most sensitive for esfenvalerate was optimized and characterized. The I50 for esfenvalerate was 30 ± 6.2 μg/L, and the lower detection limit (LDL) was 3.0 2+ 1.8 μg/L. The assay was very selective. Other pyrethroid analogues and esfenvalerate metabolites tested did not cross-react significantly in this assay. To increase the sensitivity of the overall method, a C18 sorbent-based solid-phase extraction (SPE) was used for water matrix. With this SPE step, the LDL of the overall method for esfenvalerate was 0.1 μg/L in water samples.

Halogen alkenyl azolyl microbicides

Novel halogenoalkenyl-azolyl derivatives of the formula STR1 in which R1 represents optionally substituted alkyl, optionally substituted alkenyl, optionally substituted cycloalkyl, optionally substituted aryl or represents optionally substituted heteroaryl, R2 represents alkyl, halogenoalkyl, 1-hydroxyalkyl, 2-hydroxyalkyl, 1-hydroxyhalogenalkyl, 1-alkenyl or 2-alkenyl, X1 represents fluorine, chlorine, bromine or iodine, X2 represents fluorine, chlorine, bromine or iodine, and Y represents nitrogen or a CH group, and addition products thereof with acids or metal salts are very active as microbicides in plant protection and in the protection of materials.

Pesticidal composition containing a microencapsulated organo-phosphorus or carbamate in a pyrethroid dispersion

An insecticidal and/or acaricidal and/or nematicidal composition having a rapid efficacy and residual activity which comprises a mixture of a poorly water-soluble organophosphorus insecticide and/or acaricide and/or nematicide and/or a poorly water-soluble carbamate insecticide and/or acaricide which have been microencapsulated in water-insoluble polymer coatings with a dispersing agent used in forming a microcapsule part, with a poorly water-soluble pyrethroid insecticide and/or acaricide emulsified or suspended in water with the above-mentioned dispersing agent used in forming a flowable part.

One-Pot Synthesis of Optically Active Cyanohydrin Acetates from Aldehydes via Lipase-Catalyzed Kinetic Resolution Coupled with in Situ Formation and Racemization of Cyanohydrins

A novel one-pot synthesis of optically active cyanohydrin acetates from aldehydes has been accomplished by lipase-catalyzed kinetic resolution coupled with in situ formation and racemization of cyanohydrins in an organic solvent.Racemic cyanohydrins 2, generated from aldehydes 1 and acetone cyanohydrin in diisopropyl ether under the catalysis of basic anion-exchange resin (OH- form), were acetylated stereoselectively by a lipase from Pseudomonas cepacia (Amano) with isopropenyl acetate as an acylating reagent.The (S)-isomer of 2 was preferentially acetylated by the lipase, while the unreacted (R)-isomer was continuously racemized through reversible transhydrocyanation catalyzed by the resin.These processes thus enabled one stage conversion of various aldehydes 1a-n into the corresponding (S)-cyanohydrin acetates 3a-n with up to 94 percent ee in 63-100 percent conversion yields.The racemization of the optically active cyanohydrin 2e by Amberlite IRA-904 (OH- form) was found to be much faster then the enzymatic acetylation, confirming the effective second-order asymmetric transformation.Enzymatic deacetylation of (S)-cyanohydrin acetates in an organic solvent and the synthesis of optically active pyrethroids are also described.

Enantioselective Hydrolysis of α-Cyano-3-phenoxybenzyl Acetate with Arthrobacter Lipase

Lipase-catalyzed enantioselective hydrolysis of the acetic ester of racemic α-cyano-3-phenoxybenzyl alcohol (CPBA) was examined to prepare (S)-CPBA.Most of the lipases tested hydrolyzed (S)-CPBA acetate preferentially, while Candida cylindracea lipase favored (R)-CPBA acetate.Enantioselective hydrolysis by Arthrobacter lipase gave optically pure (S)-CPBA in the reaction mixture of pH 4.0.The kinetic studies showed that (R)-CPBA acetate reacted as a competitive inhibitor.The Arthrobacter lipase solution in the water/oil biphasic reaction system could be usedrepeatedly.The lipase immobilized to resins had insufficient activity or low operational stability with the repeated batch reaction.The unhydrolyzed (R)-CPBA acetate was racemized by heating with triethylamine and could be reused as the substrate of enzymatic hydrolysis.A chemico-enzymatic process for the preparation of (S)-CPBA was developed based on these studies.

LIPASE-CATALYZED IRREVERSIBLE TRANSESTERIFICATION USING ENOL ESTERS: XAD-8 IMMOBILIZED LIPOPROTEIN LIPASE-CATALYZED RESOLUTION OF SECONDARY ALCOHOLS

Procedures for preparation of XAD-8 immobilized lipoprotein lipase and the resolution of secondary alcohols of synthetic value in organic solvents using this immobilized enzyme have been developed.

Process for preparation of an S-alpha-cyano S-alpha-isopropylphenylacetate

A method of preparing an "A-alpha" single stereoisomer of an S-alpha-cyano-3-phenoxybenzyl S-alpha-isopropylphenylacetate by precipitation from a solution of an "alpha" diastereoisomer pair, S-alpha-cyano-3-phenoxybenzyl R,S-alpha-isopropylphenylacetate, and optional hydrolysis of the mother liquor and recycle of the components thereof. The phenylacetate "alpha" is prepared from the S-alpha-cyano-3-phenoxybenzyl alcohol and racemic alpha-isopropylphenylacetic acid or reactive derivative thereof.