35554-44-0

Basic information

• Product Name: Imazalil
• Synonyms: rac-1-[(R*)-2-(Allyloxy)-2-(2,4-dichlorophenyl)ethyl]-1H-imidazole;Imazalil base;Imazalil 100mg [35554-44-0];Imazalil Solution, 100ppm;imazalil:1-(2-(2,4-dichloro-phenyl)-2-(2-propenyloxy)ethyl)-1h-IMIDAZOLE;(.+/-.)-1-(beta-(Allyloxy)-2,4-dichlorophenethyl)imidazole;(+-)-1-(beta-(allyloxy)-2,4-dichlorophenethyl)imidazole;(+or-)-1-(beta-allyloxy-2,4-dichlorophenylethyl)imidazole
• CAS NO: 35554-44-0
• Molecular Formula: C₁₄H₁₄Cl₂N₂O
• Molecular Weight: 297.18
• EINECS: 252-615-0
• Product Categories: NULL;API;CLINAFARM;FUNGICIDE
• Mol File: 35554-44-0.mol

Chemical Properties

• Melting Point: 52.7°C
• Boiling Point: >340°C
• Flash Point: 225.1 °C
• Appearance: slightly yellow to brown solidified oil
• Density: 1.348
• Vapor Pressure: 1.58 x l0-4 Pa (20 °C)
• Refractive Index: 1.5680 (estimate)
• Storage Temp.: 2-8°C
• PKA: 6.53 (weak base)
• Water Solubility: 0.018 g/100 mL
• Merck: 13,3616
• BRN: 545683
• CAS DataBase Reference: Imazalil(CAS DataBase Reference)
• NIST Chemistry Reference: Imazalil(35554-44-0)
• EPA Substance Registry System: Imazalil(35554-44-0)

Safety Data

• Hazard Codes: Xn,N
• Statements: 20/22-41-50/53
• Safety Statements: 26-39-60-61
• RIDADR: 2588
• WGK Germany: 3
• RTECS: NI4776000
• HazardClass: 6.1(b)
• PackingGroup: III
• Hazardous Substances Data: 35554-44-0(Hazardous Substances Data)

Usage

Uses

Used in Agriculture:
Imazalil is used as a systemic fungicide for the control of a wide range of fungal diseases on fruit, vegetables, and ornamentals. It is particularly effective against powdery mildew on roses and storage diseases of citrus fruit, pome fruit, bananas, and seed potatoes. It is also used as a seed dressing for the control of diseases in cereals, particularly against Fusarium and Helminthosporium spp.
Used in Animal Health:
Imazalil is used for the treatment of Microsporum spp and Aspergillus spp infections in dogs, either as a single topical agent or in combination with oral administrated itraconazole or griseofulvin.
Used as a Disinfectant:
Imazalil is used as a disinfectant for stable and kennel equipment, as well as an experimental agricultural fungicide.
Used in Fungal Infection Control:
Formulations containing imazalil have been used to control fungal infection in agriculture, particularly for crops affected by fungi attracted to tubers, such as Fusarium spp, Phoma spp, and Helminthosporium solani.
Used in Inhibiting Fungal Growth:
Imazalil is an imidazole fungicide that inhibits the growth of various fungi in vitro, including P. italicum, A. niger, U. maydis, B. alii, and C. cucumerinum in a pH-dependent manner. It also inhibits S. cerevisiae and has been shown to activate the murine pregnane X receptor (PXR) in a concentration-dependent manner, increasing hepatic CYP3A11 and CYP2B10 mRNA levels in mice when administered at a dose of 100 mg/kg.

References

http://www.vetbook.org/wiki/dog/index.php?title=Enilconazole https://en.wikipedia.org/wiki/Enilconazole https://www.mysciencework.com/publication/show/f0382c741754e9200388abe8cf2f0133

Air & Water Reactions

Water soluble.

Reactivity Profile

Imazalil is an imidazole derivative.

Safety Profile

Poison by ingestion and intraperitoneal routes. Experimental reproductive effects. A skin and eye irritant. When heated to decomposition it emits toxic fumes of Cland NOx.

Veterinary Drugs and Treatments

Although no dosage forms are currently commercially available for topical use in the USA, Enilconazole is used topically for treating dermatophytosis in small animals and horses using compounded products. A commercially available topical rinse Imaverol? (Janssen) 10% is available with canine, bovine and equine use labeling in many countries. Intranasal instillation of enilconazole after plaque debridement has also been shown useful in treating nasal aspergillosis in small animals. Use of topical enilconazole on cats with dermatophytosis is somewhat controversial as there are apparently no products with feline labeling available in Europe or Canada. There are preliminary reports of safely and successfully using enilconazole on dermatophytic cats in combination with oral itraconazole. A topical product and a poultry environmental disinfectant product (Clinafarm EC?) is available in the USA. It is technically illegal to use this product other than it is labeled; it is an EPA licensed product in the USA.

Metabolic pathway

Published information is available on the metabolism of imazalil in plants and soils. The principal metabolite in plants and soils is 1-[2-(2,4- dichlorophenyl)-2-hydroxyethyl]-1H-imidazole.

Degradation

Imazalil is very stable to hydrolysis in dilute acids and alkalis at room temperature, in the absence of light. It is also stable to light under normal storage conditions.

InChI:InChI=1/C14H14Cl2N2O/c1-2-7-19-14(9-18-6-5-17-10-18)12-4-3-11(15)8-13(12)16/h2-6,8,10,14H,1,7,9H2

Synthetic route

1-(2,4-dichlorophenyl)-2-(1H-imidazol-1-yl)ethan-1-ol (24155-42-8) + 3-chloroprop-1-ene (107-05-1) → 1-[2-(2,4-dichlorophenyl)-2-(2-propenyloxy)ethyl]-1H-imidazole (35554-44-0)

Conditions	Yield
Stage #1: 1-(2,4-dichlorophenyl)-2-(1H-imidazol-1-yl)ethan-1-ol With potassium hydroxide In water; dimethyl sulfoxide at 20℃; for 1h; Stage #2: 3-chloroprop-1-ene In water; dimethyl sulfoxide at 30℃; for 3h; Solvent; Temperature;	95.6%
Stage #1: 1-(2,4-dichlorophenyl)-2-(1H-imidazol-1-yl)ethan-1-ol With potassium hydroxide In water; dimethyl sulfoxide at 20 - 35℃; for 1h; Stage #2: 3-chloroprop-1-ene In water; dimethyl sulfoxide at 35 - 40℃; Reagent/catalyst;	68%

1H-imidazole (288-32-4) + 3-chloroprop-1-ene (107-05-1) + 2,2',4'-trichloroacetophenone (4252-78-2) → 1-[2-(2,4-dichlorophenyl)-2-(2-propenyloxy)ethyl]-1H-imidazole (35554-44-0)

Conditions	Yield
Stage #1: 2,2',4'-trichloroacetophenone With tris(triphenylphosphine)ruthenium(II) chloride; acetic acid; triethylamine at 70℃; for 9h; Stage #2: 1H-imidazole With N,N-dimethyl acetamide; sodium hydroxide at 50 - 100℃; for 5h; Stage #3: 3-chloroprop-1-ene at 105℃; for 6h; Reagent/catalyst; Solvent;	64.4%

allyl bromide (106-95-6) + 1-(2,4-dichlorophenyl)-2-(1H-imidazol-1-yl)ethan-1-ol (24155-42-8) → 1-[2-(2,4-dichlorophenyl)-2-(2-propenyloxy)ethyl]-1H-imidazole (35554-44-0)

Conditions	Yield
With sodium hydride In N,N-dimethyl-formamide	17%

1-(2,4-dichlorophenyl)-2-(1H-imidazol-1-yl)ethan-1-ol (24155-42-8) + allyl halide → 1-[2-(2,4-dichlorophenyl)-2-(2-propenyloxy)ethyl]-1H-imidazole (35554-44-0)

Conditions	Yield
With sodium hydride In N,N-dimethyl-formamide at 20℃; for 0.5h;

methylthiol (74-93-1) + 1-[2-(2,4-dichlorophenyl)-2-(2-propenyloxy)ethyl]-1H-imidazole (35554-44-0) → 1-(2-(2,4-dichlorophenyl)-2-(3-(methylthio)propoxy)ethyl)-1H-imidazole

Conditions	Yield
With C38H28Au2F12FeN2O8P2S4 In 1,4-dioxane at 45℃; for 20h; Inert atmosphere; Glovebox; Sealed tube;	99%

2,4-Dichlorobenzyl chloride (94-99-5) + 1-[2-(2,4-dichlorophenyl)-2-(2-propenyloxy)ethyl]-1H-imidazole (35554-44-0) → 1-[β-(Allyloxy)-2,4-dichlorophenethyl]-3-(2,4-dichlorobenzyl)imidazolium chloride hydrate

2-chloroaceto-p-fluoroanilide + 1-[2-(2,4-dichlorophenyl)-2-(2-propenyloxy)ethyl]-1H-imidazole (35554-44-0) → 1-[β-(Allyloxy)-2,4-dichlorophenethyl]-3-[N-(p-fluorophenyl)-carbamoylmethyl]imidazolium chloride (57265-11-9)

1-[2-(2,4-dichlorophenyl)-2-(2-propenyloxy)ethyl]-1H-imidazole (35554-44-0) → (+)-imazalil + (-)-imazalil

Conditions	Yield
With Lux Cellulose-2 (cellulose tris-(3-chloro-4-methylphenylcarbamate) In hexane; isopropyl alcohol at 20℃; Thermodynamic data; Reagent/catalyst; Temperature; Resolution of racemate;

1-[2-(2,4-dichlorophenyl)-2-(2-propenyloxy)ethyl]-1H-imidazole (35554-44-0) → S-(+)-imazalil (166734-82-3) + R-(−)-imazalil (166734-81-2)

Conditions	Yield
With CHIRALCEL OJ column (10 µm; 250*4.6 mm) In methanol; ethanol; hexane Solvent; Resolution of racemate;

2-(aminooxy)acetic acid hemihydrochloride + 1-[2-(2,4-dichlorophenyl)-2-(2-propenyloxy)ethyl]-1H-imidazole (35554-44-0) → imazalil hapten

Conditions	Yield
Stage #1: 1-[2-(2,4-dichlorophenyl)-2-(2-propenyloxy)ethyl]-1H-imidazole With potassium permanganate; sodium periodate In 1,4-dioxane at 20℃; for 4h; Stage #2: 2-(aminooxy)acetic acid hemihydrochloride In 1,4-dioxane at 60℃; for 24h;

Upstream product

• 106-95-6 allyl bromide 
• 24155-42-8 1-(2,4-dichlorophenyl)-2-(1H-imidazol-1-yl)ethan-1-ol 
• 288-32-4 1H-imidazole 
• 107-05-1 3-chloroprop-1-ene 
• 4252-78-2 2,2',4'-trichloroacetophenone 

Downstream Products

• 57265-11-9 1-[β-(Allyloxy)-2,4-dichlorophenethyl]-3-[N-(p-fluorophenyl)-carbamoylmethyl]imidazolium chloride 
• 166734-82-3 S-(+)-imazalil 
• 166734-81-2 R-(?)-imazalil 

Relevant articles and documents

O-allylation method of alpha,beta-diaryl substituted ethanol

The invention belongs to the technical field of organic synthesis technology, and specifically discloses an O-allylation method of alpha,beta-diaryl substituted ethanol. The method has the advantagesof mild reaction conditions, simple and convenient operation, and low equipment requirement, is suitable for industrial amplification, and belongs to the field of organic synthesis. According to the method, an inorganic alkali/dimethyl sulfoxide hyper-alkaline system is used to activate an alcohol substrate, and then the substrate reacts with allyl chloride. Compared with the prior art, the methodhas the advantages of quick reaction speed, high yield, mild conditions, low equipment requirements, simple and convenient operation, green, and safety, is especially suitable for industrial enlargedproduction, and has an important industrial application value; and the cost advantage is prominent.

Enilconazole bulk drug preparation method

The invention discloses an enilconazole bulk drug preparation method, which specifically comprises: dissolving imidazole ethanol as a raw material, adding a KOH solution, activating, adding allyl chloride, carrying out a reaction for 1-7 h at a temperature of 20-40 DEG C, extracting after completing the reaction, concentrating to obtain crude enilconazole, and re-crystallizing the crude enilconazole to obtain finished enilconazole. According to the present invention, DMSO is used as the solvent, KOH is used as the alkali, the reaction condition is mild, the reaction system is stable, the sidereaction is less, and the reaction yield is up to more than 98%; the used re-crystallization solvent has characteristics of low prices, easy available, low toxicity and high re-crystallization yield;the prepared enilconazole has a purity of more than 99.8%, and other indexes meet the European Pharmacopoeia standards; and compared with the process in the prior art, the method of the present invention has characteristics of short process route, low requirements on equipment, simple operation, stable process and low production cost, and is suitable for industrial production.

Enilconazole preparation method

The invention discloses an enilconazole preparation method which comprises the following steps: putting 2,4-dichloro-2'-chloroacetophenone, a reducing agent, an organic alkali and a catalyst into a reaction container, controlling the temperature to 65-75 DEG C, enabling the components to react for 8-10 hours, concentrating, adding sodium hydroxide, dimethylacetamide and imidazole, enabling the components to react for 4-6 hours at 95-105 DEG C, cooling, dropping allyl chloride, enabling the components to react for 5-7 hours at 100-110 DEG C, and performing elutriation extraction filtration so as to obtain a crude enilconazole product; crystallizing the crude product with ethanol, and drying, thereby obtaining a dried enilconazole product, wherein the reducing agent is formic acid or isopropanol, and the catalyst is RuCl2(pph3)3. Due to adoption of the catalyst and the gentle reducing agent, the method has the advantages of being high in yield, small in impurity and gentle in reaction when being compared with common methods with sodium borohydride, and has the potential of industrial production.

Design and synthesis of novel imidazole derivatives as potent inhibitors of allene oxide synthase(CYP74)

Allene oxide synthase (AOS) is a key enzyme in the oxylipin pathway in plants leading to jasmonic acid and other jasmonates (JAs), important signal mediators of defense signal networks in plants. AOS uses hydroperoxylinolenic acid as an oxygen donor as we

Aliphatic ethers of 1-(2,4-dichlorophenyl)-2-(1-H-imidazolyl)ethanol: Influence of ramification and/or unsaturation on lipophilicity and antifungal activity

Ethers of 1-(2,4-dichlorophenyl)-2-(1-H-imidazolyl)ethanol bearing influence ramification and/or unsaturated chains have been synthesized in order to specify the role of lipophilicity or steric contributions on antifungal activity against yeast for miconazole-like structures. The presence of ramifications on aliphatic chains (between 4 and 7 carbons) or unsaturation at the end, increases antifungal activity. For these compounds, lipophilicity seems to be counterbalanced by steric contributions.