10004-44-1

Basic information

• Product Name: Hymexazol
• Synonyms: TACHIGALOZE;TACHIGAREN;3-hydroxy-5-methyl-isoxazol;5-Hydroxy-3-methylisoxazole;5-methyl-3(2h)-isoxazolon;5-methyl-3-isoxazolo;bucid;bucide
• CAS NO: 10004-44-1
• Molecular Formula: C₄H₅NO₂
• Molecular Weight: 99.09
• EINECS: 233-000-6
• Product Categories: Oxazoles, Isoxazoles & Benzoxazoles;Oxazole&Isoxazole;Heterocyclic Compounds;FUNGICIDE;Heterocycles;Oxazoles, Isoxazoles & Benzoxazoles;Agro-Products
• Mol File: 10004-44-1.mol

Chemical Properties

• Melting Point: 80°C
• Boiling Point: 185.54°C (rough estimate)
• Flash Point: 173.7 °C
• Appearance: /Powder
• Density: 1.2992 (rough estimate)
• Vapor Pressure: 0.0493mmHg at 25°C
• Refractive Index: 1.4170 (estimate)
• Storage Temp.: −70°C
• Solubility: Soluble in alcohol, acetone, THF, chloroform
• PKA: 5.91 (weak acid)
• Water Solubility: 65,100 mg l-1 (20 °C)
• Sensitive: Light Sensitive
• Merck: 14,4856
• CAS DataBase Reference: Hymexazol(CAS DataBase Reference)
• NIST Chemistry Reference: Hymexazol(10004-44-1)
• EPA Substance Registry System: Hymexazol(10004-44-1)

Safety Data

• Hazard Codes: Xn,Xi
• Statements: 22-41-52/53
• Safety Statements: 26-39-61
• WGK Germany: 3
• RTECS: NY2932000
• Hazardous Substances Data: 10004-44-1(Hazardous Substances Data)

Usage

Uses

Used in Pesticide Industry:
Hymexazol is used as a pesticide for controlling soil-borne diseases caused by various pathogens such as Fusarium, Aphanomyces, Pythium, Corficium, and Typhula spp. It is effective in a range of crops, including rice, sugar beet, fodder beet, vegetables, cucurbits, ornamentals, carnations, and forest tree seedlings.
Used in Agricultural Fungicide Industry:
As an agricultural fungicide, Hymexazol plays a crucial role in protecting crops from soil-borne diseases, ensuring a healthy growth environment and increased yield.
Used in Plant Growth Regulation:
Hymexazol also serves as a plant growth regulator, stimulating some aspects of plant growth and contributing to overall crop health and productivity.
Used in Seed Dressing:
In addition to its fungicidal properties, Hymexazol is utilized as a seed dressing, providing protection for seeds against soil-borne diseases and promoting a strong start for the growing plants.

Synthesis Reference(s)

The Journal of Organic Chemistry, 48, p. 4307, 1983 DOI: 10.1021/jo00171a030

Metabolic pathway

Degradation of hymexazol in soil gave acetoacetamide and the product of rearrangement, 5-methyl-2(3H)-oxazolone.H owever, in plants the fungicide was principally converted into its O- and N-glucoside conjugates in the roots and shoots. The two main metabolites of hymexazol found in the urine of rats were the O-glucuronide and sulfate conjugates.

Degradation

Hymexazol is stable under alkaline conditions and relatively stable in acidic conditions. It is stable to sunlight and heat (PM). It should be noted that the parent molecule is tautomeric. Hymexazol is highly volatile and will be lost by volatilisation unless it is covered or incorporated into soil. The fungicide was completely biodegraded in natural water at 30 °C in 2 weeks and at 10-13 °C in 2 months (Rebenok and Kolesnikova, 1983). Hymexazol is stable in sunlight but it is readily degraded by ultraviolet light. Photolysis of an aqueous solution of the fungicide at 253.7 nm, using a low pressure Hg lamp, afforded the oxazolinone (2) as the major product and at least two unidentified minor components. The oxazolinone (2) has been found in soil studies as described below and is a product of rearrangement formed via an aziridinone intermediate as shown in Scheme 1 (Nakagawa et al., 1974).

InChI:InChI=1/C4H5NO2/c1-3-2-4(6)5-7-3/h2H,1H3,(H,5,6)

Synthetic route

carboxamido-2 ethoxy-5 methyl-5 isoxazolone-3 (110795-04-5) → 5-methyl-3(2H)isoxazolone (10004-44-1)

Conditions	Yield
With sodium methylate In methanol for 12h; Ambient temperature;

epoxybutene (930-22-3) + 5-methyl-3(2H)isoxazolone (10004-44-1) → 2-((S)-hydroxymethylallyl)-5-methylisoxazol-3-one (1174758-37-2)

Conditions	Yield
Stage #1: 5-methyl-3(2H)isoxazolone With tris(dibenzylideneacetone)dipalladium(0) chloroform complex; tetrabutylammomium bromide; (1R,2R)-(+)-1,2-diaminocyclohexane-N,N’-bis(2-diphenylphosphino-1-naphthoyl) In acetonitrile for 0.166667h; Inert atmosphere; Stage #2: epoxybutene In acetonitrile at 0℃; for 23h; Inert atmosphere; optical yield given as %ee; enantioselective reaction;	77%

5-methyl-3(2H)isoxazolone (10004-44-1) + 1-chloroadamantane (935-56-8) → 2-(1-adamantyl)-5-methyl-2,3-dihydroisoxazol-3-one (83610-15-5)

Conditions	Yield
With chloro-trimethyl-silane; triethylamine; aluminium trichloride 1.) Et2O, 5 h, room temp., 2.) CHCl3, room temp., 1 h; Yield given. Multistep reaction;

5-methyl-3(2H)isoxazolone (10004-44-1) + methyl iodide (74-88-4) → 3-methoxy-5-methylisoxazole (16864-45-2)

Conditions	Yield
With silver(l) oxide In N,N-dimethyl-formamide at 20℃;
With silver(l) oxide In N,N-dimethyl-formamide at 20℃; for 2h;

Upstream product

• 674-82-8 4-methyleneoxetan-2-one 
• 105-45-3 acetoacetic acid methyl ester 
• 90587-50-1 N-hydroxyacetoacetamide 
• 110795-04-5 carboxamido-2 ethoxy-5 methyl-5 isoxazolone-3 
• 141-97-9 ethyl acetoacetate 
• 92234-51-0 methyl β-(1-imidazolyl)crotonoate 
• 87318-59-0 N-(trimethylsilyloxy)-N-(trimethylsilyl)acetoacetamide 
• 10004-24-7 Ethyl tetrolate 
• 3075-23-8 S-ethyl acetothioacetate 

Downstream Products

• 153201-10-6 4-(bromomethyl)-2-(methoxymethyl)-5-methylisoxazol-3(2H)-one 
• 24827-14-3 3-benzoyloxy-5-methyl-isoxazole 
• 26347-20-6 2-ethyl-5-methylisoxazolin-3-one 
• 127020-20-6 3-ethoxy-5-methylisoxazole 
• 81282-07-7 3-(2-iodobenzoyloxy)-5-methylisoxazole 
• 76422-46-3 5-methyl-3-(p-toluenesulphonyloxy)isoxazole 
• 596809-68-6 5-methyl-3-isoxazolyl benzenesulfonate 
• 280579-73-9 4-Anilino-5-[(5-methylisoxazol-3-yl)oxymethyl]-2-{4-[2-hydroxy-3-(N,N-dimethylamino)propoxy]anilino}pyrimidine 
• 118938-23-1 5-methyl-2-(4-trifluoromethyl-2-nitrophenyl)-4-isoxazolin-3-one 
• 1240402-52-1 5-Methyl-4-(5-methyl-isoxazol-3-yloxymethyl)-3-phenyl-isoxazole 
• 115886-00-5 3-(benzyloxy)-5-methyl-1,2-oxazole 
• 16864-45-2 3-methoxy-5-methylisoxazole 
• 27066-53-1 5-methylisoxazol-3-yl dimethylcarbamate 

Relevant articles and documents

A Continuous Flow Process for the Synthesis of Hymexazol

Hymexazol is an efficient and low-toxicity soil fungicide. In this work, a fully continuous flow process for the synthesis of hymexazol has been developed. This process begins with combining ethyl acetoacetate and hydroxylamine hydrochloride to form a hydroxamic acid intermediate. The reaction solution is then quenched with concentrated hydrochloric acid to obtain the final product, hymexazol. Under the optimized process conditions, the total yield of the target product reached 86%. In addition, production was successfully scaled-up to a kilogram scale. The continuous flow method not only greatly decreases the reaction time but also significantly inhibits the side reactions.

Palladium-catalyzed allylation of 3-hydroxyisoxazole, 5-isoxazolone and 5-pyrazolone systems

Kinetic vs. thermodynamic control and steric hindrance are factors that determine the regioselectivity of the Pd(O)-catalyzed allylation of ambident heterocycles of the 3-hydroxyisoxazole, 5-isoxazolone and 5-pyrazolone series.

Method for synthesizing 3,5-disubstituted isoxazole compound based on three-component reaction

The invention provides a method for synthesizing a 3,5-disubstituted isoxazole compound based on three-component reaction, which comprises the following steps: mixing aldehyde, olefin and nitrite, and heating to react to generate the 3,5-disubstituted isoxazole compound. According to the scheme, the safety is greatly improved; the adopted raw materials can be commercially purchased and do not need to be prepared in advance, the reaction implementation is easier, and the reaction operation is simpler and more convenient; the application range of substrates is wider, and aliphatic hydrocarbon, aromatic hydrocarbon, condensed ring and other substrates can be suitable for the reaction system; the reaction can be carried out in both an acidic environment and an alkaline environment; the reaction can be carried out under an air condition without inert gas protection.

Photoactivatable AMPA for the study of glutamatergic neuronal transmission using two-photon excitation

We report a photoactivatable agonist of the AMPA subtype of ionotropic glutamate receptors, TMP-CyHQ-AMPA, which was designed to study the fast excitatory transmission between neurons. Upon visible light excitation, TMP-CyHQ-AMPA quantitatively released AMPA in high quantum yield on an ultra-short timescale. Intriguingly, the photolyisis can be carried out using 2-photon excitation (2PE) with remarkable efficiency, giving a two-photon uncaging action cross section (δu) value of 1.71 GM. TMP-CyHQ-AMPA is soluble in pysiological buffer and no hydrolysis was detected in the absence of light. Molecular docking experiments indicated that the photocaging strategy abolishes the affinity of AMPA for the GluR2 receptor and no GABAergic effects (as commonly observed in caged glutamates) are expected. TMP-CyHQ-AMPA can be used to study glutamatergic neuronal transmission with exceptional spatial-temporal resolution in complex tissue preparations.

Hymexazol synthesis method

The invention relates to the field of pesticides, and specifically discloses a synthesis method of hymexazol. According to the method, a sodium carbonate-sodium bicarbonate system is adopted to carry out reactions, methyl (ethyl) acetoacetate and hydroxylamine hydrochloride are taken as the raw materials; by dropwise adding sodium hydroxide and methyl (ethyl) acetoacetate, the pH of the condensation reaction system is controlled, through the reaction system, the pH can be stably controlled, after the condensation reactions, the condensation reaction products are slowly dropwise added into preheated concentrated hydrochloric acid to carry out ring-closure reactions; the provided method can obviously reduce the generation of impurities, the yield of hymexazol is increased to 70% or above, and moreover, the synthesis method is environment-friendly and is suitable for industrial production.

Production process of hymexazol technical material

The invention provides a production process of hymexazol technical material. The production process comprises the following steps: hydroxylamine hydrochloride addition, catalyst addition, ethyl acetoacetate dropwise addition, reaction and acidification. The production process of hymexazol technical has the beneficial effects that the selectivity of the catalyst is 99.7-99.9%; the purity of the prepared crude product hymexazol is 91-92%; the yield of the hymexazol technical is 94-95%; the purity of the hymexazol technical material through liquid chromatography detection is 99.98-99.99%. According to the production process of the hymexazol technical material, disclosed by the invention, the catalyst is durable to recycle, and when the catalyst is recycled for 30 times, the purity of the prepared crude product hymexazol is 89.7-90%; the selectivity of the catalyst is 98.5%; the yield of the hymexazol technical is 92-92.4%; the purity of the hymexazol technical material through liquid chromatography detection is more than 99.90%.

A method for the synthesis of the original drug of

The invention relates to the technical field of pharmaceutical chemical engineering, and discloses a synthetic method of a hymexazol raw pesticide. The synthetic method is characterized by comprising the following steps: adding methyl acetoacetate into a mixed solvent of ethylene glycol and cyclohexane, heating and refluxing, distilling to remove generated water under reduced pressure, after timely separating out the generated water, and distilling out cyclohexane under reduced pressure to obtain a compound A; after adding 8-hydroxyquinoline, ethylenediamine tetraacetic acid and water into hydroxylamine hydrochloride, stirring to completely dissolve the mixture, dropwise adding a sodium hydroxide solution at 5-10 DEG C, controlling PH to below 11-13, dropwise adding the sodium hydroxide solution while dropwise adding A, then heating up to 25-28 DEG C, and reacting to obtain a compound B; rapidly dropwise adding the compound B into concentrated hydrochloric acid while stirring, heating up to 70 DEG C, cooling to room temperature, dropwise adding the sodium hydroxide solution, filtering, cooling filtrate to 10-15 DEG C, adjusting the PH by using strong aqua, crystallizing at 5-10 DEG C, and drying. The synthetic method provided by the invention has the beneficial effects of easiness in synthesis, short reaction period, high yield, stable production, low cost, and high purity of products.

3-Oxoisoxazole-2(3H)-carboxamides and isoxazol-3-yl carbamates: Resistance-breaking acetylcholinesterase inhibitors targeting the malaria mosquito, Anopheles gambiae

To identify potential selective and resistance-breaking mosquitocides against the African malaria vector Anopheles gambiae, we investigated the acetylcholinesterase (AChE) inhibitory and mosquitocidal properties of isoxazol-3-yl dimethylcarbamates (15), and the corresponding 3-oxoisoxazole-2(3H)-dimethylcarboxamide isomers (14). In both series, compounds were found with excellent contact toxicity to wild-type susceptible (G3) strain and multiply resistant (Akron) strain mosquitoes that carry the G119S resistance mutation of AChE. Compounds possessing good to excellent toxicity to Akron strain mosquitoes inhibit the G119S mutant of An. gambiae AChE (AgAChE) with ki values at least 10- to 600-fold higher than that of propoxur, a compound that does not kill Akron mosquitoes at the highest concentration tested. On average, inactivation of WT AgAChE by dimethylcarboxamides 14 was 10-20 fold faster than that of the corresponding isoxazol-3-yl dimethylcarbamates 15. X-ray crystallography of dimethylcarboxamide 14d provided insight into that reactivity, a finding that may explain the inhibitory power of structurally-related inhibitors of hormone-sensitive lipase. Finally, human/An. gambiae AChE inhibition selectivities of these compounds were low, suggesting the need for additional structural modification.

Pyrrolidine modulators of CCR5 chemokine receptor activity

Pyrrolidine compounds of Formula I: (wherein R1, R2, R3, R4, R5, R6, R7, R8a, R8b, j, k, l, m, and n are defined herein) are described. The compounds are mo

Pyrrolidine modulators of CCR5 chemokine receptor activity

Pyrrolidine compounds of Formula I: (wherein 1, R2, R3, R4, R5,R6a, R6b, R7 and R8 are defined herein) are described. The compounds are modulators of CCR5 chemokine receptor activity. The compounds are useful, for example, in the prevention or treatment of infection by HIV and the treatment of AIDS, as compounds or pharmaceutically acceptable salts, or as ingredients in pharmaceutical compositions, optionally in combination with other antivirals, immunomodulators, antibiotics or vaccines. Methods of treating AIDS and methods of preventing or treating infection by HIV are also described.