- A Continuous Flow Process for the Synthesis of Hymexazol
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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.
- Ma, Xin-Peng,Chen, Jin-Sha,Du, Xiao-Hua
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- Palladium-catalyzed allylation of 3-hydroxyisoxazole, 5-isoxazolone and 5-pyrazolone systems
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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.
- Moreno-Manas, Marcial,Perez, Montserrat,Pleixats, Roser
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- Method for synthesizing 3,5-disubstituted isoxazole compound based on three-component reaction
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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.
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Paragraph 0033
(2021/11/27)
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- Photoactivatable AMPA for the study of glutamatergic neuronal transmission using two-photon excitation
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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.
- Asad, Naeem,Deodato, Davide,Dore, Timothy M.
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supporting information
p. 5589 - 5594
(2021/07/02)
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- Hymexazol synthesis method
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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.
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Paragraph 0025-0035; 0036-0080
(2017/09/01)
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- Production process of hymexazol technical material
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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%.
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Paragraph 0017-0024
(2017/04/28)
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- A method for the synthesis of the original drug of
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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.
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Paragraph 0017; 0020
(2017/03/14)
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- 3-Oxoisoxazole-2(3H)-carboxamides and isoxazol-3-yl carbamates: Resistance-breaking acetylcholinesterase inhibitors targeting the malaria mosquito, Anopheles gambiae
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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.
- Verma, Astha,Wong, Dawn M.,Islam, Rafique,Tong, Fan,Ghavami, Maryam,Mutunga, James M.,Slebodnick, Carla,Li, Jianyong,Viayna, Elisabet,Lam, Polo C.-H.,Totrov, Maxim M.,Bloomquist, Jeffrey R.,Carlier, Paul R.
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p. 1321 - 1340
(2015/03/04)
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- Pyrrolidine modulators of CCR5 chemokine receptor activity
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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
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- Pyrrolidine modulators of CCR5 chemokine receptor activity
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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.
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- Synthesis and biological activities of methyl 1-(5-methyl isoxazol-3-oxy acetoxy) alkyl methyl phosphinates
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Methyl 1-(5-methyl isoxazol-3-oxy acetoxy) alkyl methyl phosphinates were synthesized by the condensation of O-methyl methyl 1-hydroxyalkyl phosphinates moiety with 5-methyl isoxazol-3-oxy acetyl chloride and were tested for plant growth regulatory activity and herbicidal activity. Some compounds exhibited notable plant regulatory activity and herbicidal activity.
- He, Hongwu,Li, Meiqiang,Lu, Aihong,Liu, Zhaojie
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p. 1651 - 1655
(2007/10/03)
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- A novel route to 5-substituted 3-isoxazolols. Cyclization of N,O-diBoc β-keto hydroxamic acids synthesized via acyl Meldrum's acids
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3-Isoxazolols are most often synthesized from a β-keto ester and hydroxylamine. This cyclization typically gives rise to a major byproduct, the corresponding 5-isoxazolone. We have found that N,O-diBoc-protected β- keto hydroxamic acids can be synthesized and cyclized to 5-substituted 3- isoxazolols without formation of any byproduct. We present a novel and versatile three-step procedure in which carboxylic acid derivatives are converted into acyl Meldrum's acids which, upon aminolysis with N,O-bis(tert- butoxycarbonyl)hydroxylamine, lead to the N,O-diBoc-protected β-keto hydroxamic acids. These hydroxamic acid analogues were then, upon treatment with hydrochloric acid, cyclized to the corresponding 5-substituted 3- isoxazolols.
- Sorensen, Ulrik S.,Falch, Erik,Krogsgaard-Larsen, Povl
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p. 1003 - 1007
(2007/10/03)
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- Fungicidal composition for seed dressing
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The present invention relates to a fungicidal composition intended for the protection of the multiplication products of cultivated plants, containing: (a) 2-(4-chlorobenzylidene)-5,5-dimethyl-1-(1H-1,2,4-triazol-1-ylmethyl)-1-cyclopentanol; (b) one or more fungicides suitable for the protection of the said multiplication products, optionally one or more insecticides, (c), an agriculturally acceptable inert vehicle and an agriculturally acceptable surfactant. The invention also relates to a method for protecting the multiplication products of plants against fungal diseases using these compositions.
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- Plant-protective pesticidal composition
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The invention relates to a plant-protective solution containing 2.5 to 40 % by weight of one or more water-insoluble plant-protective ingredient(s) 20 to 71.5 % by weight of dimethylformamide and/or dimethylsulfoxide and/or acetone as water-miscible solvent, 10 to 71.5 % by weight of furfurol and/or furfuryl alcohol as partially water-miscible solvent, 1 to 15 % by weight of commonly used additives such as anionic and/or nonionic surface active agents and macromolecules. The invention also relates to the ready-for-use plant-protective suspension containing 0.2 to 10 % by weight of one or more water-insoluble plant-protective ingredient(s) with a particle size of 0.1 to 50 μm, 0 to 60 % by weight of a fertilizer, 0.2 to 10 % by weight of dimethylformamide and/or dimethylsulfoxide and/or acetone as water-miscible solvent, 0.2 to 10 % by weight of furfurol and/or furfuryl alcohol as partially water-miscible solvent, 0.05 to 2.5 by weight of a commonly used additive such as anionic and/or nonionic surface active agents macromolecules and water in an amount supplementing up to 100 % by weight.
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- Synthesis of 3-Hydroxyisoxazoles from β-Ketoesters and Hydroxylamine
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An efficient synthesis of 3-hydroxyisoxazoles from β-ketoesters and hydroxylamine was investigated.The reaction of the sodium salts of β-ketoesters and hydroxylamine at a low temperature, followed by quenching with an excess of conc.HCl under heating gave predominantly 3-hydroxyisoxazoles involving 4-sulfenylated 3-hydroxyisoxazoles.Starting from the prepared 4-(2,4-dichlorobenzyl)-3-hydroxy-5-methylisoxazole, a potential herbicidal compound, 4-(2,4-dichlorobenzoyl)-3-hydroxy-5-methylisoxazole, was also synthesized in five steps.
- Sato, Kazuo,Sugai, Soji,Tomita, Kazuo
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p. 1831 - 1838
(2007/10/02)
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- Generation and Reactions of the Dianion of 3-Hydroxy-5-methylisoxazole, a Covenient β-Keto Amide Sython. Total Synthesis of Muscimol
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The title compound (4) has been prepared by treatment of diketene with N,O-bis(trimethylsilyl)hydroxylamine (2) to give N-(trimethylsilyloxy)-N-(trimethylsilyl)acetoacetamide (3) as a stable liquid.Treatment of 3 with methanolic HCl removed the Me3Si protective groups and cyclized the resulting hydroxamic acid to isoxazole 4 in good yield.The dianion of 4 was generated with lithium diisopropylamide and was found to react exclusively at the 5-methyl group when treated with electrophiles.The reactions of the dianion which were accomplished included carboxylation with CO2, alkylation with benzyl chloride, condensation with benzophenone, and acylations with dimethyl carbonate, methyl acetate, N,N-dimethylacetamide, N-methoxy-N-methylacetamide, ethyl benzoate, and ethyl benzoylacetate.Hydrogenation of condensation products (10, 11, 13, 14, and 15) using optimum conditions of the catalyst and solvent gave the corresponding β-keto amides (16, 17, 18, 19, and 20, respectively) in excellent yields.Treatment of the dianion with isoamyl nitrite gave 3-hydroxy-5-isoxazolecarboxaldehyde oxime (21) in good yield.Acetylation of 21 to the diacetate 22 followed by reduction with BH3-THF gave muscimol (1), a constituent of the mushroom Amanita muscaria.
- Oster, Timothy A.,Harris, Thomas M.
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p. 4307 - 4311
(2007/10/02)
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