300-87-8

Basic information

• Product Name: 3,5-Dimethylisoxazole
• Synonyms: DIMETHYLISOXAZOLE(3,5-);AKOS BBS-00006705;3,5-DISO;3,5-DIMETHYLISOXAZOLE;3,5-DIMETHYLISOOXAZOLE;3,5-DIMETHOXYISOXAZOLE;3,5-dimethyl-isoxazol;3,5-Dwumetyloizoksazolu
• CAS NO: 300-87-8
• Molecular Formula: C₅H₇NO
• Molecular Weight: 97.12
• EINECS: 206-100-2
• Product Categories: Oxazole&Isoxazole;API intermediates;Building Blocks;Heterocyclic Building Blocks;Isoxazoles;Building Blocks;Chemical Synthesis;Heterocyclic Building Blocks
• Mol File: 300-87-8.mol

Chemical Properties

• Melting Point: -14℃
• Boiling Point: 142-144 °C(lit.)
• Flash Point: 88 °F
• Appearance: clear colourless to pale yellow liquid
• Density: 0.99 g/mL at 25 °C(lit.)
• Vapor Pressure: 6.51mmHg at 25°C
• Refractive Index: n20/D 1.442(lit.)
• Storage Temp.: Flammables area
• Solubility: 50.9g/l
• PKA: -1.35±0.28(Predicted)
• Water Solubility: insoluble
• BRN: 106324
• CAS DataBase Reference: 3,5-Dimethylisoxazole(CAS DataBase Reference)
• NIST Chemistry Reference: 3,5-Dimethylisoxazole(300-87-8)
• EPA Substance Registry System: 3,5-Dimethylisoxazole(300-87-8)

Safety Data

• Hazard Codes: Xn
• Statements: 10-20/21/22
• Safety Statements: 16-36
• RIDADR: UN 1993 3/PG 3
• WGK Germany: 3
• RTECS: NY2774200
• TSCA: Yes
• HazardClass: 3
• PackingGroup: III
• Hazardous Substances Data: 300-87-8(Hazardous Substances Data)

Usage

Uses

Used in Pharmaceutical Industry:
3,5-Dimethylisoxazole is used as a chemical intermediate for the development of potent inhibitors of the BET (bromodomain and extra terminal domain) bromodomain family. These inhibitors have potential applications in the treatment of various diseases by modulating the bromodomain family's interaction with acetylated histones and other proteins.
Used in Organic Synthesis:
3,5-Dimethylisoxazole is used as an organic intermediate in the preparation of 4-(chloromethyl)-3,5-dimethylisoxazole, which can be further utilized in the synthesis of various pharmaceuticals and other organic compounds.
Used in Medicinal Chemistry:
3,5-Dimethylisoxazole is used as a starting material for the design and synthesis of novel hypoglycemic agents. Its hypoglycemic activity makes it a promising candidate for the development of new drugs to treat diabetes and related metabolic disorders.

Preparation

3,5-Dimethylisozole can be synthesized from acetylacetone and hydroxylamine hydrochloride in one step off ring.

InChI:InChI=1/C5H7NO/c1-4-3-5(2)7-6-4/h3H,1-2H3

Upstream product

• 1118-66-7 4-amino-3-penten-2-one 
• 2157-56-4 pentane-2,4-dione dioxime 
• 123-54-6 acetylacetone 
• 53009-14-6 3,5-dimethyl-5-hydroxy-Δ²-isoxazoline 
• 10557-85-4 4-iodo-3,5-dimethylisoxazole 
• 55393-93-6 2-acetyl-3-methyl-2H-azirine 
• 13545-14-7 1-benzyloxy-4,6-dimethyl-2(1H)-pyrimidinone 
• 71989-66-7 4-bromo-3,5-dimethyl-1-hydroxypyrazole 2-oxide 
• 21139-18-4 4,6-dimethyl-1-phenyl-2-oxopyrimidine 
• 555-16-8 4-nitrobenzaldehdye 
• 100-52-7 benzaldehyde 
• 66-25-1 hexanal 
• 60-29-7 diethyl ether 
• 10026-13-8 phosphorus pentachloride 

Downstream Products

• 19788-37-5 4-chloromethyl-3,5-dimethylisoxazole 
• 23075-86-7 3,5,3',5'-tetramethyl-4,4'-methanediyl-bis-isoxazole 
• 10557-86-5 3,5-Dimethyl-4-chlor-isoxazol 
• 10558-25-5 4-bromo-3,5-dimethyl-1,2-oxazole 
• 1123-49-5 3,5-dimethyl-4-nitroisoxazole 
• 61449-10-3 3-Phenyl-4-(3-methyl-5-isoxazolyl)-butanal 
• 61449-09-0 1-(3-methyl-isoxazol-5-yl)-4-phenyl-but-3-en-2-ol 
• 27349-53-7 2-(3-methyl-isoxazol-5-yl)-1,1-diphenyl-ethanol 
• 19668-85-0 2-(3-methylisoxazol-5-yl)acetic acid 
• 61449-14-7 4-(3-methyl-isoxazol-5-yl)-3-phenyl-butyric acid 
• 51100-99-3 1,4-bis-(3-methyl-isoxazol-5-yl)-N,N'-di-p-tolyl-butane-2,3-diamine 
• 60729-68-2 1-(2-hydroxy-4-methoxy-6-methyl-phenyl)-2-(3-methyl-isoxazol-5-yl)-ethanone 
• 61449-04-5 1-(3-methyl-isoxazol-5-ylmethyl)-cyclohexanol 
• 61449-00-1 (+/-)-5-(2-hydroxy-2-p-tolylethyl)-3-methylisoxazole 

Relevant articles and documents

Styrylisoxazole-based fluorescent probes for the detection of hydrogen sulfide

Styrylisoxazoles bearing a nitro group linked to bulky aromatic rings have been synthesized and examined for their absorption and emission studies in organic solvents and water. The molecules showed emission in the visible region with significant solvatochromic emission shifts influenced by the extended conjugation of aromatic rings and intramolecular charge transfer. These absorption and emission changes were used for the efficient and sensitive detection of trace concentrations of hydrogen sulfide (H2S) through the reduction of the nitro group to the amine group in the presence of aqueous sodium sulfide. The experimental results indicated that the probes exhibit an excellent emission response with large shifts in the emission and sensitivity with a micromolar detection limit.

Protodeboronation of (Hetero)Arylboronic Esters: Direct versus Prehydrolytic Pathways and Self-/Auto-Catalysis

The kinetics and mechanism of the base-catalyzed hydrolysis (ArB(OR)2→ ArB(OH)2) and protodeboronation (ArB(OR)2→ ArH) of a series of boronic esters, encompassing eight different polyols and 10 polyfluoroaryl and heteroaryl moieties, have been investigated by in situ and stopped-flow NMR spectroscopy (19F,1H, and11B), pH-rate dependence, isotope entrainment,2H KIEs, and KS-DFT computations. The study reveals the phenomenological stability of boronic esters under basic aqueous-organic conditions to be highly nuanced. In contrast to common assumption, esterification does not necessarily impart greater stability compared to the corresponding boronic acid. Moreover, hydrolysis of the ester to the boronic acid can be a dominant component of the overall protodeboronation process, augmented by self-, auto-, and oxidative (phenolic) catalysis when the pH is close to the pKaof the boronic acid/ester.

Development of Gold-catalyzed [4+1] and [2+2+1]/[4+2] Annulations between Propiolate Derivatives and Isoxazoles

Two new gold-catalyzed annulations of isoxazoles with propiolates have been developed. Most isoxazoles follow an initial O attack on the alkyne to afford a [4+1] annulation product. This process results in a remarkable alkyne cleavage of initial propiolates. Unsubstituted isoxazoles proceed through an N attack step to yield formal [2+2+1]/[4+2] annulation products. These two annulation products arise initially from two seven-membered heterocyclic intermediates, which then lead to products.

Reductive ring opening of 3,5-bis(2-arylethenyl)isoxazoles with molybdenum hexacarbonyl: A novel route to symmetrical and unsymmetrical curcumin derivatives

Curcumin derivatives were successfully synthesized from 3,5-dimethylisoxazole by lateral metalation and condensation with various aromatic aldehydes sequentially at C5- and C3-methyl groups. After dehydration, further transformation of isoxazole ring to β-diketone moiety was accomplished by reductive ring opening using molybdenum hexacarbonyl [Mo(CO)6] and subsequent simple acidic hydrolysis.

Development and Scale-up of an Organocatalytic Enantioselective Process to Manufacture (S)-Pregabalin

Herein is reported the development of a new process to manufacture (S)-pregabalin. The method comprises six steps, run under the catalysis of a recyclable polymer bound phase transfer catalyst, and afforded (S)-pregabalin in overall 54% yield, starting from building blocks acetylacetone, isovaleraldehyde, and nitromethane.

Organocatalyzed asymmetric vinylogous Michael addition of α,β-unsaturated γ-butyrolactam

Highly efficient asymmetric vinylogous 1,6-Michael addition of α,β-unsaturated γ-butyrolactam to 3-methyl-4-nitro-5-alkenyl- isoxazoles and Michael addition to trichloromethyl ketones by using a chiral quinine-derived squaramide organocatalyst were described, giving products with high diastereo- and enantioselectivities (up to >25:1 dr and 96% ee).

Continuous-flow microliter microwave irradiation in the synthesis of isoxazole derivatives: An optimization procedure

An efficient method was developed for the synthesis of 3,4,5-trisubstituted and 3,5-disubstituted isoxazoles by using continuous-flow microwave-heated microreactors. A study on the separate effects of the temperature, continuous-flow regime, and microwave irradiation showed that the continuous-flow regime had important effects for less reactive diketones, where microwave heating enhanced the reaction, permitting the formation of 5-methyl-3-phenylisoxazole, which was not formed in the absence of microwaves. Georg Thieme Verlag Stuttgart · New York.

Photocycloaddition of aromatic and aliphatic aldehydes to isoxazoles: Cycloaddition reactivity and stability studies

The first photocycloadditions of aromatic and aliphatic aldehydes to methylated isoxazoles are reported. The reactions lead solely to the exo-adducts with high regio- and diastereoselectivities. Ring methylation of the isoxazole substrates is crucial for high conversions and product stability. The 6-arylated bicyclic oxetanes 9a-9c were characterized by X-ray structure analyses and showed the highest thermal stabilities. All oxetanes formed from isoxazoles were highly acid-sensitive and also thermally unstable. Cleavage to the original substrates is dominant and the isoxazole derived oxetanes show type T photochromism.

Heteropolyacids as green and reusable catalysts for the synthesis of isoxazole derivatives

Heteropolyanions with different structures, including Keggin, Dawson, Preyssler, mixed addenda, and sandwich types, catalyzed the formation of 1,3-diphenyl-isoxazole from the condensation of 1,3-diphenyl-propane-1,3-dione and hydroxylamine hydrochloride in different solvents and under heating conditions. Our data vividly indicate that H3PW11CuO40 is the catalyst of choice and could catalyze the synthesis of other isoxazole derivatives in high yields and good selectivities. Copyright Taylor & Francis Group, LLC.

An efficient, scaleable procedure for the conversion of esters to isoxazoles

A concise, regiocontrolled route to isoxazoles, based on the condensation of an ester with a metallated imine, has been developed. The intermediate vinylogous amides react smoothly with hydroxylamine to provide, after dehydration, substituted isoxazoles. The method has been used for the multi-kilo scale preparation of ABT-418, a novel cholinergic channel activator.