675-09-2

Usage

Uses

Used in Chemical Synthesis:
4,6-Dimethyl-2-pyrone is used as a key intermediate in the preparation of host-guest complex G4CMe21 by reacting with crystalline guanidinium-sulfonate-calixarene (G4C). This complex, upon UV irradiation, affords 1,3-dimethylcyclobutadiene (Me2CBD), which can be further utilized in various chemical reactions and applications.
Used in Host-Guest Chemistry:
4,6-Dimethyl-2-pyrone is used as a building block in the synthesis of G4CMe21, a host-guest complex that has potential applications in supramolecular chemistry and molecular recognition. The formation of this complex demonstrates the versatility of 4,6-dimethyl-2-pyrone in creating novel structures with specific properties and functions.

InChI:InChI=1/C7H8O2/c1-5-3-6(2)9-7(8)4-5/h3-4H,1-2H3

Upstream product

• 480-65-9 isodehydracetic acid 
• 70007-85-1 (4-methyl-6-oxo-6H-pyran-2-yl)-acetic acid 
• 368876-43-1 3-acetyl-4-methyl-2H-pyran-2,6(3H)-dione 
• 540-88-5 acetic acid tert-butyl ester 
• 86310-01-2 (E)-4-methylsulfanyl-3-penten-2-one 
• 463-49-0 1,2-propanediene 
• 38377-57-0 2,3-bis(4-methylphenyl)-2-cyclopropen-1-one 
• 77902-81-9 C₈H₁₁O₂⁽¹⁺⁾*BF₄^(1-) 
• 41463-78-9 2,6-dimethyl-4-hydroxypyrylium cation 
• 49784-51-2 4-chloropent-3-en-2-one 
• 105-53-3 diethyl malonate 
• 124-38-9 carbon dioxide 
• 74-99-7 prop-1-yne 
• 141-79-7 4-methyl-pent-3-en-2-one 

Downstream Products

• 32251-35-7 1,14-dimethyl-4,10-dioxatetracyclo[5.5.2.0^2,60^8,12]tetradec-13-ene-3,5,9,11-tetraone 
• 16115-08-5 6-Hydroxy-2,4-lutidin 
• 3720-20-5 4,6-dimethyl-tetrahydro-pyran-2-one 
• 97583-68-1 endo,endo-bis-N-phenylimide of 1,8-dimethylbicyclo<2.2.2>oct-7-ene-2,3,5,6-tetracarboxylic acid 
• 38377-57-0 2,3-bis(4-methylphenyl)-2-cyclopropen-1-one 
• 77902-81-9 C₈H₁₁O₂⁽¹⁺⁾*BF₄^(1-) 
• 50919-64-7 dimethyl 3,5-dimethylphthalate 
• 25081-39-4 methyl 3,5-dimethylbenzoate 
• 17422-71-8 6-ethyl-4-methyl-2H-pyran-2-one 
• 106319-13-5 4-ethyl-6-methyl-2H-pyran-2-one 
• 54657-87-3 4,6-dimethyl-2H-pyran-2-thione 
• 80673-41-2 1,5-Dimethyl-2-oxa-bicyclo[2.2.0]hex-5-en-3-one 
• 87239-50-7 (1S,6R,8S)-7,7,8-Trichloro-1,5-dimethyl-2-oxa-bicyclo[4.2.0]oct-4-en-3-one 
• 75487-12-6 4,5-dichloro-m-xylene 

Relevant academic research and scientific papers

A novel synthesis of 4,6-dimethyl-2-pyrone from carbon dioxide and mesityl oxide in the presence of an ethylzinc carbamate

The title synthesis, the first example of the CO2 fixation by use of an α,β-unsaturated ketone, has been successfully carried out, most preferably in triethylamine or pyridine at 120-160°C in the presence of ethylzinc diphenylcarbamate.

Unprecedented synthesis of 1,3-dimethylcyclobutadiene in the solid state and aqueous solution

Cyclobutadiene (CBD), the smallest cyclic hydrocarbon bearing conjugated double bonds, has long intrigued chemists because of its chemical characteristics. The question of whether the molecule could be prepared at all has been answered, but the parent compound and its unperturbed derivatives have eluded crystallographic characterization or synthesis "in water". Different approaches have been used to generate and to trap cyclobutadiene in a variety of confined environments: a) an Ar matrix at cryogenic temperatures, b) a hemicarcerand cage enabling the characterization by NMR spectroscopy in solution, and c) a crystalline guanidinium-sulfonate-calixarene G4C matrix that is stable enough to allow photoreactions in the solid state. In the latter case, the 4,6-dimethyl-α-pyrone precursor, Me21, has been immobilized in a guanidinium-sulfonate-calixarene G4C crystalline network through a combination of non-covalent interactions. UV irradiation of the crystals transforms the entrapped Me21 into a 4,6-dimethyl-Dewar-β-lactone intermediate, Me22, and rectangular-bent 1,3-dimethylcyclobutadiene, Me2CBDR, which are sufficiently stable under the confined conditions at 175 K to allow a conventional structure determination by X-ray diffraction. Further irradiation drives the reaction towards Me23&Me2CBD S/CO2 (63.7 %) and Me2CBDR (37.3 %) superposed crystalline architectures and the amplification of Me 2CBDR. The crystallographic models are supported by additional FTIR and Raman experiments in the solid state and by 1H NMR spectroscopy and ESI mass spectrometry experiments in aqueous solution. Amazingly, the 4,6-dimethyl-Dewar-β-lactone, Me22, the cyclobutadiene-carboxyl zwitterion, Me23, and 1,3- dimethylcyclobutadiene, Me2CBD, were obtained by ultraviolet irradiation of an aqueous solution of G4C{Me21}. 1,3-Dimethylcyclobutadiene is stable in water at room temperature for several weeks and even up to 50 °C as demonstrated by 1H NMR spectroscopy. Copyright

Development of Novel N-hydroxypyridone Derivatives as Potential Anti-Ischemic Stroke Agents

Our previous study had identified ciclopirox (CPX) as a promising lead compound for treatment of ischemic stroke. To find better neuroprotective agents, a series of N-hydroxypyridone derivatives based on CPX were designed, synthesized, and evaluated in this study. Among these derivatives, compound 11 exhibits significant neuroprotection against oxygen glucose deprivation and oxidative stress-induced injuries in neuronal cells. Moreover, compound 11 possesses good blood-brain barrier permeability and superior antioxidant capability. In addition, a complex of compound 11 with olamine-11·Ola possesses good water solubility, negligible hERG inhibition, and superior metabolic stability. The in vivo experiment demonstrates that 11·Ola significantly reduces brain infarction and alleviates neurological deficits in middle cerebral artery occlusion rats. Hence, compound 11·Ola is identified in our research as a prospective prototype in the innovation of stroke treatment.

Iron-Catalyzed Cross-Coupling of Alkenyl Acetates

Stable C-O linkages are generally unreactive in cross-coupling reactions which mostly employ more electrophilic halides or activated esters (triflates, tosylates). Acetates are cheap and easily accessible electrophiles but have not been used in cross-couplings because the strong C-O bond and high propensity to engage in unwanted acetylation and deprotonation. Reported herein is a selective iron-catalyzed cross-coupling of diverse alkenyl acetates, and it operates under mild reaction conditions (0 C, 2 h) with a ligand-free catalyst (1-2 mol%). Iron clad: Acetates are underutilized electrophiles in metal-catalyzed cross-coupling reactions because of the strong alkenyl C-O bond and their propensity to engage in unwanted reactions. Combination of a ligand-free low-valent Fe catalyst with nucleophilic organomagnesium reagents, low temperature, and short reaction times results in highly selective cross-couplings with alkenyl acetates.

Inhibition of cancer-associated mutant isocitrate dehydrogenases: Synthesis, structure-activity relationship, and selective antitumor activity

Mutations of isocitrate dehydrogenase 1 (IDH1) are frequently found in certain cancers such as glioma. Different from the wild-type (WT) IDH1, the mutant enzymes catalyze the reduction of α-ketoglutaric acid to d-2-hydroxyglutaric acid (D2HG), leading to cancer initiation. Several 1-hydroxypyridin-2-one compounds were identified to be inhibitors of IDH1(R132H). A total of 61 derivatives were synthesized, and their structure-activity relationships were investigated. Potent IDH1(R132H) inhibitors were identified with Ki values as low as 140 nM, while they possess weak or no activity against WT IDH1. Activities of selected compounds against IDH1(R132C) were found to be correlated with their inhibitory activities against IDH1(R132H), as well as cellular production of D2HG, with R2 of 0.83 and 0.73, respectively. Several inhibitors were found to be permeable through the blood-brain barrier in a cell-based model assay and exhibit potent and selective activity (EC50 = 0.26-1.8 μM) against glioma cells with the IDH1 R132H mutation.

Formal ring-opening/cross-coupling reactions of 2-pyrones: Iron-catalyzed entry into stereodefined dienyl carboxylates

Open access: Despite the exceptional level of sophistication in cross-coupling chemistry, reactions of substrates that incorporate the leaving group as an integral part into a heterocyclic scaffold are scarce. The title reaction outlines the utility of this reaction format (see scheme; acac=acetylacetonate), provides a convenient entry into stereodefined diene carboxylates, and adds a new chapter to the field of iron catalysis. Copyright

Two-stage synthesis of 3-(perfluoroalkyl)-substituted vinyldiazocarbonyl compounds and their nonfluorinated counterparts: A comparative study

Two approaches for the synthesis of fluorinated (F) and nonfluorinated (H) 4-(alkoxycarbonyl)-substituted cis- and trans-vinyldiazocarbonyl compounds with substituents of variable stereoelectronic nature (H, Me, Ph, CF3, OTBS) at the C-3 atom of the vinyl double bond from the relevant 1,3-dicarbonyl compounds were compared: a pathway using the Wittig reaction followed by a diazo transfer reaction was most efficient for the synthesis of the H-vinyldiazocarbonyl compounds (total yields of up to 60%), while the yields of their F-analogues under similar conditions did not exceed 16-37%. An approach via diazo transfer followed by the Wittig reaction, in contrast, is more effective for the preparation of F-vinyldiazocarbonyl compounds (total yields 37-69%). The configuration of the resulting F- and H-vinyldiazocarbonyl compounds is evidently controlled by the steric bulk of the substituent at the C-3 atom of the vinyl double bond and, in addition, depends on the specific synthetic pathway. Georg Thieme Verlag Stuttgart . New York.

Antifungal activity of 4-methyl-6-alkyl-2H-pyran-2-ones

A number of 4-methyl-6-alkyl-α-pyrones were synthesized and characterized on the basis of 1H NMR and mass spectroscopy. These compounds were tested in vitro against pathogenic fungi, namely, Sclerotium rolfsii Saccardo, Rhizoctonia bataticola (Taub.) Butler, Pythium aphanidermatum (Edson) Fitz., Macrophomina phaseolina (Tassi), Pythium debaryanum (Hesse), and Rhizoctonia solani Nees. Lower homologues were less effective, whereas compounds such as 4-methyl-6-butyl-α-pyrone, 4-methyl-6-pentyl-α-pyrone, 4-methyl-6-hexyl-α-pyrone, and 4-methyl-6-heptyl-α-pyrone were found effective against all of the test fungi. They inhibited mycelial growth by approximately 50% (ED50) at 15-50 μg/mL. 4-Methyl-6-hexyl-α- pyrone, which was found most effective, was tested against S. rolfsii in a greenhouse at 1, 5, and 10% concentrations. The 10% aqueous emulsion of 4-methyl-6-hexyl-α-pyrone suppressed disease development in tomato by 90-93% as compared with the untreated infested soil in the greenhouse after 35 days of treatment.

Synthesis of isocoumarins and α-pyrones via tandem Stille reaction/heterocyclization

A general route to α-pyrones and 3-substituted isocoumarins from (Z)-iodovinylic acids 1a-f or 2-iodobenzoic acids 4a-c is described, including compounds bearing a substituent on the aromatic ring. Treatment of (Z)-β-iodovinylic acids 1a-f or 2-iodobenzoic acids 4a-c with various allenyl-tributyltin reagents in the presence of palladium acetate, triphenylphosphine, and tetrabutylammonium bromide in dimethylformamide provided good yields of the corresponding α-pyrones 3a-k or 3-substituted isocoumarins 5a-g via tandem Stille reaction and 6-endo-dig oxacyclization.

Palladium-catalysed annulation reaction of allenyltins with β-iodo vinylic acids: Selective synthesis of α-pyrones

Palladium-catalysed regio- and stereoselective annulation of allenyl stannanes by β-iodo vinylic acids gives the corresponding α-pyrones in high yields. This annulation most probably proceeds through a Stille reaction/cyclisation sequence.