301693-50-5

Basic information

• Product Name: 4-(3-fluorophenyl)-2,2-dimethyl-5-(4-(methylthio)phenyl)furan-3(2H)-one
• Synonyms: 4-(3-fluorophenyl)-2,2-dimethyl-5-(4-(methylthio)phenyl)furan-3(2H)-one;4-(3-fluorophenyl)-2,2-diMethyl-5-[4-(Methylsulfanyl)phenyl]-2,3-dihydrofuran-3-one
• CAS NO: 301693-50-5
• Molecular Formula: C₁₉H₁₇FO₂S
• Molecular Weight: 328
• Mol File: 301693-50-5.mol

Chemical Properties

• Boiling Point: 448.2±45.0 °C(Predicted)
• Appearance: /
• Density: 1.25±0.1 g/cm3(Predicted)
• Storage Temp.: 2-8°C
• CAS DataBase Reference: 4-(3-fluorophenyl)-2,2-dimethyl-5-(4-(methylthio)phenyl)furan-3(2H)-one(CAS DataBase Reference)
• NIST Chemistry Reference: 4-(3-fluorophenyl)-2,2-dimethyl-5-(4-(methylthio)phenyl)furan-3(2H)-one(301693-50-5)
• EPA Substance Registry System: 4-(3-fluorophenyl)-2,2-dimethyl-5-(4-(methylthio)phenyl)furan-3(2H)-one(301693-50-5)

Safety Data

• Hazardous Substances Data: 301693-50-5(Hazardous Substances Data)

Usage

Uses

Given the lack of specific documented uses for 4-(3-fluorophenyl)-2,2-dimethyl-5-(4-(methylthio)phenyl)furan-3(2H)-one, potential applications can be hypothesized based on the properties of its constituent groups:
Used in Pharmaceutical Industry:
4-(3-fluorophenyl)-2,2-dimethyl-5-(4-(methylthio)phenyl)furan-3(2H)-one could be used as a bioactive compound for the development of new pharmaceuticals, leveraging its fluorophenyl and methylthio groups for potential medicinal properties.
Used in Perfumery Industry:
Due to the presence of a furan ring, which is often associated with aromatic properties, 4-(3-fluorophenyl)-2,2-dimethyl-5-(4-(methylthio)phenyl)furan-3(2H)-one might be utilized as a fragrance ingredient in the perfumery industry.
Used in Food Industry:
4-(3-fluorophenyl)-2,2-dimethyl-5-(4-(methylthio)phenyl)furan-3(2H)-one's aromatic characteristics could also make it a candidate for use in the food industry, potentially as a flavoring agent, although safety and regulatory approval would be required.

Synthetic route

2-bromoisobutyric acid bromide (20769-85-1) + 2-(3-fluorophenyl)-1-(4-methylsulfanylphenyl)ethanone (301699-27-4) → 2,2-dimethyl-4-(3-fluorophenyl)-5-[4-(methylthio)phenyl]-3(2H)-furanone (301693-50-5)

Conditions	Yield
Stage #1: 2-(3-fluorophenyl)-1-(4-methylsulfanylphenyl)ethanone With sodium hydride In N,N-dimethyl acetamide at 0 - 5℃; for 1h; Green chemistry; Stage #2: 2-bromoisobutyric acid bromide With 1,2,4-Triazole In N,N-dimethyl acetamide at 20℃; Solvent; Green chemistry;	86.8%
Stage #1: 2-(3-fluorophenyl)-1-(4-methylsulfanylphenyl)ethanone With bromomagnesium diisopropylamide In tetrahydrofuran; diethyl ether at -78 - 20℃; for 1h; Stage #2: 2-bromoisobutyric acid bromide In tetrahydrofuran; diethyl ether at 0 - 20℃; for 2h; Stage #3: With sodium hydride In tetrahydrofuran at 20℃; for 2h;	33%

1-(2-bromoisobutyryl)-3,5-dimethyl-1,2,4-triazole + 2-(3-fluorophenyl)-1-(4-methylsulfanylphenyl)ethanone (301699-27-4) → 2,2-dimethyl-4-(3-fluorophenyl)-5-[4-(methylthio)phenyl]-3(2H)-furanone (301693-50-5)

Conditions	Yield
Stage #1: 2-(3-fluorophenyl)-1-(4-methylsulfanylphenyl)ethanone With sodium hydride In tetrahydrofuran at 0 - 5℃; for 1h; Green chemistry; Stage #2: 1-(2-bromoisobutyryl)-3,5-dimethyl-1,2,4-triazole In tetrahydrofuran at 20℃; Green chemistry;	85.9%

1-(2-bromoisobutyryl)-3-methyl-1,2,4-triazole + 2-(3-fluorophenyl)-1-(4-methylsulfanylphenyl)ethanone (301699-27-4) → 2,2-dimethyl-4-(3-fluorophenyl)-5-[4-(methylthio)phenyl]-3(2H)-furanone (301693-50-5)

Conditions	Yield
Stage #1: 2-(3-fluorophenyl)-1-(4-methylsulfanylphenyl)ethanone With sodium hydride In tetrahydrofuran at 0 - 5℃; for 1h; Green chemistry; Stage #2: 1-(2-bromoisobutyryl)-3-methyl-1,2,4-triazole In tetrahydrofuran at 20℃; Green chemistry;	83.4%

1-(2-bromoisobutyryl)-1,2,4-triazole + 2-(3-fluorophenyl)-1-(4-methylsulfanylphenyl)ethanone (301699-27-4) → 2,2-dimethyl-4-(3-fluorophenyl)-5-[4-(methylthio)phenyl]-3(2H)-furanone (301693-50-5)

Conditions	Yield
Stage #1: 2-(3-fluorophenyl)-1-(4-methylsulfanylphenyl)ethanone With sodium hydride In tetrahydrofuran at 0 - 5℃; for 1h; Green chemistry; Stage #2: 1-(2-bromoisobutyryl)-1,2,4-triazole In tetrahydrofuran at 20℃; Green chemistry;	82.2%

2-bromo-2-methylpropanoyl cyanide (55106-47-3) + 2-(3-fluorophenyl)-1-(4-methylsulfanylphenyl)ethanone (301699-27-4) → 2,2-dimethyl-4-(3-fluorophenyl)-5-[4-(methylthio)phenyl]-3(2H)-furanone (301693-50-5)

Conditions	Yield
With sodium hydride In tetrahydrofuran at 0 - 20℃; for 5h;	81%
In tetrahydrofuran; water

1-(2-bromoisobutyryl)-3-chloro-1,2,4-triazole + 2-(3-fluorophenyl)-1-(4-methylsulfanylphenyl)ethanone (301699-27-4) → 2,2-dimethyl-4-(3-fluorophenyl)-5-[4-(methylthio)phenyl]-3(2H)-furanone (301693-50-5)

Conditions	Yield
Stage #1: 2-(3-fluorophenyl)-1-(4-methylsulfanylphenyl)ethanone With sodium hydride In tetrahydrofuran at 0 - 5℃; for 1h; Green chemistry; Stage #2: 1-(2-bromoisobutyryl)-3-chloro-1,2,4-triazole In tetrahydrofuran at 20℃; Green chemistry;	81%

1-(2-chloroisobutyryl)-1,2,4-triazole + 2-(3-fluorophenyl)-1-(4-methylsulfanylphenyl)ethanone (301699-27-4) → 2,2-dimethyl-4-(3-fluorophenyl)-5-[4-(methylthio)phenyl]-3(2H)-furanone (301693-50-5)

Conditions	Yield
Stage #1: 2-(3-fluorophenyl)-1-(4-methylsulfanylphenyl)ethanone With sodium hydride In tetrahydrofuran at 0 - 5℃; for 1h; Green chemistry; Stage #2: 1-(2-chloroisobutyryl)-1,2,4-triazole In tetrahydrofuran at 20℃; Green chemistry;	78%

2-bromo-2-methylpropionic acid 4-nitrophenyl ester (116729-21-6) + 2-(3-fluorophenyl)-1-(4-methylsulfanylphenyl)ethanone (301699-27-4) → 2,2-dimethyl-4-(3-fluorophenyl)-5-[4-(methylthio)phenyl]-3(2H)-furanone (301693-50-5)

Conditions	Yield
With sodium hexamethyldisilazane In tetrahydrofuran at -20℃; for 0.5h;	78%

C19H17FN2O2S → C19H17FO2S + 2,2-dimethyl-4-(3-fluorophenyl)-5-[4-(methylthio)phenyl]-3(2H)-furanone (301693-50-5)

Conditions	Yield
With trifluoroacetic acid In chloroform
With trifluoroacetic acid In chloroform Reflux; Overall yield = 75 percent; regioselective reaction;

C19H19FO2S → C19H17FO2S + 2,2-dimethyl-4-(3-fluorophenyl)-5-[4-(methylthio)phenyl]-3(2H)-furanone (301693-50-5)

Conditions	Yield
Multi-step reaction with 2 steps 1: 1,8-diazabicyclo[5.4.0]undec-7-ene 2: trifluoroacetic acid / chloroform View Scheme

C19H19FO2S → C19H17FO2S + 2,2-dimethyl-4-(3-fluorophenyl)-5-[4-(methylthio)phenyl]-3(2H)-furanone (301693-50-5)

Conditions	Yield
Multi-step reaction with 3 steps 1: sulfuric acid / methanol 2: 1,8-diazabicyclo[5.4.0]undec-7-ene 3: trifluoroacetic acid / chloroform View Scheme

meta-aminobenzoic acid (99-05-8) → C19H17FO2S + 2,2-dimethyl-4-(3-fluorophenyl)-5-[4-(methylthio)phenyl]-3(2H)-furanone (301693-50-5)

Conditions

Yield

Multi-step reaction with 7 steps 1.1: sodium nitrite / 1.5 h / 70 °C 1.2: Schiemann Aromatic Fluorination 1.3: 110 °C 2.1: thionyl chloride / tetrachloromethane; N,N-dimethyl-formamide / 5 h / Reflux 3.1: aluminum (III) chloride / dichloromethane / 4 h / Reflux 4.1: benzene; hydrogenchloride / water; diethyl ether 5.1: sulfuric acid / methanol 6.1: 1,8-diazabicyclo[5.4.0]undec-7-ene 7.1: trifluoroacetic acid / chloroform View Scheme

4’-(methylthio)phenyl(3’-fluorophenyl)methanone → C19H17FO2S + 2,2-dimethyl-4-(3-fluorophenyl)-5-[4-(methylthio)phenyl]-3(2H)-furanone (301693-50-5)

Conditions	Yield
Multi-step reaction with 4 steps 1: benzene; hydrogenchloride / water; diethyl ether 2: sulfuric acid / methanol 3: 1,8-diazabicyclo[5.4.0]undec-7-ene 4: trifluoroacetic acid / chloroform View Scheme

3-fluorobenzoic acid (455-38-9) → C19H17FO2S + 2,2-dimethyl-4-(3-fluorophenyl)-5-[4-(methylthio)phenyl]-3(2H)-furanone (301693-50-5)

Conditions	Yield
Multi-step reaction with 6 steps 1: thionyl chloride / tetrachloromethane; N,N-dimethyl-formamide / 5 h / Reflux 2: aluminum (III) chloride / dichloromethane / 4 h / Reflux 3: benzene; hydrogenchloride / water; diethyl ether 4: sulfuric acid / methanol 5: 1,8-diazabicyclo[5.4.0]undec-7-ene 6: trifluoroacetic acid / chloroform View Scheme

3-fluorobenzoyl chloride (1711-07-5) → C19H17FO2S + 2,2-dimethyl-4-(3-fluorophenyl)-5-[4-(methylthio)phenyl]-3(2H)-furanone (301693-50-5)

Conditions	Yield
Multi-step reaction with 5 steps 1: aluminum (III) chloride / dichloromethane / 4 h / Reflux 2: benzene; hydrogenchloride / water; diethyl ether 3: sulfuric acid / methanol 4: 1,8-diazabicyclo[5.4.0]undec-7-ene 5: trifluoroacetic acid / chloroform View Scheme

sodium hydrogencarbonate (144-55-8) + 2,2-dimethyl-4-(3-fluorophenyl)-5-[4-(methylthio)phenyl]-3(2H)-furanone (301693-50-5) → 2,2-dimethyl-4-(3-fluorophenyl)-5-[4-(methylsulfinyl)phenyl]-3(2H)furanone (301693-70-9)

Conditions	Yield
With m-chloroperoxybenzoic acid In dichloromethane

Upstream product

• 20769-85-1 2-bromoisobutyric acid bromide 
• 301699-27-4 2-(3-fluorophenyl)-1-(4-methylsulfanylphenyl)ethanone 
• 55106-47-3 2-bromo-2-methylpropanoyl cyanide 
• 116729-21-6 2-bromo-2-methylpropionic acid 4-nitrophenyl ester 
• 1711-07-5 3-fluorobenzoyl chloride 
• 455-38-9 3-fluorobenzoic acid 
• 99-05-8 meta-aminobenzoic acid 

Downstream Products

• 301693-70-9 2,2-dimethyl-4-(3-fluorophenyl)-5-[4-(methylsulfinyl)phenyl]-3(2H)furanone 

Relevant articles and documents

Acid-catalyzed decomposition and stability of diazofuranones: Experimental and mechanistic study

Reactions of substituted 4-diazotetrahydrofurane-3-ones with various acids (pKa 2 + cation was confirmed by density functional theory (DFT) calculations at the PBE0/6-31+G(d) functional due to good agreement between calculated and experimental data on the acid stability of diazoketones in different solvents.

4,5-Diaryl 3(2H)Furanones: Anti-inflammatory activity and influence on cancer growth

Apart from their anti-inflammatory action, COX inhibitors have gathered the interest of many scientists due to their potential use for the treatment and prevention of cancer. It has been shown that cyclooxygenase inhibitors restrict cancer cell growth and are able to interact with known antitumor drugs, enhancing their in vitro and in vivo cytotoxicity. The permutation of hydrophilic and hydrophobic aryl groups in COX inhibitors leads to cardinal changes in the biological activity of the compounds. In the present study, thirteen heterocyclic coxib-like 4,5-diarylfuran-3(2H)-ones and their annelated derivatives-phenanthro[9,10-b]furan-3-ones-were synthesized and studied for anti-inflammatory and COX-1/2 inhibitory action and for their cytotoxic activity on the breast cancer (MCF-7) and squamous cell carcinoma (HSC-3) cell lines. The F-derivative of the -SOMe substituted furan-3(2H)-ones exhibited the best activity (COX-1 IC50 = 2.8 μM, anti-inflammatory activity (by carrageenan paw edema model) of 54% (dose 0.01 mmol/kg), and MCF-7 and HSC-3 cytotoxicity with IC50 values of 10 μM and 7.5 μM, respectively). A cytotoxic effect related to the COX-1 inhibitory action was observed and a synergistic effect with the anti-neoplastic drugs gefitinib and 5-fluorouracil was found. A phenanthrene derivative exhibited the best synergistic effect with gefitinib.

Synthesis method of non-steroidal anti-inflammatory drug, polmacoxib key intermediate

The invention provides a synthesis method of non-steroidal anti-inflammatory drug, polmacoxib key intermediate. The synthesis method includes following steps: S1, dissolving nitrophenol in an organic solvent A, dropwise adding organic alkali A at 0-10 DEG C, dropwise adding bromoisobutyryl bromide, allowing reaction for 0.2-2h at room temperature after dropwise adding is finished, adding water for quenching reaction, separating out an organic phase, enabling the organic phase to go through an aftertreatment step, and pulping to obtain a compound 1; S2, dissolving the compound 1 and a compound 2 in tetrahydrofuran, cooling to -20 DEG C, dropwise adding organic alkali B for reaction, adding water for quenching reaction, adding an organic solvent B for extraction, combining the organic phase, using 0.5M sodium hydroxide solution to wash, drying, concentrating, and pulping to obtain the polmacoxib key intermediate. Nitrophenol bromoisobutyrate used in the method has the advantages of simplicity in synthesis, high yield, low cost, low requirements on equipment, freeness of generating an extremely toxic material, cyanide, little pollution and convenience in storage.

Acyl triazole compound as well as preparation method and application thereof

The invention discloses an acyl triazole compound as well as a preparation method and an application thereof. The structural formula of the acyl triazole compound is as shown in a formula (I) in the specification, wherein in the formula (I), X is Cl, Br, I or OSO2R3; R3 is C1-C4 alkyl, phenyl or substituted phenyl; R1 and R2 are respectively independently H, halogens, CN, NO2, C1-C6 alkyl, C1-C6 alkoxy, C1-C6 alkyl thio or NR4R5; and R4 and R5 are respectively independently C1-C6 alkyl. A polmacoxib intermediate is synthesized by using the compound. The compound disclosed by the invention is high in yield, low in cost, free of byproduct cyanogen compounds, safe, environment-friendly and suitable for industrialized production.

A facile one-pot synthesis of 4,5-diaryl-2,2-dimethyl-3(2H)-furanones

An efficient and practical one-pot synthesis of 4,5-diaryl-2,2-dimethyl-3(2H)-furanones has been achieved from 1,2-diarylethanones and 2-bromoisobutyryl cyanide in the presence of excess base, by employing the 'hard soft acid base' principle. The reaction scope of 2-bromoisobutyryl cyanide could be expanded to prepare a variety of 2,2-dimethyl-3(2H)-furanone derivatives other than 4,5-diaryl-2,2-dimethyl-3(2H)-furanones. Copyright

4,5-diaryl-3(2H)-furanone derivatives as cyclooxygenase-2 inhibitors

The present invention provides a novel class of 4,5-diaryl-3(2H)-furanone derivatives, which inhibit strongly and selectively COX-2 over COX-1. They are useful to treat inflammation, inflammation-associated disorders, and COX-2 mediated diseases.