394-32-1

Basic information

• Product Name: 1-(5-Fluoro-2-hydroxyphenyl)-1-ethanone
• Synonyms: 2-Acetyl-4-fluorophenol;5’-fluoro-2’-hydroxy-acetophenon;Ethanone, 1-(5-fluoro-2-hydroxyphenyl)-;5'-FLUORO-2'-HYDROXYACETOPHENONE;5-FLUORO-2-HYDROXYACETOPHENONE;2-HYDROXY-5-FLUOROACETOPHENONE;1-(5-Fluoro-2-hydroxyphenyl)ethan-1-one, 2-Acetyl-4-fluorophenol;1-(5-FLUORO-2-HYDROXYPHENYL)ETHAN-1-ONE
• CAS NO: 394-32-1
• Molecular Formula: C₈H₇FO₂
• Molecular Weight: 154.14
• EINECS: 206-893-5
• Product Categories: Alcohols and Derivatives;Carbonyl Compounds;Aromatic Acetophenones & Derivatives (substituted);ketone;(intermediate of nebivolol);Benzenes;Adehydes, Acetals & Ketones;Fluorine Compounds;Phenols;C7 to C8;Carbonyl Compounds;Ketones;Acetophenone series;Aryl Fluorinated Building Blocks;Building Blocks;C7 to C8;C7-C8;Chemical Synthesis;Fluorinated Building Blocks;Organic Building Blocks;Organic Fluorinated Building Blocks;Other Fluorinated Organic Building Blocks
• Mol File: 394-32-1.mol
• Article Data: 33

Chemical Properties

• Melting Point: 56-58 °C(lit.)
• Boiling Point: 65-66 °C8 mm Hg(lit.)
• Flash Point: 65-66°C/8mm
• Appearance: light yellow to beige-brown crystals
• Density: 1.1850 (estimate)
• Storage Temp.: Inert atmosphere,Room Temperature
• PKA: 10.17±0.18(Predicted)
• Water Solubility: Soluble 0.68 G/L
• BRN: 2359087
• CAS DataBase Reference: 1-(5-Fluoro-2-hydroxyphenyl)-1-ethanone(CAS DataBase Reference)
• NIST Chemistry Reference: 1-(5-Fluoro-2-hydroxyphenyl)-1-ethanone(394-32-1)
• EPA Substance Registry System: 1-(5-Fluoro-2-hydroxyphenyl)-1-ethanone(394-32-1)

Safety Data

• Hazard Codes: Xi,Xn
• Statements: 36/37/38-22
• Safety Statements: 26-37/39-36/37/39
• WGK Germany: 3
• RTECS: AM8502300
• HazardClass: IRRITANT
• Hazardous Substances Data: 394-32-1(Hazardous Substances Data)

Usage

Chemical Properties

light yellow to beige-brown crystals or

Uses

5′-Fluoro-2′-hydroxyacetophenone has been used in the preparation of:1-(5-fluoro-2-hydroxyphenyl)-3-hydroxy-5-phenyl-2,4-pentadien-1-one3-hydroxy and 3-methoxyflavones3-hydroxy and 3-methoxy 2-styrylchromones

Preparation

Preparation by Fries rearrangement of 4-fluorophenyl acetate with aluminium chloride without solvent between 115° and 150° (88–89%).

Synthetic route

4-fluorophenyl acetate (405-51-6) → 1-(5-fluoro-2-hydroxyphenyl)ethan-1-one (394-32-1)

Conditions	Yield
With aluminum (III) chloride at 140℃; for 3h; Fries Phenol Ester Rearrangement;	100%
With trifluorormethanesulfonic acid at 0 - 20℃; for 16h; Fries rearrangement; regiospecific reaction;	92%
With hydrogenchloride; aluminum (III) chloride In water at 140 - 145℃; Fries Phenol Ester Rearrangement;	92%

4-Fluorophenol (371-41-5) + acetyl chloride (75-36-5) → 1-(5-fluoro-2-hydroxyphenyl)ethan-1-one (394-32-1)

Conditions	Yield
With aluminum (III) chloride at 130℃; for 2h;	98.4%
With aluminium trichloride at 130℃; for 2h;	89%
With aluminium trichloride at 180℃; for 0.5h;	65%
Stage #1: 4-Fluorophenol; acetyl chloride In toluene at 40℃; Stage #2: With aluminium trichloride In toluene at 80℃; Further stages.;
Stage #1: 4-Fluorophenol; acetyl chloride In neat (no solvent) at 0 - 20℃; for 2h; Stage #2: With aluminum (III) chloride In neat (no solvent) at 130℃; for 2h;

1-(5-fluoro-2-methoxyphenyl)ethanone (445-82-9) → 1-(5-fluoro-2-hydroxyphenyl)ethan-1-one (394-32-1)

Conditions	Yield
With aluminum (III) chloride In dichloromethane at -5 - 25℃;	90%
With pyridine hydrochloride
With boron tribromide In dichloromethane at -78 - 23℃; for 1h;

1-(2-benzyloxy-5-fluorophenyl)-ethanone (1799-18-4) → 1-(5-fluoro-2-hydroxyphenyl)ethan-1-one (394-32-1)

Conditions	Yield
With palladium diacetate; sodium hydride In N,N-dimethyl acetamide at 25℃; for 4h; Inert atmosphere;	82%

4-Fluorophenol (371-41-5) + acetic acid (64-19-7) → 1-(5-fluoro-2-hydroxyphenyl)ethan-1-one (394-32-1)

Conditions	Yield
With aluminum oxide; methanesulfonic acid at 120℃; for 2h;	60%
With boron trifluoride at 150℃; unter Druck;

1-fluoro-4-methoxybenzene (459-60-9) + acetyl chloride (75-36-5) → 1-(5-fluoro-2-hydroxyphenyl)ethan-1-one (394-32-1)

Conditions	Yield
With aluminium trichloride In tetrachloromethane	44.1%

1-fluoro-4-methoxybenzene (459-60-9) + acetyl chloride (75-36-5) → 1-(5-fluoro-2-methoxyphenyl)ethanone (445-82-9) + 1-(5-fluoro-2-hydroxyphenyl)ethan-1-one (394-32-1)

Conditions	Yield
With carbon disulfide; aluminium trichloride
Stage #1: 1-fluoro-4-methoxybenzene; acetyl chloride With aluminum (III) chloride In dichloromethane Friedel-Crafts Acylation; Inert atmosphere; Stage #2: With water; acetic acid; sodium hydroxide at 0 - 8℃; Cooling with ice; Overall yield = 97%; Overall yield = 13.0g;

aluminium trichloride (7446-70-0) + 4-fluorophenyl acetate (405-51-6) → 1-(5-fluoro-2-hydroxyphenyl)ethan-1-one (394-32-1)

Conditions	Yield
at 150℃;

4-Fluorophenol (371-41-5) → 1-(5-fluoro-2-hydroxyphenyl)ethan-1-one (394-32-1)

Conditions	Yield
Multi-step reaction with 2 steps 1: AlCl3 / 130 °C View Scheme
Multi-step reaction with 2 steps 1: H2SO4 / 120 °C 2: AlCl3 / 160 °C View Scheme
Multi-step reaction with 2 steps 1: 84.55 percent / pyridine / CH2Cl2 / 5 °C 2: 44 percent / aluminium chloride / 2 h / 140 °C View Scheme

4-Fluorophenol (371-41-5) + p-difluoro-benzene → 1-(5-fluoro-2-hydroxyphenyl)ethan-1-one (394-32-1)

Conditions	Yield
Multi-step reaction with 2 steps 1: 80 percent / conc. H2SO4 2: 85 percent / AlCl3 / 2 h / 160 °C View Scheme

1-fluoro-4-methoxybenzene (459-60-9) → 1-(5-fluoro-2-hydroxyphenyl)ethan-1-one (394-32-1)

Conditions	Yield
Multi-step reaction with 3 steps 1: AlCl3; benzene 2: 100 °C 3: AlCl3 / 150 °C View Scheme
Multi-step reaction with 2 steps 1: AlCl3; CS2 2: pyridine hydrochloride View Scheme

4-ethoxy-1-fluorobenzene (459-26-7) → 1-(5-fluoro-2-hydroxyphenyl)ethan-1-one (394-32-1)

Conditions	Yield
Multi-step reaction with 3 steps 1: AlCl3; benzene 2: 100 °C 3: AlCl3 / 150 °C View Scheme

AlCl3 (for Friedel-Crafts reactions) + 4-fluorophenyl acetate (405-51-6) → 1-(5-fluoro-2-hydroxyphenyl)ethan-1-one (394-32-1)

3-fluoro-6-methoxybenzonitrile (189628-38-4) → 1-(5-fluoro-2-hydroxyphenyl)ethan-1-one (394-32-1)

Conditions	Yield
Multi-step reaction with 2 steps 1.1: tetrahydrofuran / 6 h / Reflux 1.2: 20 h / 75 °C 2.1: boron tribromide / dichloromethane / 1 h / -78 - 23 °C View Scheme

trifluoromethylsulfonic anhydride (358-23-6) + 1-(5-fluoro-2-hydroxyphenyl)ethan-1-one (394-32-1) → 2-acetyl-4-fluorophenyl triflate (874388-48-4)

Conditions	Yield
With pyridine at 0 - 20℃;	100%
With pyridine at 0 - 20℃; for 12h;	92%
With pyridine at 0 - 20℃;	68%

1-(5-fluoro-2-hydroxyphenyl)ethan-1-one (394-32-1) + chloroacetic acid ethyl ester (105-39-5) → (2-acetyl-4-fluorophenoxy)acetic acid ethyl ester (34849-57-5)

Conditions	Yield
With potassium carbonate In acetone for 16h; Reflux; Inert atmosphere;	100%

1-(5-fluoro-2-hydroxyphenyl)ethan-1-one (394-32-1) + ethyl iodoacetae (623-48-3) → (2-acetyl-4-fluorophenoxy)acetic acid ethyl ester (34849-57-5)

Conditions	Yield
With potassium carbonate In water; acetone	99%
With potassium carbonate In N,N-dimethyl-formamide at 90℃;

1-(5-fluoro-2-hydroxyphenyl)ethan-1-one (394-32-1) → 1-(5-fluoro-2-iodophenyl)ethan-1-ol

Conditions	Yield
With sodium tetrahydroborate In methanol at 20℃; for 1h; Cooling with ice;	99%

1-(5-fluoro-2-hydroxyphenyl)ethan-1-one (394-32-1) → 5'-fluoro-2'-hydroxy-3'-nitroacetophenone (70978-39-1)

Conditions	Yield
With nitric acid; acetic acid In acetic acid at 0 - 20℃; for 3h;	98.48%
With nitric acid In tetrachloromethane at 20℃; Reflux;	97%
With nitric acid; acetic acid at 0 - 20℃; for 16h;	89%

1-(5-fluoro-2-hydroxyphenyl)ethan-1-one (394-32-1) + dimethyl sulfate (77-78-1) → 1-(5-fluoro-2-methoxyphenyl)ethanone (445-82-9)

Conditions	Yield
With potassium carbonate In acetone at 20℃; for 18h; Reflux;	98%

propargyl p-toluenesulfonate (6165-76-0) + 1-(5-fluoro-2-hydroxyphenyl)ethan-1-one (394-32-1) → 1-(5-fluoro-2-(prop-2-yn-1-yloxy)phenyl)ethan-1-one (879216-16-7)

Conditions	Yield
With 2,3,5,6,8,9,11,12,14,15-decahydro-1,4,7,10,13,16-benzohexaoxacyclooctadecin; potassium carbonate In acetonitrile Heating;	98%

1-(5-fluoro-2-hydroxyphenyl)ethan-1-one (394-32-1) → 1-(5-fluoro-2-hydroxyphenyl)ethan-1-one oxime

Conditions	Yield
With hydroxylamine hydrochloride In pyridine; methanol at 20℃; for 14h;	98%
With hydroxylamine hydrochloride; sodium acetate In methanol at 78℃; for 4h;	88%
With hydroxylamine hydrochloride; sodium acetate In methanol at 70℃; for 4h;

1-(5-fluoro-2-hydroxyphenyl)ethan-1-one (394-32-1) + oxalic acid diethyl ester (95-92-1) → ethyl 4-(5-fluoro-2-hydroxyphenyl)-2,4-dioxobutanoate

Conditions	Yield
With sodium methylate In methanol at 65 - 70℃; Claisen Condensation;	97%
With sodium ethanolate In ethanol at 80℃; for 1.33333h; Cooling with ice;

1-(5-fluoro-2-hydroxyphenyl)ethan-1-one (394-32-1) + 4-methoxy-benzoyl chloride (100-07-2) → 1-(5-fluoro-2-hydroxyphenyl)-3-(4-methoxyphenyl)propane-1,3-dione (850799-88-1)

Conditions	Yield
Stage #1: 1-(5-fluoro-2-hydroxyphenyl)ethan-1-one With lithium hexamethyldisilazane In tetrahydrofuran; hexane at -78 - 20℃; Inert atmosphere; Stage #2: 4-methoxy-benzoyl chloride In tetrahydrofuran; hexane at -78 - 20℃; Inert atmosphere;	96.31%

1-(5-fluoro-2-hydroxyphenyl)ethan-1-one (394-32-1) + allyl bromide (106-95-6) → 1-[2-(allyloxy)-5-fluorophenyl]ethanone (1092306-36-9)

Conditions	Yield
With potassium carbonate In 4-methyl-2-pentanone for 8h; Reflux;	96%
With potassium carbonate In acetone Reflux;

1-(5-fluoro-2-hydroxyphenyl)ethan-1-one (394-32-1) → 4-Fluoro-2-((R)-1-hydroxy-ethyl)-phenol

Conditions	Yield
Stage #1: 1-(5-fluoro-2-hydroxyphenyl)ethan-1-one With (3aR)-1-methyl-3,3-diphenyl-tetrahydro-pyrrolo[1,2-c][1,3,2]oxazaborole In tetrahydrofuran at 0℃; for 0.333333h; Inert atmosphere; Stage #2: With borane-THF In tetrahydrofuran for 0.5h; Inert atmosphere; Heating;	95%
With (-)-diisopinocamphenylborane chloride In tetrahydrofuran for 12h; Ambient temperature;

Methyl 4-(bromomethyl)benzoate (2417-72-3) + 1-(5-fluoro-2-hydroxyphenyl)ethan-1-one (394-32-1) → methyl 4-((2-acetyl-4-fluorophenoxy)methyl)benzoate

Conditions	Yield
With potassium carbonate In N,N-dimethyl-formamide at 20℃; for 16h;	95%

1-(5-fluoro-2-hydroxyphenyl)ethan-1-one (394-32-1) + 4-fluorobenzoyl chloride (403-43-0) → 1-(5-fluoro-2-hydroxyphenyl)-3-(4-fluorophenyl)propane-1,3-dione (1225785-23-8)

Conditions	Yield
Stage #1: 1-(5-fluoro-2-hydroxyphenyl)ethan-1-one With lithium hexamethyldisilazane In tetrahydrofuran; hexane at -78 - 20℃; Inert atmosphere; Stage #2: 4-fluorobenzoyl chloride In tetrahydrofuran; hexane at -78 - 20℃; Inert atmosphere;	94.5%

ethyl bromide (74-96-4) + 1-(5-fluoro-2-hydroxyphenyl)ethan-1-one (394-32-1) → 2'-ethoxy-5'-fluoroacetophenone (1466-79-1)

Conditions	Yield
With potassium carbonate In N,N-dimethyl-formamide at 20℃;	94%

1-(5-fluoro-2-hydroxyphenyl)ethan-1-one (394-32-1) + 5-chloro-1-methyl-1H-imidazole-2-carbaldehyde (37050-18-3) → (E)-3-(5-Chloro-1-methyl-1H-imidazol-2-yl)-1-(5-fluoro-2-hydroxy-phenyl)-propenone

Conditions	Yield
With sodium hydroxide In ethanol Ambient temperature;	93%

1-(5-fluoro-2-hydroxyphenyl)ethan-1-one (394-32-1) + 2-Fluorobenzaldehyde (446-52-6) → 3-(2-fluorophenyl)-1-(5-fluoro-2-hydroxyphenyl)-2-propen-1-one (224294-29-5)

Conditions	Yield
With sodium hydroxide In ethanol	93%

1-(5-fluoro-2-hydroxyphenyl)ethan-1-one (394-32-1) + methyl iodide (74-88-4) → 1-(5-fluoro-2-methoxyphenyl)ethanone (445-82-9)

Conditions	Yield
With potassium carbonate In N,N-dimethyl-formamide at 20℃;	93%
With potassium carbonate In acetone at 20℃;

2,6-difluorobenzaldehyde (437-81-0) + 1-(5-fluoro-2-hydroxyphenyl)ethan-1-one (394-32-1) → 3-(2,6-difluorophenyl)-1-(5-fluoro-2-hydroxyphenyl)-2-propen-1-one (224294-27-3)

Conditions	Yield
With sodium hydroxide In ethanol	92%

1-(5-fluoro-2-hydroxyphenyl)ethan-1-one (394-32-1) + cyclopentanone (120-92-3) → 6-fluorospiro[chroman-2,1'-cyclopentan]-4-one (111478-02-5)

Conditions	Yield
With pyrrole In toluene for 20h; Reflux;	92%
pyrrolidine In acetonitrile

[Pd(CH2-C6H4-P(o-tolyl)2-κC,P)(μ-OOCCH3)]2 + 1-(5-fluoro-2-hydroxyphenyl)ethan-1-one (394-32-1) → 2-acetyl-4-fluorophenolato-[o-(di-o-tolylphosphino)benzyl]palladium(II) (209810-53-7, 209743-84-0)

Conditions	Yield
With potassium tert-butoxide In toluene Ar-atmosphere; stirring (12 h); filtering, evapn. (vac.), crystn. (toluene / pentane); elem. anal.;	92%

1-(5-fluoro-2-hydroxyphenyl)ethan-1-one (394-32-1) + cyanoacetic acid (372-09-8) → C11H6FNO2 (288399-90-6)

Conditions	Yield
With 2,4,6-tripropyl-1,3,5,2,4,6-trioxatriphosphinane-2,4,6-trioxide; triethylamine In acetic acid butyl ester; ethyl acetate at 120℃; Perkin condensation;	92%

1-(5-fluoro-2-hydroxyphenyl)ethan-1-one (394-32-1) + Diethyl carbonate (105-58-8) → 6-fluoro-4-hydroxycoumarin (1994-13-4)

Conditions	Yield
With sodium hydride In mineral oil at 0 - 100℃;	91%
With potassium tert-butylate In tetrahydrofuran at 20℃; for 10h; Inert atmosphere;	78%
With sodium hydride In dimethyl sulfoxide at 0 - 100℃; for 2h;	29%

1,1,1-trifluoroacetophenone (434-45-7) + 1-(5-fluoro-2-hydroxyphenyl)ethan-1-one (394-32-1) → (S)-4,4,4-trifluoro-1-(5-fluoro-2-hydroxyphenyl)-3-hydroxy-3-phenylbutan-1-one

Conditions	Yield
With C19H25F6N3S In toluene at 0℃; for 96h; Aldol Addition; Inert atmosphere; enantioselective reaction;	91%

6-chloro-8-formyl-1,3-benzodioxane (63944-31-0) + 1-(5-fluoro-2-hydroxyphenyl)ethan-1-one (394-32-1) → (E)-3-(6-Chloro-4H-benzo[1,3]dioxin-8-yl)-1-(5-fluoro-2-hydroxy-phenyl)-propenone (147722-92-7)

Conditions	Yield
With sodium hydroxide In ethanol Ambient temperature;	90%

1-(5-fluoro-2-hydroxyphenyl)ethan-1-one (394-32-1) + 4-fluorobenzaldehyde (459-57-4) → (E)-1-(2-hydroxy-5-fluorophenyl)-3-(4-fluorophenyl)prop-2-en-1-one (224294-26-2)

Conditions	Yield
With sodium hydroxide In ethanol	90%
With potassium hydroxide In ethanol; water at 20℃; Claisen-Schmidt Condensation;	80%
With sodium hydroxide In ethanol; water at 30℃; for 24h;	19%

1-(5-fluoro-2-hydroxyphenyl)ethan-1-one (394-32-1) + N,N-dimethyl-formamide dimethyl acetal (4637-24-5) → 3-(dimethylamino)-1-(5-fluoro-2-hydroxyphenyl)prop-2-en-1-one

Conditions	Yield
In toluene at 80℃; Sealed tube; Inert atmosphere;	90%
at 95℃; for 4h;	69%
at 100℃; for 2h;

Upstream product

• 445-82-9 1-(5-fluoro-2-methoxyphenyl)ethanone 
• 371-41-5 4-Fluorophenol 
• 64-19-7 acetic acid 
• 1799-18-4 1-(2-benzyloxy-5-fluorophenyl)-ethanone 
• 189628-38-4 5-fluoro-2-methoxybenzonitrile 
• 405-51-6 4-fluorophenyl acetate 
• 459-60-9 1-fluoro-4-methoxybenzene 
• 7446-70-0 aluminium trichloride 
• 75-36-5 acetyl chloride 
• 459-26-7 4-ethoxy-1-fluorobenzene 

Downstream Products

• 1493-48-7 4-fluoro-2-[2-(3-fluoro-anilino)-thiazol-4-yl]-phenol 
• 16108-86-4 1-<4-Fluor-benzolsulfonylhydrazono>-1-<5-fluor-2-hydroxy-phenyl>-aethan 
• 1493-76-1 4-fluoro-2-[2-(2,4,6-tribromo-anilino)-thiazol-4-yl]-phenol 
• 70978-39-1 5'-fluoro-2'-hydroxy-3'-nitroacetophenone 
• 147722-92-7 (E)-3-(6-Chloro-4H-benzo[1,3]dioxin-8-yl)-1-(5-fluoro-2-hydroxy-phenyl)-propenone 
• 147722-93-8 (E)-3-(6-Bromo-4H-benzo[1,3]dioxin-8-yl)-1-(5-fluoro-2-hydroxy-phenyl)-propenone 
• 126581-65-5 α-bromo-(2-hydroxy-5-fluoro)acetophenone 
• 445-82-9 1-(5-fluoro-2-methoxyphenyl)ethanone 
• 170807-24-6 8-[(E)-3-(5-Fluoro-2-hydroxy-phenyl)-3-oxo-propenyl]-4H-benzo[1,3]dioxine-6-carboxylic acid 
• 797054-19-4 (S)-2-[(R)-2,2-dimethyl-1,3-dioxolan-4-yl]-6-fluoro-2,3-dihydrochromen-4-one 
• 797054-18-3 (R)-2-[(R)-2,2-dimethyl-1,3-dioxolan-4-yl]-6-fluoro-2,3-dihydrochromen-4-one 
• 59835-92-6 6-Fluoro-flavon-oxim 
• 321976-79-8 6-fluoro-2-(4-hydroxy-phenyl)-chromen-4-one oxime 
• 165456-46-2 diethyl 4-[3-(5-fluoro-2-hydroxyphenyl)-1,3-dioxopropyl] benzylphosphonate 

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