6305-04-0

Basic information

• Product Name: 2-CHLORO-4'-HYDROXYACETOPHENONE
• Synonyms: 2-chloro-1-(4-hydroxyphenyl)-ethanon;2-chloro-4’-hydroxy-acetophenon;4-hydroxyphenacylchloride;chlorophenacyle;p-(chloroacetyl)phenol;2-chloro-1-(4-hydroxyphenyl)ethan-1-one;4'-Hydroxy-α-chloroacetophenone;α-Chloro-4'-hydroxyacetophenone
• CAS NO: 6305-04-0
• Molecular Formula: C₈H₇ClO₂
• Molecular Weight: 170.59298
• EINECS: 228-613-0
• Mol File: 6305-04-0.mol
• Article Data: 10

Chemical Properties

• Melting Point: 145-146 °C
• Boiling Point: 241.44°C (rough estimate)
• Flash Point: 157.7 ºC
• Appearance: /
• Density: 1.2315 (rough estimate)
• Vapor Pressure: 5.48E-05mmHg at 25°C
• Refractive Index: 1.5100 (estimate)
• PKA: 7.72±0.15(Predicted)
• CAS DataBase Reference: 2-CHLORO-4'-HYDROXYACETOPHENONE(CAS DataBase Reference)
• NIST Chemistry Reference: 2-CHLORO-4'-HYDROXYACETOPHENONE(6305-04-0)
• EPA Substance Registry System: 2-CHLORO-4'-HYDROXYACETOPHENONE(6305-04-0)

Safety Data

• Hazardous Substances Data: 6305-04-0(Hazardous Substances Data)

Usage

Uses

2-Chloro-1-(4-hydroxy-phenyl)-ethanone is a reagent that is used in the preparation of hydroxypyrimidine derivatives and their HDAC (histone deacetylases) inhibitory activity.

Preparation

Also obtained by reaction of acetyl chloride with anisole in the presence of aluminium chloride in n-heptane at 35° for 4 h 30 min (20%).

InChI:InChI=1/C8H7ClO2/c9-5-8(11)6-1-3-7(10)4-2-6/h1-4,10H,5H2

Synthetic route

4-Hydroxyacetophenone (99-93-4) → p-hydroxyphenacyl chloride (6305-04-0)

Conditions	Yield
With N,N,N-trimethylbenzenemethanaminium dichloroiodate In methanol; 1,2-dichloro-ethane for 10h; Heating;	95%
With 2,2,3,4,5,6-hexachloro-cyclohexa-2,4-dien-1-one In ethanol for 5h; Heating;	77%
With hydrogenchloride; ammonium nitrate; iodine; oxygen In water; acetonitrile at 60℃; for 22h; Green chemistry; chemoselective reaction;	64%
With N-chloro-succinimide; toluene-4-sulfonic acid In acetonitrile at 40℃;	45%

chloroacetyl chloride (79-04-9) + phenol (108-95-2) → p-hydroxyphenacyl chloride (6305-04-0)

Conditions	Yield
With aluminum (III) chloride In dichloromethane at 0 - 30℃; for 7h; Solvent;	94%
With aluminium trichloride In various solvent(s) at 70℃; for 5h;	50%
Stage #1: chloroacetyl chloride; phenol; aluminum (III) chloride In 1,2-dichloro-ethane at 0 - 65℃; for 13h; Stage #2: With hydrogenchloride In dichloromethane; water	15%

2-chloro-1-(4-chloroacetoxy-phenyl)-ethanone (868746-76-3) → p-hydroxyphenacyl chloride (6305-04-0)

Conditions	Yield
With sodium hydroxide In methanol; water at 0 - 20℃; for 0.5h;	85%

phenyl chloroacetate (620-73-5) → 2-(2-chloroacetyl)phenol (53074-73-0) + p-hydroxyphenacyl chloride (6305-04-0)

Conditions	Yield
With beryllium(II) chloride at 130 - 140℃;
With aluminium trichloride at 120℃;

phenyl chloroacetate (620-73-5) → p-hydroxyphenacyl chloride (6305-04-0)

Conditions	Yield
With aluminium trichloride

methoxybenzene (100-66-3) + chloroacetyl chloride (79-04-9) → 2-(2-chloroacetyl)phenol (53074-73-0) + p-hydroxyphenacyl chloride (6305-04-0)

Conditions	Yield
With aluminium trichloride; 1,1,2,2-tetrachloroethane
With aluminium trichloride; 1,1,2,2-tetrachloroethane

methoxybenzene (100-66-3) + chloroacetyl chloride (79-04-9) → p-hydroxyphenacyl chloride (6305-04-0)

Conditions	Yield
With aluminium trichloride; Petroleum ether
With aluminium trichloride
With carbon disulfide; aluminium trichloride
With aluminium trichloride

Dimethyl-<4-hydroxy-phenacyl>-sulfoniumchlorid → p-hydroxyphenacyl chloride (6305-04-0)

Conditions	Yield
at 110℃;

phenyl chloroacetate (620-73-5) + aluminium trichloride (7446-70-0) → p-hydroxyphenacyl chloride (6305-04-0) + ω-chloro-2-oxy-acetophenone

Conditions	Yield
at 120℃;

phenyl chloroacetate (620-73-5) → p-hydroxyphenacyl chloride (6305-04-0) + ω-chloro-2-oxy-acetophenone

Conditions	Yield
With aluminium trichloride at 120℃;

phenyl chloroacetate (620-73-5) → p-hydroxyphenacyl chloride (6305-04-0) + 2-chloro-1-<2-hydroxy-phenyl>-ethanone-(1)

Conditions	Yield
With beryllium(II) chloride at 130 - 140℃;

α,α-dichloro-4-hydroxyacetophenone → p-hydroxyphenacyl chloride (6305-04-0) + 4-Hydroxyacetophenone (99-93-4)

Conditions	Yield
With indium(I) bromide In tetrahydrofuran at 20℃; for 24h;

2-chloro-1-(4-methoxyphenyl)ethanone (2196-99-8) → p-hydroxyphenacyl chloride (6305-04-0)

Conditions	Yield
With aluminium trichloride In n-heptane for 2.5h; Heating;	9.5 g

methoxybenzene (100-66-3) + enanthoyl chloride → p-hydroxyphenacyl chloride (6305-04-0)

Conditions	Yield
Multi-step reaction with 2 steps 1: AlCl3 / heptane / 1.5 h / 35 °C 2: 9.5 g / AlCl3 / heptane / 2.5 h / Heating View Scheme

o-hydroxyacetophenone (118-93-4) + palladium/charcoal → p-hydroxyphenacyl chloride (6305-04-0)

Conditions	Yield
Multi-step reaction with 2 steps 1: HCl / methanol / 10 °C 2: 110 °C View Scheme

p-hydroxyphenacyl chloride (6305-04-0) + benzyl bromide (100-39-0) → 1-(4-(benzyloxy)phenyl)-2-chloroethane-1-one (63365-56-0)

Conditions	Yield
Stage #1: p-hydroxyphenacyl chloride With potassium carbonate In N,N-dimethyl-formamide at 20 - 30℃; for 0.5h; Stage #2: benzyl bromide In N,N-dimethyl-formamide at 30 - 40℃; for 4h; Solvent; Reagent/catalyst;	97.5%

p-hydroxyphenacyl chloride (6305-04-0) + tert-butyldimethylsilyl chloride (18162-48-6) → 1-(4-(tert-butyldimethylsilyloxy)phenyl)-2-chloroethanone (130798-41-3)

Conditions	Yield
With 1H-imidazole In N,N-dimethyl-formamide at 23℃; for 0.05h;	97%

p-hydroxyphenacyl chloride (6305-04-0) + 4-methoxybenzoic acid hydrazide (3290-99-1) → 3-(4-methoxyphenyl)-6-(4-hydroxyphenyl)-1,2,4-triazine

Conditions	Yield
With ammonium propionate; propionic acid at 190℃; for 30h;	92%

1-(2-hydroxy-5-nitrophenyl)ethanone (1450-76-6) + p-hydroxyphenacyl chloride (6305-04-0) → 2-(4-hydroxy benzoyl) 3-methyl 5-nitro benzofuran (141645-21-8)

Conditions	Yield
With 1,8-diazabicyclo[5.4.0]undec-7-ene In dichloromethane at 20℃; for 4h; Solvent; Molecular sieve; Inert atmosphere;	91.1%

methyl magnesium iodide (917-64-6) + p-hydroxyphenacyl chloride (6305-04-0) → 4-methoxyphenylacetone (770-39-8) + 1-[(4-hydroxy)phenyl]-2-methyl-2-propanol (98815-43-1) + 1-chloro-2-(4-hydroxyphenyl)propan-2-ol (98815-45-3)

Conditions	Yield
In tetrahydrofuran at 20℃; for 2h; Title compound not separated from byproducts;	A 5% B 90% C n/a

methyl magnesium iodide (917-64-6) + p-hydroxyphenacyl chloride (6305-04-0) → 4-methoxyphenylacetone (770-39-8) + 1-chloro-2-(4-hydroxyphenyl)propan-2-ol (98815-45-3)

Conditions	Yield
In tetrahydrofuran at 20℃; for 2h; Title compound not separated from byproducts;	A 90% B 90%

p-hydroxyphenacyl chloride (6305-04-0) + sodium methylate (124-41-4) → alpha-methoxy-4-hydroxyacetophenone (32136-81-5)

Conditions	Yield
In methanol for 24h; Ambient temperature;	90%
In methanol pH=8; pH-value;	18.3 g

4'-hydroxy-2'-methylacetophenone (6921-64-8) + p-hydroxyphenacyl chloride (6305-04-0) → (3,6-dimethylbenzofuran-2-yl)(4-hydroxyphenyl)methanone

Conditions	Yield
With 1,8-diazabicyclo[5.4.0]undec-7-ene In dichloromethane at 20℃; for 3h; Solvent; Molecular sieve; Inert atmosphere;	88.54%

6-(phenylmethyl)-3,4-dihydro-3-thioxo-1,2,4-triazin-5(2H)-one (7338-80-9) + p-hydroxyphenacyl chloride (6305-04-0) → 6-benzyl-3-(4-hydroxyphenyl)-7H-thiazolo[3,2-b]-1,2,4-triazin-7-one

Conditions	Yield
With sodium acetate; acetic acid Reflux;	85%
With sodium acetate In acetic acid Reflux;	79.2%
With sodium acetate; acetic acid

1-(2-hydroxy-4-methoxyphenyl)ethanone (552-41-0) + p-hydroxyphenacyl chloride (6305-04-0) → (4-hydroxyphenyl)(6-methoxy-3-methylbenzofuran-2-yl)methanone

Conditions	Yield
With 1,8-diazabicyclo[5.4.0]undec-7-ene In dichloromethane at 20℃; for 3h; Solvent; Molecular sieve; Inert atmosphere;	81%

p-hydroxyphenacyl chloride (6305-04-0) + 6-[(4-methoxyphenyl)methyl]-3,4-dihydro-3-thioxo-1,2,4-triazin-5(2H)-one (112517-73-4) → 3-(4-hydroxyphenyl)-6-(4-methoxybenzyl)-7H-thiazolo-[3,2-b][1,2,4]triazin-7-one

Conditions	Yield
With sodium acetate In acetic acid Reflux;	80.1%
With sodium acetate; acetic acid Reflux;	64%
With sodium acetate In acetic acid Reflux;	62.7%
With sodium acetate; acetic acid
With sodium acetate In acetic acid Reflux;

p-hydroxyphenacyl chloride (6305-04-0) + 5-p-Tolyloxymethyl-2,4-dihydro-[1,2,4]triazole-3-thione (143540-96-9) → 4-(2-p-Tolyloxymethyl-thiazolo[3,2-b][1,2,4]triazol-6-yl)-phenol

Conditions	Yield
In propan-1-ol for 20h; Heating;	75%

p-hydroxyphenacyl chloride (6305-04-0) → 4-hydroxyphenylacetate (156-38-7) + 1,4-bis(4-hydroxyphenyl)butan-1,4-dione (108791-64-6) + 4-Hydroxyacetophenone (99-93-4)

Conditions	Yield
With methyloxirane In water; acetonitrile for 4h; Irradiation;	A 75% B 10% C 5%

p-hydroxyphenacyl chloride (6305-04-0) + isopropylamine (75-31-0) → 1-(4-hydroxy-phenyl)-2-isopropylamino-ethanone; hydrochloride (69716-74-1)

Conditions	Yield
Stage #1: p-hydroxyphenacyl chloride; isopropylamine In methanol at 20℃; for 3h; Stage #2: With hydrogenchloride In methanol; water	75%

p-hydroxyphenacyl chloride (6305-04-0) + 3-methyl-8-bromoxanthine (93703-24-3) → 8-bromo-3,7-dihydro-7-[2-(4-hydroxyphenyl)-2-oxoethyl]-3-methyl-1H-purine-2,6-dione (1192215-81-8)

Conditions	Yield
Stage #1: 3-methyl-8-bromoxanthine With N-ethyl-N,N-diisopropylamine In N,N-dimethyl-formamide at 25℃; for 0.0833333h; Inert atmosphere; Stage #2: p-hydroxyphenacyl chloride In N,N-dimethyl-formamide at 25℃; Inert atmosphere;	74%

p-hydroxyphenacyl chloride (6305-04-0) + 4'-bromo-2'-hydroxyacetophenone (30186-18-6) → (6-bromo-3-methylbenzofuran-2-yl)(4-hydroxyphenyl)methanone

Conditions	Yield
With 1,8-diazabicyclo[5.4.0]undec-7-ene In dichloromethane at 20℃; for 3h; Solvent; Molecular sieve; Inert atmosphere;	73.2%

p-hydroxyphenacyl chloride (6305-04-0) + WHI-P131 (202475-60-3) → 1-(4-hydroxyphenyl)-2-(4-((6,7-dimethoxyquinazolin-4-yl)amino)phenoxy)ethanone

Conditions	Yield
With potassium carbonate In N,N-dimethyl-formamide at 20℃; for 18h;	73%

p-hydroxyphenacyl chloride (6305-04-0) + 5-o-Tolyloxymethyl-2,4-dihydro-[1,2,4]triazole-3-thione (143540-95-8) → 4-(2-o-Tolyloxymethyl-thiazolo[3,2-b][1,2,4]triazol-6-yl)-phenol

Conditions	Yield
In propan-1-ol for 20h; Heating;	72%

p-hydroxyphenacyl chloride (6305-04-0) + o-hydroxyacetophenone (118-93-4) → (4-hydroxy-phenyl)-(3-methyl-benzofuran-2-yl)-methanone (32730-17-9)

Conditions	Yield
With 1,8-diazabicyclo[5.4.0]undec-7-ene In dichloromethane at 20℃; for 4h; Solvent; Molecular sieve; Inert atmosphere;	72%

p-hydroxyphenacyl chloride (6305-04-0) + 5-Phenoxymethyl-2,4-dihydro-[1,2,4]triazole-3-thione (78171-88-7) → 4-(2-Phenoxymethyl-thiazolo[3,2-b][1,2,4]triazol-6-yl)-phenol

Conditions	Yield
In propan-1-ol for 20h; Heating;	70%

p-hydroxyphenacyl chloride (6305-04-0) + 5-m-Tolyloxymethyl-2,4-dihydro-[1,2,4]triazole-3-thione (372164-14-2) → 4-(2-m-Tolyloxymethyl-thiazolo[3,2-b][1,2,4]triazol-6-yl)-phenol

Conditions	Yield
In propan-1-ol for 20h; Heating;	70%

p-hydroxyphenacyl chloride (6305-04-0) + 6-(4-chlorobenzyl)-3-thioxo-3,4-dihydro-[1,2,4]-triazin-5(2H)-one (33401-57-9) → 6-(4-chlorobenzyl)-3-(4-hydroxyphenyl)-7H-thiazolo[3,2-b]-1,2,4-triazin-7-one

Conditions	Yield
With sodium acetate; acetic acid Reflux;	65%
With sodium acetate In acetic acid Reflux;	65.4%
With sodium acetate; acetic acid

6-phenyl-1,2,4-triazine-3(2H)-thione-5(4H)-one (447-00-7) + p-hydroxyphenacyl chloride (6305-04-0) → 3-(4-hydroxyphenyl)-6-phenyl-7H-thiazolo[3,2-b][1,2,4]triazin-7-one (1186078-85-2)

Conditions	Yield
With acetic acid for 12h; Reflux;	60%

p-hydroxyphenacyl chloride (6305-04-0) + acetic acid (64-19-7) → α,α-dimethyl-p-hydroxyphenacyl acetate (20816-46-0)

Conditions	Yield
With triethylamine In acetonitrile for 3h; Heating;	50%
With triethylamine In acetonitrile for 3h; Heating;	40%

p-hydroxyphenacyl chloride (6305-04-0) + C11H11N3O2S → 3-(4-hydroxyphenyl)-6-(4-ethoxyphenyl)-7H-thiazolo[3,2-b]-1,2,4-triazin-7-one

Conditions	Yield
With sodium acetate In acetic acid Reflux;	42.8%

p-hydroxyphenacyl chloride (6305-04-0) + Benzilic acid (76-93-7) → 2-(4-hydroxyphenyl)-2-oxoethyl 2,2-diphenyl-2-hydroxyacetate

Conditions	Yield
With sodium hydroxide; sodium iodide for 3.5h; Heating;	38%

p-hydroxyphenacyl chloride (6305-04-0) + thiosemicarbazide (79-19-6) → 2-amino-5-(p-hydroxyphenyl)-1,3,4-thiadiazine hydrochloride (74495-46-8)

Conditions	Yield
In ethanol Heating;	27%

Upstream product

• 79-04-9 chloroacetyl chloride 
• 108-95-2 phenol 
• 868746-76-3 2-chloro-1-(4-chloroacetoxy-phenyl)-ethanone 
• 118-93-4 o-hydroxyacetophenone 
• 100-66-3 methoxybenzene 
• 2196-99-8 2-chloro-1-(4-methoxyphenyl)ethanone 
• 4974-60-1 α,α-dichloro-4-hydroxyacetophenone 
• 620-73-5 phenyl chloroacetate 
• 7446-70-0 aluminium trichloride 
• 99-93-4 4-Hydroxyacetophenone 

Downstream Products

• 777795-74-1 1-(4-hydroxy-phenyl)-2-morpholin-4-yl-ethanone 
• 88693-95-2 2-(dibenzylamino)-1-(4-hydroxyphenyl)ethanone 
• 141645-21-8 2-(4-hydroxy benzoyl) 3-methyl 5-nitro benzofuran 
• 32730-17-9 (4-hydroxy-phenyl)-(3-methyl-benzofuran-2-yl)-methanone 
• 1542156-59-1 4-(4-hydroxyphenyl)thiazol-2-yl-Ala-Phe-Gly 
• 1157421-56-1 2-((4-hydroxy-6-methylpyrimidin-2-yl)thio)-1-(4-hydroxyphenyl)ethanone 
• 1186078-85-2 3-(4-hydroxyphenyl)-6-phenyl-7H-thiazolo[3,2-b][1,2,4]triazin-7-one 
• 1135306-45-4 C₁₄H₁₄N₂O₂S 
• 1192215-81-8 8-bromo-3,7-dihydro-7-[2-(4-hydroxyphenyl)-2-oxoethyl]-3-methyl-1H-purine-2,6-dione 
• 4973-17-5 2-chloro-1-(4-hydroxy-phenyl)-ethanol 
• 6169-06-8 (S)-2-Octanol 
• 5978-70-1 (R)-Octan-2-ol 
• 871266-52-3 C₈H₉ClO₂ 
• 69716-74-1 1-(4-hydroxy-phenyl)-2-isopropylamino-ethanone; hydrochloride 

Relevant articles and documents

Preparation method of 2-(4-benzyloxyphenyl)ethanol

The invention provides a preparation method of 2-(4-benzyloxyphenyl)ethanol. The preparation method comprises the following steps: 1) subjecting phenol to reacting with chloroacetyl chloride under the catalysis of aluminum trichloride to obtain a compound as shown in a formula II; 2) subjecting the compound as shown in the formula II to reacting with benzyl halide under an alkaline condition to obtain a compound as shown in a formula III, wherein the benzyl halide is one selected from benzyl bromide and benzyl chloride; 3) performing reduction treatment on the compound as shown in the formula III, and adjusting a reaction system to be an alkaline system to obtain a compound as shown in a formula IV; and 4) under the action of a catalyst, reducing the compound as shown in the formula IV under a hydrogen condition to obtain the 2-(4-benzyloxyphenyl)ethanol as shown in the formula I. The preparation method has the advantages of low cost, mild reaction conditions, safety in operation and less three-waste pollution, and is beneficial to being applied to industrial production.

The α-chlorination of aryl methyl ketones under aerobic oxidative conditions

The novel reaction system air/ammonium nitrate/iodine/hydrochloric acid [air/NH4NO3(cat.)/I2(cat.)/HCl] is introduced as a simple, safe, cheap, efficient and regioselective mediator for the α-chlorination of aryl, heteroaryl and alkyl methyl ketones under aerobic oxidative conditions. The inventive use of a catalytic amount of iodine enabled the moderate to quantitative, regioselective chlorination of a comprehensive scope of different methyl ketone derivatives including those bearing oxidizable heteroatom (S, N) substituents, some of which possess declared potential biological and pharmaceutical activity. Air oxygen under a slight overpressure plays the role of the terminal oxidant catalytically activated by redox cycles of nitrogen oxides released from the catalytic amount of ammonium nitrate (NH4NO3) under acidic conditions of hydrochloric acid (HCl) and co-catalyzed by elemental iodine (I2), which was found to be essential for the high efficiency of the reaction system.

Synthesis of [4-14C]-pelargonidin chloride and [4- 14C]-delphinidin chloride

The synthesis of [4-14C]-pelargonidin chloride and [4- 14C]-delphinidin chloride via [formyl-14C]-2-(benzoyloxy)- 4,6-dihydroxybenzaldehyde, ω,4-diacetoxyacetophenone and ω,3,4,5-tetraacetoxyacetophenone is described. The first step comprised labelling of the carbonyl group of 2-(benzoyloxy)-4,6-dihydroxybenzaldehyde, verifying that the coupling with ω,4-diacetoxyacetophenone or ω,3,4,5-tetraacetoxyacetophenone under hydrogen chloride atmosphere resulted in the formation of [4-14C] labelled anthocyanidins. Copyright