37148-48-4

Basic information

• Product Name: 4-Amino-3,5-dichloroacetophenone
• Synonyms: 1-(4-Amino-3,5-dichloro-phenyl)-2-ethanone;5-AMINO-3,5-DICHLORO ACETOPHENONE;4''-AMINO-3'',5''-DICHLOROACETOPHENONECLENBUTEROL;1-(4-Amino-3,5-dichlorophenyl)-ethanone, 3,5-Dichloro-4-aminoacetophenone;4-Amino-3,5-dichloroacetophenone,98%;4′-Amino-3′,5′-dichloroacetophenone,1-(4-Amino-3,5-dichlorophenyl)-ethanone, 3,5-Dichloro-4-aminoacetophenone;3,5-dichloro-p-aMino acetophenone;4-AMino-3,5-dichloroacetophenone, 98% 5GR
• CAS NO: 37148-48-4
• Molecular Formula: C₈H₇Cl₂NO
• Molecular Weight: 204.05
• EINECS: 253-368-1
• Product Categories: Aromatic Acetophenones & Derivatives (substituted);(intermediate of leflunomide);Chemical Amines;Amines;Aromatics
• Mol File: 37148-48-4.mol
• Article Data: 3

Chemical Properties

• Melting Point: 162-166 °C(lit.)
• Boiling Point: 351.5 °C at 760 mmHg
• Flash Point: 166.4 °C
• Appearance: /
• Density: 1.2748 (rough estimate)
• Vapor Pressure: 4.1E-05mmHg at 25°C
• Refractive Index: 1.5500 (estimate)
• Storage Temp.: Refrigerator
• Solubility: DMSO (Slightly), Methanol (Slightly)
• PKA: -1.72±0.10(Predicted)
• CAS DataBase Reference: 4-Amino-3,5-dichloroacetophenone(CAS DataBase Reference)
• NIST Chemistry Reference: 4-Amino-3,5-dichloroacetophenone(37148-48-4)
• EPA Substance Registry System: 4-Amino-3,5-dichloroacetophenone(37148-48-4)

Safety Data

• Hazard Codes: Xi
• Statements: 36/37/38
• Safety Statements: 26-36-37/39
• WGK Germany: 3
• Hazardous Substances Data: 37148-48-4(Hazardous Substances Data)

Usage

Description

4-Amino-3,5-dichloroacetophenone is an intermediate in the synthesis of the antitussive and antiasthmatic drug gramtin.

Storage

4-Amino-3,5-dichloroacetophenone should be stored in a cool, dry place in a small, well filled, well-closed container, protected from light. When a partially filled container is used, the air should be replaced by nitrogen or another inert gas. 4-Amino-3,5-dichloroacetophenone oxidizes on exposure to air, resulting in an increase in the peroxide value.

Chemical Properties

4-Amino-3,5-dichloroacetophenone is a white to light yellow crystal powder. Insoluble in cold water, slightly soluble in hot water.

Uses

4-Amino-3,5-dichloroacetophenone is used to synthesize the drug Clenbuterol. Clenbuterol is a steroid-like chemical that was initially developed to treat asthma in horses, working by relaxing the airways in the animals'lungs.

Preparation

4-Amino-3,5-dichloroacetophenone was synthesized by chlorination of 4-aminoacetophenone. Add 4-aminoacetophenone and acetic acid (80%) into the reaction pot, stir and dissolve, quickly add chlorine-containing glacial acetic acid solution, the temperature of the addition is 5°C. After the addition is completed, immediately put into ice water to precipitate, filter, and wash with water to obtain the crude product. Recrystallize with ethanol to obtain the finished product of 4-Amino-3,5-dichloroacetophenone.

Application

4-Amino-3,5-dichloroacetophenone is a compound useful in organic synthesis.

InChI:InChI=1/C8H7Cl2NO/c1-4(12)5-2-6(9)8(11)7(10)3-5/h2-3H,11H2,1H3

Synthetic route

acetic anhydride (108-24-7) + 2,6-Dichloroaniline (608-31-1) → 1-(4-amino-3,5-dichlorophenyl)-1-ethanone (37148-48-4)

Conditions	Yield
With aluminum (III) chloride In dichloromethane at 0 - 20℃;	98.9%

acetyl chloride (75-36-5) + 2,6-Dichloroaniline (608-31-1) → 1-(4-amino-3,5-dichlorophenyl)-1-ethanone (37148-48-4)

Conditions	Yield
With iron(III) chloride In chloroform at 0 - 20℃; for 6h;	88.6%

4-Aminoacetophenone (99-92-3) → 1-(4-amino-3-chlorophenyl)ethan-1-one (6953-83-9) + 1-(4-amino-3,5-dichlorophenyl)-1-ethanone (37148-48-4)

Conditions	Yield
With N-chloro-succinimide In acetonitrile at 20℃; for 3.5h;	A 18% B 80%
With N-chloro-succinimide In acetonitrile at 20℃; for 4.5h;	A 45% B 20%

4-Aminoacetophenone (99-92-3) → 1-(4-amino-3,5-dichlorophenyl)-1-ethanone (37148-48-4)

Conditions	Yield
With chlorine; acetic acid

chlorine (7782-50-5) + 4-Aminoacetophenone (99-92-3) + acetic acid (64-19-7) → 1-(4-amino-3,5-dichlorophenyl)-1-ethanone (37148-48-4) + 2,4,6-trichloroaniline (634-93-5)

1-(4-amino-3,5-dichlorophenyl)-1-ethanone (37148-48-4) → C8H8Cl2N2O (120215-63-6)

Conditions	Yield
With hydroxylamine In tetrahydrofuran	100%

1-(4-amino-3,5-dichlorophenyl)-1-ethanone (37148-48-4) → 1-(4-amino-3,5-dichlorophenyl)-2-bromoethan-1-one (37148-47-3)

Conditions	Yield
With bromine at 20℃; for 3h;	95.2%
Stage #1: 1-(4-amino-3,5-dichlorophenyl)-1-ethanone With bromine In chloroform for 0.5h; Reflux; Inert atmosphere; Stage #2: With triethylamine; phosphonic acid diethyl ester In tetrahydrofuran at 0 - 20℃; for 0.166667h; Inert atmosphere;	89%
Stage #1: 1-(4-amino-3,5-dichlorophenyl)-1-ethanone With bromine In tetrahydrofuran; chloroform for 0.416667h; Reflux; Stage #2: With diethyl phosphite; triethylamine In tetrahydrofuran at 20℃; for 0.166667h;	89%

1-(4-amino-3,5-dichlorophenyl)-1-ethanone (37148-48-4) → 3,5-dichloro-4-bromoacetophenone

Conditions	Yield
With hydrogen bromide; copper(I) bromide; sodium nitrite In water at 0 - 5℃; for 4.5h;	90%

1-(4-amino-3,5-dichlorophenyl)-1-ethanone (37148-48-4) + acetonitrile (75-05-8) → 2,6-dichloro-4-(2,6-dimethylpyrimidin-4-yl)aniline

Conditions	Yield
With sodium hydroxide; copper dichloride at 120℃; for 24h; Schlenk technique; Inert atmosphere;	84%
With sodium hydroxide; copper dichloride at 110℃; for 20h; Inert atmosphere;	84%

1-(4-amino-3,5-dichlorophenyl)-1-ethanone (37148-48-4) + copper dichloride → 3’,4’,5’-Trichloroacetophenone (35981-65-8)

Conditions	Yield
With tert.-butylnitrite In acetonitrile at 65℃; for 1h; Glovebox; Schlenk technique; Reflux;	80%

1-(4-amino-3,5-dichlorophenyl)-1-ethanone (37148-48-4) → α-methyl-4-amino-3,5-dichlorobenzylamine (918451-58-8)

Conditions	Yield
With ammonia; hydrogen In tetrahydrofuran at 120℃; for 20h;	79%

concentrated acetic acid + 1-(4-amino-3,5-dichlorophenyl)-1-ethanone (37148-48-4) + hypophosphorous acid (6303-21-5) → 2-(3,5-dichlorophenyl)acetaldehyde (109346-95-4)

Conditions	Yield
With hydrogenchloride; sodium nitrite In water	70%

1-(4-amino-3,5-dichlorophenyl)-1-ethanone (37148-48-4) → 4-amino-bromo-3,5-dichloroacetophenone

Conditions	Yield
With bromine In chloroform at 20℃; for 1h;	67%

di-tert-butyl dicarbonate (24424-99-5) + 1-(4-amino-3,5-dichlorophenyl)-1-ethanone (37148-48-4) → N,N-Bis(tert-butoxycarbonyl)-2,6-dichloro-4-acetylaniline

Conditions	Yield
With dmap In tetrahydrofuran Reflux; Inert atmosphere;	56%
With dmap In tetrahydrofuran at 20℃; for 50h; Reflux;	56%

3-fluoro-4-hydroxybenzaldehyde (405-05-0) + 1-(4-amino-3,5-dichlorophenyl)-1-ethanone (37148-48-4) → (E)-1-(4-amino-3,5-dichlorophenyl)-3-(3-fluoro-4-hydroxyphenyl)prop-2-en-1-one

Conditions	Yield
With potassium hydroxide In ethanol at 120℃;	49%

1-(4-amino-3,5-dichlorophenyl)-1-ethanone (37148-48-4) → 3',5'-dichloroacetophenone (14401-72-0)

Conditions	Yield
With pyridine; hydrogenchloride; sodium nitrite Behandeln der Reaktionsloesung mit wss. H3PO2 unterhalb 5grad;

phosgene (75-44-5) + 1-(4-amino-3,5-dichlorophenyl)-1-ethanone (37148-48-4) → 2,6-dichloro-4-acetylphenyl isocyanate (60677-17-0)

Conditions	Yield
In toluene
In toluene
In toluene

phosgene (75-44-5) + 1-(4-amino-3,5-dichlorophenyl)-1-ethanone (37148-48-4) + dimethyl amine (124-40-3) → 3,5-Dichlor-4-N,N-dimethylcarbamoylaminoacetophenon (60677-46-5)

Conditions	Yield
(i) toluene, (ii) /BRN= 605257/; Multistep reaction;

phosgene (75-44-5) + 1-(4-amino-3,5-dichlorophenyl)-1-ethanone (37148-48-4) + aniline (62-53-3) → 3,5-dichloro-4-phenylcarbamoylaminoacetophenone (60677-48-7)

Conditions	Yield
(i) toluene, (ii) /BRN= 605631/; Multistep reaction;

phosgene (75-44-5) + 1-(4-amino-3,5-dichlorophenyl)-1-ethanone (37148-48-4) + cyclohexanol (108-93-0) → 3,5-dichloro-4-cyclohexyloxycarbonylaminoacetophenone (60677-50-1)

Conditions	Yield
(i) toluene, (ii) /BRN= 906744/; Multistep reaction;

1-(4-amino-3,5-dichlorophenyl)-1-ethanone (37148-48-4) → 4-carbamoylamino-3,5-dichloroacetophenone (60677-37-4)

Conditions	Yield
Multi-step reaction with 2 steps 1: toluene 2: NH3 / toluene View Scheme

1-(4-amino-3,5-dichlorophenyl)-1-ethanone (37148-48-4) → 4-carbamoylamino-3,5-dichloro-α-bromo-methyl benzyl alcohol (60677-39-6)

Conditions	Yield
Multi-step reaction with 4 steps 1: toluene 2: NH3 / toluene 3: Br2 / acetic acid 4: NaBH4 View Scheme

1-(4-amino-3,5-dichlorophenyl)-1-ethanone (37148-48-4) → 3,5-dichloro-4-methylcarbamoylaminoacetophenone (60677-35-2)

Conditions	Yield
Multi-step reaction with 2 steps 1: toluene 2: toluene View Scheme

1-(4-amino-3,5-dichlorophenyl)-1-ethanone (37148-48-4) → 3,5-dichloro-4-methoxycarbonylaminoacetophenone (60677-86-3)

Conditions	Yield
Multi-step reaction with 2 steps 1: toluene 2: toluene View Scheme

1-(4-amino-3,5-dichlorophenyl)-1-ethanone (37148-48-4) → 4-carbamoylamino-3,5-dichloro-α-bromoacetophenone (60677-38-5)

Conditions	Yield
Multi-step reaction with 3 steps 1: toluene 2: NH3 / toluene 3: Br2 / acetic acid View Scheme

1-(4-amino-3,5-dichlorophenyl)-1-ethanone (37148-48-4) → 3,5-dichloro-4-ethylcarbamoylaminoacetophenone (60677-52-3)

Conditions	Yield
Multi-step reaction with 2 steps 1: toluene View Scheme

1-(4-amino-3,5-dichlorophenyl)-1-ethanone (37148-48-4) → 3,5-dichloro-4-ethoxycarbonylaminoacetophenone (60677-26-1)

Conditions	Yield
Multi-step reaction with 2 steps 1: toluene 2: toluene View Scheme

1-(4-amino-3,5-dichlorophenyl)-1-ethanone (37148-48-4) → 3,5-dichloro-4-methoxycarbonylamino-α-bromomethylbenzyl alcohol (60677-19-2)

Conditions	Yield
Multi-step reaction with 4 steps 1: toluene 2: toluene 3: Br2 / acetic acid 4: NaBH4 View Scheme

1-(4-amino-3,5-dichlorophenyl)-1-ethanone (37148-48-4) → 3,5-dichloro-4-isopropoxycarbonylaminoacetophenone (60677-30-7)

Conditions	Yield
Multi-step reaction with 2 steps 1: toluene View Scheme

1-(4-amino-3,5-dichlorophenyl)-1-ethanone (37148-48-4) → 3,5-dichloro-4-n-propoxycarbonylaminoacetophenone (60677-28-3)

Conditions	Yield
Multi-step reaction with 2 steps 1: toluene View Scheme

Upstream product

• 99-92-3 p-aminobenzophenone 
• 75-36-5 acetyl chloride 
• 608-31-1 2,6-Dichloroaniline 
• 108-24-7 acetic anhydride 
• 7782-50-5 chlorine 
• 64-19-7 acetic acid 

Downstream Products

• 109346-95-4 2-(3,5-dichlorophenyl)acetaldehyde 
• 51-39-8 3,4,5-trichlorobenzoic acid 

Relevant articles and documents

3,5-dichloro-4-bromoisoquinoline derivative, and preparation method and application thereof

The invention specifically relates to a novel compound, i.e., a 3,5-dichloro-4-bromoisoquinoline derivative, and a preparation method and application thereof, belonging to the technical field of pharmaceutical synthesis. 3,5-dichloro-4-bromoisoquinoline and the derivative thereof are obtained by ring closure of 3,5-dichloro-4-bromobenzene haloethylamine through a Friedel-Crafts alkylation reaction. The 3,5-dichloro-4-bromoisoquinoline and the derivative can be used for synthesizing the important intermediate 3,5-dichloro-4-carboxylisoquinoline of Lifitegrast. According to a technical scheme in the invention, low-cost and well-supplied 2,6-dichloroaniline is used as a starting material; and the preparation method comprises a plurality steps of reactions with mild conditions, mature operation and yield of 85% or more, and each step of reaction has passed pilot-scale test, so the feasibility of industrial conversion of the method is very high and overall production cost can be greatly reduced.

Stable isotope labeling Clenproperol compound and synthesis method thereof

The invention relates to a stable isotope labeling Clenproperol compound and a synthesis method thereof. The method comprises the following steps of (1) using stable isotope labeling 2,6-dichloroaniline as raw materials to generate stable isotope labeling 3,5-dichloro-4-aminoacetophenone through Friedel-Crafts acyl reaction; (2) performing bromination on the stable isotope labeling 3,5-dichloro-4-aminoacetophenone to obtain stable isotope labeling 3,5-dichloro-4-amino-alpha-bromo acetophenone; (3) enabling the stable isotope labeling 3,5-dichloro-4-amino-alpha-bromo acetophenone and isopropylamine to take a reaction for obtaining stable isotope labeling 1-(4-amino-3,5-dichlone)-2-isopropyl amino ethyl ketone; (4) enabling the stable isotope labeling 1-(4-amino-3,5-dichlone)-2-isopropyl amino ethyl ketone and a reducing agent to take a reaction to generate stable isotope labeling Clenproperol. The stable isotope labeling Clenproperol compound and the synthesis method have the advantages that the process route is simple; the synthesis is easy; the stable isotope atom utilization rate is high; the obtained product can be easily separated and purified; the chemical purity and the fractional isotopic abudance are 99 percent or higher; the trace detection requirements in the food safety field can be sufficiently met.