2-Bromo-3'-chloropropiophenone Chemical Properties

Boiling point:

148-148.5 °C(Press: 9 Torr)

Density 

1.532

refractive index 

1.5770

storage temp. 

Refrigerator, Under Inert Atmosphere

solubility 

Soluble in acetonitrile, chloroform, dichloromethane and ethyl acetate.

form 

Liquid

color 

Colorless to pale yellow

Major Application

pharmaceutical

InChI

InChI=1S/C9H8BrClO/c1-6(10)9(12)7-3-2-4-8(11)5-7/h2-6H,1H3

InChIKey

OFNMQTRHMBQQEA-UHFFFAOYSA-N

SMILES

C(C1=CC=CC(Cl)=C1)(=O)C(Br)C

CAS DataBase Reference

34911-51-8(CAS DataBase Reference)

Safety Information

WGK Germany 

WGK 3

HazardClass 

IRRITANT

HS Code 

2914790000

Storage Class

12 - Non Combustible Liquids

Hazard Classifications

Skin Irrit. 2
Skin Sens. 1B

2-Bromo-3'-chloropropiophenone Usage And Synthesis

Health Hazard

2-Bromo-3'-chloropropiophenone is irritating to the eyes, respiratory system, and skin.

Uses

2-Bromo-3'-chloropropiophenone is used as an important intermediate for raw material and intermediate used in organic synthesis agrochemical, pharmaceutical and dyestuff field.

Definition

2-Bromo-3'-chloropropiophenone (BCP), a yellow oil, is an intermediate used in the synthesis of bupropion and is also found as an impurity of bupropion hydrochloride. Bupropion is a second-generation antidepressant that was originally approved by the United States Food and Drug Administration (FDA) in 1985. It is a norepinephrine and dopamine transporter inhibitor and an antagonist at neuronal nicotinic acetylcholine receptors. Bupropion is also approved for smoking cessation[1].

Safety

The current United States Pharmacopeia (USP) specification is for no more than 0.1% BCP in the bupropion hydrochloride monograph. The Material Safety Data Sheet from a manufacturer indicates that BCP is irritating to the eyes, respiratory system, and skin. 2-Bromo-3'-chloropropiophenone was mutagenic with S9 metabolic activation, increasing the mutant frequencies in a concentration-dependent manner, up to 22- and 145-fold induction over the controls in Salmonella strains TA100 and TA1535, respectively. BCP was also positive in the in vitro micronucleus assay, resulting in up to 3.3- and 5.1-fold increase of micronucleus frequency for treatments in the absence and presence of S9, respectively; and 9.9- and 7.4-fold increase of aneuploidies without and with S9, respectively. The addition of N-acetyl-l-cysteine, an antioxidant, reduced the genotoxicity of BCP in both assays. Further studies showed that BCP treatment resulted in induction of reactive oxygen species (ROS) in the TK6 cells. The results suggest that BCP is mutagenic, clastogenic, and aneugenic, and that these activities are mediated via generation of reactive metabolites[1].

Synthesis

The reactor equipped with reflux condenser tube and dropping funnel was added with magnesium powder 48.0g (2.0mol), tetrahydrofuran (THF) solution 400mL, and ethidium bromide 218.0g (2.0mol) was added slowly from the dropping funnel, the temperature of the reaction solution was controlled at 50-60??C, so that the solution was kept in a slightly boiled state all the time, and the solution was heated and refluxed for 1.0-1.5h after completion of the dropwise addition to ensure that magnesium The reaction was complete to obtain Grignard reagent. Under stirring, m-chlorobenzonitrile 275.2g (2.0 mol) was slowly added dropwise to the Grignard reagent prepared above, and after the dropwise addition was completed, the reaction was carried out for 3.0-4.0h to produce the intermediate, the reaction was completed without separation, and the hydrolysis of the intermediate was carried out by slowly adding dropwise 3 mol/L hydrochloric acid, the inorganic phase was separated out, and the organic phase was frequently distilled at atmospheric pressure to remove THF, and then distilled under reduced pressure to obtain 3-chloropropiophenone.

In a four-necked reaction flask equipped with an electric stirrer, a reflux condenser and a thermometer, 33.7 g of 3-chloropropiophenone, 16.8 g of liquid bromine, 50.0 g of solvent, and 0.75 g of catalyst were added sequentially, a reflux condenser tube and a thermometer were fitted, and the stirrer was turned on, and the timing was started when the temperature was controlled to be 15 ??, and the reaction time was 2.5 h. After the reaction was finished, the solvent was distilled out, the remaining The solution was washed with water, added the refined solvent for dissolution, then cooled down, crystallized, and filtered to get the refined 2-bromo-3'-chloropropiophenone product, the yield of 2-bromo-3'-chloropropiophenone reached 97.13%, and the melting point was 76-77 ??.

References

[1] Meng, Fanxue , et al. "Genotoxicity of 2-bromo-3′-chloropropiophenone." Toxicology & Applied Pharmacology 270.2(2013):158-163.

2-Bromo-3'-chloropropiophenone(34911-51-8)Related Product Information

• Propiophenone
• Chlorphenamine maleate
• BROMOACETONE
• Calcium pyruvate
• 3'-Chloropropiophenone
• Pyruvic acid
• Acetylacetone
• 3-Chloropropiophenone
• Propane
• 1-(3-Chlorophenyl)-1,2-propanedione
• Bupropion Impurity 1
• 2-(tert-Butylamino)-3',5'-dichloropropiophenone Hydrochloride
• Bupropion IMpurity ((3R,5RS,6RS)-6-(3-Chlorophenyl)-6-Hydroxy-5-Methyl-3-ThioMorpholine Carboxylic Acid)
• (3S,5S,6S)-Bupropion Impurity
• 3-Chlorobenzoic acid
• Bupropion Impurity 6
• Bupropion Impurity 10
• (3S,5R,6R)-Bupropion Impurity