4-Bromo-3,5-difluoroaniline

4-Bromo-3,5-difluoroaniline Property

Melting point:

99-101°C

Boiling point:

223.7±35.0 °C(Predicted)

Density 

1.788±0.06 g/cm3(Predicted)

storage temp. 

Sealed in dry,Room Temperature

form 

powder to crystal

pka

1.86±0.10(Predicted)

color 

White to Light gray to Light orange

InChI

InChI=1S/C6H4BrF2N/c7-6-4(8)1-3(10)2-5(6)9/h1-2H,10H2

InChIKey

DKKUSFDAHRASGO-UHFFFAOYSA-N

SMILES

C1(N)=CC(F)=C(Br)C(F)=C1

CAS DataBase Reference

203302-95-8(CAS DataBase Reference)

Safety

Hazard Codes 

Xi

RIDADR 

UN2811

Hazard Note 

Irritant

HazardClass 

6.1

PackingGroup 

III

HS Code 

2921420090

Hazard and Precautionary Statements (GHS)

Symbol(GHS)

Signal word

Warning

Hazard statements

H302Harmful if swallowed

H312Harmful in contact with skin

H315Causes skin irritation

H319Causes serious eye irritation

H331Toxic if inhaled

H335May cause respiratory irritation

Precautionary statements

P261Avoid breathing dust/fume/gas/mist/vapours/spray.

P264Wash hands thoroughly after handling.

P264Wash skin thouroughly after handling.

P270Do not eat, drink or smoke when using this product.

P271Use only outdoors or in a well-ventilated area.

P280Wear protective gloves/protective clothing/eye protection/face protection.

P304+P340IF INHALED: Remove victim to fresh air and Keep at rest in a position comfortable for breathing.

P305+P351+P338IF IN EYES: Rinse cautiously with water for several minutes. Remove contact lenses, if present and easy to do. Continuerinsing.

P405Store locked up.

P501Dispose of contents/container to..…

4-Bromo-3,5-difluoroaniline Chemical Properties,Usage,Production

Chemical Properties

Pale yellow powder

Uses

4-Bromo-3,5-difluoroaniline is a useful reactant in organic synthesis.

Synthesis

General procedure for the synthesis of 3,5-difluoro-4-bromoaniline from 3,5-difluoroaniline: 1. 3,5-difluoroaniline (10.0 g, 77.5 mmol) was dissolved in DMF (100 mL), then NBS (13.9 g, 78.0 mmol) was added in batches at room temperature. The reaction mixture was stirred overnight at room temperature and then diluted with Et2O and washed with brine. The organic phase was separated, dried over Na2SO4 and concentrated to give an oil. Purification by column chromatography afforded 4-bromo-3,5-difluoroaniline (i) (12.9 g, 80.2%). 2. A mixture of 4-bromo-3,5-difluoroaniline(i) (6.0 g, 28.8 mmol), ferrous sulfate (1.82 g), glycerol (8.6 mL), nitrobenzene (1.79 mL) and concentrated sulfuric acid (5.0 mL) was gently heated. After the first vigorous reaction, the mixture was boiled for 5 hours. Nitrobenzene was removed by vacuum distillation and the aqueous solution was acidified with glacial acetic acid to isolate a dark brown precipitate. Purification by rapid chromatography (silica gel, petroleum ether/ethyl acetate = 12/1) gave 6-bromo-5,7-difluoroquinoline (ii) as a white solid (3.5 g, 49.8%). 3. To a solution of 6-bromo-5,7-difluoroquinoline(ii) (250 g, 1.02 mol) in anhydrous THF (2200 mL) was added dropwise a hexane solution of n-BuLi (2.5 M, 408 mL, 1.02 mol) at -78 °C. The resulting mixture was stirred at -78 °C for another 30 min. Then, anhydrous THF (200 mL) solution of DMF (79 mL, 1.02 mol) was added while the temperature was kept below -70 °C and the mixture was stirred at the same temperature for 30 min. The reaction mixture was slowly warmed to room temperature and diluted with saturated aqueous NH4Cl solution (1000 mL) and water (800 mL). The mixture was extracted twice with ethyl acetate and the combined organic layers were washed with water and brine, dried over anhydrous sodium sulfate and concentrated to give a brown oil. Purification by silica gel column chromatography, eluting with petroleum ether and ethyl acetate (10:1), afforded 5,7-difluoroquinoline-6-carbaldehyde (Intermediate H) as a yellow solid (100 g, 50%). 1H NMR (DMSO, 300 MHz) δ (ppm): 10.38 (s, 1H), 9.10~9.12 (m, 1H), 8.62~8.66 (m, 1H), 7.68~7.78 (m, 2H).

References

[1] Patent: WO2011/18454, 2011, A1. Location in patent: Page/Page column 59-60
[2] Patent: WO2004/48314, 2004, A1. Location in patent: Page 31-32
[3] Patent: US2017/137385, 2017, A1. Location in patent: Paragraph 0243; 0244; 0245; 0246