O-Phenylenediamine → 4-Bromobenzene-1,2-diamine

Temperature

65 °C

In 64 ml of acetic acid, 8.0 g of o-phenylene diamine was dissolved, to which 15.3 ml of acetic anhydride was added drop-wise under cooling. Then the mixture was heated for 30 minutes in an oil bath at 65° C. After cooling to room temperature, a solution of bromine (4.6 ml bromine in 16 ml acetic acid) was quickly added, followed by heating for 40 minutes in an oil bath at 50° C. About 10 minutes after adding bromine, crystals started to precipitate. The reaction mixture was cooled to room temperature, and poured into 300 ml ice water containing 4.0 g sodium hydrogen sulfite. The resulting white precipitates were collected by filtration, washed with water and dried under reduced pressure (14.0 g; yield 70%). Into a 150 ml solution of water: methanol (2:1) containing 33.6 g potassium hydroxide, the white solid was dissolved and heated with stirring for 12 hours in an oil bath at 75-80° C. After cooling the reaction mixture, and adding 400 ml water thereto, the mixture was extracted with 100 ml ether five times. The ether phase was washed with 200 ml of saturated salt water two times, and dried with anhydrous sodium sulfate. The solvent was evaporated under reduced pressure. The residue was purified by silica gel column chromatography (hexane ethyl acetate=3:1 to 1:1) so as to obtain compound 13 as colorless crystals (5.5 g, total yield 40%).

1. additionwas added drop-wise
2. temperatureunder cooling
3. temperatureAfter cooling to room temperature
4. temperatureby heating for 40 minutes in an oil bath at 50° C
5. customto precipitate
6. temperatureThe reaction mixture was cooled to room temperature
7. additionpoured into 300 ml ice water containing 4.0 g sodium hydrogen sulfite
8. customThe resulting white precipitates
9. filtrationwere collected by filtration
10. washwashed with water
11. customdried under reduced pressure (14.0 g; yield 70%)
12. additionInto a 150 ml solution of water: methanol (2:1) containing 33.6 g potassium hydroxide
13. dissolutionthe white solid was dissolved
14. temperatureheated
15. temperatureAfter cooling the reaction mixture
16. additionadding 400 ml water
17. extractionthe mixture was extracted with 100 ml ether five times
18. washThe ether phase was washed with 200 ml of saturated salt water two times
19. dry with materialdried with anhydrous sodium sulfate
20. customThe solvent was evaporated under reduced pressure
21. customThe residue was purified by silica gel column chromatography (hexane ethyl acetate=3:1 to 1:1) so as

ORD record

ord-b4ec3ce543164a6db6a826915d15433e

Source dataset

uspto-grants-2002_02

DOI

10.6084/m9.figshare.5104873.v1

Patent number

US06350863B1