Ammonium Chloride → 4-Chloro-5-iodobenzene-1,2-diamine

Temperature

60 °C

To a mixture of 5-chloro-4-iodo-2-nitroaniline 1-5 (31.7 g, 106 mmol) and iron powder (59.0 g, 1060 mmol) in 880 mL ethanol was added a solution of NH4Cl (28 g, 530 mmol) in 240 mL of water. The resulting mixture was mechanically stirred at 60° C. for 40 h. After cooling to rt the mixture was filtered and the filtrate reduced to about 500 mL by rotary evaporation. This filtrate was diluted with 1 L of EtOAc and 1 L of water, and shaken. The organic layer separated, washed with brine, dried (MgSO4) and evaporated to provide crude product. The crude product was dissolved in 80 mL of EtOAc, diluted with 80 mL of hexanes and injected onto a 330 g column of SiO2, which was pre-eluted with 33% EtOAc in hexanes. The column was subjected to MPLC eluting at 100 mL/min with 33% EtOAc in hexanes (15 min) and then 50% EtOAc (20 min) to provide 5-chloro-4-iodo-1,2-phenylenediamine 1-6. Impure fractions of residue were resubjected to MPLC on a 330 g column of SiO2 by the same method to provide additional 5-chloro-4-iodo-1,2-phenylenediamine 1-6 as an amorphous solid. 1H NMR (500 MHz, DMSO-d6): δ 4.77 (s, 2H), 4.91 (s, 2H), 6.66 (s, 1H), 6.93 (s, 1H); LC-MS: calculated for C6H6ClIN2 267.9, observed Dole 269.0 (M+H)+.

1. temperatureAfter cooling to rt the mixture
2. filtrationwas filtered
3. customthe filtrate reduced to about 500 mL by rotary evaporation
4. additionThis filtrate was diluted with 1 L of EtOAc and 1 L of water
5. stirringshaken
6. customThe organic layer separated
7. washwashed with brine
8. dry with materialdried (MgSO4)
9. customevaporated
10. customto provide crude product
11. washwas pre-eluted with 33% EtOAc in hexanes
12. washeluting at 100 mL/min with 33% EtOAc in hexanes (15 min)

ORD record

ord-fa7ac1660a374924bdeb16acda7ad0fb

Source dataset

uspto-grants-2013_04

DOI

10.6084/m9.figshare.5104873.v1

Patent number

US08410284B2