Methanol → 1,2-Diamino-4,5-difluorobenzene
Reaction equation
[F:1][C:2]1[C:8]([F:9])=[CH:7][C:5]([NH2:6])=[C:4]([N+:10]([O-])=O)[CH:3]=1.[O-]S(S([O-])=O)=O.[Na+].[Na+].C([O-])(O)=O.[Na+].CO>C1COCC1.O.C(OCC)(=O)C>[F:1][C:2]1[CH:3]=[C:4]([NH2:10])[C:5]([NH2:6])=[CH:7][C:8]=1[F:9]Participants
Procedure
A solution of 4,5-difluoro-2-nitroaniline (6)(1.0 g) in 30 mL of THF was treated with a solution comprised of 6 g of Na2S2O4 and 3 g NaHCO3 in 30 mL of water. Methanol (10 mL) was added after the addition of the aqueous solution so that the mixture remained homogeneous. The mixture was stirred for two hours and then diluted with 100 mL of ethyl acetate and 100 mL of water. The organic layer was separated and the aqueous layer was extracted again with 100 mL of methylene chloride. The combined organic layers were dried over sodium sulfate, filtered, and concentrated to provide the crude intermediate 4,5-difluorobenzene-1,2-diamine (7). The intermediate was refluxed with (ethoxymethylene)malononitrile (1.1 g) in 25 mL of isopropyl alcohol for 16 h. The mixture was concentrated in vacuo and the resulting crude product was suspended in water and filtered. The precipitate was washed with water and air-dried to provide 380 mg of 5,6-difluoro-1H-benzo[d]imidazole (8).
Workup
- additionafter the addition of the aqueous solution so that the mixture
- customThe organic layer was separated
- extractionthe aqueous layer was extracted again with 100 mL of methylene chloride
- dry with materialThe combined organic layers were dried over sodium sulfate
- filtrationfiltered
- concentrationconcentrated
Sources & evidence
- ORD record
- ord-e560448e351743bb90dc39b7f5c74b14
- Source dataset
- uspto-grants-2011_02
- Patent number
- US07884109B2
Reaction notes
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