1(2H)-Phthalazinone → 1-Chlorophthalazine
Reaction equation
[C:1]1(=O)[C:10]2[C:5](=[CH:6][CH:7]=[CH:8][CH:9]=2)[CH:4]=[N:3][NH:2]1.P(Cl)(Cl)([Cl:14])=O>>[Cl:14][C:1]1[C:10]2[C:5](=[CH:6][CH:7]=[CH:8][CH:9]=2)[CH:4]=[N:3][N:2]=1Participants
Conditions
- Temperature
- 80 °C
Procedure
One mole equivalent (250 g) of 1(2H)-phthalazinone and 3.8 mole equivalents (775 g) of phosphorus oxychloride were charged into a 3-L, 3-necked flask fitted with a temperature probe and condenser. The slurry was stirred and heated to 80° C., maintained at that temperature for 30 minutes, and then the heat source was removed. Thin layer chromatographic analysis indicated that conversion to 1-chlorophthalazine was complete. The mixture was allowed to cool to room temperature, and 1.6 L of hexanes was added. The resulting slurry was stirred for several minutes, and the hexane layer was decanted. Addition of hexanes and decantation was repeated two more times. Then 1.6 L of tetrahydrofuran was added; as the solution was stirred, an off-white precipitate formed. The solid was isolated by filtration and washed with 250 mL of cold tetrahydrofuran to afford an 85–100% yield of 1-chlorophthalazin, the desired product, as an off-white powder that could be dried and characterized.
Workup
- customfitted with a temperature probe and condenser
- temperaturemaintained at that temperature for 30 minutes
- customthe heat source was removed
- temperatureto cool to room temperature
- addition1.6 L of hexanes was added
- stirringThe resulting slurry was stirred for several minutes
- customthe hexane layer was decanted
- additionAddition of hexanes and decantation
- additionThen 1.6 L of tetrahydrofuran was added
- stirringas the solution was stirred
- customan off-white precipitate formed
- customThe solid was isolated by filtration
- washwashed with 250 mL of cold tetrahydrofuran
Sources & evidence
- ORD record
- ord-2081bdbf6a434e85aa4a42590e9e75e5
- Source dataset
- uspto-grants-2007_05
- Patent number
- US07220858B2
Reaction notes
Loading…