Hydrochloric Acid → Esacure KIP 160
Reaction equation
[OH-:1].[Na+].[OH2:3].Cl[C:5]([CH3:28])([CH3:27])[C:6]([C:8]1[CH:13]=[CH:12][C:11]([O:14][C:15]2[CH:20]=[CH:19][C:18]([C:21](=[O:26])[C:22](Cl)([CH3:24])[CH3:23])=[CH:17][CH:16]=2)=[CH:10][CH:9]=1)=[O:7].Cl>CO.C1(C)C=CC=CC=1>[OH:1][C:5]([CH3:28])([CH3:27])[C:6]([C:8]1[CH:13]=[CH:12][C:11]([O:14][C:15]2[CH:20]=[CH:19][C:18]([C:21](=[O:26])[C:22]([OH:3])([CH3:24])[CH3:23])=[CH:17][CH:16]=2)=[CH:10][CH:9]=1)=[O:7]Participants
Conditions
- Temperature
- 50 °C
Procedure
208.0 g (1.56 mol) of 30% NaOH and 208 ml of deionised water and 205.7 g of methanol are combined. The temperature rises to approximately 36° C. The mixture is then heated to 50° C. using an oil bath. While stirring well, 249.5 g (0.65 mol tq) of the crude product bis[4-(2-chloro-2-methyl-propionyl)-phenyl] ether from the chlorination reaction, dissolved while warm with 230 ml of toluene and with 102.8 g of methanol, are then added dropwise in the course of approximately one hour. The internal temperature slowly rises to 55-60° C. The alkaline mixture (approximately pH 12) is then stirred for approximately from two to three hours at 55-60° C. The conversion is checked using a GC sample and using a 1H-NMR sample. The mixture is then cooled to 50° C. and adjusted to a pH of approximately 1-2 by the dropwise addition of approximately 68 g of 16% hydrochloric acid. The colour of the emulsion changes from a strong yellow to yellow. The mixture is subsequently stirred for approximately 30-60 minutes. When the hydrolysis is complete, the reaction mixture is rendered neutral with a small amount of dilute sodium hydroxide solution. The two phases are separated at approximately 50° C. in a separating funnel. 200 ml of water are added to the organic phase, which is stirred and separated off again. The warm organic phase is partially concentrated (approximately 100 ml) using a rotary evaporator in order to remove residual methanol and water. It is then diluted with 660 ml of warm toluene. The solution is seeded at 45° C. and is cooled later, after crystallisation. The thick suspension is filtered and washed with toluene. The white crystals, bis[4-(2-hydroxy-2-methyl-propionyl)-phenyl] ether, are dried in vacuo. 190.5 g of white crystals, which melt at 97.2-97.6° C., are obtained. In the 1H-NMR spectrum, the product 1,2-bis[4-(2-hydroxy-2-methyl-propionyl)-phenyl] ether is isomerically pure.
Workup
- customrises to approximately 36° C
- dissolutiondissolved
- additionare then added dropwise in the course of approximately one hour
- customslowly rises to 55-60° C
- stirringThe alkaline mixture (approximately pH 12) is then stirred for approximately from two to three hours at 55-60° C
- temperatureThe mixture is then cooled to 50° C.
- stirringThe mixture is subsequently stirred for approximately 30-60 minutes
- customThe two phases are separated at approximately 50° C. in a separating funnel
- addition200 ml of water are added to the organic phase, which
- stirringis stirred
- customseparated off again
- concentrationThe warm organic phase is partially concentrated (approximately 100 ml)
- customa rotary evaporator in order
- customto remove residual methanol and water
- additionIt is then diluted with 660 ml of warm toluene
- customis seeded at 45° C.
- temperatureis cooled later
- customafter crystallisation
- filtrationThe thick suspension is filtered
- washwashed with toluene
- dry with materialThe white crystals, bis[4-(2-hydroxy-2-methyl-propionyl)-phenyl] ether, are dried in vacuo
- custommelt at 97.2-97.6° C.
- customare obtained
Sources & evidence
- ORD record
- ord-1fc3653425db40a8aa934dda915b4662
- Source dataset
- uspto-grants-2010_05
- Patent number
- US07723397B2
Reaction notes
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