Sodium hydride → Tioconazole
Reaction equation
[H-].[Na+:2].[Cl:3][C:4]1[CH:9]=[C:8]([Cl:10])[CH:7]=[CH:6][C:5]=1[CH:11]([OH:18])[CH2:12][N:13]1[CH:17]=[CH:16][N:15]=[CH:14]1.[Cl:19][C:20]1[S:21][CH:22]=[CH:23][C:24]=1[CH2:25][Br:26]>C1CCCCC1.C(O)(C)C>[CH:7]1[C:8]([Cl:10])=[CH:9][C:4]([Cl:3])=[C:5]([CH:11]([O:18][CH2:25][C:24]2[CH:23]=[CH:22][S:21][C:20]=2[Cl:19])[CH2:12][N:13]2[CH:14]=[N:15][CH:16]=[CH:17]2)[CH:6]=1.[Br-:26].[Na+:2]Participants
Procedure
A second reactor was charged with NaH (about 16.0 g) and cyclohexane (about 193.8 g) and stirred. Isopropanol (about 157.7 g) was charged to an addition funnel and slowly added to the reactor as H2 evolved. The mixture was heated to reflux for about 1 hour. 1-(2,4-dichlorophenyl)-2-(1-imidazolyl)ethanol (about 102.8 g) and isopropanol (about 286.6 g) were charged to an Erlynmeyer and heated with stirring until all solids dissolved. The hot solution was then transferred to the refluxing reactor and the resulting solution continued to reflux for about 2.5 hours. After cooling to room temperature, the cyclohexane solution of 2-chloro-3-bromomethylthiophene was added to the reactor containing the imidazolyl mixture and the contents were stirred at room temperature overnight yielding a solution of crude tioconazole and solid sodium bromide. Water (about 37.1 g) was charged to the reactor. The crude reaction yield was ca. 44.6% based on 2-chloro-3-methylthiophene.
Workup
- additionslowly added to the reactor as H2
- temperatureThe mixture was heated
- temperatureto reflux for about 1 hour
- temperatureheated
- stirringwith stirring until all solids
- dissolutiondissolved
- temperatureto reflux for about 2.5 hours
- stirringthe contents were stirred at room temperature overnight
Sources & evidence
- ORD record
- ord-c1e6d2912d854fdca77baf74a792280e
- Source dataset
- uspto-grants-2003_04
- Patent number
- US06545163B1
Reaction notes
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