Reaktion #9378

Reaktionsgleichung

AlCl3

Thionyl chloride

3-chloro-2-methyl-benzoic acid

benzene

→

6-chloro-7-methyl-1-indanone

Ausbeute 72.0%

Lösungsmittel

dichloroethane

Reaktionsbedingungen

Aufarbeitung

1. 1
   Einengenwas concentrated
2. 2
   workup.ADDITIONThe concentrate was diluted with dichloroethane
3. 3
   SonstigeEthylene was bubbled through the mixture for 4 h.
4. 4
   SonstigeThe mixture was quenched with 4 N HCl
5. 5
   SonstigeThe resulting layers were separated
6. 6
   Extraktionthe aqueous layer was extracted with Et2O (3×250 mL)
7. 7
   ExtraktionThe combined organic extract
8. 8
   Waschenwas washed with H2O (3×150 mL), saturated NaHCO3 (3×150 mL), brine (1×150 mL)
9. 9
   Trocknendried over MgSO4
10. 10
    Einengenconcentrated
11. 11
    workup.ADDITIONConcentrated sulfuric acid was added
12. 12
    workup.STIRRINGthe mixture was stirred at 85° C. for 1 h
13. 13
    TemperaturAfter cooling to rt
14. 14
    Sonstigethe reaction mixture was quenched with ice-water
15. 15
    ExtraktionThe mixture was extracted with Et2O (3×250 mL)
16. 16
    Waschenthe combined organic extracts were washed with H2O (3×200 mL), saturated NaHCO3 (3×200 mL), brine (1×100 mL)
17. 17
    Trocknendried over MgSO4
18. 18
    Einengenconcentrated

Vorschrift

Thionyl chloride (10.0 mL, 1.5 eq) and 3-chloro-2-methyl-benzoic acid (commercially available from Aldrich) (15.6 g, 91.4 mmol) in benzene was refluxed until no more gas evolution was observed. After cooling to rt the mixture was concentrated. The concentrate was diluted with dichloroethane and added to a solution of AlCl3 (12.2 g, 1.0 eq) in dichloroethane at 10–20° C. Ethylene was bubbled through the mixture for 4 h. and the mixture was stirred overnight. The mixture was quenched with 4 N HCl. The resulting layers were separated and the aqueous layer was extracted with Et2O (3×250 mL). The combined organic extract was washed with H2O (3×150 mL), saturated NaHCO3 (3×150 mL), brine (1×150 mL), dried over MgSO4 and concentrated. Concentrated sulfuric acid was added and the mixture was stirred at 85° C. for 1 h. After cooling to rt, the reaction mixture was quenched with ice-water. The mixture was extracted with Et2O (3×250 mL) and the combined organic extracts were washed with H2O (3×200 mL), saturated NaHCO3 (3×200 mL), brine (1×100 mL), dried over MgSO4 and concentrated. Pure 6-chloro-7-methyl-1-indanone (11.9 g, 72%) was obtained after column chromatography using 20% EtOAc:hexane as eluant. Use of 6-chloro-7-methyl-1-indanone in Method NINETEEN produced 4-(5-chloro-4-methyl-indan-2-yl)-1,3-dihydro-imidazole-2-thione (Compound 152).

Quelle