Reaction #9378

Reaction equation

AlCl3

Thionyl chloride

3-chloro-2-methyl-benzoic acid

benzene

→

6-chloro-7-methyl-1-indanone

Yield 72.0%

Solvents

dichloroethane

Conditions

Workup

1. 1
   Concentrationwas concentrated
2. 2
   workup.ADDITIONThe concentrate was diluted with dichloroethane
3. 3
   OtherEthylene was bubbled through the mixture for 4 h.
4. 4
   OtherThe mixture was quenched with 4 N HCl
5. 5
   OtherThe resulting layers were separated
6. 6
   Extractionthe aqueous layer was extracted with Et2O (3×250 mL)
7. 7
   ExtractionThe combined organic extract
8. 8
   Washwas washed with H2O (3×150 mL), saturated NaHCO3 (3×150 mL), brine (1×150 mL)
9. 9
   Dryingdried over MgSO4
10. 10
    Concentrationconcentrated
11. 11
    workup.ADDITIONConcentrated sulfuric acid was added
12. 12
    workup.STIRRINGthe mixture was stirred at 85° C. for 1 h
13. 13
    TemperatureAfter cooling to rt
14. 14
    Otherthe reaction mixture was quenched with ice-water
15. 15
    ExtractionThe mixture was extracted with Et2O (3×250 mL)
16. 16
    Washthe combined organic extracts were washed with H2O (3×200 mL), saturated NaHCO3 (3×200 mL), brine (1×100 mL)
17. 17
    Dryingdried over MgSO4
18. 18
    Concentrationconcentrated

Procedure

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).

Source