反応 #9378

反応方程式

AlCl3

Thionyl chloride

3-chloro-2-methyl-benzoic acid

benzene

→

6-chloro-7-methyl-1-indanone

収率 72.0%

溶媒

dichloroethane

反応条件

後処理

1. 1
   濃縮was concentrated
2. 2
   workup.ADDITIONThe concentrate was diluted with dichloroethane
3. 3
   その他Ethylene was bubbled through the mixture for 4 h.
4. 4
   その他The mixture was quenched with 4 N HCl
5. 5
   その他The resulting layers were separated
6. 6
   抽出the aqueous layer was extracted with Et2O (3×250 mL)
7. 7
   抽出The combined organic extract
8. 8
   洗浄was washed with H2O (3×150 mL), saturated NaHCO3 (3×150 mL), brine (1×150 mL)
9. 9
   乾燥dried over MgSO4
10. 10
    濃縮concentrated
11. 11
    workup.ADDITIONConcentrated sulfuric acid was added
12. 12
    workup.STIRRINGthe mixture was stirred at 85° C. for 1 h
13. 13
    温度After cooling to rt
14. 14
    その他the reaction mixture was quenched with ice-water
15. 15
    抽出The mixture was extracted with Et2O (3×250 mL)
16. 16
    洗浄the combined organic extracts were washed with H2O (3×200 mL), saturated NaHCO3 (3×200 mL), brine (1×100 mL)
17. 17
    乾燥dried over MgSO4
18. 18
    濃縮concentrated

実験手順

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).

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