2-Chlorocyclohexanone → 2-Propyl-4-(4,5,6,7-tetrahydro-benzothiazol-2-yl)-phenol

HRID 734408Notes

Reaction equation

HRID 734408 reaction equation
[OH:1][C:2]1[CH:7]=[CH:6][C:5]([C:8](=[S:10])[NH2:9])=[CH:4][C:3]=1[CH2:11][CH2:12][CH3:13].Cl[CH:15]1[CH2:20][CH2:19][CH2:18][CH2:17][C:16]1=O>C1(C)C=CC=CC=1.O.C1(C)C=CC(S(O)(=O)=O)=CC=1>[CH2:11]([C:3]1[CH:4]=[C:5]([C:8]2[S:10][C:15]3[CH2:20][CH2:19][CH2:18][CH2:17][C:16]=3[N:9]=2)[CH:6]=[CH:7][C:2]=1[OH:1])[CH2:12][CH3:13]

Participants

5

Reactant 2

HCID 132032-ChlorocyclohexanoneHCID 1359745034-Hydroxy-3-propylbenzenecarbothioamide

Product 1

HCID 1359745042-Propyl-4-(4,5,6,7-tetrahydro-benzothiazol-2-yl)-phenolYield 98%

Reagents, catalysts & solvents 2

HCID 521998p-Toluenesulfonic acid monohydrateCatalystHCID 1140TolueneSolvent

Procedure

A suspension of 4-hydroxy-3-propyl-thiobenzamide (5 g, 0.026 mol) (Example 34), 2-chlorocyclohexanone (4.07 g, 0.031 mol), and p-toluenesulfonic acid monohydrate (0.244 g, 1.28 mmol) in anhydrous toluene (100 mL) was heated to reflux in a Dean-Stark apparatus under argon for 12 h. At about 90° C., the mixture became a red orange oil and after 4 h of refluxing, precipitation was observed. The reaction mixture was cooled and diluted with ethyl acetate (50 mL). The organic layer was washed successively with saturated sodium bicarbonate (2×50 mL), water (2×50 mL), brine, dried over sodium sulfate, and concentrated to give the desired product as a tan solid (6.89 g, 98%). LC/MS m/z 274.3 (M+H)+, RT 2.99 min. 1H NMR (400 MHz, DMSO-d6) δ 9.75 (s, 1H), 7.53-7.44 (m, 2H), 6.81 (d, 1H), 2.72-2.68 (m, 4H), 2.54-2.49 (m, 2H), 1.78 (b, 4H), 1.58-1.53 (m, 2H), 0.90 (t, 3H).

Workup

  1. temperaturewas heated
  2. temperatureto reflux in a Dean-Stark apparatus under argon for 12 h
  3. customAt about 90° C.
  4. temperatureafter 4 h of refluxing
  5. customprecipitation
  6. temperatureThe reaction mixture was cooled
  7. additiondiluted with ethyl acetate (50 mL)
  8. washThe organic layer was washed successively with saturated sodium bicarbonate (2×50 mL), water (2×50 mL), brine
  9. dry with materialdried over sodium sulfate
  10. concentrationconcentrated

Sources & evidence

ORD record
ord-68813b8856aa4b00b3b78e359ff2f290
Source dataset
uspto-grants-2009_09
Patent number
US07592361B2

Reaction notes

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