Toluene → 5,6-Dihydro-4H-thieno[2,3-b]thiopyran-4-one

HRID 2248435Notes

Reaction equation

HRID 2248435 reaction equation
C1(C)C=CC=CC=1.[S:8]1[CH:12]=[CH:11][CH:10]=[C:9]1[S:13][CH2:14][CH2:15][C:16]([OH:18])=O.FC(F)(F)C(OC(=O)C(F)(F)F)=O.[OH-].[Na+]>C(Cl)(Cl)Cl.C(OCC)(=O)C.CCCCCC.O>[S:8]1[C:9]2[S:13][CH2:14][CH2:15][C:16](=[O:18])[C:10]=2[CH:11]=[CH:12]1

Participants

9

Reactant 4

HCID 1140TolueneHCID 9845Trifluoroacetic anhydrideHCID 14798Sodium HydroxideHCID 139116455-(2-Carboxyethylthio)thiophene

Product 1

HCID 110302745,6-Dihydro-4H-thieno[2,3-b]thiopyran-4-one

Reagents, catalysts & solvents 4

HCID 962WaterSolventHCID 6212ChloroformSolventHCID 8058HexaneSolventHCID 8857Ethyl AcetateSolvent

Procedure

In a 2-L three-neck round-bottom flask fitted with an overhead mechanical stirrer, thermometer, addition funnel, reflux condenser, and nitrogen bubbler vented through an acid-vapor scrubber was placed the toluene solution of 7 (130.7 g, 695 mmol). The reaction mixture was brought to an initial temperature of 20° C. and trifluoroacetic anhydride (161 g, 765 mmol) was added over 5 minutes to the stirred solution of 7. The reaction was then heated to 35°-38° C. and stirred for about 1.5 hours. The reaction was then slowly added to water (500 mL) maintaining the temperature at <25° C. A pH probe was placed in the vessel and the mixture was titrated to pH 7.0 with 50% sodium hydroxide (123 g, 1.53 mole). The layers were separated and the aqueous phase was extracted once with toluene (200 mL). The combined organic extracts were then concentrated under vacuum (43 mbar) to a volume of 200 mL and then diluted to 1.2 L with ethyl acetate for the next step (oxidation). A small sample was chromatographed to obtain the following data: Rf =0.29 (85:15 hexane:ethyl acetate). m.p. 61°-62° C. IR (CHCl3): 3120 w, 3090 w, 3010 m, 2930 w, 1660 s (C=O), 1500 m, 1390 s, 1315 w, 1280 w, 1265 m, 1190 w, 1035 w, 890 w. 1H NMR: δ7.42 (d, J=5.4, H2); 6.98 (d, J=5.4, H3); 3.33 (m, C5H2); 2.82 (m, C6H2). 13C NMR: δ188.9 (C4), 150.9, 135.0 (C3a, C7a), 126.1, 121.8 (C2, C3), 38.1 (C6), 30.0 (C5).

Workup

  1. customIn a 2-L three-neck round-bottom flask fitted with an overhead mechanical stirrer
  2. additionthermometer, addition funnel
  3. temperaturereflux condenser
  4. additionwas added over 5 minutes to the stirred solution of 7
  5. temperatureThe reaction was then heated to 35°-38° C.
  6. temperaturemaintaining the temperature at <25° C
  7. customThe layers were separated
  8. extractionthe aqueous phase was extracted once with toluene (200 mL)
  9. concentrationThe combined organic extracts were then concentrated under vacuum (43 mbar) to a volume of 200 mL
  10. additiondiluted to 1.2 L with ethyl acetate for the next step (oxidation)
  11. customA small sample was chromatographed
  12. customto obtain the following data
  13. custom3120 w, 3090 w, 3010 m, 2930 w, 1660 s (C=O), 1500 m, 1390 s, 1315 w, 1280 w, 1265 m, 1190 w, 1035 w, 890 w

Sources & evidence

ORD record
ord-782d55e00aa542249feda3cfe36f7fd2
Source dataset
uspto-grants-1991_08
Patent number
US05039802

Reaction notes

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