Hydrochloric Acid → 1-(4-Bromo-5-ethylthiophen-2-yl)ethan-1-one

HRID 552300Notes

Reaction equation

HRID 552300 reaction equation
Cl[Sn](Cl)(Cl)Cl.C(C1SC=CC=1)C.C(Cl)(=O)C.Cl.[OH-].[Na+].[CH2:20]([C:22]1[S:26][C:25]([C:27](=[O:29])[CH3:28])=[CH:24][CH:23]=1)[CH3:21].C([O-])(=O)C.[Na+].[Br:35]Br>CCCCCC.O>[Br:35][C:23]1[CH:24]=[C:25]([C:27](=[O:29])[CH3:28])[S:26][C:22]=1[CH2:20][CH3:21]

Participants

11

Reactant 8

HCID 313Hydrochloric Acid2×HCID 6367Acetyl chlorideHCID 133882-EthylthiopheneHCID 14798Sodium Hydroxide2×HCID 24287Tin tetrachloride2×HCID 24408Bromine3×HCID 517045Sodium Acetate2×HCID 6737161-(5-Ethylthiophen-2-yl)ethan-1-one

Product 1

HCID 671656661-(4-Bromo-5-ethylthiophen-2-yl)ethan-1-oneYield 91.6%

Reagents, catalysts & solvents 2

HCID 962WaterSolventHCID 8058HexaneSolvent2×

Conditions

Temperature
100 °C

Procedure

Over a period of 20 min a solution of SnCl4 (60.9 g, 234 mmol) in hexane (20 mL) is added to a solution of 2-ethylthiophene (25 g, 223 mmol) and acetylchloride (18.4 g, 234 mmol) in hexane (80 mL). Evolving HCl gas is trapped in a NaOH solution. Evolution of HCl stops when about half of the SnCl4 solution is added. The black viscous mixture is warmed to 100° C. for 30 min, before it is cooled again to rt. The mixture is poured into ice/water (600 mL), extracted with diethyl ether (3×) and the combined etheral extracts are washed with NaOH (1M), sat. NaHCO3 solution and brine, dried over MgSO4, filtered and evaporated. The crude 1-(5-ethyl-thiophen-2-yl)-ethanone (35 g) is added to a solution of sodium acetate (16.0 g, 195 mmol) in water (160 mL) and the resulting emulsion is stirred vigorously. To this emulsion bromine (28.5 g, 178 mmol) is added dropwise over a period of 25 min. Upon complete addition of the bromine, sodium acetate (60 g, 731 mmol) is added and the pH of the mixture is adjusted to 9 by adding 10 M aq. NaOH solution. A further portion of bromine (12.4 g, 78 mmol) is added and stirring is continued for 15 min. The reaction is quenched by adding 1 M aq. Na2S2O3 solution and the mixture is extracted three times with diethyl ether. The organic extracts are washed with 1 N aq. NaOH, 2 N aq. HCl and brine, dried over MgSO4, filtered and evaporated to give 1-(4-bromo-5-ethyl-thiophen-2-yl)-ethanone (38 g) as a brown oil; LC-MS: tR=0.97 min, [M+1+CH3CN]+=274.20.

Workup

  1. additionis added
  2. temperatureis cooled again to rt
  3. extractionextracted with diethyl ether (3×)
  4. washthe combined etheral extracts are washed with NaOH (1M), sat. NaHCO3 solution and brine
  5. dry with materialdried over MgSO4
  6. filtrationfiltered
  7. customevaporated
  8. additionis added
  9. stirringstirring
  10. customThe reaction is quenched
  11. additionby adding 1 M aq. Na2S2O3 solution
  12. extractionthe mixture is extracted three times with diethyl ether
  13. washThe organic extracts are washed with 1 N aq. NaOH, 2 N aq. HCl and brine
  14. dry with materialdried over MgSO4
  15. filtrationfiltered
  16. customevaporated

Sources & evidence

ORD record
ord-298db4923cd84a3d9282dc1d2ff40c2d
Source dataset
uspto-grants-2011_05
Patent number
US07951794B2

Reaction notes

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