4-(4-Bromophenyl)butanethioamide → 5-(4-Methylthiophenyl)thiazole

HRID 1378582Notes

Reaction equation

HRID 1378582 reaction equation
FC1C=CC([C:8](=O)[CH:9]([C:11]2[CH:16]=[CH:15][C:14]([S:17][CH3:18])=[CH:13][CH:12]=2)Br)=CC=1.BrC1C=CC(CCC[C:30]([NH2:32])=[S:31])=CC=1>C(#N)C.C(O)C>[CH3:18][S:17][C:14]1[CH:15]=[CH:16][C:11]([C:9]2[S:31][CH:30]=[N:32][CH:8]=2)=[CH:12][CH:13]=1

Participants

5

Reactant 2

HCID 541321334-(4-Bromophenyl)butanethioamideHCID 541605321-(4-Fluorophenyl)-2-(4-methylthiophenyl)-2-bromoethanone

Product 1

HCID 537957645-(4-Methylthiophenyl)thiazoleYield 85.5%

Reagents, catalysts & solvents 2

HCID 702EthanolSolventHCID 6342AcetonitrileSolvent

Procedure

To a solution of 2-bromo-2-(4-fluorophenyl)-1-(4-methylthiophenyl) ethanone (Example 1, Step 3 ) (2.70 g, 7.90 mmol) in acetonitrile (90 mL) and ethanol (10 mL) in a 125 mL round bottom flask was added 4-(4-bromophenyl) thiobutyramide from Step 1, (1.4 g, 7.90 mmol) and the mixture was heated to reflux for 7 hours. The reaction was cooled to room temperature and let stand overnight. The crude product was concentrated in vacuo yielding an oil which was purified by flash chromatography (1: 1 hexane:methylene chloride) yielding 2-(3-[4-bromophenyl]propyl)-4- (4-fluorophenyl))-5-(4-methylthiophenyl)thiazole (1.4 g, 36%) as a clear colorless oil (ca. 90% purity by 1H NMR): 1H NMR (CDCl3) 3 00 mHz δ7.50-7.46 (m, 2H), 7.41 (d, J=8.46 Hz, 2H), 7.22 (d, J=8.66 Hz, 2H), 7.16 (d, J=8.66 Hz, 2H), 7.10 (d, J=8.26 Hz, 2H), 6.97 (t, J=8.86, 2H), 3.03 (t, J=7.45 Hz, 2H), 2.74 (t, J=7.45 Hz, 2H), 2.49 (s, 3H), 2.20-2.09 (m, 2H). MS (EI): m/z 529, 531 (M+) 497, 499. HRMS Δ=-2.1 mmu.

Workup

  1. temperaturethe mixture was heated
  2. temperatureto reflux for 7 hours
  3. concentrationThe crude product was concentrated in vacuo
  4. customyielding an oil which
  5. customwas purified by flash chromatography (1: 1 hexane:methylene chloride)

Sources & evidence

ORD record
ord-6be2c88afa0848db8ad55ada66500071
Source dataset
uspto-grants-1997_09
Patent number
US05668161

Reaction notes

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