Chloroacetaldehyde → 2-(3-Nitrophenyl)-1,3-thiazole

HRID 889431Notes

Reaction equation

HRID 889431 reaction equation
[N+:1]([C:4]1[CH:5]=[C:6]([CH:10]=[CH:11][CH:12]=1)[C:7](=[S:9])[NH2:8])([O-:3])=[O:2].Cl[CH2:14][CH:15]=O.C(O)(=O)C.[OH-].[Na+]>C(OCC)(=O)C>[N+:1]([C:4]1[CH:5]=[C:6]([C:7]2[S:9][CH:14]=[CH:15][N:8]=2)[CH:10]=[CH:11][CH:12]=1)([O-:3])=[O:2]

Participants

6

Reactant 4

HCID 33ChloroacetaldehydeHCID 176Acetic AcidHCID 14798Sodium HydroxideHCID 126681823-Nitrobenzene-1-carbothioamide

Product 1

HCID 118058602-(3-Nitrophenyl)-1,3-thiazoleYield 93.1%

Reagents, catalysts & solvents 1

HCID 8857Ethyl AcetateSolvent

Procedure

A yellow suspension of 3-nitrobenzothioamide (2.0 g, 10.98 mmol), 2-chloroacetaldehyde (45% in H2O) (2.01 g, 11.53 mmol), and acetic acid (7.32 mL) was heated to reflux for 1 hour. The mixture was cooled to room temperature, poured into ice water, and rendered alkaline using 30 mL of 12 N NaOH solution. Ethyl acetate was then added, and the resulting emulsion was filtered through CELITE®. The aqueous layer was extracted twice with ethyl acetate, and the combined organic layers were dried over magnesium sulfate. Filtration and concentration under reduced pressure afforded Intermediate 57A (2.107 g, 91% yield) as a brown solid. HPLC: Rt=3.331 min. (YMC S5 ODS 4.6×50 mm, 10-90% aqueous methanol containing 0.2% H3PO4, 4 min. gradient, monitored at 220 nm). MS (ES): m/z=207.0 [M+H]+. 1H NMR (400 MHz, DMSO-d6) δ ppm 8.68 (1H, t, J=1.89 Hz), 8.34-8.41 (1H, m), 8.28-8.34 (1H, m), 8.00-8.05 (1H, m), 7.94 (1H, d, J=3.27 Hz), 7.80 (1H, t, J=8.06 Hz).

Workup

  1. temperaturewas heated
  2. temperatureto reflux for 1 hour
  3. filtrationthe resulting emulsion was filtered through CELITE®
  4. extractionThe aqueous layer was extracted twice with ethyl acetate
  5. dry with materialthe combined organic layers were dried over magnesium sulfate
  6. filtrationFiltration and concentration under reduced pressure

Sources & evidence

ORD record
ord-d2bd142e479a467fbc040460dd11d072
Source dataset
uspto-grants-2012_08
Patent number
US08252795B2

Reaction notes

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