Hydrochloric Acid → 2-Acetyl-4-chlorothiophene

2-Acetylthiophene (21.6 ml, 0.20 mol) was dissolved in chloroform (200 ml) at −10° C. AlCl3 (54 g, 0.40 mole) was added in small portions at such a rate as to keep temperature below 5° C. A saturated solution of chlorine, Cl2, in chloroform (100 ml) was then added dropwise at −10° C. over a period of 30 minutes. After the addition was completed, the reaction mixture was immediately poured into a mixture of 1 L ice water and 500 ml of 1 N HCl and stirred for 30 minutes. The organic layer was separated, dried over Na2SO4, and concentrated under vacuum to a yellow liquid. NMR analysis showed this to be a 3:1 mixture of 4-chloro-2-acetylthiophene and 4,5-dichloro-2-acetylthiophene. Partial purification was achieved by a Kugelrohr distillation, yielding 4-chloro-2-acetylthiophene (31 g, 83% pure, 80% yield). This material was used without further purification in the next step. 1H NMR (300 MHz, CDCl3) δ7.53 (1H, d, J=1.2 Hz), 7.41 (1H, d, J=1.2 Hz), 2.54 (3H, s).

1. customtemperature below 5° C
2. additionAfter the addition
3. customThe organic layer was separated
4. dry with materialdried over Na2SO4
5. concentrationconcentrated under vacuum to a yellow liquid
6. additiona 3:1 mixture of 4-chloro-2-acetylthiophene and 4,5-dichloro-2-acetylthiophene
7. customPartial purification
8. distillationwas achieved by a Kugelrohr distillation

ORD record

ord-3a863c5d051240c6bb28d1b80bf52648

Source dataset

uspto-grants-2003_09

DOI

10.6084/m9.figshare.5104873.v1

Patent number

US06613786B2