Thionyl Chloride → 2-(3,4-Dichlorophenyl)acetyl chloride

Participants

Reaction Steps

A solution of 3,4-dichlorophenylacetic acid (23.59 g, 115 mmol) in thionyl chloride (66 mL, 905 mmol) was heated at 76° C. for 2.5 h and then evaporated under reduced pressure to yield 3,4-dichlorophenylacetyl chloride. A solution of 3,4-dichlorophenylacetyl chloride in cold, dry CH2Cl2 (90 mL) was added dropwise to an ice-cold solution of 13 (26.025 g, 104 mmol) and Et3N (16 mL, 115 mmol) in dry CH2 Cl2 (150 mL) with stirring under argon and ice-cooling over 30 min. The mixture was stirred at 25° C. for 21 h before the solvent was removed under reduced pressure. The residue was then dissolved in EtOAc and washed with 3N NaOH. The organic fraction was dried (MgSO4), filtered, and evaporated to yield 43.5 g (95%) of crude product. Two crystallizations from boiling MeOH yielded 14.HCl (10.24 g, 21%): mp (14.HCl)>260° C.; [α]D25°C. +137° (c=0.2, 14.HCl:, MeOH); 1H NMR (14.HCl, DMSO-d6) δ 1.89-2.01 (m, 4H, --CH2CH2 --), δ 2.83 (s, 3H, NCH3), δ 3.15-4.19 (complex, 6H, 3 --CH2N), δ 3.85 (d, J=17 Hz, 1H, ArCH2CO), δ 3.99 (d, J=16 Hz, 1H, ArCH2 CO), δ 6.21 (m, 1H, CH), δ 7.28-7.30 (m, 1H, Cl2C6 H3 --), δ 7.56-7.57 (m, 2H, Cl2C6H3 --), δ 7.71-7.72 (m, 2H, m-NO2C6H4), δ 8.08 (s, 1H, m-NO2C6H4), δ 8.21-8.22 (m, 1H, m-NO2 C6H4). MS (FAB) m/z 436.1. Anal. (C21H23N3 O3Cl2.HCl.0.5 H2O) calcd.: C 52.35, H 5.23, N 8.72, Cl 22.08; found: C 52.18, H 5.22, N 8.58, Cl 22.00.

Provenance & Evidence