Hydrochloric Acid → 2-Chloro-4,5-difluoro-3-methylbenzonitrile

HRID 1722274Notes

Reaction equation

N([O-])=O.[Na+].S(=O)(=O)(O)O.N[C:11]1[C:18]([CH3:19])=[C:17]([F:20])[C:16]([F:21])=[CH:15][C:12]=1[C:13]#[N:14].C(OCC)(=O)C.[ClH:28]>C(O)(=O)C>[Cl:28][C:11]1[C:18]([CH3:19])=[C:17]([F:20])[C:16]([F:21])=[CH:15][C:12]=1[C:13]#[N:14]

Participants

Conditions

Temperature: 70 °C

Procedure

Sodium nitrite (5.6 g) is added to conc. sulfuric acid (59 ml) at below 70° C. The mixture is heated at 70° C. for 10 minutes and then cooled, and thereto is added dropwise a solution of 2-amino-4,5-difluoro-3-methylbenzonitrile (12.3 g) in acetic acid (123 ml) at below 40° C. The mixture is stirred at the same temperature for 30 minutes and then added in portions to a solution of cuprous chloride (20 g) in conc. hydrochloric acid (200 ml), and thereafter is heated at 80° C. for 30 minutes. After cooling, to the reaction mixture is added ice water, and ethyl acetate is distilled off. The resulting residue is purified by silica gel column chromatography (solvent, dichloromethane:n-hexane=1:1) to give 2-chloro-4,5-difluoro-3-methylbenzonitrile (8.0 g), as a white crystal, m.p. 59°-61° C.

Workup

temperaturecooled
temperatureis heated at 80° C. for 30 minutes
temperatureAfter cooling, to the reaction mixture
distillationis distilled off
customThe resulting residue is purified by silica gel column chromatography (solvent, dichloromethane:n-hexane=1:1)

Sources & evidence

ORD record: ord-5becf71997d541e5bbb5f364cd79e205
Source dataset: uspto-grants-1989_08
DOI: 10.6084/m9.figshare.5104873.v1
Patent number: US04855292

Reaction notes

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