Hydrochloric Acid → 2-Chloro-5-(2,4-dichloro-phenyl)-isonicotinonitrile

Reaction equation

N[C:2]1[CH:3]=[C:4]([C:7]([C:10]2[CH:15]=[CH:14][C:13]([Cl:16])=[CH:12][C:11]=2[Cl:17])=[CH:8][N:9]=1)[C:5]#[N:6].N([O-])=O.[Na+].[ClH:22]>>[Cl:22][C:2]1[CH:3]=[C:4]([C:7]([C:10]2[CH:15]=[CH:14][C:13]([Cl:16])=[CH:12][C:11]=2[Cl:17])=[CH:8][N:9]=1)[C:5]#[N:6]

Participants

Reactant 3

HCID 313Hydrochloric Acid

HCID 23668193Sodium Nitrite

HCID 451233422-Amino-5-(2,4-dichlorophenyl)isonicotinonitrile

Product 1

HCID 451233412-Chloro-5-(2,4-dichloro-phenyl)-isonicotinonitrileYield 48%

Procedure

A mixture of 2-amino-5-(2,4-dichloro-phenyl)-isonicotinonitrile (880 mg, 3.3 mmol) in HCl conc. (15 mL) was vigorously stirred and cooled to −15° C. (ice/MeOH bath). NaNO2 (4.6 g, 66.7 mmol) was carefully added, then the reaction mixture was slowly warmed to RT and stirred for 24 h. The formed precipitate was filtered, washed with water, and purified by Combi-Flash Companion™ (Isco Inc.) column chromatography (SiO2; gradient elution, [hexane/DCM 1:1]/TBME 95:5→5:95) to yield the title compound (453 mg, 1.6 mmol, 48%). MS: 284 [M+1]+; HPLC: AtRet=2.70.