Hydrochloric Acid → 2-Chloro-5-cyanobenzoic acid

HRID 1397417Notes

Reaction equation

HRID 1397417 reaction equation
N([O-])=O.[Na+].N[C:6]1[CH:7]=[CH:8][C:9]([Cl:15])=[C:10]([CH:14]=1)[C:11]([OH:13])=[O:12].Cl.[K].[C-:18]#[N:19].[K+]>O.[O-]S([O-])(=O)=O.[Cu+2]>[Cl:15][C:9]1[CH:8]=[CH:7][C:6]([C:18]#[N:19])=[CH:14][C:10]=1[C:11]([OH:13])=[O:12]

Participants

8

Reactant 5

HCID 313Hydrochloric Acid2×HCID 9032Potassium CyanideHCID 378795-Amino-2-chlorobenzoic acidHCID 5462222PotassiumHCID 23668193Sodium Nitrite

Product 1

HCID 142030952-Chloro-5-cyanobenzoic acidYield 64.5%

Reagents, catalysts & solvents 2

HCID 24462Copper SulfateCatalystHCID 962WaterSolvent4×

Conditions

Temperature
-5 °C

Procedure

A solution of NaNO2 (2.21 g, 32 mmol) in water (10 mL) was added to a solution of 5-amino-2-chlorobenzoic acid (5.0 g, 29.14 mmol) in water (40 mL) at 0° C., followed addition of by conc. HCl (10 mL) at −5° C. The reaction mixture was stirred at −5° C. for an additional 1 h and then the diazonium solution was added dropwise into a solution of potassium cuprotetracyanide [prepared by dropwise addition of a solution of KCN (10 g, 15.38 mmol) in water (18 mL) to a solution of CuSO4 (7 g, 43.8 mmol) in water (12 mL) at 70° C.] at 50° C. for 1 h. The reaction mixture was acidified with 1.5 N HCl solution and the product was extracted with EtOAc. The combined extracts were washed with water and brine, dried over anhydrous sodium sulfate, and concentrated under reduced pressure. The crude product was purified by column chromatography (silica 60-120 mesh, eluant 1-2% MeOH in CHCl3) to get 2-chloro-5-cyanobenzoic acid (1.8 g, yield 34%). 1H NMR (400 MHz, DMSO-d6) δ 13.92 (br s, 1H), 8.24 (d, J=2.1 Hz, 1H), 8.02-7.99 (d, J=8.4 Hz, 2.1 Hz, 1H), 7.80-7.78 (d, J=8.2 Hz, 1H). MS (ESI) m/z: Calculated for C8H4ClNO2: 180.99. found: 179.6 (M−H)−.

Workup

  1. extractionthe product was extracted with EtOAc
  2. washThe combined extracts were washed with water and brine
  3. dry with materialdried over anhydrous sodium sulfate
  4. concentrationconcentrated under reduced pressure
  5. customThe crude product was purified by column chromatography (silica 60-120 mesh, eluant 1-2% MeOH in CHCl3)

Sources & evidence

ORD record
ord-629457479391455c8085559117f8a29f
Source dataset
uspto-grants-2014_12
Patent number
US08901156B2

Reaction notes

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