Hydrogen Peroxide → HCID 18796975, compound

HRID 235066

Reaction equation

HRID 235066 reaction equation
[Cl:1][C:2]1[C:3]([C:8]#[N:9])=[N:4][CH:5]=[CH:6][CH:7]=1.OO.S([O-])([O-])=[O:13].[Na+].[Na+]>C(O)(=O)C.O>[Cl:1][C:2]1[C:3]([C:8]#[N:9])=[N+:4]([O-:13])[CH:5]=[CH:6][CH:7]=1

Participants

6

Reactant 3

HCID 784Hydrogen PeroxideHCID 24437Sodium SulfiteHCID 8182583-Chloropyridine-2-carbonitrile

Product 1

HCID 18796975HCID 18796975, compoundYield 51.3%

Reagents, catalysts & solvents 2

HCID 176Acetic AcidSolventHCID 962WaterSolvent

Conditions

Temperature
90 °C

Procedure

To a solution of 3-chloro-2-cyanopyridine (40g, 0.29 mol) in 500 mL acetic acid added hydrogen peroxide (30%, 52 g, 0.45 mol) dropwise. After stirring at 90° C. for 18 h, the reaction is cooled to 25° C. and a solution of sodium sulfite (57 g, 0.45 mol) in H2O is added dropwise. The reaction is concentrated to remove the bulk of the acetic acid and the residue is partitioned between 1M NaOH and CH2Cl2. The CH2Cl2 layer is dried (MgSO4), filtered, concentrated, and recrystallized from EtOAc to provide 23 g (51%) of 3-chloro-2-cyanopyridine-N-oxide. The N-oxide from above (12.2 g, 79 mmol) was taken up in DMF (160 mL) at 0° C. Methyl thioglycolate (7.1 mL, 79 mmol) was added followed by sodium methoxide (8.5 g, 160 mmol) in portions. The RXN was stirred for 1 h. The RXN was poured onto ice and the resulting solid was collected by filtration, washed with water, dissolved in CH2Cl2, dried (MgSO4), filtered, concentrated, and recrystallized from EtOAc. 10.6 g (60%) of 3-amino-2-carbomethoxythieno[3,2-b]pyridine-4-oxide was obtained. The pyridine-N-oxide (10.6 g, 47 mmol) is mixed with phosphorous oxychloride (100 mL). The RXN is heated to 80° C. for 30 min. The RXN is concentrated and partitioned between CH2Cl2 and NaHCO3 sln. The CH2Cl2 layer is dried (MgSO4), filtered, cone, and chromatographed (5:1 hex:EtOAc). 8.3g (73%) of the 5-chloro and 2.0 g (18%) of the 7-chloro product were obtained: 1H NMR (300 MHz, CDCl3 (5-chloro)) δ3.92 (s, 3H), 6.15 (bs, 2H), 7.37 (d, 1H), 7.99 (d, 1H); MS (DCI/NH3) m/e 243 (M+H)+. 1H NMR (300 MHz, CDCl3 (7-chloro)) δ3.93 (s, 3H), 6.20 (bs, 2H), 7.41 (d, 1H), 8.54 (db, 1H); MS (DCI/NH3) m/e 243 (M+H)+.

Workup

  1. temperaturethe reaction is cooled to 25° C.
  2. concentrationThe reaction is concentrated
  3. customto remove the bulk of the acetic acid
  4. customthe residue is partitioned between 1M NaOH and CH2Cl2
  5. dry with materialThe CH2Cl2 layer is dried (MgSO4)
  6. filtrationfiltered
  7. concentrationconcentrated
  8. customrecrystallized from EtOAc

Sources & evidence

ORD record
ord-13a18932739844ca964128d5d2968a2a
Source dataset
uspto-grants-1997_01
Patent number
US05597823

Linked notes

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