Ammonia → 4-Chloro-nicotinonitrile

HRID 506145Notes

Reaction equation

HRID 506145 reaction equation
O[C:2]1[C:7]([C:8]#[N:9])=[CH:6][N:5]=[CH:4][CH:3]=1.N.C([O-])(=O)C.[NH4+].OC1C=CC=CN=1.P(Cl)(Cl)([Cl:25])=O>CN(C=O)C.C(O)C>[Cl:25][C:2]1[C:7]([C:8]#[N:9])=[CH:6][N:5]=[CH:4][CH:3]=1

Participants

8

Reactant 5

HCID 222AmmoniaHCID 24813Phosphorus oxychlorideHCID 517165Ammonium AcetateHCID 178510337HCID 178510337, compoundHCID 178516071HCID 178516071, compound

Product 1

HCID 134111124-Chloro-nicotinonitrile

Reagents, catalysts & solvents 2

HCID 702EthanolSolventHCID 6228DimethylformamideSolvent

Procedure

Acetic acid ester i is converted to 3-oxo-butyronitrile ii by reaction with the anion of acetonitrile prepared by reaction of acetonitrile (CH3CN) with a strong base such as n-butyl lithium (n-BuLi) in a solvent such as THF. Reaction of oxo-butyronitrile ii with dimethylformamide-dimethyl acetal (DMF-DMA) in a solvent such as DMF at high temperature (e.g., 122° C.) results in the formation of bisdimethylaminomethylene intermediate iii which is converted to 4-hydroxy-nicotinonitrile iv by reaction with ammonia (NH3) or ammonium acetate (NH4OAc) in a solvent such as ethanol at reflux. Reaction of the hydroxypyridine with refluxing phosphorous oxychloride (POCl3) with or without catalytic DMF for 2 to 6 hours results in conversion to 4-chloro-nicotinonitrile v.

Workup

  1. temperatureat reflux

Sources & evidence

ORD record
ord-95069fefdf964af796d4cd9a060fb506
Source dataset
uspto-grants-2010_08
Patent number
US07781591B2

Reaction notes

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