p-Toluenesulfonic acid → N-(3-formyl-phenyl)pyridine-2-carboxamide

HRID 414840Notes

Reaction equation

HRID 414840 reaction equation
[N:1]1[CH:6]=[CH:5][CH:4]=[CH:3][C:2]=1[C:7](Cl)=[O:8].C([O:12][CH:13](OCC)[C:14]1[CH:19]=[CH:18][CH:17]=[C:16]([NH2:20])[CH:15]=1)C.C(OC(OCC)C1C=CC=C([N+]([O-])=O)C=1)C.[N+](C1C=C(C=CC=1)C=O)([O-])=O.C(OC(OCC)OCC)C.C1(C)C=CC(S(O)(=O)=O)=CC=1>C(Cl)Cl.C(O)C.O.C(N(CC)CC)C>[CH:13]([C:14]1[CH:15]=[C:16]([NH:20][C:7]([C:2]2[CH:3]=[CH:4][CH:5]=[CH:6][N:1]=2)=[O:8])[CH:17]=[CH:18][CH:19]=1)=[O:12]

Participants

11

Reactant 6

HCID 6101p-Toluenesulfonic acidHCID 74493-NitrobenzaldehydeHCID 31214Ethyl orthoformateHCID 135034Pyridine-2-carbonyl chlorideHCID 3261611-(Diethoxymethyl)-3-nitrobenzeneHCID 156806583-(Diethoxymethyl)aniline2×

Product 1

HCID 14349158N-(3-formyl-phenyl)pyridine-2-carboxamide

Reagents, catalysts & solvents 4

HCID 702EthanolSolventHCID 962WaterSolventHCID 6344DichloromethaneSolventHCID 8471TriethylamineSolvent

Procedure

To a solution of pyridine-2-carboxylic acid chlorid (6.5 g) in methylene chloride (75 ml) was added a mixture of triethylamine (6.3 g) and 3-aminobenzaldehyde diethylacetal (9.75 g); (3-aminobenzaldehyde diethylacetal was prepared by reducing (H2, Pd/C, MeHH) 3-nitrobenzaldehyde diethyl acetal, which in turn was made by acetalization of 3-nitrobenzaldehyde with triethylorthoformate and p-toluenesulfonic acid in ethanol). The mixture of the acid chloride and the primary amine was stirred at room temperature overnight, and poured carefully into cold water. The organic layer was separated, dried over anhydrous magnesium sulfate, and then all solvent removed. The residue was dissolved in tetrahydrofuran, and then dilute HCl solution (1N) was added until the acidic mixture remained homogeneous. This mixture was stirred at room temperature for one hour, and then most of the volatile solvent was removed. The aqueous solution was neutralized with NaHCO3, extracted with ethyl acetate, and the organic extract was washed with water and brine. All volatiles were removed, and the residual solid was crystallized from methanol-hexanes to give N-(3-formyl-phenyl)pyridine-2-carboxamide.

Workup

  1. customThe organic layer was separated
  2. dry with materialdried over anhydrous magnesium sulfate
  3. customall solvent removed
  4. dissolutionThe residue was dissolved in tetrahydrofuran
  5. additiondilute HCl solution (1N) was added until the acidic mixture
  6. custommost of the volatile solvent was removed
  7. extractionextracted with ethyl acetate
  8. extractionthe organic extract
  9. washwas washed with water and brine
  10. customAll volatiles were removed
  11. customthe residual solid was crystallized from methanol-hexanes

Sources & evidence

ORD record
ord-e11d2e86969042e2afcef0cd7fe26e23
Source dataset
uspto-grants-1988_12
Patent number
US04794188

Reaction notes

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