Ammonium Chloride → HCID 76677914, compound

HRID 1642205Notes

Reaction equation

HRID 1642205 reaction equation
[S:1]1[CH:5]=[CH:4][C:3]([CH:6]=[N:7][OH:8])=[CH:2]1.ClN1C(=O)CCC1=O.[NH4+].[Cl-].[CH3:19][C:20]1[NH:24][N:23]=[N:22][N:21]=1>CN(C=O)C.ClCCl>[CH3:19][C:20]1[N:24]([C:6]([C:3]2[CH:4]=[CH:5][S:1][CH:2]=2)=[N:7][OH:8])[N:23]=[N:22][N:21]=1.[CH3:19][C:20]1[N:21]=[N:22][N:23]([C:6]([C:3]2[CH:4]=[CH:5][S:1][CH:2]=2)=[N:7][OH:8])[N:24]=1

Participants

8

Reactant 4

HCID 25517Ammonium Chloride2×HCID 31398ChlorosuccinimideHCID 2781921N-(thiophen-3-ylmethylidene)hydroxylamineHCID 178434708HCID 178434708, compound

Product 2

HCID 76677914HCID 76677914, compoundYield 37.6%HCID 76677921HCID 76677921, compoundYield 13.7%

Reagents, catalysts & solvents 2

HCID 6228DimethylformamideSolventHCID 6344DichloromethaneSolvent

Procedure

To a solution of 3-thiophene carboxaldehyde oxime (8 g, 62.9 mmol) in DMF (80 ml) is added N-chlorosuccinimide (8.8 g, 66 mmol) portionwise, while maintaining the reaction temperature below 45° C. On complete addition, the mixture is stirred one hour at room temperature before being poured into a saturated aqueous NH4Cl solution. The mixture is extracted with ethyl acetate. The organic layer is washed successively with water and brine, dried (MgSO4), filtered and concentrated. The residue and 5-methyltetrazole (5.3 g, 62.9 mmol) are diluted in dichloromethane (80 ml) and treithylamine (11.4 ml, 82.1 mmol) is added dropwise at room temperature. After stirring overnight, a saturated aqueous NH4Cl solution is added. The aqueous layer is extracted with ethyl acetate. The combined organic layers are washed successively with water and brine, dried (MgSO4), filtered and concentrated. Silica-gel chromatography of the residue affords 5.5 g of 5-methyl-1-(3-thiophenecarbohydroximoyl)-tetrazole [yield 37.6%; 1H-NMR (DMSO-d6) δppm: 2.48 (s, 3H), 7.42 (d, 1H), 7.51 (d, 1H), 7.74 (dd, 1H), 12.7 (s, 1H)] and 2 g 5-methyl-2-(3-thiophenecarbohydroximoyl)-tetrazole [yield 13.7%; 1H-NMR (DMSO-d6) δppm: 2.62 (s, 3H), 7.40 (m, 2H), 7.73 (dd, 1H), 12.6 (s, 1H)].

Workup

  1. temperaturewhile maintaining the reaction temperature below 45° C
  2. additionOn complete addition
  3. extractionThe mixture is extracted with ethyl acetate
  4. washThe organic layer is washed successively with water and brine
  5. dry with materialdried (MgSO4)
  6. filtrationfiltered
  7. concentrationconcentrated
  8. additiontreithylamine (11.4 ml, 82.1 mmol) is added dropwise at room temperature
  9. stirringAfter stirring overnight
  10. extractionThe aqueous layer is extracted with ethyl acetate
  11. washThe combined organic layers are washed successively with water and brine
  12. dry with materialdried (MgSO4)
  13. filtrationfiltered
  14. concentrationconcentrated

Sources & evidence

ORD record
ord-efacd7ae2a5c49e3abf176defc6e59a6
Source dataset
uspto-grants-2012_02
Patent number
US08119645B2

Reaction notes

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