Chloroacetonitrile → 2H-1,4-benzothiazin-3-amine

HRID 1966056Notes

Reaction equation

HRID 1966056 reaction equation
[NH2:1][C:2]1[CH:7]=[CH:6][CH:5]=[CH:4][C:3]=1[SH:8].Cl[CH2:10][C:11]#[N:12]>[OH-].[Na+].C(Cl)Cl.S([O-])(O)(=O)=O.C([N+](CCCC)(CCCC)CCCC)CCC>[NH2:12][C:11]1[CH2:10][S:8][C:3]2[CH:4]=[CH:5][CH:6]=[CH:7][C:2]=2[N:1]=1

Participants

6

Reactant 2

HCID 7856ChloroacetonitrileHCID 87132-Aminothiophenol

Product 1

HCID 8200282H-1,4-benzothiazin-3-amineYield 32%

Reagents, catalysts & solvents 3

HCID 94433Tetrabutylammonium hydrogen sulfateCatalystHCID 6344DichloromethaneSolventHCID 14798Sodium HydroxideSolvent

Procedure

A mixture of 2-aminothiophenol (1.6 ml, 15 mmol) in 25% NaOH (10 ml) and chloroacetonitrile (0.95 ml, 15 mmol) in CH2Cl2 (20 ml) is stirred at room temperature for 20 hours, in the presence of tetrabutylammonium hydrogensulphate (0.51 g, 1.5 mmol). The organic phase is then separated, washed with H2O, dried over Na2SO4 and concentrated. The residue is taken up with 5% HCl/EtOH (20 ml) and the resulting solution refluxed for 2 hours. The solvent is evaporated under vacuum and the resulting solid taken up in H2O then washed with CHCl3, basified with NH4OH and the precipitate obtained extracted with CHCl3. The organic phase is dried over Na2SO4 and concentrated. The residue is purified by chromatography through silica, eluting with AcOEt/Triethylamine (8:2). The product is obtained as a yellowish solid, with a yield of 32%. Recrystallisation from ethyl acetate gives the product with an m.p. of 168-172° C., 1H-NMR (CDCl3): 3.18 (s, 2H), 4.38 (br s, 2H), 6.89-7.25 (m, 4H). MS (ESI): m/z 165 (M+H+). MS (ESI): m/z 165 (M+H+). The product is more stable as the oxalate salt, white solid m.p. 182-184° C.

Workup

  1. customThe organic phase is then separated
  2. washwashed with H2O
  3. dry with materialdried over Na2SO4
  4. concentrationconcentrated
  5. temperaturethe resulting solution refluxed for 2 hours
  6. customThe solvent is evaporated under vacuum
  7. washthen washed with CHCl3
  8. customthe precipitate obtained
  9. extractionextracted with CHCl3
  10. dry with materialThe organic phase is dried over Na2SO4
  11. concentrationconcentrated
  12. customThe residue is purified by chromatography through silica
  13. washeluting with AcOEt/Triethylamine (8:2)
  14. customThe product is obtained as a yellowish solid, with a yield of 32%
  15. customRecrystallisation from ethyl acetate
  16. customgives the product with an m.p. of 168-172° C., 1H-NMR (CDCl3): 3.18 (s, 2H), 4.38 (br s, 2H), 6.89-7.25 (m, 4H)

Sources & evidence

ORD record
ord-372a3af249f04b85b373c21e18609b80
Source dataset
uspto-grants-2013_04
Patent number
US08420634B2

Reaction notes

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