Hydrochloric Acid → 2-hydroxy-4-isothiocyanatobenzoic acid

HRID 385181Notes

Reaction equation

HRID 385181 reaction equation
[C:1](=[S:3])=S.[NH2:4][C:5]1[CH:13]=[CH:12][C:8]([C:9]([OH:11])=[O:10])=[C:7]([OH:14])[CH:6]=1.C(N(CC)CC)C.II.Cl.S([O-])([O-])=O.[Na+].[Na+].C(=O)([O-])O.[Na+]>O.C(OCC)(=O)C.O1CCCC1>[N:4]([C:5]1[CH:13]=[CH:12][C:8]([C:9]([OH:11])=[O:10])=[C:7]([OH:14])[CH:6]=1)=[C:1]=[S:3]

Participants

11

Reactant 7

HCID 313Hydrochloric AcidHCID 807IodineHCID 46494-Aminosalicylic AcidHCID 6348Carbon DisulfideHCID 8471TriethylamineHCID 24437Sodium SulfiteHCID 516892Sodium Bicarbonate

Product 1

HCID 3484922-hydroxy-4-isothiocyanatobenzoic acidYield 64%

Reagents, catalysts & solvents 3

HCID 962WaterSolvent2×HCID 8028TetrahydrofuranSolvent2×HCID 8857Ethyl AcetateSolvent2×

Procedure

Carbon disulfide (0.26 mL, 4.4 mmol) was added to a mixture comprising 4-amino-2-hydroxybenzoic acid (0.23 g, 1.5 mmol), tetrahydrofuran (1.0 mL), water (1.0 mL) and triethylamine (0.51 mL, 3.6 mmol), followed by stirring at room temperature for 31 hours. To the obtained reaction mixture, a tetrahydrofuran (1.0 mL) solution of iodine (0.41 g, 1.6 mmol) was dropwise added over a period of 3 minutes at 0° C., followed by stirring at 0° C. for further 2.5 hours. Thereafter, 1M hydrochloric acid (1.5 mL) and sodium sulfite (38 mg, 0.30 mmol) were added and mixed. Then, ethyl acetate (6 mL) was added, and the organic layer was separated and concentrated under reduced pressure to dryness. To the obtained residue, ethyl acetate (6 mL), water (2 mL) and sodium hydrogencarbonate (13 mg, 0.15 mmol) were added, and the organic layer was washed twice with water (2 mL) and then concentrated under reduced pressure to dryness. To the obtained residue, chloroform (1 mL) and hexane (3 mL) were added and thoroughly mixed, and then, an insoluble matter was removed by filtration. The filtrate was concentrated under reduced pressure to dryness to obtain 4-isothiocyanato-2-hydroxybenzoic acid as a brown-colored solid (0.18 g, yield: 64%, HPLC purity: 86%, HPLC retention time: 4.6 min). LC-MS ES-194 (retention time: 4.4 min, condition 1).

Workup

  1. customTo the obtained reaction mixture
  2. stirringby stirring at 0° C. for further 2.5 hours
  3. additionmixed
  4. customthe organic layer was separated
  5. concentrationconcentrated under reduced pressure to dryness
  6. washthe organic layer was washed twice with water (2 mL)
  7. concentrationconcentrated under reduced pressure to dryness
  8. additionTo the obtained residue, chloroform (1 mL) and hexane (3 mL) were added
  9. additionthoroughly mixed
  10. customan insoluble matter was removed by filtration
  11. concentrationThe filtrate was concentrated under reduced pressure to dryness

Sources & evidence

ORD record
ord-7c8c90f2729b40c588a672c5b5630bcf
Source dataset
uspto-grants-2013_02
Patent number
US08367857B2

Reaction notes

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