Hydrochloric Acid → 3-Isothiocyanato-4-methoxybenzoic acid

HRID 385183

Reaction equation

HRID 385183 reaction equation
[C:1](=[S:3])=S.[NH2:4][C:5]1[CH:6]=[C:7]([CH:11]=[CH:12][C:13]=1[O:14][CH3:15])[C:8]([OH:10])=[O:9].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:6]=[C:7]([CH:11]=[CH:12][C:13]=1[O:14][CH3:15])[C:8]([OH:10])=[O:9])=[C:1]=[S:3]

Participants

11

Reactant 7

HCID 313Hydrochloric AcidHCID 807IodineHCID 6348Carbon DisulfideHCID 8471TriethylamineHCID 178233-Amino-4-methoxybenzoic acidHCID 24437Sodium Sulfite2×HCID 516892Sodium Bicarbonate

Product 1

HCID 442063063-Isothiocyanato-4-methoxybenzoic acidYield 94%

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 3-amino-4-methoxybenzoic acid (0.25 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 6 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 5 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), sodium hydrogencarbonate (6 mg, 0.07 mmol) and sodium sulfite (9 mg, 0.07 mmol) were added, the organic layer was separated and concentrated under reduced pressure to dryness to obtain 3-isothiocyanato-4-methoxybenzoic acid as a colorless solid (0.29 g, yield: 94%, HPLC purity: 99%, HPLC retention time: 3.5 min). LC-MS ES-208 (retention time: 21.6 min, condition 3).

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. customthe organic layer was separated
  7. concentrationconcentrated under reduced pressure to dryness

Sources & evidence

ORD record
ord-16fb188c3b9b4fe390f9e99aa88604e7
Source dataset
uspto-grants-2013_02
Patent number
US08367857B2

Linked notes

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