Hydrochloric Acid → 4-Isothiocyanatobenzeneacetic acid

HRID 385187Notes

Reaction equation

HRID 385187 reaction equation
[C:1](=[S:3])=S.[NH2:4][C:5]1[CH:10]=[CH:9][C:8]([CH2:11][C:12]([OH:14])=[O:13])=[CH:7][CH:6]=1.C(N(CC)CC)C.II.Cl.S([O-])([O-])=O.[Na+].[Na+]>C(OCC)(=O)C.O1CCCC1.O>[N:4]([C:5]1[CH:6]=[CH:7][C:8]([CH2:11][C:12]([OH:14])=[O:13])=[CH:9][CH:10]=1)=[C:1]=[S:3]

Participants

10

Reactant 6

HCID 313Hydrochloric AcidHCID 807IodineHCID 6348Carbon DisulfideHCID 8471TriethylamineHCID 145334-Aminophenylacetic acidHCID 24437Sodium Sulfite

Product 1

HCID 109433474-Isothiocyanatobenzeneacetic acidYield 75%

Reagents, catalysts & solvents 3

HCID 962WaterSolventHCID 8028TetrahydrofuranSolvent2×HCID 8857Ethyl AcetateSolvent

Procedure

Carbon disulfide (0.26 mL, 4.4 mmol) was added to a mixture comprising 2-(4-aminophenyl)acetic 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 24 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 8 minutes at 0° C., followed by stirring at 0° C. for further 1.5 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 the aqueous layer was extracted once with a solvent mixture of ethyl acetate (3 mL) and tetrahydrofuran (1 mL). The organic layers were combined and concentrated under reduced pressure to dryness. To the obtained residue, water (8.0 mL) and saturated sodium hydrogencarbonate aqueous solution (2.0 mL) were added and thoroughly mixed. The insoluble matter was filtered off, and to the filtrate, 1M hydrochloric acid (3.0 mL) was added. The precipitated solid was collected by filtration to obtain 2-(4-isothiocyanatophenyl)acetic acid as a colorless solid (0.22 g, yield: 75%, HPLC purity: 95%, HPLC retention time: 3.4 min). LC-MS ES-192 (retention time: 20.5 min, condition 3).

Workup

  1. customTo the obtained reaction mixture
  2. stirringby stirring at 0° C. for further 1.5 hours
  3. additionmixed
  4. customthe organic layer was separated
  5. extractionthe aqueous layer was extracted once with a solvent mixture of ethyl acetate (3 mL) and tetrahydrofuran (1 mL)
  6. concentrationconcentrated under reduced pressure to dryness
  7. additionTo the obtained residue, water (8.0 mL) and saturated sodium hydrogencarbonate aqueous solution (2.0 mL) were added
  8. additionthoroughly mixed
  9. filtrationThe insoluble matter was filtered off
  10. additionto the filtrate, 1M hydrochloric acid (3.0 mL) was added
  11. filtrationThe precipitated solid was collected by filtration

Sources & evidence

ORD record
ord-c52a8823a8b44be09aaf4cd56eebccc7
Source dataset
uspto-grants-2013_02
Patent number
US08367857B2

Reaction notes

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