Thionyl Chloride → Indole-3-carboxylic acid, hydrazide

HRID 1697443Notes

Reaction equation

HRID 1697443 reaction equation
[NH:1]1[C:9]2[C:4](=[CH:5][CH:6]=[CH:7][CH:8]=2)[C:3]([C:10]([OH:12])=O)=[CH:2]1.S(Cl)(Cl)=O.O.[NH2:18][NH2:19]>O1CCCC1>[NH:1]1[C:9]2[C:4](=[CH:5][CH:6]=[CH:7][CH:8]=2)[C:3]([C:10]([NH:18][NH2:19])=[O:12])=[CH:2]1

Participants

5

Reactant 3

HCID 24386Thionyl ChlorideHCID 24654Hydrazine hydrate (1:1)HCID 69867Indole-3-Carboxylic Acid

Product 1

HCID 27199Indole-3-carboxylic acid, hydrazide

Reagents, catalysts & solvents 1

HCID 8028TetrahydrofuranSolvent

Procedure

Indole-3-carboxylic acid (500 mg, 3.1 mmol) was stirred at room temperature with thionyl chloride (5 mL, 68 mmol) for 20 hours. The solution was concentrated under vacuum and the residue was taken up in ether (10 mL) and concentrated to dryness (repeated three times) to ensure removal of the thionyl chloride. The resulting solid was dissolved in ether (5 mL) and added to an ice cooled solution of hydrazine hydrate (600 mg, 12 mmol) in tetrahydrofuran (5 mL). After 30 minutes, the solid was collected by filtration, washed with 5% NaOH and water, and dried under vacuum at 50° C. The crude hydrazide was recrystallized from 95% ethanol to provide the title compound. 1H NMR (300 MHz, CD3OD) δ 7.11-7.22 (m, 2 H), 7.42 (dd, J=7, 2 Hz, 1 H), 7.83 (s, 1 H), 8.02-8.08 ppm (m, 1 H); MS (DCI/NH3) m/z 176 (M+H)+.

Workup

  1. concentrationThe solution was concentrated under vacuum
  2. concentrationconcentrated to dryness (repeated three times)
  3. customremoval of the thionyl chloride
  4. dissolutionThe resulting solid was dissolved in ether (5 mL)
  5. filtrationthe solid was collected by filtration
  6. washwashed with 5% NaOH and water
  7. customdried under vacuum at 50° C
  8. customThe crude hydrazide was recrystallized from 95% ethanol

Sources & evidence

ORD record
ord-41c6a027f4aa45b89a94eb2eb72bfc1b
Source dataset
uspto-grants-2012_04
Patent number
US08163915B2

Reaction notes

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