Iodine → 3-Iodo-4-methoxybenzoic acid

HRID 1976348Notes

Reaction equation

HRID 1976348 reaction equation
[C:1]([OH:11])(=[O:10])[C:2]1[CH:7]=[CH:6][C:5]([O:8][CH3:9])=[CH:4][CH:3]=1.[I:12]I.[N+]([O-])(O)=O>C(O)(=O)C.OS(O)(=O)=O.O>[I:12][C:6]1[CH:7]=[C:2]([CH:3]=[CH:4][C:5]=1[O:8][CH3:9])[C:1]([OH:11])=[O:10]

Participants

7

Reactant 3

HCID 807IodineHCID 944Nitric AcidHCID 74784-Methoxybenzoic Acid

Product 1

HCID 6241583-Iodo-4-methoxybenzoic acidYield 65.2%

Reagents, catalysts & solvents 3

HCID 176Acetic AcidSolvent2×HCID 962WaterSolventHCID 1118Sulfuric AcidSolvent

Conditions

Temperature
45 °C

Procedure

To a mechanically stirred suspension of p-anisic acid (59.90 g, 394 mmol) and iodine (100.0 g, 394 mmol) in a mixture of 325 mL glacial acetic acid and 60 g conc H2SO4, heated to 45° C. with a water bath, was added dropwise a solution of 40 g conc HNO3 in 60 mL HOAc at such a rate that the temperature was maintained between 40-50° C. (ca. 90 min). After addition, the mixture was stirred for 30 min at 50° C., then diluted with 400 mL H2O, which produced a pink solid. The material was collected on a Büchner funnel, rinsed with 1 L 10% Na2S2O4 and 1 L H2O, then air dried. Recrystallization from 700 mL pyridine/MeOH (1:1) provided colorless plates. The crystals were collected on a Büchner funnel, rinsed with 500 mL MeOH, then allowed to air dry. After drying under high vacuum overnight, 71.4 g (65.2%) of the desired product was obtained; mp 243-244° C. (lit.10 mp 238° C.); 1H NMR (DMSO-d6) δ 3.91 (s, 3 H), 7.00 (d, 1 H, J=8.7 Hz), 7.95 (dd, 1 H, J=8.7, 1.8 Hz), 8.27 (d, 1 H, J=1.8 Hz), 12.89 (br s, 1 H).

Workup

  1. temperaturewas maintained between 40-50° C. (ca. 90 min)
  2. additionAfter addition
  3. customproduced a pink solid
  4. customThe material was collected on a Büchner funnel
  5. washrinsed with 1 L 10% Na2S2O4 and 1 L H2O
  6. customair dried
  7. customRecrystallization from 700 mL pyridine/MeOH (1:1)
  8. customprovided colorless plates
  9. customThe crystals were collected on a Büchner funnel
  10. washrinsed with 500 mL MeOH
  11. customto air dry
  12. customAfter drying under high vacuum overnight

Sources & evidence

ORD record
ord-84057e5ac32f451fba108cfc00b4db0a
Source dataset
uspto-grants-2001_05
Patent number
US06225481B1

Reaction notes

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