Sulfuric Acid → Indazole-3-carboxylic acid

HRID 1743360Notes

Reaction equation

HRID 1743360 reaction equation
[NH:1]1[C:11]2[C:6](=[CH:7][CH:8]=[CH:9][CH:10]=2)[C:4](=O)[C:2]1=O.[OH-:12].[Na+].[N:14]([O-])=O.[Na+].OS(O)(=O)=O.[OH2:23].O.[Sn](Cl)Cl>O.Cl>[NH:1]1[C:11]2[C:6](=[CH:7][CH:8]=[CH:9][CH:10]=2)[C:4]([C:2]([OH:23])=[O:12])=[N:14]1

Participants

8

Reactant 5

HCID 1118Sulfuric AcidHCID 7054IsatinHCID 14798Sodium HydroxideHCID 61436Stannous chloride dihydrateHCID 23668193Sodium Nitrite

Product 1

HCID 78250Indazole-3-carboxylic acidYield 31.3%

Reagents, catalysts & solvents 2

HCID 313Hydrochloric AcidSolventHCID 962WaterSolvent3×

Conditions

Temperature
0 °C

Procedure

Isatin (10 g, 0.067 mol) was added to a solution of NaOH (2.8 g, 0.07 mol) in H2O (44 mL) at 50° C. The stirred clear solution was cooled to 0° C. and a solution of sodium nitrite (4.69 g, 0.067 mol) in H2O (17 mL) was added and stirring continued. A solution of concentrated H2SO4 (12.9 g) in H2O (136 mL) was cooled to 0° C. and added dropwise to the reaction mixture in such a way that the dropper was below the level of the reaction mixture. Stirring was continued for 15 min and a cooled solution of tin(II) chloride dihydrate (36.7 g, 0.16 mol) in concentrated HCl (58 mL) was added over 20 min. The reaction mixture was stirred for 1 h and the orange solid was filtered then heated in H2O at 100° C. The insoluble solids were removed by filtration and the product crystallised from the solution affording the title compound as a yellow solid (3.4 g, 31%). Mp 261–263° C. d, lit 260–261° C. v.Auwers, Dereser Chem. Ber. 1919, 52, 1343. 1H NMR (300 MHz, DMSO-d6) ppm 7.26–7.31 (m, 1H), 7.40–7.46 (m, 1H), 7.63–7.66 (m, 1H), 8.08–8.10 (m, 1H), 12.95 (s, 1H), 13.80 (s, 1H). MS(EI) m/z 162 [M+].

Workup

  1. additionadded dropwise to the reaction mixture in such a way that the dropper
  2. stirringStirring
  3. stirringThe reaction mixture was stirred for 1 h
  4. filtrationthe orange solid was filtered
  5. temperaturethen heated in H2O at 100° C
  6. customThe insoluble solids were removed by filtration
  7. customthe product crystallised from the solution

Sources & evidence

ORD record
ord-c7ecac92c2c24ccbb025160f94dd48e3
Source dataset
uspto-grants-2006_03
Patent number
US07009056B2

Reaction notes

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