3-Aminobenzoic Acid → 2-(Methylamino)-1,3-benzothiazole-7-carboxylic acid

HRID 844599Notes

Reaction equation

HRID 844599 reaction equation
[CH3:1][N:2]=[C:3]=[S:4].[NH2:5][C:6]1[CH:7]=[C:8]([CH:12]=[CH:13][CH:14]=1)[C:9]([OH:11])=[O:10].BrBr>C(O)(=O)C>[CH3:1][NH:2][C:3]1[S:4][C:7]2[C:8]([C:9]([OH:11])=[O:10])=[CH:12][CH:13]=[CH:14][C:6]=2[N:5]=1

Participants

5

Reactant 3

HCID 74193-Aminobenzoic AcidHCID 11167Methyl isothiocyanateHCID 24408Bromine

Product 1

HCID 155100792-(Methylamino)-1,3-benzothiazole-7-carboxylic acidYield 97%

Reagents, catalysts & solvents 1

HCID 176Acetic AcidSolvent3×

Conditions

Temperature
95 °C

Procedure

A solution of 39.2 g of methyl isothiocyanate and 50 g of 100% acetic acid is added dropwise to a suspension of 70 g of 3-amino-benzoic acid and 250 g of 100% acetic acid at 75-80° C. in the course of 50 minutes. A solution from which 3-(N′-methylthioureido)-benzoic acid slowly precipitates out in crystalline form is temporarily formed. After the mixture has been allowed to react completely for 2 hours, it is cooled to 50° and a solution of 81.5 g of bromine and 50 g of 100% acetic acid is added dropwise at 45-50° C. in the course of 2 hours. The mixture is then heated to 90-100° C. in the course of 2 hours and allowed to react completely for 2 hours, until the release of gas has ended. After 160 g of acetic acid have been distilled oft at 75-80° C. under reduced pressure, 200 g of water have been added to the residue, 67 g of 30% sodium hydroxide solution have been added dropwise, the mixture has been filtered with suction at 75-80° C. and the residue has been washed with water, 73 g of product of melting point >330° C. are obtained. HPLC analysis shows a content of 97% of the title compound, in addition to 0.7% of isomeric 2-methylamino-benzothiazole-5-carboxylic acid. Yield: 68% of theory.

Workup

  1. customA solution from which 3-(N′-methylthioureido)-benzoic acid slowly precipitates out in crystalline form
  2. customis temporarily formed
  3. customto react completely for 2 hours
  4. temperatureit is cooled to 50°
  5. customto react completely for 2 hours, until the release of gas
  6. distillationAfter 160 g of acetic acid have been distilled oft at 75-80° C. under reduced pressure, 200 g of water
  7. additionhave been added to the residue, 67 g of 30% sodium hydroxide solution
  8. additionhave been added dropwise
  9. filtrationthe mixture has been filtered with suction at 75-80° C.
  10. washthe residue has been washed with water, 73 g of product of melting point >330° C.
  11. customare obtained

Sources & evidence

ORD record
ord-baa17a027355484ba24c53a71b172828
Source dataset
uspto-grants-2002_04
Patent number
US06380422B1

Reaction notes

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