Hexamethylenetetramine → 6-Hydroxy-2-methyl-1,3-benzothiazole-7-carbaldehyde

To a 3-necked flask equipped with a thermometer and an addition funnel were added 6-hydroxy-2-methyl-benzothiazole (1.0 gm, 6.05 mmol) and hexamethylenetetramine (3.4 gm, 24.3 mmol). After cooling in an ice-bath, trifluoroacetic acid (10 mL) was added dropwise with stirring while maintaining the temperature below 60° C. The reaction mixture was stirred overnight at 70°-75° C., cooled, and evaporated. The residue was taken up in ethyl acetate and neutralized with saturated NaHCO3 solution. The organic layer was washed with saturated brine solution and dried (Na2SO4). The solution was filtered, and the filtrate evaporated. The residue was triturated with a mixture of methylene chloride/methanol and filtered. The filtrate was evaporated, and the residue dissolved in a small volume of methylene chloride and chromatographed on a column of silica gel that was eluted with 25% acetone in hexane affording pure title compound.

1. customTo a 3-necked flask equipped with a thermometer and an addition funnel
2. temperatureAfter cooling in an ice-bath
3. temperaturewhile maintaining the temperature below 60° C
4. stirringThe reaction mixture was stirred overnight at 70°-75° C.
5. temperaturecooled
6. customevaporated
7. washThe organic layer was washed with saturated brine solution
8. dry with materialdried (Na2SO4)
9. filtrationThe solution was filtered
10. customthe filtrate evaporated
11. customThe residue was triturated with a mixture of methylene chloride/methanol
12. filtrationfiltered
13. customThe filtrate was evaporated
14. dissolutionthe residue dissolved in a small volume of methylene chloride
15. customchromatographed on a column of silica gel that
16. washwas eluted with 25% acetone in hexane affording pure title compound

ORD record

ord-f77ab3d2128847ea909d5344d5c61c0d

Source dataset

uspto-grants-1998_05

DOI

10.6084/m9.figshare.5104873.v1

Patent number

US05750549