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19th June 2014 @ 12:25
  [blog=9390]Synthesis of 3-bromo-4-methyl-benzenesulfonamide (PT-17)[/blog] was repeated on a 0.5x scale (2g sulfonamide (11.7 mmol), 0.4g iron, 6mL bromine). Bromine was added dropwise with cooling in an ice-water bath, and the reaction stirred at room temperature for 16 hours. NMR indicated the reaction was not complete, so stirring was continued at room temperature for a further 48 hours. NMR indicated a trace of starting material but otherwise a very clean conversion so stirring was continued for a further 48 hours until no starting material was observed by NMR. The reaction mixture was purged of excess bromine under a stream of nitrogen, and then diluted with dichloromethane (200 mL) and washed with sodium thiosulfate (2M, 2 x 150 mL), saturated sodium carbonate solution, and brine. The organic layers were combined and treated with activated carbon and magnesium sulfate, and filtered through celite to yield a white solid B1 (ca. 560 mg, 19% [1]). The product was purified by dry column vacuum chromatography (ethyl acetate in heptane gradient: 0-25% in 4 fractions, 25% for 2 fractions, 25-50% in 10 fractions) to give the title compound as a white solid C1 (456 mg, 15%)[2,3]   NMR: [data]12195[/data][data]12197[/data] Consistent with literature values (below) Literature: US2006199817 (page 53)  InChI: Reactant: InChI=1S/C7H9NO2S/c1-6-2-4-7(5-3-6)11(8,9)10/h2-5H,1H3,(H2,8,9,10) Product: InChI=1S/C7H8BrNO2S/c1-5-2-3-6(4-7(5)8)12(9,10)11/h2-4H,1H3,(H2,9,10,11)     Notes: [1] Low yield is due to losses in workup. Previous attempts to minimises these losses have also lead to impurity problems. [2] I strongly suspect the sulfur problem has been solved, as this is the first batch that has passed the (highly scientific) "sniff test". [3] The lower than expected mass recovery from the chromatography could, again, be due to the removal of elemental sulfur or other non-organic but organic-soluble impurities.
Attached Files
PT-17-3-C1 1H NMR DMSO.pdf
PT-17-3-C1 1H NMR CDCL3.pdf
CJCOSDD_ptm173c1dmso_010714_1H_av500.tar
CJCOSDD_ptm173c1cdcl3_020714_1H_av500.tar