Grad Dip Arylpyrrole

Formation of a sulfonate as an alternative to the sulfonamides (MD 29-1)

Reaction start time: 7:30 PM EST, 9/5/13

MD 27-5 (65 mg, 0.23 mmol, 1 equiv.) was dissolved in pyridine (5 mL). Methyl glycolate (102 mg, 1.1 mmol, 4.9 equiv.) was added and the reaction stirred overnight.

Risk and Hazard assessment:

Reaction start time: 1:30 PM EST, 8/5/13

MD 6-7 (0.11 g, 0.18 mmol, 1 equiv.) was stirred in dry DCM (3 mL) followed by addition of dry DMF (14 uL, 0.18 mmol, 1 equiv.). Dropwise oxalyl chloride (0.14 mL, 1.6 mmol, 8 equiv.). The reaction mixture was stirred at room temperature for 3 hours.

Risk and Hazard assessment:
Chlorination of sodium 1-(4-fluorophenyl)-2,5-dimethyl-1H-pyrrole-3-sulfonate using oxalyl chloride (MD 27-1)

Formation of arryl pyrrole sulfonate salt to be chlorinated later on to produce a sulfonamide.

Reaction start time: 12:30 PM EST 13/4/13

MD 22-2 (3.0 g, 15 mmol, 1 equiv. ) and Sulfur trioxide pyridine (2.6 g, 15 mmol, 1 equiv.) were refluxed in toluene (15 mL) for 16 hours.

Reaction was concentrated under reduced atmosphere followed by addition of water and heated to 100° C, the boiling reaction was then neutralised with sodium carbonate (approx. 3 g). Water was removed under reduced pressure. A 90:10 ethanol:water mix (30 mL) was added to the residue and the solution heated to 90° C then filtered. The the dark brown solid was then concentrated  (2.1 g).

NMR showed the presence of only one methyl peak indicating a symmetrical product thus the desired product was not formed:

Risk assessment and safety:

Same as: Synthesis of sodium 1-(4-fluorophenyl)-2,5-dimethyl-1H-pyrrole-3-sulfonate (MD 6-1)

Synthesis of the aryl pyrrole core to be synthesised into a sulfonamide.

Reaction start time: 4:00 PM EDST, 12/4/13

This reaction was done in duplicates designated A and B. 4-fluoroaniline (8.8 mL, 93 mmol, 1 equiv.) and 2,5-hexanedione (10 mL, 93 mmol, 1 equiv.) were mixed and heated to 110 °C and left overnight. In the morning, the reaction was cooled to room temperature. The mixture was dissolved in hot EtOH (15 mL) after which a mixture of EtOH (10 mL) and aqueous solution of 10% citric acid (10 mL) was added. Reaction was cooled in an ice bath. The resulting brown crystals were filtered. Black contaminant remainedd in the reaction vessel so the crystals were redissolved in hot EtOH (10 mL) and a solution of 10% citric acid (10 mL) was added and the mixture was cooled with stirring. The resulting brown crystals were filtered and washed with water. Light brown crystals were isolated for reaction A (2.47 g) and reaction B (2.29 g), more crystals still appeared to be in the mother liquor.