All Notebooks | Help | Support | About
19th June 2014 @ 12:25

 

Synthesis of 3-bromo-4-methyl-benzenesulfonamide (PT-17) 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:

PT-17-3-C1 1H NMR DMSO.pdf
PT-17-3-C1 1H NMR CDCL3.pdf

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.

Linked Posts
Attached Files
16th June 2014 @ 16:54


The previous reaction Synthesis of 3-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)-4-methylbenzenesulfonamide (PT-1-20) was repeated on 0.25x scale with the semi-purified (but hopefully sulfur-free product from Resynthesis of 3-bromo-4-methyl-benzenesulfonamide (PT-17-2).

3-bromo-4-methylbenzenesulfonamide (280 mg), bis(pinacolato)diboron (427 mg), potassium acetate (440 mg) was dissolved in 1,4-dioxan (6 mL) and degassed with argon for ten minutes. Pd(dppf)2.CH2Cl2 (46 mg) was added and the reaction heated to 100°C in a sealed tube for 16 hours. The reaction mixture was diluted with methanol (20 mL) and dichloromethane (20 mL) and treated with activated carbon then filtered through celite and evaporated to give a dark solid. NMR indicated the same material as previous, with signals corresponding to pinacol but no arylboronate. Could be the dimer?

Linked Posts
12th June 2014 @ 11:35

 

Amination of bromochlorothienopyrimidine (AT-6-4) was repeated on 100 mg of substrate in 2ml of IPA and 4ml of ammonia at 120°C in a sealed tube for 3 hours. The solvents were removed in vacuo and the resulting orange solid was sufficiently pure to use as-is (B1, 102 mg, quantitative yield with 1eq ammonium chloride)

Linked Posts
Attached Files
12th June 2014 @ 11:33

 

  Synthesis of 3-bromo-4-methyl-benzenesulfonamide (PT-17) was set up as before. Bromine was added all at once and the reaction allowed to exotherm. After 22 hours the reaction was worked up as before but contained significant starting material. To be repeated with slow addition.

Linked Posts
9th June 2014 @ 16:28


3-bromo-4-methylbenzenesulfonamide (1.12g, 4.488 mmol)[1], bis(pinacolato)diboron (1.710 g, 6.735 mmol), potassium acetate (1.762 g, 17.96 mmol) was dissolved in 1,4-dioxan (22.5 mL) and degassed with argon for ten minutes. Pd(dppf)2.CH2Cl2 (184 mg, 0.226 mmol) was added and the reaction heated to reflux under argon for 22 hours. The reaction was cooled to room temperature, diluted with methanol (40 mL) and dichloromethane (40 mL). Sonication was used to disperse solids and the resulting mixture was filtered through celite and evaporated under reduced pressure to give a black solid B1 (4.01 g), NMR and TLC indicated consumption of starting material and the appearance of a single new product.[1]

 

NMR and mass spec indicated that this was not the desired product. Starting material to be re-purified or re-synthesised in a purer form.

 

Literature NMR (CDCl3): http://www.sciencedirect.com/science/article/pii/S0960894X10014587

 

Literature M/S (ESI): http://worldwide.espacenet.com/publicationDetails/biblio?CC=US&NR=2006199817&KC=&FT=E&locale=en_EP (page 53)

  

  

Notes:

[1] Material contaminated with an unknown (but substantial) quantity of an insoluble impurity thought to be elemental sulfur. Trying this as a test reaction due to material availability.

Linked Entries
Attached Files