Org Prep Daily

August 20, 2007

2-(2′-bromophenylamino)-thiazole-4-carboxylic acid

Filed under: procedures — milkshake @ 8:38 pm

bromothiaz.gif 

2-Bromophenyl isothiocyanate 1.0mL (1.593g, 7.44 mmol) was added dropwise into a stirred 7M anh NH3 solution in methanol (40mL), the mixture was stirred for 1 hour and then evaporated. The residue was dissolved in ethanol 25mL, heated to reflux, cooled, filtered from a small amount of cloudy precipitate and the filtrates were evaporated. The residue was induced to crystallization by addition of few drops of water, the solidified mass was dried on highvac. The obtained crude thiourea (1.737 g of a light tan crystalline solid) was dissolved in ethanol 50 mL with a gentle heating.The solution was cooled to RT and solid bromopyruvic acid 1.242g (7.44 mmol) was added, the mixture was stirred for 30 min and then evaporated. The residue was suspended in water 50mL with sonication (for 10 min), anhydrous sodium acetate solid 840mg was added to raise the pH of the mixture and the slurry was sonicated for additional 5 min. The precipitated product was collected by filtration, washed with water, dried by suction and then on highvac.
Y=1.749g (78.5%) of a white crystalline solid.

1H-NMR(d6-DMSO, 400MHz): 12.681 (very br s, 1H), 9.629(very br s, 1H), 8.144(dd, 8.2Hz, 1.6Hz, 1H), 7.718(s, 1H), 7.652(dd, 8.0Hz, 1.5Hz, 1H), 7.394(m, 1H), 7.039(m, 1H); LC-MS(+ESI): 299, 301

Using the same procedure, 1.0mL of 2-chlorophenyl isothiocyanate (1.310g, 7.72mmol) and 40mL of 7M methanolic NH3 provided 1.452g of a crude thiourea that was cyclized with bromopyruvic acid 1.289g (7.72 mmol) and neutralized with AcONa 900mg to provide 1.401g (71%) of 2-(2′-chlorophenylamino)-thiazole-4-carboxylic acid as a white crystalline solid. 1H-NMR(d6-DMSO, 400MHz): 12.705 (very br s, 1H), 9.779(very br s, 1H), 8.358(dd, 8.3Hz, 1.5Hz, 1H), 7.748(s, 1H), 7.477(dd, 8.0Hz, 1.4Hz, 1H), 7.350(m, 1H), 7.070(m, 1H); LC-MS(+ESI): 255, (257)

5 Comments »

  1. Anything you post containing that ring has my attention. ;)

    Comment by Ψ*Ψ — August 21, 2007 @ 1:29 am

  2. 2,4-disubst thiazoles are always ready to please – just thiourea (or thioamide) and alpha haloketone

    Comment by milkshake — August 21, 2007 @ 1:47 am

  3. Where do you get your bromopyruvic acid? I’ve been using chloropyruvic acid and HATE to make/purify the stuff…..black tar + sublimation apparatus makes for an unhappy grad student.

    Comment by ... — August 22, 2007 @ 8:52 pm

  4. Aldrich sells it – it is not cheap but I liked it better than the Et ester that is cheap but only available as 90% technical product.

    Bromopyruvic acid 98% Aldrich 238341-5G; 5 grams $50

    Comment by milkshake — August 22, 2007 @ 9:20 pm

  5. That SO2Cl2 chlorination ofpyruvic acid is a nightmare sometimes (and trying to get the 3,3-dichloroacid is even worse). Hot tip – dump the sublimation apparatus, and grab your local kugehlrohr.
    The technical ethyl ester from merck is actually surprisingly well behaved all things considered – most things involving pyruvate esters are typically sold ~90% purity because they are right bastards to get clean.

    Comment by kiwi — August 31, 2007 @ 10:38 pm


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