Oxidation of Methylthiophenes to Thiophenecarboxylic Acids

1 0.5 1.80 9.7 200 4 43 2 0.52 1.90 9.3 150 16 28 3 0.5 1.82 9.0 190 6 64 4 0.5 1.80 8.5 200 8 75 After purification. In the course of our continuing study on the positional effect of five-membered monoheteroaromatic compounds, we were in need of 3-thiophenecarboxylic acid (2a). Although 2a is commercially available, the price is about 70 times more expensive than the 2-isomer (4a). Therefore, we have explored various methods of preparation of 2a from relatively inexpensive sources. To our surprise, there have been a small number of reports on the synthesis of 2a. One of the older methods is the conversion of 3-methylthiophene (1a) to 3-bromomethylthiophene by Nbromosuccinimide (NBS), which is converted to 3-thiophenecarboxaldehyde by hexamethylenetetramine, and subsequent oxidation of the aldehyde to 2a by silver oxide. Oxidation of 1a to 2a was reported in a couple of patents using N-hydroxyphthalimide, Mn(OAc)2 and Co(OAc)2 at 150 C for 5 h in AcOH or using Co(OAc)2, Mn(OAc)2, and NaBr in an autoclave at 140 C for 2 h. Enzymatic oxidation of the methyl group in 1a to a carboxylic group was also reported with a yield of 70%. On the other hand, oxidation of 1a by Na2Cr2O7 using an rocking autoclave at 250 C for 16 h resulted in 2a in 82% yield. However, the scale of the reaction was quite large (30 g of 1a, 110 g of Na2Cr2O7 and unknown amount of water), and it was not suitable for a few gram scale. A very similar reaction was carried out at a half scale of the reactants, but a lower yield (60%) resulted.