3-Chlorothiophene-2-carboxylic acid

white to light yellow crystal powder

To a solution of methyl 3-chlorothiophene-2-carboxylate (50 g, 0.28 mol) in MeOH(100 mL) was added a solution of aq. NaOH (2M) (400 mL) dropwise at 0 °C. The resulting mixture was stirred at RT for 2h. After removing MeOH, the aqueous was washed with ether and acidified with 2 N HCl. The solid formed was collected by filtration and dried to give 45 g of 3-chlorothiophene-2-carboxylic acid in 98percent yield. MS (M+Hl-(5-Bromo-3-chlorothiophen-2-yl)ethanone (ketone in Table 1 1, entry 2) was prepared as follows: To a solution of methyl 3-chlorothiophene-2-carboxylate (50 g, 0.28 mol) in MeOH (100 mL) was added a solution of aq. NaOH (2M) (400 mL) dropwise at 0 °C. The resulting mixture was stirred at RT for 2h. After removing MeOH, the aqueous was washed with ether and acidified with 2 N HCl. The solid formed was collected by filtration and dried to give 45 g of 3-chlorothiophene-2-carboxylic acid. MS (M+H): 163.1-(5-Bromo-3-chlorothiophen-2-yl)ethanone (ketone in Table 11, entry 2) was prepared as follows: To a solution of methyl 3-chlorothiophene-2-carboxylate (50 g, 0.28 mol) in MeOH (100 mL) was added a solution of aq. NaOH (2M) (400 mL) dropwise at 0° C. The resulting mixture was stirred at RT for 2 h. After removing MeOH, the aqueous was washed with ether and acidified with 2 N HCl. The solid formed was collected by filtration and dried to give 45 g of 3-chlorothiophene-2-carboxylic acid. MS (M+H): 163.Preparation of 1-(3-chlorothiophen-2-yl)-1, 4-dihydro-5H-tetrazol-5-one 6w EXAMPLE 5 3-CHLOROTHIOPHENE-2-CARBOXYLIC ACID (IV) 14.5 liters of absolute carbon tetrachloride (refluxed for 1 hour with 500 g of P2 O5 and then distilled) is placed in a 25 liter apparatus equipped with stirrer, dropping funnel, drainage cock and reflux condenser with gas outlet; while stirring, 2, 200 g (10.05 moles) of PCl5 is added. Upon refluxing the mixture the PCl5 goes into solution (a small amount of PCl5 settles in the drainage cock). 660 g (4.18 moles) of methyl 3-hydroxythiophene-2-carboxylate (prepared as described in German Pat. No. 1, 020, 641) dissolved in 2 liters of absolute carbon tetrachloride is allowed to flow at a just continuous rate over a period of 4 hours into the boiling solution (vigorous evolution of HCl). The yellow solution is then refluxed for a further 15 hours. Subsequently, 12 liters of carbon tetrachloride is distilled off over a period of 2 hours. After the concentrated solution has been cooled to 40° C it is allowed to drain through the cock. 2 liters of water and 4 kg of ice are now placed in the apparatus. While stirring, the organic phase is quickly run in to hydrolyze the phosphoroxy chloride; the temperature is kept at -2° C. by gradual addition of a total of 2 kg of ice. While stirring rapidly, the temperature is kept for 30 minutes at +2° C. and for a further 90 minutes at +5° C. by cooling with a total of 5 kg of dry ice introduced directly into the solution. The heavier organic phase, which now only contains the acid chloride of IV, is drained off through the cock. The apparatus is cleaned, 12 liters of water is introduced and heated to 90° C. and the organic phase is dripped in over a period of 2 hours in such a way that the carbon tetrachloride distills off azeotropically with water at the same rate. A dark brown oily impurity which still contains acid chloride settles out in the cock. The hot aqueous solution of the carboxylic acid is transferred through the cock into an enamel vessel in which it is once again boiled and cooled overnight to +5° C. The needle-shaped crystals which precipitate out are interspersed with a dark brown tar. They are mixed with 320 g of sodium hydrogen carbonate, the mixture is dissolved while boiling in 5 liters of water, the solution is cooled to 80° C. and the tar settling out on the surface is skimmed off. The solution is then cooled to 40° C., 100 g of activated carbon is stirred in, and suction filtration carried out. The filtrate is made strongly acid with about 750 ml of concentrated hydrochloric acid, whereupon IV precipitates out as a thick crystal slurry. After cooling the slurry to 10° C. it is suction filtered and the pale brown crystals are dried at 110° C. in a through-circulation drier. The product may be used in the next stage without further purification. Melting point: 186° C.; yield: 272 g (40percent).