反应详情

To a stirred suspension of 7-amino-3-acetoxymethylceph-3-em-4-carboxylic acid (13.5 g., 0.05 mole) in water (100 ml.) and acetone (50 ml.) was added a solution of sodium bicarbonate (9.45 g., 0.113 mole) in water (50 ml.). When a homogeneous solution was obtained, 2-methyl-1,2,4-thiadiazole-5-thiol(10 g., 0.075 mole) was added and the mixture heated at 40°-50° under nitrogen while the pH was adjusted to 7.6 by the addition of a solution of 3N HCl. The pH was maintained at 7.6 and the course of the reaction was followed by removing 0.3 ml. aliquots, adjusting the pH to 3 with 1NHCl, filtering the precipitate, washing it with acetone and then ether and examining it by infra red for the disappearance of the carbonyl absorption. The reaction was complete after 10.5 hours and the whole reaction was worked in the same way as described above for the aliquots. There was thus obtained 7-amino-3-[(2-methyl-1,3,4-thiadiazol-5-yl)thiomethyl]ceph-3-em-4-carboxylic acid. In a similar manner, but using an equivalent amount of 1-methyl-1H-tetrazole-5-thiol in place of 2-methyl-1,2,4-thiadiazole- 5-thiol, but making the initial adjustment of pH to 7.6 with sodium bicarbonate, and carrying out the reaction for 5 hours under reflux, there was obtained 7-amino-3-[(1-methyl-1H-tetrazol-5-yl)thiomethyl]ceph-3-em-4-carboxylic acid.

1. customWhen a homogeneous solution was obtained
2. temperaturethe mixture heated at 40°-50° under nitrogen while the pH
3. temperatureThe pH was maintained at 7.6
4. customby removing 0.3 ml
5. filtrationfiltering the precipitate
6. washwashing it with acetone
7. customred for the disappearance of the carbonyl absorption
8. customthe whole reaction
9. customthe reaction for 5 hours
10. temperatureunder reflux