Ohle quinoxaline synthesis

What is Ohle quinoxaline synthesis?

In 1887, Griess and Harrow reported this reaction first, then in 1893 it was reported by Hinsberg, and later investigated by Ohle starting in 1934. The Ohle quinoxaline synthesis involves the condensation of a monosaccharide with o-phenylenediamine to produce 2-tetrahydroxybutyl-quinoxaline, although yields are typically low (15-30%).

Ohle quinoxaline synthesis - general reaction scheme
Ohle quinoxaline synthesis

Ohle quinoxaline synthesis involves reacting fructose with hydrazine, o-phenylenediamine, and boric acid in dilute acetic acid while bubbling oxygen into the solution. While atmospheric oxygen is the typical hydrogen acceptor, hydrazine is believed to be a better acceptor and produces higher yields.

Other oxidation reagents such as hydrogen peroxide, benzoyl peroxide, hydroxylamine, methylhydrazine, phenylhydrazine, and semicarbazide have not been found to be superior to Ohle’s protocol. It is important to note that hydroxylamine, methylhydrazine, phenylhydrazine, and semicarbazide may not function as oxidation reagents under these conditions.

The tetrahydroxybutyl-quinoxaline product can be converted into flavazole derivatives when refluxed with excess hydrazine or phenylhydrazine, and the side chain of quinoxaline can be modified or removed by oxidation.

References

  • Griess, P. and Harrow, G., Ber., 1887, 20, 2205
  • Hinsberg, O., Ber., 1893, 26, 3092
  • Ohle, H., Ber., 1934, 67, 155
  • Erlbach, H. and Ohle, H., Ber., 1934, 67, 555
  • Ohle, H. and Melkonian, G. A., Ber., 1941, 74, 279
  • Ohle, H. and Hielscher, M., Ber., 1941, 71, 13
  • Ohle, H. and Iltgen, A., Ber., 1943, 76, 1
  • Ohle, H. and Kruyff, J. J., Ber., 1944, 77, 507
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