Bobbitt reaction

What is Bobbitt reaction?

Bobbitt reaction is the synthesis of 1,2,3,4-tetrahydroisoquinoline through cyclo-condensation of substituted benzylaminoacetals with hydrochloric acid, HCl, and was first reported by Bobbitt in 1965.

Bobbitt reaction
Bobbitt reaction

Bobbitt reaction is not limited to the preparation of 1-substituted isoquinolines but can also be used for the synthesis of 4-substituted and N-substituted isoquinolines. Although Quelet and Vinot initially developed a method for preparing 1-alkylisoquinolines, the use of boron trifluoride as a cyclizing reagent made it unsuitable for synthesizing oxygenated isoquinolines.

The Bobbitt reaction, on the other hand, can be modified to overcome these issues, such as by adding aliphatic Grignard reagents to the Schiff bases followed by cyclization. Additionally, N-substituted 1,2,3,4-isoquinoline can be easily prepared through reductive alkylation of benzylamine and cyclization, while 4-substituted 1,2,3,4-isoquinoline (4-OH-1,2,3,4-isoquinoline) can be synthesized through the condensation of 1,2-dihydroisoquinolines with aldehyde.

The synthesis of 1-, 4-, and N-substituted 1,2,3,4-tetrahydroisoquinolines as well as 1- and 4-substituted isoquinolines can be achieved using this reaction. Moreover, Bobbitt reaction has been utilized for synthesizing several alkaloids, including salsoline, salsolidine, carnegine, and lophocerine.

References

  • Vinot, N., Ann. Chim., 1958, 3, 461
  • Vinot, N. and Quelet, R., Bull. Soc. Chim. Fr., 1959, 1164
  • Bobbitt, J. M. and Chou, T.-T., J. Org. Chem., 1959, 24, 1106
  • Bobbitt, J. M.; Kiely, J. M.; Khanna, K. L. and Ebermann, R., J. Org. Chem., 1965, 30, 2247.
  • Bobbit J. M., Winter D. P. and Kiely J. M., J. Org. Chem., 1965, 30, 2459
  • Bobbitt, J. M.; Roy, D. N.; Marchand, A. and Allen, C. W., J. Org. Chem. 1967, 32, 2225
  • Bobbit J. M. and MooreT. E., J. Org. Chem., 1968, 33, 2958
  • Bobbitt, J. M. and Sih, J. C., J. Org. Chem. 1968, 33, 856
  • Bobbitt, J. M. and Dutta, C. P., J. Org. Chem., 1969, 34, 2001
  • Bobbitt, J. M.; Steinfeld, A. S.; Weisqraber, K. H. and Dutta, S., J. Org. Chem., 1969, 34, 2478
Shares