Moureau-Mignonac ketimine synthesis

What is Moureau-Mignonac ketimine synthesis?

Blaise first reported this reaction in 1901, and it has since been extensively explored by Moureau and Mignonac since 1913. This reaction, known as the Moureau-Mignonac ketimine synthesis, involves the direct synthesis of ketimine through the reaction of a nitrile with a Grignard reagent, followed by careful hydrolysis with hydrogen chloride at low temperatures and ammonia.

Moureau-Mignonac ketimine synthesis - general reaction scheme
Moureau-Mignonac ketimine synthesis

R1, R2 = alkyl, aryl

Interestingly, the ratio of Grignard reagent to nitrile has little effect on the yield of ketimine. While some resulting ketimines can be hydrolyzed to ketones or reduced to amines, others are stable towards hydrolysis, such as 2,2,6-trimethylcyclohexyl phenyl ketimine, t-butyl-o-tolyl ketimine, and isopropyl 1-methyl-3-isopropylcyclopentyl ketimine. In fact, some ketimines, like the latter, can withstand refluxing with 6 N HCl for up to two days.

The hydrolysis of ketimine is dependent on the ketimine-enamine tautomerization and/or resonance and the steric hindrance. For monosubstituted aryl ketimine, the hydrolysis rate follows the order of meta > ortho > para.

Over time, the reaction has been improved by decomposing the nitrile-Grignard complex in a toluene solution with anhydrous ammonia. Additionally, copper (I) salt has been used to catalyze the addition of a Grignard reagent to nitrile, and the decomposition of the nitrile-Grignard complex has been improved in anhydrous methanol MeOH.

References

  • Blaise, E. E., Compt. Rend., 1901, 132, 38
  • Moureu, C. and Mignonac, G., Compt. Rend., 1913, 156, 1801
  • Moureau, C. and Mignonac, G., Compt. Rend., 1914, 158, 1395
  • Moureau, C. and Mignonac, G., Compt. Rend., 1914, 159, 149
  • Mignonac, G., Compt. Rend., 1919, 169, 237
  • Mignonac, G., Compt. Rend., 1920, 170, 936
  • Moureau, C. and Mignonac, G., “The ketimines” Ann. Chim., 1920, 14, 322
  • Moureau, C. and Mignonac, G., Compt. Rend., 1920, 170, 1353
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