Craig 2-bromo-pyridine synthesis

What is Craig 2-bromo-pyridine synthesis?

In 1915, Chichibabin and Ryasanjev reported the preparation of 2-bromopyridine from 2-aminopyridine, but the yield was low. Later, in 1934, Craig reported a modified method for producing high yields of 2-bromo-pyridine (α-position) from 2-amino-pyridine. As a result, this reaction is commonly referred to as the Craig 2-bromo-pyridine synthesis or Craig method.

Craig 2-bromo-pyridine synthesis - Craig method
Craig 2-bromo-pyridine synthesis

The Craig 2-bromo-pyridine synthesis involves adding a concentrated aqueous solution of sodium nitrite NaNO2 and 2-amino-pyridine to concentrated hydrobromic acid that has been saturated with bromine, followed by warming. To obtain an optimal yield of 2-bromo-pyridine, it has been suggested that at least 2 moles of bromine and 2.5 moles of sodium nitrite are required.

This method has been successfully employed for the preparation of both 2-bromo-pyridine and 2-bromo-pyrimidine.

Mechanism of reaction

Craig 2-bromo-pyridine synthesis mechanism

References

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