Hammick reaction

The Hammick reaction, named after Dalziel Hammick, is a chemical reaction described as a thermal decarboxylation of α-picolinic (or related) acids in the presence of carbonyl compounds to form 2-pyridyl-carbinols. [cite journal | author = Dyson, P.; Hammick, D. L. | journal = J. Chem. Soc. | year = 1937 | pages = 1724 | doi = 10.1039/jr9370001724 | title = 362. Experiments on the mechanism of decarboxylation. Part I. Decomposition of quinaldinic and isoquinaldinic acids in the presence of compounds containing carbonyl groups] [cite journal | author = Hammick, D. L.; Dyson, P. | journal = J. Chem. Soc. | year = 1939 | pages = 809 | doi = 10.1039/jr9390000809 | title = 172. The mechanism of decarboxylation. Part II. The production of cyanide-like ions from α-picolinic, quinaldinic, and isoquinaldinic acids] [cite journal | author = Brown, E. V.; Shambhu, M. B. | title = Hammick reaction of methoxypyridine-2-carboxylic acids with benzaldehyde. Preparation of methoxy-2-pyridyl phenyl ketones | journal = J. Org. Chem. | year = 1971 | volume = 36 | pages = 2002 | doi = 10.1021/jo00813a034 ]

Using p-cymene as solvent has been shown to increase yields. [cite journal | author = Sperber, N.; Papa, D.; Schwenk, E.; Sherlock, M. | journal = J. Am. Chem. Soc. | year = 1949 | volume = 71 | pages = 887 | doi = 10.1021/ja01171a034 | title = Pyridyl-Substituted Alkamine Ethers as Antihistaminic Agents]

Reaction mechanism

Upon heating α-picolinic acid will spontaneously decarboxylate forming a zwitterion (2). In the presence of a strong electrophile, such as an aldehyde, the zwitterion will react with the carbonyl faster than protonating. Upon proton transfer the desired carbinol (4) is formed.

References