Hammick reaction
Hammick reaction | |
---|---|
Named after | Dalziel Hammick |
Reaction type | Coupling reaction |
The Hammick reaction, named after Dalziel Hammick, is a chemical reaction in which the thermal decarboxylation of α-picolinic (or related) acids in the presence of carbonyl compounds forms 2-pyridyl-carbinols.[1][2][3]
![The Hammick reaction](http://178.128.105.246/cars-http-upload.wikimedia.org/wikipedia/commons/thumb/d/d2/Hammick_Reaction_Scheme.png/300px-Hammick_Reaction_Scheme.png)
Using p-cymene as solvent has been shown to increase yields.[4]
Reaction mechanism
[edit]Upon heating α-picolinic acid will spontaneously decarboxylate forming the so-called 'Hammick Intermediate' (3). This was initially thought to be an aromatic ylide, but is now believed to be a carbene[5][6] In the presence of a strong electrophile, such as an aldehyde or ketone, this species will undergo nucleophilic attack faster than proton transfer. After nucleophilic attack intramolecular proton transfer yields the desired carbinol (6).
![The mechanism of the Hammick reaction](http://178.128.105.246/cars-http-upload.wikimedia.org/wikipedia/commons/thumb/2/23/Hammick-Reaktion_M-v3.svg/650px-Hammick-Reaktion_M-v3.svg.png)
The scope of the reaction is effectively limited to decarboxylating acids where the carboxyl group is α to the nitrogen, (reactivity has been reported when the acids are located elsewhere on the molecule but with low yields)[7][8] thus suitable substrates are limited to the derivatives of α-picolinic acid[3][9] including the α-carboxylic acids of quinoline and isoquinoline.
See also
[edit]References
[edit]- ^ Dyson, P.; Hammick, D. L. (1937). "362. Experiments on the mechanism of decarboxylation. Part I. Decomposition of quinaldinic and isoquinaldinic acids in the presence of compounds containing carbonyl groups". J. Chem. Soc.: 1724. doi:10.1039/jr9370001724.
- ^ Hammick, D. L.; Dyson, P. (1939). "172. The mechanism of decarboxylation. Part II. The production of cyanide-like ions from α-picolinic, quinaldinic, and isoquinaldinic acids". J. Chem. Soc.: 809–812. doi:10.1039/jr9390000809.
- ^ a b Brown, E. V.; Shambhu, M. B. (1971). "Hammick reaction of methoxypyridine-2-carboxylic acids with benzaldehyde. Preparation of methoxy-2-pyridyl phenyl ketones". J. Org. Chem. 36 (14): 2002. doi:10.1021/jo00813a034.
- ^ Sperber, N.; Papa, D.; Schwenk, E.; Sherlock, M. (1949). "Pyridyl-Substituted Alkamine Ethers as Antihistaminic Agents". J. Am. Chem. Soc. 71 (3): 887–90. doi:10.1021/ja01171a034. PMID 18113525.
- ^ Hollóczki, Oldamur; Nyulászi, László (July 2008). "Stabilizing the Hammick Intermediate". The Journal of Organic Chemistry. 73 (13): 4794–4799. doi:10.1021/jo8000035. PMID 18543975.
- ^ Lavorato, David; Terlouw, Johan K.; Dargel, Thomas K.; Koch, Wolfram; McGibbon, Graham A.; Schwarz, Helmut (1 January 1996). "Observation of the Hammick Intermediate: Reduction of the Pyridine-2-ylid Ion in the Gas Phase". Journal of the American Chemical Society. 118 (47): 11898–11904. doi:10.1021/ja961954l.
- ^ Mislow, Kurt (October 1947). "An Extension of the Scope of the Hammick Reaction". Journal of the American Chemical Society. 69 (10): 2559. doi:10.1021/ja01202a508.
- ^ Betts, M. J.; Brown, B. R. (1967). "Extension of the Hammick reaction to 2-pyridylacetic acid". Journal of the Chemical Society C: Organic: 1730. doi:10.1039/J39670001730.
- ^ Cantwell, Nelson H.; Brown, Ellis V. (March 1953). "An Investigation of the Hammick Reaction". Journal of the American Chemical Society. 75 (6): 1489–1490. doi:10.1021/ja01102a515.