:Hammick reaction
{{Reactionbox
| Name = Hammick reaction
| Type = Coupling reaction
| NamedAfter = Dalziel Hammick
}}
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.{{cite journal |author1=Dyson, P. |author2=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 |author1=Hammick, D. L. |author2=Dyson, P. | journal = J. Chem. Soc. | year = 1939 | pages = 809–812 | 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 |author1=Brown, E. V. |author2=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 | issue = 14 }}
Image:Hammick Reaction Scheme.png
Using p-cymene as solvent has been shown to increase yields.{{cite journal |author1=Sperber, N. |author2=Papa, D. |author3=Schwenk, E. |author4=Sherlock, M. | journal = J. Am. Chem. Soc. | year = 1949 | volume = 71 | pages = 887–90 | doi = 10.1021/ja01171a034 | title = Pyridyl-Substituted Alkamine Ethers as Antihistaminic Agents | pmid=18113525 | issue = 3}}
Reaction mechanism
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{{cite journal|last1=Hollóczki|first1=Oldamur|last2=Nyulászi|first2=László|title=Stabilizing the Hammick Intermediate|journal=The Journal of Organic Chemistry|date=July 2008|volume=73|issue=13|pages=4794–4799|doi=10.1021/jo8000035|pmid=18543975}}{{cite journal |last1=Lavorato |first1=David |last2=Terlouw |first2=Johan K. |last3=Dargel |first3=Thomas K. |last4=Koch |first4=Wolfram |last5=McGibbon |first5=Graham A. |last6=Schwarz |first6=Helmut |title=Observation of the Hammick Intermediate: Reduction of the Pyridine-2-ylid Ion in the Gas Phase |journal=Journal of the American Chemical Society |date=1 January 1996 |volume=118 |issue=47 |pages=11898–11904 |doi=10.1021/ja961954l}} 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).
Image:Hammick-Reaktion M-v3.svg
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){{cite journal|authorlink1=Kurt Mislow|last1=Mislow|first1=Kurt|title=An Extension of the Scope of the Hammick Reaction|journal=Journal of the American Chemical Society|date=October 1947|volume=69|issue=10|pages=2559|doi=10.1021/ja01202a508}}{{cite journal|last1=Betts|first1=M. J.|last2=Brown|first2=B. R.|title=Extension of the Hammick reaction to 2-pyridylacetic acid|journal=Journal of the Chemical Society C: Organic|date=1967|pages=1730|doi=10.1039/J39670001730}} thus suitable substrates are limited to the derivatives of α-picolinic acid{{cite journal|last1=Cantwell|first1=Nelson H.|last2=Brown|first2=Ellis V.|title=An Investigation of the Hammick Reaction|journal=Journal of the American Chemical Society|date=March 1953|volume=75|issue=6|pages=1489–1490|doi=10.1021/ja01102a515}} including the α-carboxylic acids of quinoline and isoquinoline.