Hammick reaction

Formation of an ylide, which can react further with an electrophile or by proton abstraction, is defined as Type E behaviour (Scheme 51)- The ylide may arise either by nucleophilic attack at a hydrogen atom (equation 74) or by, f°r instance, an a-elimination of carbon dioxide, the Hammick reaction (Scheme 52) (70LA(732)43). 

The relatively easy decarboxylation of a- (682) and y-carboxylic acids is a result of inductive stabilization of intermediate ylides of type (683) (cf. Section 3.2.1.8.2). By carrying out the decarboxylation in the presence of aldehydes or ketones, products of type (684) are formed (Hammick Reaction). 

Hammick reaction. Decarboxylation of a-pi-colinic or related acids in the presence of carbonyl compounds accompanied by the formation of a new carbon-carbon bond. 

There is little to differentiate these derivatives from benzenoid acids and esters, save for the easy decarboxylation of quinoline-2- and isoquinoline-1-acids, via an ylide that can be trapped with aldehydes as electrophiles - the Hammick reaction. Loss of carbon dioxide from A-methylquinolinium-2- and -isoquinolinium-1-acids, and trapping of resulting ylides, can be achieved with stronger heating. ... 

The Hammick reaction ipso substitution by an electrophile of a carboxylic group under decarboxylation conditions) with pyridazine-3-carboxylic acid is not very successful, but it is considerably improved by the use of the TMS ester. Thus, trimethylsilyl pyridazine-3-carboxylate reacts with aldehydes to give, probably via an ylide, good yields of TMS protected alcohols (Scheme 50). The trimethylsilyloxy product is readily desilylated, so this process is equivalent to the reaction of a 3-pyridazinyl organometallic reagent with an aldehyde <88T328i>. 

These compounds all closely resemble the corresponding benzene compounds in their reactivity because the carbonyl group cannot interact mesomerically with the ring nitrogen. The pyridine 2- (picolinic), 3- (nicotinic), and 4- (isonicotinic) acids exist almost entirely in their zwitterionic forms in aqueous solution they are slightly stronger acids than benzoic acid. Decarboxylation of picolinic acids is relatively easy and results in the transient formation of the same type of ylide which is responsible for specific proton a-exchange of pyridine in acid solution (see section 5.1.2. ). This transient ylide can be trapped by aromatic or aliphatic aldehydes in a reaction known as the Hammick reaction. As implied by this mechanism, quaternary salts of... 

Mechanism of Hammick reaction was studied using intramolecular cyclization reactions with 3-0-acylated-3-hydroxypicolinic acids (94H(37)1731>. 

Other references related to the Hammick reaction are cited in the literature. ... 

Haller-Bauer Reaction Haloform Reaction Hammick Reaction Hantzsch Dihvdropvridine Synthesis Hantzsch Pyrrole Synthesis Harries Ozonide Reaction... 

An attempt to perform a Hammick reaction on 2-pyridylacetic acid to obtain a variety of alcohols gave only 2-picoline. However, the sodium salt of this acid was successfully converted to a variety of alcohols (XI-78). Apparently, the free add provides the proton necessary to form 2-picoline, whereas the sodium salt does not. 

HaLothienylaa inopyridines, 90 Hammick reaction, with 2-pyridy-lacetlc acid, 351 Hexamethylene-bis-2- [6-p-meth-oxyphenyl-4-(lff)-pyr idone), 610... 

Hammick reaction 705 Hinsberg synthesis of amines 54 Hofmann elimination, eis elimination 415... 

Ultimately, then, all of the peraminoethylene syntheses from dipolar halves have depended upon the acidity of the central proton of a formamidinium ion. Thus all were foreshadowed by the pioneering work of Breslow on the mechanism of thiamine action and, more remotely, by Hammick s study of the decarboxylation of certain heterocyclic acids The Hammick reaction, illustrated in equation (4), led its discoverer to conclude that decarboxylation yields dipolar... 

Concerning the pyridine-carboxylic acids Table 6.2), there has already been mentioned their tautomerism (p. 154), betaine and ester formation with alkylating reagents (p. 182), and the Hammick reaction (p. 163). 

The Hammick reaction (p. 163) provides some evidence for this view. Kinetic data for the decarboxylation of picolinic and methylpicolinic acids are given in Table 6,3. Methyl groups have the expected effect, but the results and those for reaction in a range of solvents do not permit choice between the zwitterion (10) and the form (11) as the entity undergoing decarboxylation" . 

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