Pyridine-2-carbaldehydes, 6-substituted

In the classical lithiation of triazolopyridines at —40 °C with LDA in THF, the 7-lithio derivatives 71 formed are trapped by electrophiles giving 7-substituted triazolopyridines 138a-d. When the starting material was 3-(2-pyridyl)-triazolopyridine 33,19a was formed (Scheme 32), using as electrophiles 2-pyridine carbaldehyde (98T15287), 2-cyanopyridine, and in better yield, ethyl picolinate (04T5785). 

An interesting intermediate 30 was proposed to result from the sequential addition of pyridine to tetrachlorocyclopropene (31). Compound 30 represents an alkyl nitrogen ylide with two 1-chloroalkyl pyridinium moieties in the same molecule. Pyridines with electron-withdrawing groups and heterocycles with an electron-deficient nitrogen, for example, pyridine-3-carbaldehyde or quinoline, react with 31 to yield the corresponding mono-substituted products 32a and 32b (83JOC2629) (Scheme 8). 

In contrast to wild-type BFD, BAL accepts aromatic aldehydes substituted in the ortho position as well. Only a few aromatic aldehydes, such as pyridine 3- and 4-carbaldehyde as well as sterically exceedingly demanding aldehydes, resulted either in very low yields or in no benzoin condensation at all [62]. Moreover, mono- and dimethoxyacetaldehyde are good substrates for BAL, leading to highly functionalized enantiopure hydroxypropiophenone derivatives (Scheme 2.2.7.22) [63]. 

The reaction of furans with ammonia and its derivatives is of considerable synthetic utility (B-73MI31 too). Substituted furan-2-carbaldehydes and 2-acylfurans on heating with ammonia and ammonium salts, often under pressure, yield 3-hydroxypyridines. The mechanism of this reaction is thought to involve nucleophilic attack of ammonia at the 2-position. Ring opening affords an amino aldehyde or ketone and thence, by reclosure, the 3-hydroxy-pyridine (Scheme 29). A wide range of substitutents is tolerated. Primary amines with furan-2-carbaldehydes yield A-substituted pyrroles, the closure of the intermediate... 

One equivalent each of unsubstituted aniline, substituted aniline, and pyridine-2-carbaldehyde were mixed in DMSO. Following equilibration, no free aldehyde could be detected An equilibrium mixture of imines and free anilines was observed in each case. Once the equilibrium had stabilized, half of an equivalent of copper( I) was added, and the equilibrium population of the two free anilines was again measured. 

Numerous 3-(2-cyanovinyl)-substituted 1,8-naphthyridines 392 were prepared by refluxing l,8-naphthyridine-3-carbaldehydes 393 with substituted acetonitriles in alcohol in the presence of catalytic amounts of pyridine. Compounds 392 were covered by a patent as promising starting compounds for the synthesis of new drugs for the treatment of cancer, psoriasis and atherosclerosis (1996FRP2706898). 

A modification of the Westphal synthesis is based on 2-substituted pyridines 18. They are obtained by (9-acylation of the aldol adducts 17 obtained from pyridine-2-carbaldehyde and methylene ketones. The pyridines 18 are quatemized with bromoacetic ester or bromoacetonitrile to 19, followed by base-catalysed cyclization giving 2,3,4-trisubstituted quinolizinium ions 20 ... 

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