Hantzsch dihydropyridines dehydrogenation

A series of 4-aryl-6-(l//-indol-3-yl)-2,2-bipyridine-5-carbonitriles 9 was synthesized by Perumal and co-workers [60] via a one-pot MCR of an aromatic aldehyde, a 3-(cyanoacetyl)indole, 2-acetyl pyridine and ammonium acetate by microwave irradiation under solvent-free conditions. The compounds were obtained in high yields and in a very short period of time as compared to conventional heating. Remarkably, when 2,4-dichlorobenzaldehyde was used in this reaction, only the Hantzsch 1,4-dihydropyridine was isolated which had to be separately dehydrogenated to get the targeted pyridine (Scheme 9). 

Dihydropyridine derivatives resulting from the Hantzsch synthesis are dehydrogenated to pyridines by heating with a dilute mixture of nitric acid and sulfuric acid (yields 58-65%) [ 5S] (see equation 41). 

Pyridines. Hantzsch 1,4-dihydropyridines undergo dehydrogenation on exposure to bismuth nitrate pentahydrate in HOAc at room temperature (7 examples, 50-90%). 

Aromatization. Dehydrogenation of Hantzsch 1,4-dihydropyridines occurs under an oxygen atmosphere in the presence of RuClj. 

The Hantzsch synthesis of pyridine is a method of considerable scope and flexibility. In a condensation of four components, two molecules of a p-dicarbonyl compound react with an aldehyde and ammonia giving 1,4-dihydropyridines 165 which can be dehydrogenated to pyridines 166 ... 

Aromatization. Rapid dehydrogenation of Hantzsch 1,4-dihydropyridines occurs on exposure to manganese dioxide under sonochemical conditions. 

A diverse range of carbocycles and heterocycles has been aromatized by aerobic dehydrogenation under AC catalysis [80]. Substrates include 9,10-dihydroanthracenes [81], a l,8-diaza-9,10-dihydroanthracene [82], Hantzsch 1,4-dihydropyridines [83], pyrazolines [83], 2-arylimidazolines [84, 85], indolines [86], 3,4-dihydropyrimidin-2(l//)-ones [87, 88], and various... 

The 1,4-dihydropyridines produced in this approach, carrying conjugating substituents at each p-position, are stable, and can be easily isolated before dehydrogenation classically the oxidation has been achieved with nitric acid, or nitrous acid, but other oxidants such as ceric ammonium nitrate, cupric nitrate on montmorillonite, and manganese dioxide on bentonite also all achieve this objective smoothlyIt is a corollary that Hantzsch esters can be viewed as reducing agents they have selectivity for the carbon-carbon double bond in a nitroalkene. ... 

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