Pyridines 2-alkoxy-3-cyano

Hoomaert has studied Diels-Alder reactions of pyridine oquinodimethane analogs generated from functionalized o-bis(chloromethyl)pyridines <96T(52)11889>. The photochemical cycloaddition of 2-alkoxy-3-cyano-4,6-dimethylpyridine with methacrylonitrile gives a bicyclic azetine, 6-alkoxy-3,5-dicyano-2,5,8-trimethyl-7-azabicyclo[4.2.0]octa-2,7-diene, in moderate yield <96CC1349>. Regiospecific hydroxylation of 3-(methylaminomethyl)pyridine to 5-(methylaminomethyl)-2-(17/)-pyridone by Arthrobacter ureafaciens has been reported <96MI173>. 

Photochemical [2+2]cycloaddition between benzo[b]furan and 3-cyano-2-alkoxy-pyridines in benzene has been reported to follow a very interesting mechanism supported also by Frontier-MO calculations using the PM3 Hamiltonian. It is believed that the singlet excited state of the pyridine and the ground state benzofuran react to form a [2+2] adduct and is followed by ring opening to the cyclooctatriene, which cyclizes to the secondary endo- and exo-isomers shown below <00CC1201>. 

It is known that 3-aminobenzo[6]furan can be prepared from o-cyanophenols and a-halogenocarbonyl compounds with subsequent Thorpe cyclization (73JPR779). The extension of this synthesis to heteroatom substituted benzo[6]furans is straightforward (76JPR313). The reaction of potassium salts of 3-cyano-2-pyridones (e.g. 27) with a-halogenocarbonyl compounds (esters, ketones) yields 2-alkoxy-3-cyanopyridines which can be cyclized in the presence of sodium ethoxide to give 3-aminofuro[2,3-6]pyridines (Scheme 6). 

Pentafluoropyridine is known to undergo photocycloaddition with ethylene [89,90] and cycloalkenes [91] at the 3,4-position of the pyridine ring. Recently, Sakamoto et al. reported that metacrylonitrile adds to the 2,3-position of 2-alkoxy-3-cyano-4,6-dimethylpyridines (24a,b) to give 7-azabicyclo[4.2.0]octa-2,7-di-enes (25a,b) [92] (Scheme 10). This work was developed to the photocycloaddition of furan to pyridine ring as a first example (Scheme 10) [93],... 

Cyanide ion does not react with pyridine iV-oxide nor does this substance undergo the Reissert reaction. 4-Halopyridine iV-oxides are exceptional in reacting with cyanide ion in the presence of benzoyl chloride, giving the 2-cyano-4-halopyridines (149).350 In contrast to this, N-alkoxy-quaternary salts of pyridine have been found to yield... 

The presence of both electron-donor (alkoxy) and electron-acceptor (cyano or carbomethoxy) substituents at the 2- and 3-positions respectively of the pyridine ring, have unlocked its photocycloaddition chemistry, and in recent years several such reactions of these heteroarenes have been described. Previously reported additions of ethenes involved acrylonitrile derivatives, but similar processes are now described with vinyl ethers as the addend. In these systems, however, it seems that the regiochemistry of addition is very sensitive to steric influences. Thus, although the dihydroazocine (48) is formed selectively from the 3-cyano-... 

Ultraviolet irradiation of pyridines can prodnce highly strained species that can lead to isomerised pyridines or can be trapped. The three picolines and the three cyano-substituted pyridines constitute photochemical triads irradiation of any isomer, in the vaponr phase at 254 nm, results in the formation of all three isomers. From pyridines and from 2-pyridones 2-azabicyclo[2.2.0]-hexadienes and -hexenones can be obtained in the case of pyridines these are nsnally nnstable and revert thermally to the aromatic heterocycle. Pyridone-derived bicycles are relatively stable, 4-alkoxy- and -acyloxy-pyridones are converted in particnlarly good yields. Irradiation of iV-methyl-2-pyridone in aqueous solution prodnces a mixture of regio- and stereoisomeric 4n pins 4n photo-dimers. ... 

When the iV-alkoxypyridinyl compound is subjected to cyanide, it imdergoes the Reissert-Henze reaction to afford the 2-cyano-derivative with loss of the alkoxy group. Ethylation of W-oxide 311 with diethylsulfate afforded intermediate 312, which was treated with cyanide to afford the corresponding cyano-pyridine 313, an intermediate used in the synthesis of 5-adenosylmethionine decarboxylase inhibitor 314. ... 

The synthesis of this library began with the preparation of either 4- or 5-alko)y-2-cyano pyridines in parallel. While the access to 4-alkoxy derivative was easily accomplished via adulation of 5-hydroxy-2-cyano pyridine using a polymer bound base/ preparation of the 4-alko>y derivatives required the... 

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