Pyridines alkoxy- from

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. ... 

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>. 

Many analogs of 75 with substituents in the pyridine rings have also been prepared ° although 6-alkoxy-2,2 -bipyridines react with ethylene dibromide to afford the pyridone 76 rather than 4-alkoxy analogs of 75. Derivatives of 75 with alkyl substituents on the ethylene bridge (i.e., 6 and/or 7 positions) can likewise be prepared from 2,2 -bipyridines and appropriate dibromoalkanes. " " 6-Hydroxy-substituted derivatives of 75, for example, compound 78, are accessible by ring closure of j8-carbonyl monoquaternary salts of 2,2 -bipyridine, such as compound 77, with acid. 

Finally, we point to the possibility of P = 0 bond formation from 1-alkoxy-X -phosphorin derivatives 124 or 125 by cleavage of alkyl cations. Also the reverse process, /. e. alkylation of the P = O moiety to form P—O—R groups is possible. The synthesis of X -phosphorins having functional groups at the C-atoms of the phosphorin ring was first made possible by the preparation of new stable X -phosphorin carbenium ions 140. Here again, the fundamental difference between phosphorin and pyridine systems comes to light Whereas carbanionic structures 139 b are stabilized in the pyridine series, in the X -phosphorin series carbenium ions as 140 b are stabilized. 

Diels-Alder reactions of oxazoles afford useful syntheses of pyridines (Scheme 53) (74AHC( 17)99). A study of the effect of substituents on the Diels-Alder reactivity of oxazoles has indicated that rates decrease with the following substituents alkoxy > alkyl > acyl >> phenyl. The failure of 2- and 5-phenyl-substituted oxazoles to react with heterodienophiles is probably due to steric crowding. In certain cases, bicyclic adducts of type (359) have been isolated and even studied by an X-ray method (87BCJ432) they can also decompose to yield furans (Scheme 54). With benzyne, generated at 0°C from 1-aminobenzotriazole and lead tetraacetate under dilute conditions, oxazoles form cycloadducts (e.g. 360) in essentially quantitative yield (90JOC929). They can be handled at room temperature and are decomposed at elevated temperatures to isobenzofuran. 

The monobenzo-fused derivatives of 1,4-dioxin, 1,4-oxathiin and 1,4-dithiin, (345), (346) and (347), can all be prepared by base-catalyzed reaction between the appropriate 1,2-disubstituted benzene and an a-haloketal via an intermediate 2-alkoxy-2,3-dihydro derivative (348). The pyrolysis of the acetoxy derivative (349) at 450°C gives (345 80%) (67ZC152). 2-Hydroxy-2-phenyl-l,4-benzodioxane, from catechol and phenacyl bromide, is dehydrated to (345) by thionyl chloride in pyridine. 

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). 

Pyridylarenes undergo Cu(II)-catalysed diverse oxidative C-H functionalization reactions. The tolerance of alkene, alkoxy, and aldehyde functionality is a synthetically useful feature of this reaction. A radical-cation pathway (Scheme 4) has been postulated to explain the data from mechanistic studies. A single electron transfer (SET) from the aryl ring to the coordinated Cu(II) leading to the cation-radical intermediate is the rate-limiting step. The lack of reactivity of biphenyl led to the suggestion that the coordination of Cu(II) to the pyridine is necessary for the SET process. The observed ortho selectivity is explained by an intramolecular anion transfer from a nitrogen-bound Cu(I) complex.53... 

As mentioned above, amines of the thienopyridine series synthesized by the Thorpe reaction always contain an electron-withdrawing substituent (acyl, alkoxy-carbonyl, etc.) at position 2. The presence of the o-aminocarbonyl fragment in these compounds makes these compounds useful as synthons for pyridine ring construction in the Friedlaender synthesis. Generally, condensation occurs in the presence of a basic catalyst. The acid-promoted synthesis can be exemplified by the preparation of tetracyclic structure 59 from pyranothienopyridine 60 (1996RFP1417446). 

Photochemical cycloaddition of 2-cyanofuran with 2-alkoxy-3-cyanopyridine results in the formation of [4+4] photoadducts 228 and 229. The latter compound is seen to arise through the intermediate 230 (Scheme 40) <2004TL4437>. Mechanistic studies show that the photoadditions proceed from the singlet-excited state of the pyridine. The preference for the formation of 228 over 229 is explained by the two heteraromatics approaching each other such as to avoid proximity of their electronegative heteroatoms. 

Fu and co-workers have shown that the l-chloro-boracyclohexa-2,4-diene 97 reacts with 4-phenylpyridine at room temperature to provide the />-terphenyl analog 26 in 76% yield as an early example of a borabenzene-pyridine-type complex (Equation 6). The X-ray structure of 26, discussed in Section 7.14.3, shows the three rings not to be coplanar <1997OM1501>. Exposure of the l-chloro-boracyclohexa-2,4-diene 98 to a stabilized carbene results in formation of the complex 29 in 83% yield as an air- and moisture-sensitive colorless powder (Equation 7), crystals of which were grown from toluene the X-ray structure of 29 has been discussed in Section 7.14.3. The use of bulky lithium bases to deprotonate the bis(amido) or bis(alkoxy)boranes 19 allows for the formation of the dianionic 2,2 -diboratabiphenyl derivatives 20 (X = NHPh, OBn), the solid-state structures of which have been discussed (Equation 8) <2006CJC81>. 

Analogous alkoxy and aryloxyrhenium complexes do not show the same reactivity. However, Brown and Mayer discovered soon thereafter that a different rhenium complex could mediate C—O bond formation.68 Photolysis of the Re(V) complex 13 led to C—H activation and formation of a phenyl rhenium oxo, 14. Yields were improved from 30-40% to 90% upon addition of pyridine to the photolysis mixture. The role of pyridine was unclear, because other tertiary amines provided no such improvement in yield. Substituted benzenes showed a preference for para activation over meta fluorobenzene also gave a significant amount of ortho activation. 

---