Radicals addition to pyridines

The rate constant for OH radical addition cannot be calculated because the effect of the -OP(=S)(OCH2CH3)2 substituent is not known. However, because the rate constant for OH radical addition to pyridine is -3.7 x 10-13 cm3 molecule-1 s-1 (Atkinson, 1989) and the three Cl atom sustituents will markedly deactivate the ring (Brown and Okamoto, 1958) [as observed, for example, for the OH radical reactions with chlorobenzene, 1,2-, 1,3- and 1,4-dichlorobenzene, and for 1,2,4-trichlorobenzene relative to that for benzene (Atkinson, 1989)], OH radical addition to the pyridine ring is expected to be minor, and its neglect will lead to an estimated lower limit to the total reaction rate constant. 

Radical Additions to Pyridines, Quinolines, and Isoquinolines 04PHC27. 

One possible solution of this problem is to differentiate a radical first as electrophilic or nucleophilic with respect to its partner, depending upon its tendency to gain or lose electron. Then the relevant atomic Fukui function (/+ or / ) or softness f.v+ or s ) should be used. Using this approach, regiochemistry of radical addition to heteratom C=X double bond (aldehydes, nitrones, imines, etc.) and heteronuclear ring compounds (such as uracil, thymine, furan, pyridine, etc.) could be explained [34], A more rigorous approach will be to define the Fukui function for radical attack in such a way that it takes care of the inherent nature of a radical and thus differentiates one radical from the other. 

Radical addition to the pyridine ring is another known facile process and coupling of radical intermediates from the reduction of ketones to pyridines in... 

A tin-free radical cyclization of the xanthate 272 using dilauroyl peroxide (DLP), as the radical initiator, in chlorobenzene was used to give the 5//-pyrido[2,3-A azepin-8-one 273 (Scheme 35) <20040L3671>. The xanthate 272 was also made by an intermolecular free radical addition to allyl acetate, using the xanthate 271, as the radical precursor. Somewhat surprisingly in this latter case, intramolecular free radical attack on the pyridine ring did not take place. 

OH radical reaction with chloropyrofos is anticipated to proceed via OH radical addition to the pyridine ring, OH radical "interaction" with the P=S group [with a group rate constant k >P=S (Table 14.4)], and H-atom abstraction from the two -OCH2CH3 groups bonded to the P atom. The total OH radical reaction rate constant is given by ... 

A new method of preparing pyrazolopyridines from A -azinylpyridinium iV-aminides has been developed by Alvarez-Builla et al. <02SL1093> and features a radical addition to a pyridine. Initially, attempts to convert aminide 142 into pyrazolopyridine 143, through the slow addition of tris(trimethylsilyl)silane and AIBN to a refluxing acetonitrile - benzene solution of the two components, was thwarted by a competitive reduction of the N-N bond. Indeed, aminopyridine 144 was formed as the major product in 60% yield. However, through the simple expedient of adding potassium carbonate to the solution of aminide 142, that reduction pathway was almost completely shut down and the yield of pyrazolopyridine 143 was elevated from 2% to 56% (Scheme 39). 

The rates of radical additions to protonated heteroarenes correlate with the nucleophihcities of the attacking radicals [112] for example, electrophihc radicals such as CH2C02H, CH2CN and CH2N02 do not react with protonated pyridines. Furthermore, the reactivity towards aromatic substitution depends on the electro-philicity of the arene moiety, with the highest rates being observed for addition to the electron-poor 4-cyanopyridinium salts (Scheme 13.15). Similar reactions with the para-methoxy derivative may be up to 3.5 x 10 times slower [112, 113]. 

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