N(1)-C(5 ')-linked dimer hydrates of 5-substituted uracils produced by anodic oxidation in aqueous solution

Electrochemical dimerization reactivity has been studied for 5-substituted uracils (5XU) including thymine(1a: X = Me) and B-halouracil derivatives(1b : X = F; 1c: X = Cl; 1d: X = Br; 1e: X = I). Upon galvanostatic electrolysi s of Ar-saturated aqueous solution 1a underwent anodic oxidation to produce N(1)-C(5')- and N(1)-C(6')-linked dimer hydrates, 1-(6'-hydroxy-5',6'-dihy drothymin5'-yl)thymine (5a) and 1-(5'-hydroxy-5',6'-dihydrothymin-61-yl) (6 a), as the major products. These N-C-linked dimerizations were accompanied by the formation of novel stereoisomeric C(5)-C(5')-linked dimers (meso iso mer: 13a[meso]; racemic isomer: 13a[rac]) with a condensed tetrahydrofuran ring skeleton. Similar electrolyses of 5-fluorouracil (1b) and 5-chlorourac il (1c) also afforded the corresponding N(1)-C(5')-linked dimer hydrates, 1 -(5'-fluoro-6'-hydroxy-5",6'dihydrouracil-5'-yl)-5-fluorouracil (5b) and 1- (5'-chloro-6'-hydroxy-5',6'-dihydrouracil-5'-yl)-5-chlorouracil (5c), respe ctively, while resulting in neither N(1)-C(6')-linked dimer analogues nor C (5)C(5')-linked dimers, unlike the reactivity of la. In contrast to 1a-c, n o dimeric products were obtained from 5-bromouracil (1d) and 5-iodouracil ( 1e). The present electrochemical method was applicable to the cross-dimeriz ation into N(1)-C(5')-linked heterodimer hydrates composed of binary 5-subs tituted uracils that occurred in competition with the formation of homodime r hydrates. A mechanism of the N(1)-C(5')-linked dimerization of 1a-c has b een proposed, by which allyl-type radical intermediates with limiting mesom eric forms of N(1)-centered and C(5)-centered pyrimidine radicals (2a-c [N( 1)]/2a-c [C(5)1) are generated via anodic one-electron oxidation and subseq uent deprotonation at N(1) and undergo a head-to-tail coupling.