H. Hatta et al., N(1)-C(5 ')-linked dimer hydrates of 5-substituted uracils produced by anodic oxidation in aqueous solution, J ORG CHEM, 66(7), 2001, pp. 2232-2239
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.