10045-58-6Relevant articles and documents
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Cadet et al.
, p. 2743,2747 (1979)
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Synthesis and reactivity of 5-methylenehydantoins
Fraile, José M.,Lafuente, Gustavo,Mayoral, José A.,Pallarés, Antonio
experimental part, p. 8639 - 8647 (2011/11/30)
5-Methylenehydantoin, as well as the N-mono- and N,N-di-protected derivatives, can be obtained by different synthetic routes. These compounds can undergo a large variety of reactions, such as Diels-Alder, epoxidation, methanol addition and conjugate addition reactions of different types of nucleophiles, including carbon (cyanide), nitrogen (piperidine) and sulfur (thiols, thioacetate) nucleophiles. The reactivity with electrophilic reagents, such as m-CPBA or methanol in acidic medium, and the need for Lewis acids to promote the conjugate addition reactions indicate that hydantoin is a poor electron-withdrawing group.
The reactions of thymine and thymidine with ozone
Flyunt, Roman,Theruvathu, Jacob A.,Leitzke, Achim,Von Sonntag, Clemens
, p. 1572 - 1582 (2007/10/03)
The ozonolysis of thymine and thymidine has been investigated by a product study complemented by kinetic studies using spectrophotometry, conductometry and stopped-flow with optical and conductometric detection. Material balance has been obtained. Ozonolysis of thymine (k = 3.4 × 104 dm3 mol-1 s-1) leads to the formation of the acidic (pKa = 4) hydroperoxide 1-hydroperoxymethylene-3-(2-oxopropanoyl)urea 5 (～34%), neutral hydroperoxides (possibly mainly 1-hydroperoxyhydroxymethyl-3-(2-oxopropanoyl)urea 6, total ～41%) and H2O2 (25%, with corresponding formation of 1-formyl-5-hydroxy-5-methylhydantoin 11). The organic hydroperoxides decay (～1.1 × 10-3 s-1 at 20°C, 1.3 × 10-4 s-1 at 3°C) releasing formic acid (formation of 5-hydroperoxy-5-methylhydantoin 18) and also to some extent H2O2 (and 11). After 100 min, the formic acid yield is 75%. Upon treatment at high pH, it increases to 100%. Reduction of the organic hydroperoxides with bis(2-hydroxyethyl) sulfide (k = 50 dm3 mol-1 s-1) leads to 11 whose subsequent treatment with base yields 5-hydroxy-5-methylhydantoin 13 in 100% yield. It is suggested that the Criegee ozonide formed upon reaction with ozone at the C(5)-C(6) double bond opens heterolytically in two directions with subsequent opening of the C(5)-C(6) bond. In the preferred route (75%), the positive charge resides at C(6). Deprotonation at N(1) gives rise to 5, while its reaction with water yields 6. Loss of formic acid yields 5-hydroperoxy-5-methylhydantoin 18. Reduction of 5 and 6 with the sulfide yields 11. In the minor route (25%), the positive charge remains at C(5) followed by a reaction with water. The resulting α-hydroxy hydroperoxide rapidly loses H2O2 (formation of 11). In basic solution, singlet dioxygen is formed (8%). The concomitant product, 5,6-dihydroxy-5,6-dihydrothymine has been detected. In the ozonolysis of thymidine, the rapid formation of conductance (k = 0.55 s-1) is due to the release of acetic acid (18%). In this reaction a short-lived hydroperoxide is destroyed. As a consequence of this, 25 s after ozonolysis the total hydroperoxide yield is only ～78% (including 8% H2O2). The products corresponding to acetic acid are suggested to be CO2 and N-(2-deoxy-β-D-erythropentofuranosyl)formylurea 22. A number of organic hydroperoxides have been detected by HPLC by post-column derivatisation with iodide. An acidic hydroperoxide such as 5 in the case of thymine is not among the products. Upon sulfide reduction, the organic hydroperoxides yield mainly (43-50%) N1-(2-deoxy-β-D-erythropentofuranosyl)-5-hydroxy-5- methylhydantoin 23. The reasons for some striking differences in the ozonolyses of thymine and thymidine are discussed.
EFFECT ON THYMINE HYDROPEROXIDE ON DNA BASES
Nagamatsu, Tomohisa,Yoneda, Fumio,Wang, Shiin Yi
, p. 561 (2007/10/02)
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