22275-34-9Relevant articles and documents
Barbituric acids as carbon acids. Acidity relationships and 1H and 2H transfer in 1,3-dimethyl-5-tert-butyl- and 5-tert-butylbarbituric acids
Buckingham, D. A.,Clark, C. R.,McKeown, R. H.,Wong. O.
, p. 466 - 476 (1987)
Slow ionization and reprotonation at the C5 carbon atom has been observed for 1,3-dimethyl-5-tert-butyl- (1,3-Me2-5-t-Bu), 5-tert-butyl- (5-t-Bu), 1,3-diisopropyl-(1,3-iPr2), and 1,5-diisopropyl- (1,5-i-Pr2) barbituric acids (BA) in aqueous solution at 25.0 deg C and I = 0.1 mol/dm3 (NaCl).For 1,3-Me2-5-t-Bu(BA) (pK = 9.41) deprotonation follows the rate law kf = k1H2O + k1OH-> with k1H2O = 4.0E-4/s, k1OH = 192 dm3/mol.s and reprotonation the rate law kr = k-1H2O + k-1H+> with k-1H2O = 8.9E-3/s, k-1H = 1.12E6 dm3/mol.s (pH range 6.91-12.89).For the 2H(C5) derivative the corresponding dedeuteration rates are k1H2O = 7.7E5/s (kH/kD = 5.5) and K1OH = 54 dm3/mol.s (kH/kD = 3.5).Deprotonation is catalysed by general bases (kB dm3/mol.s, kH/kD), 2,6-lutidine (0.0108, 10.0), dabco (29.6, 5.5), NH3 (1.06, 7.1), EtNH2 (14.7, 5.8), Et2NH (18.0,7.2), Et3N(1.30,7.2), but a linear correlation with pKBH is not observed, and structural effects appear to play an important role.The measurement of precise primary kinetic isotope ratios (kH/kd) in water is discussed.In 5-t-Bu(BA)(KH3) ionization at C5 (pK = 8.09+/-0.12) to produce the enolate anion (EH2-) comes into competition with ionization at imide nitrogen (pK = 7.88 +/- 0.04) to produce the keto monoanion (KH2-).In strongly alkaline solution the species deprotonated at both imide nitrogen centers (KH2- is preferred by about 20:1 over the enolate dianion (EH2-)) (C5, and imide nitrogen deprotonated).Such ionizations complicate a study of proton exchange at C5 but this has been clarified by use of the 2H(C5) substituted acid (KDH2)).Deprotonation at C5 occurs via pH independent (k1H2O = 2.59E-3/s, kH/D = 8.1) and OH(1-) dependent (k1OH = 800 dm3/mol.s, kH/kD = 3.4) reactions and via the OH(1-) dependent reactions of KH2(1-) (k2OH = 0.54 dm3/mol.s).Coresspondigly, pathways for reprotonation of the enolate anions are available through the H(1+) dependent (k-1H = 3.2E5 dm3/mol.s) and pH independent (k-1H2O = 1.62E-3/s) reactions of EH1- and through the pH independent reaction of EH(2-) (k-2H2O ca. 0.4/s).The known rates of C5 deprotonation (k1H2O) and reprotonation (k-1H) for barbituric acids have been correlated with carbon acidity (Kc) via linear Broenstead relationships of slope 0.80 and 0.20, respectively (pKc range 2.2-9.6).Barbituric acid carbon acidity is thus demonstrated to be controlled largely by substituent effects on the deprotonation reaction.
Derivatives of 1-(2-deoxy-2-fluoro-β-D-arabinofuranosyl)-5-phenyluracil and 5-benzyluracil synthesis and biological properties
Dziewiszek,Schinazi,Chou,Su,Dzik,Rode,Watanabe
, p. 77 - 94 (2007/10/02)
A number of 1-(2-deoxy-2-fluoro-β-D-arabinofuranosyl)uracil and -cytosine nucleosides substituted at the 5 position with a nitrophenyl or nitrobenzyl group were synthesized from 5-phenyl- and 5-benzyluracil via condensation of the fluorinated sugar, followed by nitration. The corresponding amino analogues were also prepared by reduction of the nitro nucleosides. The uracil nucleosides were converted into the corresponding cytosine nucleosides by way of the triazole intermediates. None of these nucleosides exhibited significant activity against herpes simplex virus type 1 in Vero cells. However, cytosine nucleosides containing the o-nitrophenyl, p-nitrophenyl, p- nitrobenzyl or p-aminobenzyl substituent were found to be toxic (even at 1 μM) to uninfected Vero cells, although they were essentially nontoxic in HL- 60 cells. The 5'-monophosphates of the uracil nucleosides were inhibitors of the reaction catalyzed by purified Ehrlich ascites carcinoma thymidylate synthase, the 5-phenyluracil nucleotides causing a strong inhibition, competitive vs dUMP, described by the K(i) value of 0.01 μM.
Azidobarbiturates. I. Preparation of barbituric acid derivatives with an azido group at position 5
Toth,Makleit
, p. 139 - 145 (2007/10/02)
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