Barbituric acids as carbon acids. Acidity relationships and 1H and 2H transfer in 1,3-dimethyl-5-tert-butyl- and 5-tert-butylbarbituric acids

Article abstract of DOI:10.1021/ja00236a027

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 k_f = k₁^H2O + k₁^OH-> with k₁^H2O = 4.0E-4/s, k₁^OH = 192 dm³/mol.s and reprotonation the rate law k_r = k_-1^H2O + k_-1^H+> with k_-1^H2O = 8.9E-3/s, k_-1^H = 1.12E6 dm³/mol.s (pH range 6.91-12.89).For the 2H(C₅) derivative the corresponding dedeuteration rates are k₁^H2O = 7.7E5/s (k_H/k_D = 5.5) and K₁^OH = 54 dm³/mol.s (k_H/k_D = 3.5).Deprotonation is catalysed by general bases (k^B dm³/mol.s, k_H/k_D), 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 pK_BH is not observed, and structural effects appear to play an important role.The measurement of precise primary kinetic isotope ratios (k_H/k_d) 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 (KH^2- is preferred by about 20:1 over the enolate dianion (EH^2-)) (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 (k₁^H2O = 2.59E-3/s, k_H/_D = 8.1) and OH(1-) dependent (k₁^OH = 800 dm³/mol.s, k_H/k_D = 3.4) reactions and via the OH(1-) dependent reactions of KH₂(1-) (k₂^OH = 0.54 dm³/mol.s).Coresspondigly, pathways for reprotonation of the enolate anions are available through the H(1+) dependent (k_-1^H = 3.2E5 dm³/mol.s) and pH independent (k_-1^H2O = 1.62E-3/s) reactions of EH^1- and through the pH independent reaction of EH(2-) (k_-2^H2O ca. 0.4/s).The known rates of C₅ deprotonation (k₁^H2O) and reprotonation (k_-1^H) for barbituric acids have been correlated with carbon acidity (K_c) via linear Broenstead relationships of slope 0.80 and 0.20, respectively (pK_c range 2.2-9.6).Barbituric acid carbon acidity is thus demonstrated to be controlled largely by substituent effects on the deprotonation reaction.