Premium
Substituent and solvent effects on tautomeric equilibria of barbituric acid derivatives and isoterically related compounds
Author(s) -
Jovanovic Misa V.,
Biehl Edward R.
Publication year - 1987
Publication title -
journal of heterocyclic chemistry
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 0.321
H-Index - 59
eISSN - 1943-5193
pISSN - 0022-152X
DOI - 10.1002/jhet.5570240136
Subject(s) - tautomer , chemistry , barbituric acid , adduct , solvent , substituent , chemical shift , thio , medicinal chemistry , solvent effects , computational chemistry , stereochemistry , organic chemistry
Abstract N ‐Mono and N,N ‐dialkyl/diarylbarbituric acids exist in solution as a single tautomer. The 13 C nmr spectroscopy shows that they are present in the triketo form in a number of polar and non‐polar solvents. 2‐Thiobarbituric acid derivatives, however, show extensive tautomerization. Their 13 C chemical shift assignments were achieved by utilizing models 11a , 11c , 12b and 12d and from which relative tautomer distribution ratios were determined. These ratios were correlated with the dielectric constant of the various solvents (ϵ). Thio‐barbituric acids also formed adducts with solvents having carbonyl groups, characteristic observed only with barbiturates possessing the thione or thiophenolic group. 6‐Amino and 6‐methyluracils and thiouracils exist in DMSO solution as stable “ ene ” forms as do orotic acid, 24 , and its thio analogue 25. Compound 25 undergoes disproportionantion and tautomerization when heated or on prolonged standing in solution. Literature contradictions regarding the structure of “4,6‐dihydroxypyrimidine,” 26 , were resolved and its tautomers in solution correctly assigned by 13 C nmr. Anions of barbiturics and related systems exist in one of the two possible types A and B, depending on whether ring nitrogens are substituted (type A), or not (type B). Rapid H/D exchange at C 5 was evident from C‐deuterium coupling. The redistribution of charge through C 4 (C 6 ) carbonyl groups shown by 13 C shifts of carbonyl carbon atoms of up to 10 ppm as compared to the CO carbons of the neutral species was evident.