A comprehensive analysis of solutions of 5‐fluorouracil (5FU) in water and an organic medium (dimethylsulfoxide, DMSO) was carried out using quantum chemical methods and nuclear magnetic resonance (NMR) spectroscopy. The details of anionic form generation in the solution of 5FU with an equimolar amount of potassium hydroxide were studied by 13С, 1Н, 15N and 19F NMR. Interpretation of NMR spectral data was carried out using quantum chemical calculations at the TPSSTPSS/6‐311+G(d,p) level of theory. Specific solvation of 5FU and 1THF‐5FU was modeled in approximation using the five‐water cluster model and solvate complex including two DMSO molecules. It was established that in an alkaline medium in DMSO 5FU occurred mainly as a type of an anion with a deprotonation on N(1) position of a pyrimidine ring whereas in water alkaline solution—as a mixture of two anions with a deprotonation on N(1) and N(3) positions with a predominant content of the latter form. For the quantitative definition of the deprotonation forms of 5FU the technique based on the data of theoretical and experimental NMR 13C spectroscopy, tested on a model compound 1‐(tetrahydrofuranyl‐2)‐5‐fluoro‐pyrimidinedione‐2,4 (tegafur, THF‐5FU), was offered. The N(3) anion was found from spectral data to be more thermodynamically stable than the N(1) anion by 2.40 kJ mol−1 (calculated value 2.24 kJ mol−1) in an alkaline–water solution. Both alkaline–water and alkaline–DMSO solutions of THF‐5FU (THF‐5FU/KOH = 1/1) were characterized by the ratio of the equilibrium concentrations of the anion and diketo‐tautomer as 9:1 and 4.3:1, respectively. Copyright © 2014 John Wiley & Sons, Ltd.

1,3-Dipolar cycloaddition of methyl diazoacetate to methyl acrylate was investigated by kinetic 1 Н NMR spectroscopy. It was established that the mechanism of the process includes parallel formation of trans-and cis-dimethyl-4,5-dihydro-3H-pyrazol-3,5-dicarboxylates as a result of [3 + 2]-cycloaddition of methyl diazoacetate to methyl acrylate; the corresponding rate constants were denoted k 1t and k 1c . The reaction rate of the isomerization of 3Нpyrazolines to 4,5-dihydro-1H-pyrazol-3,5-dicarboxylate (3Н → 1Н-pyrazoline rearrangement) was found to be sensitive to both the methyl acrylate (k 2t , k 2c ) and 1Н-pyrazoline concentrations (k 3t , k 3c ). Kinetic analysis showed that the proposed scheme is valid for various reagent concentrations. The numerical solution of the system of differential equations corresponded to the reaction scheme and was used to determine the complete set of reaction rate 500 OVCHINNIKOV ET AL. constants (k (× 10 5 M -1 ·s -1 ), 298 K; solvent, benzene-d 6 ): k 1t = 2.3 ± 0.3, k 1c = 1.6 ± 0.2, k 2t = 1.1 ± 0.3, k 2c = 1.8 ± 0.5, k 3t = 1.2 ± 0.4, k 3c = 2.2 ± 0.7. C 2013 Wiley Periodicals, Inc. Int J Chem Kinet 45: 499-

No abstract

No abstract

A scheme for the pK a estimation of organic acids in dimethylsulfoxide (DMSO) solution based on quantum chemical calculations is proposed. The procedure of pK a calculation requires several steps. The first is the calculation of the gas phase acidity of the compound. The G3MP2B3, G4MP2 as well as CBS-QB3 composite methods made it possible to estimate values of gas phase acidities of an extensive set of structures with a high confidence level (standard deviations equal to 1.15, 1.13 and 1.29 kcal mol À1 , respectively; the test set included 91 compounds). The second step is the computation of the solvation correction with the integral equation formalism version of polarizable continuum model (IEF-PCM)-B3LYP/6-311+G(d,p) approximation. Within the bounds of our approach, the medium properties were covered only by the PCM model, i.e. the proposed procedure neglects specific interactions between DMSO and the solute. It was determined that the approach to pK a estimation mentioned above is the most balanced in terms of accuracy, resource intensity and computation time cost. In the third step, the error of the pK a calculation was decreased by correlation allowances. Correlation allowances were determined for each acid class (62 С-Н, 55 N-Н, 24 O-Н and 5 S-Н acids) in the range of 50 units in terms of logarithmic scale using the test set including 146 compounds. Seven O-H acids showing the ability to form cyclic dimers were separated into a discrete group. The proposed methodology was applied to the estimation of pK a for trans-and cis-dimethyl-4,5-dihydro-3H-pyrazol-3,5-dicarboxylates as well as for 5-fluorouracil subject to competitive dissociation, the latter by N1-H or N3-H bonds.