1,5-naphthyridines and their N-oxides

The N-oxidation reactions of 2-hydroxy- and 2-amino-1,5-naphthyridines were investigated. 2-Hydroxy-1,5-naphthyridine 5-oxide and 2-hydroxy-, 2-amino-, and 2-acetamido-1,5-naphthyridine 1,5-dioxides were obtained. The structures of the compounds obtained were proved by means of IR and PMR spectroscopy.Translated from Khimiya Geterotsiklicheskikh Soedinenii, No. 9, pp. 1237–1240, September, 1972.     

Mass spectra of some aminonaphthyridines and aminoquinolines

The mass spectra of all the aminoquinolines, the 2–, 3– and 4-amino-1,5-naphthyridines, some amino-1,6-naphthyridines, and two amino-1,8-naphthyridines with methyl substituents are reported. The major fragment in the aminoquinolines is formed by the loss of HCN from the molecular ion. The most abundant fragment in the aminonaphthyridines is formed by the loss of HCN from the molecular ion except in the 2-amino-1,5-naphthyridine isomer. In both 1,8-naphthyridine isomers investigated, the loss of C₂H₂ is an alternate fragmentation pathway of significance. In all of the compounds investigated, the loss of the primary amino group from the molecular ion was found to be an insignificant fragmentation.     

Synthesis and study of the azide-tetrazole tautomerism in 2-azido-4-(trifluoromethyl)-6-R-pyrimidines (R = H, 4-ClC<Subscript>6</Subscript>H<Subscript>4</Subscript>)

Azide-tetrazole equilibrium in azidopyrimidines bearing trifluoromethyl group on the example of 2-azidopyrimidines has been studied. The latter were synthesized via nitrosation of 2-hydrazino-4-trifluoromethylpyrimidine and reaction of NaN₃ with 4-trifluoromethyl-2- chloro-6-(4-chlorophenyl)pyrimidine. The tautomeric equilibrium 5-trifluoro methyl tetrazolo[1,5-a]pyrimidine ? 2-azido-4-trifluoromethylpyrimidine was observed in the absence of solvent and in DMSO-d₆ solution, whereas in CDCl³ only an azide form exists. For 2-azido- 4-trifluoromethyl-6-(4-chlorophenyl)pyrimidine, only an azide isomer was detected in CDCl³ solution, and in DMSO-d₆ solution it is in equilibrium with 5-(trifluoromethyl)-7-(4-chlorophenyl) tetrazolo[1,5-a]pyrimidine (the tautomer ratio is 99 : 1). Thermodynamic and kinetic parameters of 5-trifluoromethyltetrazolo[1,5-a]pyrimidine ? 2-azido-4-trifluoromethylpyri midine tautomeric rearrangement in DMSO-d₆ for 5-trifluoromethyltetrazolo[1,5-a]pyrimidine were determined using the exchange spectroscopy (EXSY) technique.     

Tautomerism of pyrimidyl-2-methane derivatives: medium effects,thermodynamics, kinetics and mechanism

The Investigation of tautomeric equilibria among pyrimidyl-2-methanes has been undertaken. Pyrimidyl-pyrimidyledene equilibrium has been found in the case of 5-substituted 2-pyrimidyl-cyanoacetic esters. Unsymmetrically substituted pyrimidyl-2-methanes form two types (1-NH and 3-NH) of ylidene tautomers, which differ in ring proton spin coupling constants. The effect of substituents in the pyrimidine ring and of the solvent on tautomeric equilibrium are discussed. A drastic effect is produced by acids (CF₃ COOH) which shift the equilibrium toward the ylidene tautomer of higher basicity. The thermodynamic and kinetic characteristics and the mechanism of the tautomeric equilibrium were examined.     

Investigation of the structure of and the properties of the potentially tautomeric 1,2,3,4-tetrahydro-5,7-dimethyl-6H-pyrrolo[3,4-d]pyridazine-1,4-diones in the gaseous and aqueous phases using the AM1 semi-empirical method

Potentially tautomeric 1,2,3,4-tetrahydro-5,7-dimethyl-6H-pyrrolo[3,4-d]pyridazine-1,4-diones and their fixed tautomeric forms have been studied in order to predict their tautomeric equilibrium constants and pK_a values using semi-empirical AM1 quantum-chemical calculations at the SCF level in the gas phase and in aqueous solution. Hydroxy-oxo forms were found to be more stable than dioxo and dihydroxy forms. The results obtained from the tautomeric equilibria and basicity calculations are in good agreement with experimental data.     

Benzoid-quinoid tautomerism of schiff bases and their structural analogs: LIII. Schiff bases derived from 5-hydroxy- and 5-hydroxy-6-nitro-2,3-diphenyl-1-benzofuran-4-carbaldehydes

4-Aryl(alkyl)iminomethyl-5-hydroxy-and 4-aryl(alkyl)iminomethyl-5-hydroxy-6-nitro-2,3-diphenyl-1-benzofurans were synthesized and were shown to exist in solution as equilibrium mixtures of benzoid and quinoid tautomers. The fraction of the quinoid form increases with rise in the solvent polarity and in going from N-aryl to N-alkyl derivatives; introduction of an electron-acceptor substituent (nitro group) into the 6-position of the benzofuran system also favors formation of the quinoid tautomer. Complex formation of alkali and alkaline-earth metal cations with the 5-hydroxy-6-nitro-2,3-diphenyl-1-benzofuran-4-carbaldehyde imine having a benzo-15-crown-5 fragment on the nitrogen atom is accompanied by specific changes in the luminescence spectrum and in the state of tautomeric equilibrium, so that this system may be regarded as tautomeric fluorogenic chemosensor for metal cations.     

Tautomerism of azine derivatives. 7. Thermodynamic parameters of the 1,3-prototropic tautomeric equilibrium of azahetarylmethanes

The constants of the hetaryl-ylidene tautomeric equilibrium in CDCl₃ over a wide range of temperatures were measured for azinylmalonic and azinylcyanoacetic acid esters. High-temperature sensitivity of the position of the equilibrium for 2-pyrimidinylcyanoacetic acid esters was demonstrated. The differences in the S values of the equilibrium for derivatives of malonic and cyanoacetic acid esters were explained by different freedoms of rotation about the exocyclic C-C bond in the aromatic tautomeric form.See [1] for communication 6.Translated from Khimiya Geterotsiklicheskikh Soedinenii, No. 6, pp. 832–834, June, 1984.     

Investigation of the tautomeric equilibrium of nucleic acid bases in aqueous solution

Relative constants of acidity and basicity of nucleic acid bases (NABs) and their tautomeric forms are calculated. The general characteristic of the effect of an aqueous solvent on the tautomeric equilibrium of NABs is formulated. It is shown that during the tautomeric transformation of NABs their acid-base properties change to the opposite ones. One of possible causes of the formation of complementary pairs with rare tautomeric forms of NABs is considered.     

NMR investigation and theoretical studies on the tautomerism of β,β′-tricarbonyl compounds

The behaviour on keto–enol tautomeric equilibration of ethyl 2-benzoyl-5-(2-furyl)-3-hydroxy-penta-2,4-dienoate (1) and ethyl 2-acetyl-3-hydroxy-5-phenyl-penta-2,4-dienoate (2) was investigated by ¹H and ¹³C NMR spectroscopy in different solvents and BP86/TZVP density functional theory computations. The spectral assignment to enol and keto tautomers was performed with one- and two-dimensional techniques. The percentage of the keto form in the tautomeric equilibrium depends on solvents and rises by increasing solvent polarity. The enol–enol tautomerism is also discussed on the basis of the coupling constants ²J_C,OH, ³J_C,OH and ⁴J_H,OH, respectively.     

Protonation of 1, 5-naphthyridine derivatives

The direction of protonation (1-N or 5-N) or 2-, 2,3-, and 2,6-substituted derivatives of 1,5-naphthyridine was determined on the basis of the basicity constants.Translated from Khimiya Geterotsiklicheskikh Soedinenii, No. 7, pp. 965–968, July, 1977.     

1,2,4-Triazolo[1,5-a]benzimidazoles: Tautomerism and alkylation

The position of the tautomeric equilibrium in unsubstituted 1,2,4-triazolo[1,5-a] benzimidazole, as well as in its 2-methyl and 2-phenyl derivatives, was investigated by UV, IR, and PMR spectroscopy and by determination of the ionization constants. In all cases the amount of the 4H tautomer in the equilibrium mixture is two to three orders of magnitude greater than the amount of the 3H tautomer, while signs of the existence of the 1 H form are not observed. The synthesis of unsubstituted triazolo [1,5-a]-benzimidazole was accomplished for the first time. The alkylation of the indicated triazolo [1,5-a]benzimidazoles was studied and a relationship between the regiospecificity of this reaction and the position of the tautomeric equilibrium was established.Translated from Khimiya Geterotsiklicheskikh Soedinenii, No. 2, pp. 209–220, February, 1989.     

Benzoid-quinoid tautomerism of azomethines and their structural analogs: LIV. Dibenzo(benzo)-18-crown-6-containing Imines of 5-hydroxy-2,3-tetramethylene- and 5-Hydroxy-2,3-diphenylbenzo[<Emphasis Type="Italic">b</Emphasis>]furan-4-carbaldehydes

Dibenzo(benzo)-18-crown-6-containing N-arylimines of 5-hydroxy-2,3-tetramethylene- and 5-hydroxy-2,3-diphenylbenzo[b]-furan-4-carbaldehydes were synthesized and their spectral luminescence properties were investigated. In solutions of 6-bromo- and 6-nitro-substituted compounds a tautomeric equilibrium exists between the benzoid and quinoid forms. In the course of complexing of crown-ether-imines of 5-hydroxy-6-nitro-2,3-diphenylbenzo[b]furan-4-carbaldehyde and 5-hydroxy-6-nitro-2,3-tetramethylenebenzo[b]furan-4-carbaldehyde with cations of alkali and alkaline earth metals the content of the quinoid form was found to decrease. This phenomenon was accompanied by essential changes in the absorption and fluorescence spectra characteristic of chemosensor systems with an intramolecular charge transfer (ICT).     

Investigation of the structure of and the properties of the potentially tautomeric 1,2,3,4-tetrahydro-5,7-dimethyl-6H-pyrrolo[3,4-d]pyridazine-1,4-diones in the gaseous and aqueous phases using the AM1 semi-empirical method

Potentially tautomeric 1,2,3,4-tetrahydro-5,7-dimethyl-6H-pyrrolo[3,4-d]pyridazine-1,4-diones and their fixed tautomeric forms have been studied in order to predict their tautomeric equilibrium constants and pK_a values using semi-empirical AM1 quantum-chemical calculations at the SCF level in the gas phase and in aqueous solution. Hydroxy-oxo forms were found to be more stable than dioxo and dihydroxy forms. The results obtained from the tautomeric equilibria and basicity calculations are in good agreement with experimental data.     

Naphthyridine chemistry. VIII. The mass spectra of the 1,X-naphthyridines and some of their methyl derivatives

The mass spectra of the four parent 1,X-naphthyridines, the 2,3 and 4-monomethyl-1,5-,1,6-. and 1,8- naphthyridincs, seven dimethyl-1,8-naphthyridines, and one trimethyl-1,8-naphthyridine are reported. Evidence for an azatropylium ion intermediate in the fragmentation of the methyl compounds is presented. The fragmentation modes of the naphthyridines are similar to those for the quinolines in addition to several new processes     

New heterocyclic systems derived from pyridine: new substrates for the investigation of the azide/tetrazole equilibrium

By exploiting the reactivity of 7-alkyl-3-chloro-4-cyano-1-hydrazino-5,6,7,8-tetrahydro-2,7-naphthyridines 5 some 7-alkyl-1-azido-3-chloro-4-cyano-5,6,7,8-tetrahydro-2,7-naphthyridines 6 were synthesized. Looking at their chemical properties we have ascertained that in these compounds the azide/tetrazole equilibrium is completely shifted towards the azido form (both in solid state and in solution). Their behaviour with some amines was tested as well. Moreover by exploiting the reactivity of the chlorine and of the nitrile group we have fused on the pyridine system two new rings (pyrazole or thiophene), thus obtaining previously unknown heterocyclic systems (10 and 11). Interestingly, in these new systems, the position of the above equilibrium is reversed.     

Supramolecular solid-state structure,potential energy surfaces and evaluation of antiproliferative effect of 2-benzothiazolylhydrazone derivatives in vitro

The in situ condensation reaction of 2-hydrazinobenzothiazole with salicylaldehyde, 3,4-dihydroxybenzaldehyde, 2,4-dihydroxybenzaldehyde, 2,5-dihydroxybenzaldehyde, 2,3-dihydroxybenzaldehyde, 2-hydroxy-1-naphthaldehyde, 2-methoxy-1-naphthaldehyde, 4-methoxy-1-naphthaldehyde and 6-methoxy-2-naphthaldehyde produced 9 hydrazone Schiff bases (L1–L9, respectively) which were identified and characterized by elemental analysis, IR and NMR spectroscopy. The crystal and molecular structures of four Schiff bases (L1, L7–L9) have been determined by the single-crystal X-ray diffraction method confirming the imino form of L1 and the amino tautomeric form of L7–L9 compounds. Molecular structure analysis also confirmed that reported compounds are E-isomers relative to exo C = N imino bond. The N_hydrazino–H group of amino tautomers forms N_hydrazino–H···N_thiazolyl intermolecular hydrogen bonds shaping molecules into R ₂ ² (8) rings, while imino tautomer of L1 forms C(4) infinite helical chains via N_thiazolyl–H···N_hydrazino type of intermolecular hydrogen bond. The methoxy group (L7–L9) further shaped these primary supramolecular synthons into different supramolecular arrangements via C–H···O, C–H···N and C–H···S intermolecular hydrogen bonds. The role of aryl substituents in the shaping and stabilization of supramolecular architectures of L1, L7–L9 is supported by quantum chemical calculations. Strong antiproliferative effects on tumor cells and cytotoxic effects on fibroblasts are shown for all ligands L1–L9 with exception of L6 and L7 that had no effect on fibroblast cells.     

Mass spectral structure elucidation of substituted 4-oxazolidones,the photocycloexpansion products of 2,4-azetidindiones

Abstract-2-Methoxy-4-oxazolidone structures are assigned to the photocycloexpansion products of the substituted 2,4-azetidindiones on the basis of mass spectral evidence. A discussion is given of the mass spectra of 2-methoxy-4-oxazolidones and of their hydrolysis products, the 2-hydroxy-4-oxazolidones and the ring opened substituted 2-hydroxy-N-formyl acetamides. Ring and chain forms, when both isolated, yield completely different mass spectra, indicating that no rapid tautomeric equilibrium is established in the gas phase.     

Syntheses of di- and tetrahydropyrroles

The constants and thermodynamic parameters of the ring-chain tautomeric equilibrium of p-substituted (benzene ring) 2,3,3-trimethyl-1-aryl-2-hydroxy-5-pyrrolidones in aqueous pyridine solution were determined by PMR spectroscopy. Conversion of the ring tautomer to the open form is accompanied by an increase in the enthalpy and entropy. The AH value decreases by a factor of 2.8 kcal/mole on passing from electron-donor substituents to electron-acceptor substituants, whereas the AS value remains approximately constant and decreases by 2–4 eu only for strong electron acceptors (COOCH₃, CN, and NO₂). The correlation between the free energies and the a substituent constants in the benzene ring is discussed.See [1] for communication XII.Translated from Khimiya Geterotsiklicheskikh Soedinenii, No. 5, pp. 634–638, May, 1977.     

Reduction of 4H-imidazole N-oxides with sodium borohydride

The reduction of derivatives of 4H-imidazole N-oxides with sodium borohydride leads, depending on the presence and position of an N-oxide group, to 1-hydroxyimidazoline or imidazolidine derivatives. Under the same conditions 4H-imidazole N,N-dioxides form 1,3-dihydroxyimidazolidines. The reduction of 1-hydroxy-2,4,5,5-tetramethyl-3-imidazoline 3-oxide leads to N-(3-oximino-2-methyl-2-butyl) ethylhydroxylamine. It was observed by UV spectroscopy that 1-hydroxy-2-imidazolines exist in a tautomeric equilibrium with 2-imidazoline 3-oxides.Translated from Khimiya Geterotsiklicheskikh Soedinenii, No. 11, pp. 1557–1561, November, 1976.