1H NMR studies of solvent effects on hydrogen bonding in some pyridine trifluoroacetates

The chemical shifts of hydrogen bonded protons in complexes of 11 substituted pyridines with trifluoroacetic acid were examined, in five dry solvents of different activity, with respect to proton transfer and aggregation effects. The results were correlated with ΔpK_a, the Kirkwood function and E _T parameters. The solvent effect on the intersection point obtained from the plot of the chemical shift of the hydrogen bonded protons against ΔpK_a can be used, similar to an isotopic effect, to differentiate strong hydrogen bonds. The aggregation of acid–base complexes can lead to downfield or upfield shifts; the variation of chemical shift with aggregation depends on the position of the proton in the hydrogen bridge.     

The protonation of ortho-methoxy- and hydroxy-benzaldehydes in FSO3H?SbF5?SO2 solution

The protonation of o-methoxy- and o-hydroxy-benzaldehydes in FSO₃H? SbF₅? SO₂ solution was investigated by ¹H NMR spectroscopy. The formation of the Z-carbonyl protonated molecule is explained by intramolecular hydrogen bonding.     

Facile and Versatile Room-Temperature Synthesis of N,N-Disubstituted Cyanoacetamides from Malonic Ester Chloride

A general method for the synthesis of various N,N-disubstituted cyanoacetamides from readily available methyl malonyl chloride and secondary amines, including sterically demanding aliphatic and aromatic amines, is described.     

Studies on Pyrazine Derivatives,XLIII: Synthesis and Antituberculosis Activity of 6-(1,2,3,4-Tetrahydroisoquinolino) and 6-(1,3,3-Trimethyl-6-azabicyclo-[3, 2, 1]-octano)-pyrazinocarboxylic Acid Derivatives

The reactivity of the chloride atom of 2-cyano-6-chloropyrazine was used in the reactions with amines, 1,2,3,4-tetrahydroisoquinoline and 1,3,3-trimethyl-6-azabicyclo-[3,2,1]-octane, which yielded the substrates for the syntheses of a series of new derivatives. The bulk of them were tested for their tuberculostatic activity. MIC values of the most active ones ( 2a , b , 5b , 7a , 9b , and 11b ) were within 3.1–50 μ g/mL.     

Synthesis and Tuberculostatic Activity of Some 1,1-Bis-methylthio-2-nitro-ethene Derivatives

1,1-bis-methylthio-2-nitro-ethene was used as a substrate to the syntheses of new heterocyclic compounds. In the reactions, with 1-phenylpiperazine—the corresponding diaminonitroethane 1 , 1,3-diaminonitropropane, and 1,3-diaminonitropropanol—the nitromethylenotetrahydropyrimidine derivatives 2 and 3 were prepared, whereas, with o-phenylenediamine—2-nitromethyleno-benzimidazole 4 were obtained. In the condensation reactions of compounds 2 , 3 , and 4 with benzoyl isothiocyanate, the products 5 , 6 , and 7 were obtained, and afterwards two of them, 5 and 6 , were transformed into the isothiazolines 8 and 9 .

1,1-bis-(4-phenylpiperazino)-2-nitroethane ( 1 ) was exposed to the action of phenyl isothiocyanate and the derivative obtained ( 10 ) was transformed, in the reaction with phenacylbromide, in to benzoylonitrothiophene 11 . The diazo compounds 12 , 13 , and 14 were obtained in the reactions of nitromethylenotetrahydropyrimidines 2 and 3 and of 2-nitromethylenobenzimidazole 4 with benzenediazonium chloride. The derivatives obtained were tested in vitro for their tuberculostatic activity. The compounds 7 (MIC 8–32 μg/mL) and 14 (MIC 16–63 μg/mL) appeared to be the most active compounds.     

Synthesis of Some New Imidazo[4,5-B]Pyridine Derivatives Using 2-Cyanomethyl-1-Methyl-1H-Imidazo[4,5-B]Pyridine

Abstract

The reactions of 2-cyanomethyl-1-methyl-1H-imidazo[4,5-b]pyridine with isothiocyanates, nitroso compounds, acid chlorides, and thioglycolic acid were investigated. New imidazo[4,5-b]pyridine derivatives with various substituents in 2-position and derivatives of the new pyrrolo[2′,1′:2,3]imidazo[4,5-b]pyridine ring system were synthesized. The compounds obtained were tested in vitro for their tuberculostatic activity.     

Effects of low-dose ionizing radiation on α,β-globulins solutions studied by DSC

An attempt has been made to detect the effect of a small dose of ionizing radiation on the course of α,β-globulin thermal denaturation in aqueous solutions. Doses of 0.1 and 1.8 Gy have been delivered using γ-rays emitted by ⁶⁰Co isotope while doses of 10 and 100 Gy have been supplied by X-rays produced by linear accelerator. The highest dose has visibly changed DSC curve of protein solution while the changes due to lower doses are hardly detectable. Although very weak, the irradiation effect found has been dose dependent. The results suggest that the influence of ionizing radiation on globulins solution is bigger when the dose rate is lower at given dose. The opposite direction of differences between irradiated and control samples for fresh and stored protein solutions suggests various characters of changes in initial and later period of sample aging. This may be an important reason for difficulties in an investigation of the effect of ionizing radiation on protein solution, especially for low doses delivered very slowly.     

Studies on Pyrazine Derivatives,XLV: Synthesis,Reactions, and Tuberculostatic Activity of N-Methyl-N′-(pyrazine-2-carbonyl)-hydrazinecarbodithioic Acid Methyl Ester

Methyldithiocarbonyl derivative 2 of pyrazine-2-carboxylic acid N′-methyl-hydrazide 1 was synthesized by methylation of CS₂ adduct. Benzylamine caused the decomposition of compound 2 to pyrazine-2-carboxylic acid benzylamide 5 and 1,3-dibenzylthiourea 6. N-methyl-N′-(pyrazine-2-carbonyl)-hydrazinecarbodithioic acid methyl ester 2 were evidenced to cyclize to 3-methyl-5-pyrazin-2-yl-3H-[1, 3, 4]oxadiazole-2-thione 8 in the presence of triethylamine. In the reactions with secondary amines such as morpholine, pyrrolidine and phenylpiperazine pyrazinoyl derivatives (9–11) of thiosemicarbazide were obtained. Hydrazine, methylhydrazine, aminoalcohols, and N-alkylamino-substituted cyclic amines reacted with cyclization to 4-substituted 1,2,4-triazole-3-thiones 12, 13, and 18–22. Synthesized compounds exhibited low tuberculostatic activity in vitro (MIC 50–100 μg/mL).