Vol. 14 No. 2(54) (2016)
Published:
2016-06-21
Full Issue
Original Researches
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Polycyclic systems with the pyridopyrimidine and pteridine nuclei
The literary sources relating to the methods for obtaining polycyclic compounds with pyridopyrimidine and pteridine subunits have been systematized and analyzed. The synthetic potential of two main approaches to the processes of formation of these types of structures has been revealed: 1) annelation of the fused pyrimidine rings to the pyridine or diazine nuclei; 2) cyclization based on functional derivatives of fused pyrimidines. It has been shown that the core structures for implementation of the first approach are usually amino(iso)nicotinic acids, heteroaromatic halogen acids, isotiocyanatopyridine carboxylates, 1H-pyrido[2,3-d][1,3]oxazine-2,4-diones and 2-amino derivatives of pyridines or diazines. The convenient tools for formation of a fused pyrimidine ring such as the cross-coupling reaction by Buchwald-Hartwig through amination of haloarenes, the radical cascade cyclization of N-acylcyanamides and the intramolecular reaction of aza-Wittig have been described. The second approach focuses on the cycle formation processes involving hydrazinopyrimidines, 2-aminopyridopyrimidines and 2-thioxopyridopyrimidones. It has been noted that the electrophilic intramolecular cyclization under the action of halogenarylchalcogenides and mineral acids is an important factor for the directed synthesis of polycyclic systems based on alkenyl fused pyridopyrimidones or pteridones. In this review a considerable attention is paid to structures that exhibit pronounced biological effects. -
The use of aliphatic aldehydes in the synthesis of new pyran annulated derivatives of 1h-2,1-benzothiazin-4-one 2,2-dioxide via domino-type interactions. The antimicrobial activity of the compounds synthesized
Domino-type Knoevenagel-Michael-hetero-Thorpe-Ziegler and Knoevenagel-hetero-Diels-Alder interactions using 1-ethyl-1H-2,1-benzothiazin-4(3H)-one 2,2-dioxide and aliphatic aldehydes as initial compounds have been studied. These reactions have led to 2-amino-3-cyano-4H-pyran and 2H-3,4-dihydropyran derivatives, respectively. It has been shown that the three-component one-pot interaction of 1-ethyl-1H-2,1-benzothiazin-4(3H)one 2,2-dioxide with saturated aliphatic aldehydes and malononitrile proceeds under rather mild conditions and results in formation of 2-amino-6-ethyl-4-alkyl-4,6-dihydropyrano[3,2-c][2,1]benzothiazin-3-carbonitrile 5,5-dioxides with moderate and high yields. At the same time, the yields of target products decrease with the increase of the length of the aliphatic aldehyde carbon chain. In this regard, the use of citronellal allowed us to obtain the product of the three-component interaction with a low yield. To date, there is no information in the literature about the possible application of aliphatic dialdehydes in such three-component interactions. It has been found that the use of glutaric aldehyde results in the synthesis of a new class of bis-derivatives of 2-amino-4H-pyran, in which two fragments are linked by the polymethylene bridge. The use of α,β-unsaturated aldehydes in the three-component interaction with 1-ethyl-1H-2,1-benzothiazin-4(3H)-one 2,2-dioxide and malononitrile was accompanied by decrease in the process efficiency compared to saturated aliphatic aldehydes. The target fused 2-amino-3-cyano-4H-pyran was obtained only when α-methylcinnamic aldehyde was used in the reaction. A two-component interaction of 1-ethyl-1H-2,1-benzothiazin-4(3H)-one 2,2-dioxide with citronellal has been also studied. It has been shown that this reaction is stereospecific. It proceeds through domino Knoevenagel-heteroDiels-Alder sequence resulting in a new heterocyclic system – 2,2a,3,4,5,6,6a,8-octahydroisochromeno[4,3-c] [2,1]benzothiazine 7,7-dioxide. The study of the antimicrobial activity of the compounds synthesized has allowed finding compounds with a moderate activity against P. aeruginosa і C. albicans. -
The study of the Complexation of Calix[4]arene and Calix[4]resorcinarene with resin acids by the RP HPLC method. binding constants determination
The Host-Guest complexation of octakis-(diphenoxyphosphoryloxy)tetramethylcalix[4]resorcinarene (CR) and 5,17-bis-(N-tolyliminomethyl)-25,27-dipropoxycalix[4]arene (CA) with 6 diterpenoid (resin) acids has been studied by the reversed phase high-performance liquid chromatography (RP HPLC). The chromatographic characteristics (retention time tR and retention factor k’) of resin acids have been determined. The lipophilicity values log P of the acids, binding constants KA (395-682 M-1 for CR and 844-1268 M-1 for CA), as well as Gibbs free energies ∆G (-14.79 – -16.14 kJ/mol for CR and -16.70 – -17.67 kJ/mol for CA) of the complexes with resin acids have been calculated. Molecular modelling of CA complexes has revealed the presence of hydrogen bonds between carboxylic groups of acids and nitrogen atoms of imino groups at the upper rim or oxygen atoms of the hydroxyl groups at the lower rim of the CA macrocycle. Molecular modelling of CR complexes has shown the presence of hydrogen bonds between carboxylic groups of acids and oxygen atoms of diphenoxyphosphoryloxy groups at the upper rim of the CR macrocycle. The effect of log P values on KA values of the CR/CA complexes has been assessed. The linear dependence of the binding constants on the acid lipophilicity indicates a significant role of solvophobic interactions on the complexation. The relationship between supramolecular (KA) and physicochemical (log P, pKa) characteristics of acids has been determined. -
5,6-dihydro-[1,2,4]triazolo[1,5-с]quinazolines. Message 3. Synthesis of 2-aryl-5-trichloromethyl-5,6-dihydro[1,2,4]triazolo[1,5-с]quinazolines and their reactivity towards n-nucleophiles
Features of 5-trichloromethyl-2-aryl-5,6-dihydro-[1,2,4]triazolo[1,5-c]quinazolines formation as result of [5+1]-cyclocondensation of the corresponding [2-(3-aryl-1H-1,2,4-triazole-5-yl)phenyl]amines with chloral hydrate are described in the article. It has been shown that this transformation is regioselective, occurs by refluxing of the initial compounds in acetic acid with formation of 2-aryl-5-trichloromethyl-5,6-dihydro-[1,2,4]triazolo[1,5-c]quinazolines. The possible mechanism of 5,6-dihydro-[1,2,4]triazolo[1,5-c]quinazolines has been proposed and substantiated. It has been shown that the reaction proceeds as step-by-step transformation that includes ANE and AN processes. The 2-phenyl-5-trichloromethyl-5,6-dihydro-[1,2,4]triazolo[1,5-c]quinazoline obtained was studied in reactions with N-nucleophiles. It has been found that regardless of the nature of nucleophile the reaction mentioned above leads to formation of 2-phenyl5-(dichloromethyl)-[1,2,4]triazolo[1,5-c]qinazoline. The mechanism of the transformation mentioned above is given; it is β-elimination on the E1cb-mechanism followed by isomerisation. The structure of the compounds synthesized has been confirmed by the complex of physicochemical methods, including 1H-, 13C-NMR-spectrometry, chromato-massspectrometry, mass-spectrometry and X-ray structural study. A detailed analysis of 1H and 13C-NMR spectral data of the compounds synthesized has been conducted. It has been found that the signals of the carbon atom in position 5 at 79.25-77.95 ppm were characteristic for 2-aryl-5-trichloromethyl-5,6-dihydro-[1,2,4]triazolo[1,5-c]quinazolines, whereas aromatization of the molecule leads to significant deshielding of this carbon atom (163.41 ppm). The prospects of further chemical modification of 2-aryl-5-(dichloromethyl)-[1,2,4]triazolo[1,5-c]quinazolines has been discussed. -
The experimental and theoretical study of tautomerism of 3-substituted 2-methyl-quinoline-4 (1h)-ones
4-Hydroxy-/4-oxo tautomerism in the series of 3-substituted 2-methyl-quinolin-4(1H)-ones has been studied by 13C NMR-spectroscopy and quantum-chemical methods in various approximations (restricted Hartree-Fock method, DFT and MP2) for the isolated molecules and for solutions using empirical correction of effects for solvents (PCM COSMO procedure). Substituents that are different in their nature have no significant influence on the value of the chemical shift of carbon in position C4 of the quinolone cycle. The only exception is the carbon shielding associated with the bromine atom in the molecule of 3-bromo-2-methyl-1,4-dihydroquinoline-4-one. Significant deshielding detected in all cases in 13C NMR-spectra of the carbon nuclei in position 4 of the ring is in favour of the existence of all derivatives studied as 4-oxo forms in DMSO-d6 solution. The experimental and calculated values for the chemical shift of carbon in position C4 of 4-oxo and 4-hydroxy isomers differ considerably and can be used as a criterion for assigning quinolin-4 (1H)-ones to a particular tautomeric form. -
The synthesis and the antimicrobial activity of anionarylation products containing the sulfonamide fragment
Products containing the sulfonamide fragment have been synthesized by anionarylation reaction. 3-(4-Sulfonamidophenyl)2-thiocyanato(bromo)propanamides, 4-(2-thiocyanato(bromo, chloro)-2-phenylethyl)benzenesulfonamides, 2-(4-sulfonamidophenyl)fumaric and 2-bromo-3-(4-sulfonamidophenyl)butanedioic acids have been obtained by the copper-catalyst reaction of 4-sulfonamidophenyldiazonium tetrafluoroborate with acrylamide, styrene and fumaric acid with the yields of 36-82%. The anionarylation competing process is formation of 4-(iso)thiocyanato(chloro, bromo)benzenesulfonamides as Sandmeyer reaction products. In case of thiocyanatoarylation of fumaric acid 2-(4-sulfonamidophenyl)fumaric acid is selectively formed as an arylation product. The structure of the compounds synthesized has been confirmed by IR- and 1H NMR-spectra. The antimicrobial activity of these compounds in relation to the museum strains of staphylococcus, E.coli, aerobic bacillus and yeasts fungi has been studied. It has been found that sulfonamide derivatives are characterized by a high antibacterial and antifungal activity, which is the most pronounced for arylalkyl thiocyanates based on acrylamide. The research conducted has confirmed the positive impact of the sulfonamide fragment introduction in the structure of anionarylation products of unsaturated compounds to expand the range of the antimicrobial activity and decrease of the minimum inhibitory concentration.
