Synthesis,reactions, and antimicrobial activity of some novel pyrazolo[3,4-d]pyrimidine,pyrazolo[4,3-e][1,2,4]triazolo[1,5-c]pyrimidine,and pyrazolo[4,3-e][1,2,4]triazolo[3,4-c]pyrimidine derivatives

Treatment of N-phenyl-substituted benzenecarbo-hydrazonoyl chlorides 1a - d with malononitrile in sodium ethoxide solution gave 5-amino-4-cyanopyrazole derivatives 2 - 5 . Compounds 2 - 5 were converted to formidate derivatives 6 - 9 upon treatment with TEOF in acetic anhydride. The reaction of the latter products 6 - 9 with hydrazine hydrate gave imino-amino derivatives 10 - 13 , which was converted to hydrazino derivatives 14 - 17 by refluxing with hydrazine hydrate. Hydrazino as well as imino-amino derivatives undergo condensation, cyclization, and cycloaddition reactions to give pyrazolo[3,4-d]pyrimidine 18 - 21 , pyrazolo[4,3-e][1,2,4]triazolo-[3,4-c]pyrimidine 22 - 27 , and pyrazolo[3′,4′:4,5]pyrimido[1,6-b][1,2,4]triazine 42 - 44 derivatives. Antimicrobial studies are performed using two Gram-positive bacteria and two Gram-negative bacteria. Data indicated that compounds 5 , 28D , 29B , and 31D are exploring elevated antibacterial effects against all strains tested. Compound 28D is the most promising antibacterial agent against the delicate bacterial strain Bacillus subtilis and Pseudomonas aeruginosa with high effectiveness (low minimum inhibitory concentration [MIC] value) 40 and 60 μg/mL, respectively.     

SYNTHESIS AND CRYSTAL STRUCTURE OF 3-(METHYLMER-CAPTO)PHENANTHRO[9,10-e] 1,2,4-TRIAZINE

<正> The title compound was synthesized by a new method and its crystal structure was determined by X-ray diffraction analysis. C16H11N3S, Mr = 277. 34, triclinic system, space group P1, cell parameters: a = 10. 410(4), b = 17. 953(5), c = 7. 468(3)(?), α=101. 47(3)°,β=110. 85(3)°, γ = 81. 53(3)°, V = 1273.8(8) (?)3, Z = 4 and Dc=1. 45gcm-3. Refinements of full-matrix least-squares converged at R = 0. 053 and Kw = 0.065 for 2794 observed reflections. There are two independent molecules in an asymmetric unit. All non-hydrogen atoms of phenanthro[9,10-e]-1,2,4-triazine make up a 18 18 large conjugated plane.     

Unusual scission of 3,7-dichlorobisisothiazolo[4,5-b:4",5"-e]pyrazine by nucleophiles

The reaction of 3,7-dichlorobisisothiazolo[4,5-b:4",5"-e]pyrazine with MeONa in MeOH afforded 3-chloro-5,6-dimethoxyisothiazolo[4,5-b]pyrazine. The reactions of the former with benzylamine, morpholine, and aniline gave rise to the corresponding N,N"-bis(5-amino-3-chloroisothiazol-4-yl)diazenes. In the case of benzylamine, 3,7-bis(benzylamino)bisisothiazolo[4,5-b:4",5"-e]pyrazine was isolated as a by-product. The crystal structure of N,N"-bis(5-benzylamino-3-chloroisothiazol-4-yl)diazene was established by X-ray diffraction analysis.     

Fused-ring thiadiazines: preparation and crystallographic characterization of 3-phenyl derivative of benzo-, pyridio[2,3-e]-, pyrazino[2,3-e]-, and tetrafluorobenzo-[1,2,4]thiadiazines

Four bicyclic 4H-[1,2,4]thiadiazines 1a-d were prepared in 74-88% yields in two steps from the corresponding amidines 2. Three of them, 1a, 1b, and 1d, were obtained by thermal elimination of propene from the intermediate S-propylsulfilimines 12. The pyrazino derivative 1c was formed upon thermolysis of sulfoxide 14c obtained from 2c. The E(i) mechanism was investigated using DFT methods. The elimination in the sulfilimine appears to be more favorable by about 2 kcal/mol than in the analogous sulfoxide. Crystal and molecular structures of three out of the four thiadiazines were established by single-crystal X-ray analysis. All thiadiazines were found as the 4H tautomers with the heterocyclic ring puckered along the S(1)...N(4) line. The benzo derivative 1a forms a unidimensional N(4)-H...N(2) chain, the pyrazino derivative 1c forms dimeric pairs with two synergistic hydrogen bonds, and the crystal structure of 1d is characterized by strong C(6)F(4)...C(6)H(5) quadrupolar interactions.     

Functional [6]pericyclynes: aromatization to substituted carbo-benzenes

Reductive treatment of stereoisomeric mixtures of variously substituted hexaoxy[6]pericyclynes with SnCl(2)/HCl led to the corresponding substituted carbo-benzenes. Tetramethoxyhexaphenyl[6]pericylynediol and dimethoxyhexaphenyl[6]pericyclynetetrol thus proved to be alternative precursors of hexaphenyl-carbo-benzene, previously described. Another hexaaryl-carbo-benzenic chromophore with 4-pyridyl and 4-anisyl substituents was targeted for its second-order nonlinear optical properties and was obtained by aromatization of a dimethoxy[6]pericyclynetetrol. Two alkynyl substituents in para positions were also found to be compatible with the C(18) carbo-benzene ring, provided that the four remaining vertices are substituted by phenyl groups. In the protected series, bis(trimethylsilylethynyl)hexaphenyl-carbo-benzene (C(18)Ph(4)(C triple bond C-TMS)(2)) could be isolated and fully characterized, even by X-ray crystallography. In the bis-terminal series, the diethynylhexaphenyl-carbo-benzene C(18)Ph(4)(C triple bond C-H)(2) could not be isolated in the pure form. It could, however, be generated by two different methods and identified by the corresponding (1)H NMR spectra. Unsubstituted carbo-benzene C(18)H(6) remains unknown, but tetraphenyl-carbo-benzenes C(18)Ph(4)H(2) with two unsubstituted vertices proved to be viable molecules. Whereas the "para" isomer could be characterized by MS and (1)H and (13)C NMR spectroscopy only in a mixture with polymeric materials, the "ortho" isomer (with adjacent CH vertices) could be isolated, and its structure was determined by using X-ray crystallography. The structure calculated at the B3PW91/6-31G** level of theory turned out to be in excellent agreement with the experimental structure. The (1)H and (13)C NMR chemical shifts of hexa- and tetraphenyl-carbo-benzenes were also calculated at the B3LYP/6-31+G** level of theory and were found to correlate with experimental spectra. The remote NMR deshielding of peripheral protons (through up to five bonds) revealed a very strong diatropic circulation around the C(18) ring, regardless of the substitution pattern. In full agreement with theoretical investigations, it has been demonstrated experimentally that the carbo-benzene ring is "independently" aromatic, in accord with structural-energetic and -magnetic criteria.     

Diacenaphtho[1,2-c:1,2-e]-1,2-dithiin: synthesis, structure and reactivity

Diacenaphtho[1,2-c:1^′,2^′-e]-1,2-dithiin 2 was synthesized in 23% yield by the reaction of acenaphthylene with elemental sulfur at 120 °C. This reaction also afforded either diacenaphtho[1,2-b:1^′,2^′-d]thiophene 1 or diacenaphtho[1,2-b:1^′,2^′-e]-dihydro[e]-1,4-dithiin 3 depending on the reaction time. Compound 2 was desulfurized and converted to 1 under UV-vis irradiation in a benzene solution. Reaction of 2 with Pt(COD)₂ yielded the complex Pt(COD)(C₂₄H₁₂S₂) 4 (COD=1,5-cyclooctadiene) by insertion of a Pt(COD) group into the S-S bond of 2. When heated, 4 was desulfurized and converted to 1 by elimination of a (COD)PtS grouping. Compounds 1-4 were characterized crystallographically.     

60]Fullerene adducts with improved electron acceptor properties [In Process Citation

The synthesis of C(60)-based dyads in which the C(60) core is covalently attached to a strong electron acceptor moiety such as quinones, TCNQ or DCNQI derivatives, has been carried out by 1, 3-dipolar cycloaddition of "in situ" generated azomethyne ylides or nitrile oxides to C(60). As expected, the obtained pyrrolidino[3', 4':1,2][60]fullerenes exhibit reduction potentials of the C(60) framework which are cathodically shifted in comparison with the parent C(60). In contrast, isoxazolo[4',5':1,2][60]fullerenes show reduction waves for the fullerene core that are anodically shifted in comparison with the parent C(60), which indicates that they are remarkably stronger acceptors than C(60).The electron acceptor organic addend also undergoes an anodic shift due to the electronic interaction with the C(60) moiety. The molecular geometry of pyrrolidinofullerenes has been calculated at the semiempirical PM3 level and reveals a highly distorted geometry for the acceptor moiety in compound 13, and a most stable conformation in which both dicyanomethylene units are far away from the C(60) surface.     

Pyrazolo[3,4-e] [1,4] thiazepines: Synthesis and structure proof

Pyrazolo[3,4-e][1,4]thiazepine derivatives were obtained by reacting 5-amino-1,3-dimethylpyrazole with arylaldehydes or ketones and mercaptoacetic acid. The structure proof of these derivatives was carried out by identifying the benzylpyrazole products obtained by desulfurization and subsequent hydrolysis, and by comparison of the spectral data of a series of analogous pyrazolothiazepines. Treating the pyrazolothiazepines with sodium hydride and methyl iodide in dimethylformamide or dimethylsulfoxide resulted in a ring contraction with the elimination of sulfur, to yield the pyrazolopyridones in addition to the N-methylpyrazolothiazepines.     

Benzofurobenzthiazole: VI—1H- und 13C-NMR-Spektren von 2-Aminobenzofuro[2,3-f] benzthiazol und 2-Aminobenzofuro[2,3-e]benzthiazol im Vergleich mit Dibenzofuran und 2-Aminobenzthiazol

Cyclization of 3-dibenzofurylthiourea under the conditions of the Hugershoff reaction gives the linear structure 1. ¹H n.m.r. and ¹³C n.m.r. spectra of the two isomeric aminobenzofurobenzothiazoles (1 and 3), recorded at 220 MHz, 60 MHz and 22,62 MHz respectively, were used as aids for the structure determination. The magnetic parameters were obtained partly by first-order analysis and partly by simulation of spectra using LAOCOON 3. The assignments were made by comparing the chemical shifts and coupling constants with those of the parent compounds dibenzofuran (4a) and 2-aminobenzothiazole (5c). In so far as the assignments of ¹H n.m.r. and ¹³C n.m.r. frequencies of the parent compounds themselves were unknown or supported by analogy only, they have been determined using experimental criteria such as deuterium substitution and investigation of changes in chemical shifts caused by derivation.     

Efficient synthesis of some novel furo[3,2-e]pyrazolo[3,4-b]pyrazines and related heterocycles

A series of novel 6-functionalized-5-amino-3-methyl-1-phenyl-1H-furo[3,2-e]pyrazolo[3,4-b]pyrazines (4a–c) was synthesized by the reaction of 3-methyl-6-oxo-1-phenyl-6,7-dihydro-1H-pyrazolo[3,4-b]pyrazine-5-carbonitrile (2) with α-halocarbonyl compounds such as: diethyl 2-bromomalonate, phenacyl bromide and chloroacetone. Cyclocondensation of the amino benzoyl 4b with diethyl malonate yielded the oxopyridine carboxylate derivative 5. Also, the starting intermediate amino ester compound 4a was allowed to react with ethanol amine to afford the hydroxyethyl caboxamide derivative 6. Furthermore, hydrazinolysis of the amino ester 4a afforded the corresponding amino carbohydrazide 7 which was used as a versatile precursor for synthesis of other heterocyclic compounds attached or fused to the furopyrazolopyrazine moiety. The chemical structures of the newly synthesized compounds were confirmed on the basis of elemental and spectral analyses containing FT-IR, ¹H NMR, ¹³C NMR, and mass spectrometry hoping these molecules should allow us to investigate their pharmacological activities in the future study.     

Bispyrazole[3,4-b∶4′,3′-e]pyrazines as. self-condensation products from 4,5-diaminopyrazoles

Bispyrazolo[3,4-b4,3-e]pyrazines have been obtained by self-condensation of 4,5-diaminopyrazoles and their structures confirmed by independent synthesis. The spectral data for these compounds is discussed.Translated from Khimiya Geterotsiklicheskikh Soedinenii, No. 9, pp. 1222–1225, September, 1988.     

6,7,8,9-Tetrahydrodipyrimido[4,5-b][4′,5′-e][1,4]thiazine derivatives. Synthesis and structure

The reaction of 5-amino-6-mercaptopyrimidines with 1,3-dimethyl-5-nitro-6-chlorouiracil in the presence of bases results in derivatives of 6,7,8,9-tetrahydrodipyrimido[4,5-b][4,5-e][1,4]-thiazine. If the 5-amino-6-mercaptopyrimdine contains a free or alkyl-substituted amino group at the 4-position, the tetrahydrodipyramidothiazines formed exist in a free radical form. The structure of the compounds formed has been established by spectral methods.Translated from Khimiya Geterotsiklicheskikh Soedinenii, No. 2, pp. 258–264, February, 1989.     

Synthesis of crown containing imidazo[4,5-e] and-[5,4-e][1,4]diazepines

Starting from benzocrown substituted 4(5)-aminoimidazole-5(4)-carboxamides we have, for the first time, prepared benzocrown imidazo[4,5-e]-and-[5,4-e][1,4]diazepines-cyclic homologs of the corresponding xanthines.A. V. Bogatskii Physicochemical Institute, National Academy of Sciences of Ukraine, Odessa 270080. Translated from Khimiya Geterotsiklicheskikh Soedinenii No. 6, pp 828–831, June, 1998.     

Fullerene encapsulation with calix[5]arenes

This paper presents the synthesis of the fullerene hosts based on the calix[5]arenes and their binding properties. Calix[5]arenes 1a, 2, 3a bind C₆₀ or C₇₀ in organic solvents. The solvent effect of the fullerene complexation was clearly observed; the association constant decreases in a solvent with high solubility for C₆₀. Covalently linked double-calix[5]arenes 4-6 were also investigated on their binding properties for fullerenes in organic solvents. Their binding abilities for both C₆₀ and C₇₀ are extremely high in toluene solution. Higher binding selectivity toward C₇₀ is observed by all the double-calix[5]arenes. The selectivity of 5a toward C₇₀/C₆₀ is highest in toluene with a value of 10. The structures of the supramolecular complexes of the calix[5]arene hosts and C₆₀ or C₇₀ were investigated by using ¹H and ¹³C NMR studies. The molecular mechanics calculation and X-ray structure reveal that the interior of the calix[5]arene is complementary to the exterior of C₆₀ molecule. In contrast, the host-guest complexes of C₇₀ with the simple calix[5]arenes take many conformational options due to its less symmetric shape. The molecular mechanics calculation and our chemical shift simulation nicely worked to estimate the reliable structures; the calix[5]arene cavity takes up C₇₀ molecule, and the C₇₀ molecule tilts significantly from the C5 axis of the calix[5]arene. In the case of the host-guest complex of C₇₀ with the double-calix[5]arene, the molecular dynamics simulation of the host-guest complex represented the realistic movement of the bound C₇₀ inside the cavity. The combination of the molecular dynamics simulation and the chemical shift simulation of the host-guest complex suggested that the C₇₀ molecule rapidly moves inside the cavity.     

Synthetic, electrochemical, and theoretical studies of tetrairidium clusters bearing mono- and bis[60]fullerene ligands

Heating a mixture of Ir(4)(CO)(9)(PPh(3))(3) (1) and 2 equiv of C(60) in refluxing chlorobenzene (CB) affords a "butterfly" tetrairidium-C(60) complex Ir(4)(CO)(6){mu(3)-kappa(3)-PPh(2)(o-C(6)H(4))P(o-C(6)H(4))PPh(eta(1)-o-C(6)H(4))}(mu(3)-eta(2):eta(2):eta(2)-C(60)) (3, 36%). Brief thermolysis of 1 in refluxing chlorobenzene (CB) gives a "butterfly" complex Ir(4)(CO)(8){mu-k(2)-PPh(2)(o-C(6)H(4))PPh}{mu(3)-PPh(2)(eta(1):eta(2)-o-C(6)H(4))} (2, 64%) that is both ortho-phosphorylated and ortho-metalated. Interestingly, reaction of 2 with 2 equiv of C(60) in refluxing CB produces 3 (41%) by C(60)-assisted ortho-phosphorylation, indicating that 2 is the reaction intermediate for the final product 3. On the other hand, reaction of Ir(4)(CO)(8)(PMe(3))(4) (4) with excess (4 equiv) C(60) in refluxing 1,2-dichlorobenzene, followed by treatment with CNCH(2)Ph at 70 degrees C, affords a square-planar complex with two C(60) ligands and a face-capping methylidyne ligand, Ir(4)(CO)(3)(mu(4)-CH)(PMe(3))(2)(mu-PMe(2))(CNCH(2)Ph)(mu-eta(2):eta(2)-C(60))(mu(4)-eta(1):eta(1):eta(2):eta(2)-C(60)) (5, 13%) as the major product. Compounds 2, 3, and 5 have been characterized by spectroscopic and microanalytical methods, as well as by single-crystal X-ray diffraction studies. Cyclic voltammetry has been used to examine the electrochemical properties of 2, 3, 5, and a related known "butterfly" complex Ir(4)(CO)(6)(mu-CO){mu(3)-k(2)-PPh(2)(o-C(6)H(4))P(eta(1)-o-C(6)H(4))}(mu(3)-eta(2):eta(2):eta(2)-C(60)) (6). These cyclic voltammetry data suggest that a C(60)-mediated electron transfer to the iridium cluster center takes place for the species 3(3)(-) and 6(2)(-) in compounds 3 and 6. The cyclic voltammogram of 5 exhibits six well-separated reversible, one-electron redox waves due to the strong electronic communication between two C(60) cages through a tetrairidium metal cluster spacer. The electrochemical properties of 3, 5, and 6 have been rationalized by molecular orbital calculations using density functional theory and by charge distribution studies employing the Mulliken and Hirshfeld population analyses.     

Gas-phase methylation of [60]fullerene

Direct methylation of [60]fullerene via a gas-phase reaction in a CH4/H2 atmosphere was performed using a modified hot filament chemical vapor deposition method. Pressures were varied from 10 to 60 mbar and the substrate was maintained at 690 degrees C. High-resolution matrix-assisted laser desorption ionization (MALDI) mass spectrometry analysis showed signals corresponding to C60H18-2n(H,CH3)n. Collision-induced dissociation experiments confirmed a maximum of 18 ligands possible to the [60]fullerene cage.     

Synthesis of 1H-pyrazolo[3,4-e]-s-triazolo[3,4-c]-as-triazines, 8H-pyrazolo[3,4-e]tetrazolo[5,1-c]-as-triazine and 1,7-dihydro-8H-pyrazolo[3,4-e]-as-triazine derivatives

3-Hydrazino-7-methyl-5-phenyl-5H-pyrazolo[3,4-c]-as-triazine 1 underwent ring closure and/or condensation reaction with formic acid, acetic acid, acetic anhydride and benzoyl chloride to afford 1H-pyrazolo-[3,4-d]-s-triazolo[3,4-c]-as-triazines 2, 5 and 7a and/or N-acyl derivatives 3, 4 and 6 . N-Acyl derivatives 3 and 6 underwent cyclisation reaction on treatment with phosphoryl chloride to give 5 and 7a . 3-Methyl-1-phenyl-8-aryl-1H-pyrazolo[3,4-e]-s-triazolo[34,-c]-as-triazines 7 were also prepared by the reaction of the hydrazono derivatives 8 wit thionyl chloride. On treatment of 1 with nitrous acid gave the 8H-pyrazolo[3,4-e]tetrazolo-[5,1-c]-as-triazine 9 . Compound 1 underwent ring closure with carbon disulphide or ethyl chloroformate to 1,7-dihydro-8H-pyrazolo[3,4-e]-s-triazolo[3,4-c]-as-triazine derivatives 10 and 12 . Reaction of 1 with ethyl acetoacetate or acetylacetone gave 3-pyrazolo derivatives 13 and 14 .     

Alkylation of 1-hydroxy-1H-[1,2,3]triazolo[4,5-e][1,2,3,4]tetrazine 5,7-dioxide

Alkylation of 1-hydroxy-1H-[1,2,3]triazolo[4,5-e][1,2,3,4]tetrazine 5,7-dioxide 1 and its silver salt 10 with different alkylating agents (diazomethane, diazoacetone, bromoacetone, α-bromoacetophenone, methyl iodide, methyl vinyl ketone) was studied. Alkylation of compound 1 with diazo compounds and salt 10 with halocompounds results predominantly in O-alkylation products, 1-alkoxy-1H-[1,2,3]triazolo[4,5-e][1,2,3,4]tetrazine 5,7-dioxides. The Michael reaction of compound 1 with methyl vinyl ketone involves the triazole nitrogen atom to give 1-(3-oxobutyl)-1H-[1,2,3]triazolo[4,5-e][1,2,3,4]tetrazine 3,4,6-trioxide. The structures of the compounds synthesized were established by ¹H, ¹³C, ¹⁴N NMR spectroscopy and mass spectrometry.     

Synthesis of pyrido[3,2-e]pyrrolo[2,1-c][1,2,4]triazines from pyrido[3,2-e][1,2,4]triazine derivatives

In carrying on our interest in heteropolycyclic structures with biological activities, we projected the preparation of compounds containing the pyrido[3,2-e][1,2,4]triazine or pyrido[2,3-b][1,4]triazepine systems. The established synthetic approach for the preparation of latter system led to the triazine derivatives 5a-f while a new bicyclic triazepine structure 6 is accomplished with difficulty. In expanding the pyridotriazine structure, we obtained derivatives of a new tricyclic structure, 5-substituted-6a-ethyloxycarbonyl-5,6,6a,7-tetrahydropyrido[2,3-e]pyrrolo[2,1-c][1,2,4]triazin-9(8H)-ones 8 in which the triazine ring is fused with a pyrrole nucleus. Compounds 5a-f and 8a,b will be tested as potential CNS depressant, antiinflammatory, analgesic and antibacterial agents.     

Stereoelectronic effects in ring-chain tautomerism of 1,3-diarylnaphth[1,2-e][1,3]oxazines and 3-alkyl-1-arylnaphth[1,2-e][1,3]oxazines

The disubstitution effects of X and Y in 1-(Y-phenyl)-3-(X-phenyl)-2,3-dihydro-1H-naphth[1,2-e][1,3]oxazines on the ring-chain tautomerism, the delocalization of the nitrogen lone pair (anomeric effect), and the (13)C NMR chemical shifts were analyzed by using multiple linear regression analysis. Study of the three-component equilibrium B<==>A<==>C revealed that the chain<==>trans (A<==>B) equilibrium constants are significantly influenced by the inductive effect (sigma(F)) of substituent Y on the 1-phenyl ring. In contrast, no significant substituent dependence on Y was observed for the chain<==>cis (A<==>C) equilibrium. There was an analogous dependence for the epimerization (C<==>B) constants of 1-(Y-phenyl)-3-alkyl-2,3-dihydro-1H-naphth[1,2-e][1,3]oxazines. With these model compounds, significant overlapping energies of the nitrogen lone pair was observed by NBO analysis in the trans forms B (to sigma*(C1-C1'), sigma*(C1-C10b), and sigma*(C3-O4)) and in the cis forms C (to sigma*(C1-H), sigma*(C1-C10b), and sigma*(C3-O4)). The effects of disubstitution revealed some characteristic differences between the cis and trans isomers. However, the results do not suggest that the anomeric effect predominates in the preponderance of the trans over the cis isomer. When the (13)C chemical shift changes induced by substituents X and Y (SCS) were subjected to multiple linear regression analysis, negative rho(F)(Y) and rho(F)(X) values were observed at C-1 and C-3 for both the cis and trans isomers. In contrast, the positive rho(R)(Y) values at C-1 and the negative rho(R)(X) values at C-3 observed indicated the contribution of resonance structures f (rho(R) > 0) and g (rho(R) < 0), respectively. The classical double bond-no-bond resonance structures proved useful in explaining the substituent sensitivities of the donation energies and the behavior of the SCS values.