Quinoxalines XIV. Synthesis, H, C, N NMR spectroscopic, and quantum chemical study of 1H-pyrazolo[3,4-b]quinoxalines (flavazoles)

The synthesis of a series of 1H-pyrazolo[3,4-b]quinoxalines (flavazoles) by acylation, alkylation, halogenation, and aminomethylation of the parent compound is reported and their structure is investigated by ¹H, ¹³C, and ¹⁵N NMR spectroscopy. The restricted rotation about the partial C, N double bond of the N-acyl derivatives 7-10 is studied by dynamic NMR spectroscopy and the barriers to rotation are determined. In order to assign unequivocally the ¹⁵N chemical shifts of N-4 and N-9, in case of 3-substituted flavazoles, exemplary the ¹H, ¹³C, and ¹⁵N NMR chemical shifts of 34, 35, and 39 are also theoretically calculated by quantum chemical methods [ab initio at different levels of theory (HF/6-31G* and B3LYP/6-31G*)].     

NMR-Spectroscopic, computational and mass-spectrometric investigations on the cis/trans analogues of 2,3,4-trihydronaphthalene-1-one

NMR-Spectroscopic, computational and mass-spectrometric studies of the cis/trans isomers of N-[8-(acetylamino)-4-(2,2-dimethyl-1,1-diphenyl-silapropoxy)-6-fluoro-5-methyl-1-one-2,3,4-trihydronaphthyl]acetamide (1a and 1b), obtained as intermediates in the synthesis of an important class of alkaloid molecules, are reported. ¹H and ¹³C NMR analyses show an unusual axial preference of the TBDPSi- (tert-butyldiphenylsilyl) group in position 4 in both the isomers. Mass spectrometric evidence demonstrates that trans isomer has a higher affinity for ammonium ions than the cis isomer and that only the ammonium adduct [1b+NH₄]⁺ and the protonated molecule [1b+H]⁺ show the fragmentation in which loss of benzene is observed. Moreover, molecular mechanics and semi-empirical calculations indicate that a group of trans conformers tend to place one of the phenyl rings of the TBDPSiO- group in a offset π-stacked geometry with the compound's aromatic ring. The combination and the detailed analyses of these experimental and theoretical results could support the π-π interaction obtained as a conformational preference in the trans isomer.     

Synthesis of crownophanes possessing bipyridine moieties: bipyridinocrownophanes exhibiting perfect extractability toward Ag ion

Novel crownophanes with two bipyridine moieties (bipyridinocrownophanes 1a and 1b) were conveniently prepared by means of intramolecular [2+2] photocycloaddition of vinylbipyridine derivatives. In the liquid-liquid extraction of heavy metal cations, 1a and 1b exhibited perfect selectivity toward Ag⁺ with high efficiency. It was found that the ethereal oxygen atoms and the four nitrogen atoms in 1a and 1b acted as ligating sites, according to the high extractability and complexing stability constant for Ag⁺ compared to those of the corresponding pyridinocrownophanes 4a and 4b. ¹H NMR and ESI-MS analyses suggested that the crownophanes formed a 1:1 complexes with the Ag⁺ ion.     

Synthesis, NMR characterization and ion binding properties of 1,3-bridged p-tert-butyldihomooxacalix[4]crown-6 bearing pyridyl pendant groups

1,3-Di(2-pyridylmethoxy)-p-tert-butyldihomooxacalix[4]arene-crown-6 (2) was synthesized for the first time. 2 was isolated in a cone conformation in solution at room temperature, as established by NMR spectroscopy (¹H, ¹³C and NOESY). Complete assignment of both proton and carbon NMR spectra was achieved by a combination of COSY, HSQC and HMBC experiments. The binding properties of ligand 2 towards alkali, alkaline earth, transition and heavy metal cations have been assessed by phase transfer and proton NMR titration experiments. The results are compared to those obtained with other dihomooxacalix[4]arene-crowns-6 and closely-related calix[4]arene-crown derivatives. 2 shows a preference for the soft heavy metal cations (except for Cd²⁺), with a very strong affinity for Ag⁺. Some transition metal cations are also well extracted. 2 forms 1:1 complexes with K⁺, Ca²⁺ and Ag⁺, and ¹H NMR titrations indicate that they should be encapsulated into the cavity defined by the crown ether unit and by the two pyridyl pendant arms. A 1:2 (ML₂) complex is formed with Zn²⁺ and two species, probably 1:1 and 1:2 complexes, are obtained with Pb²⁺.     

Synthesis and characterization of half-sandwich Rh, Ir complexes containing mono-thiolate-ortho-carborane ligand

Two binuclear complexes [Cp^∗M(Cl)Carb^S]₂ (Cp^∗ = η⁵-C₅Me₅, M = Rh (1a), Carb^S = SC₂(H)B₁₀H₁₀, Ir (1b)) were synthesized by the reaction of LiCarb^S with the dimeric metal complexes [Cp^∗MCl(μ-Cl)]₂ (M = Rh, Ir). Four mononuclear complexes Cp^∗M(Cl)(L)Carb^S (L = BuⁿPPh₂, M = Rh (2a), Ir (2b); L = PPh₃, M = Rh (4a), Ir (4b)) were synthesized by reactions of 1a or 1b with L (L = BuⁿPPh₂ (2); PPh₃ (4)) in moderate yields, respectively. Complexes 3a, 3b, 5a, 5b were obtained by treatment of 2a, 2b, 4a, 4b with AgPF₆ in high yields, respectively. All of these compounds were fully characterized by IR, NMR, and elemental analysis, and the crystal structures of 1a, 1b, 2a, 2b, 4a, 4b were also confirmed by X-ray crystallography. Their structures showed 3a, 3b and 5a, 5b could be expected as good candidates for heterolytic dihydrogen activation. Preliminary experiments on the dihydrogen activation driven by these half-sandwich Rh, Ir complexes were done under mild conditions.     

Complexing properties of two benzocrown-ether moieties arranged at a cyclobutane ring system

Biscrown ethers 2a-c and 3a-c arranged at a cyclobutane ring were prepared by intermolecular [2+2] photocycloaddition of vinylated benzocrown ethers. The complexing behavior of 2a-c toward alkali metal cations was evaluated by ESI-MS analysis, liquid-liquid extraction, and the comparison of complexing stability constant. An intramolecular sandwich-type 1:1 (host/guest) complexation was observed by ESI-MS analysis in the competitive system where 2a-Na⁺, 2b-K⁺, and 2c-Cs⁺ were formed selectively. In the liquid-liquid extraction, however, 2a hardly extracted any cation, while both 2b and 2c efficiently extracted larger cations such as K⁺, Rb⁺, and Cs⁺. It was found that the complexing stability constant of 2a-Na⁺ is lower than that of benzo-15-crown-5-Na⁺ though extraordinarily high values were obtained for 2b-K⁺ and 2c-Cs⁺ complexes compared with those of 18-crown-6-K⁺ and dibenzo-24-crown-8-Cs⁺ complexes, respectively. Hence, the excellent complexing ability was achieved by using the cyclobutane ring, which strongly preorganized two benzocrown-ether moieties for the larger alkali metal cations.     

Synthesis and characterization of (N→B) phenyl[N-alkyl-N-(2-alkyl)aminodiacetate-O,O′,N]boranes and phenyl[N-alkyl-N-(2-alkyl) aminodiacetate-O,O′,N]boranes

The reaction of boron heterocycles 1 and 2 with n-butyl lithium and alkyl halides led to (N→B) phenyl[N-alky-N-(2-alkyl)aminodiacetate-O,O′,N]boranes 3–6(a–b), 7(b) and 9(b), where alkyl can be in exo and/or endo position, and phenyl[N-alkyl-N-(2-alkyl)aminodiacetate-O,O′,N]boranes 7(c) and 8(c) isomers, which do not display the intramolecular N→B coordination bond. The existence of steric interactions between N-benzyl and the alkyl group at 2 position was indicated by ¹H and ¹³C NMR, while, the δ(¹¹B) values confirm the tetrahedral and trigonal environment of the ¹¹B nucleus in these compounds. Moreover, the compounds were characterized by COSY, HETCOR and homonuclear proton decoupling experiment. The study of the intramolecular N→B coordination by dynamic NMR afforded a ΔG‡ value of 81.09 kJ/mol for compound 6(b).     

Synthesis, IR-, NMR- and X-ray investigations on some novel N-hetaryl-dihydro-pyrazolyl ferrocenes. Study on ferrocenes, part 16

Cyclocondensation of 1-aryl-3-ferrocenyl-2-propen-1-ones (1) with hetaryl hydrazines resulted in N-hetaryl-3-aryl-5-ferrocenyl pyrazolines (3, 4). The analogous 3-aryl-1-ferrocenyl-2-propen-1-ones (5) gave the isomeric N-hetaryl-5-aryl-3-ferrocenyl-pyrazolines (6, 10), but in lower yield. The reaction of aryl-chalcones (7) with 4-hydrazino-phthalazinone led to 3,5-bis-aryl-N-hetaryl-pyrazolines (8) or to the corresponding ene-hydrazones (9). The structure of the new compounds was established by IR, ¹H and ¹³C NMR spectroscopy, including DNOE, HMQC, HMBC and DEPT methods. For compounds 1b, 3b and 8b the stereo structure was elucidated also by X-ray diffraction.     

Polymer-supported calix[4]arenes for sensing and conversion of NO2/N2O4

The use of simple calix[4]arenes 1a,b for NO₂/N₂O₄ sensing and conversion is demonstrated, both in solution and in the solid state. Upon reacting with these gases, compounds 1a,b encapsulate reactive NO⁺ cations within their cavities with the formation of deeply colored (λ_max∼570 nm) charge-transfer complexes 2a,b. Further functionalization of the calix[4]arene platform is reported for attachment to solid supports. Polymer-supported calixarene material 3 was prepared, which reversibly traps NO₂/N₂O₄ with the formation of nitrosonium storing polymer 4. Material 4 was effectively used for nitrosation of amides.     

Synthesis, single crystal X-ray structure and optical properties of 3,4-dimethyl-dithieno[2,3-b:3′,2′-d]thiophene-7,7-dioxide

The synthesis of the title compound (4), starting from commercial 3-bromo-4-methylthiophene, is described. The single crystal packing mode of 4, as well as the absorption and photoluminescence properties in solution and in the solid state are reported and analyzed in relation to those of the isomeric 3,5-dimethyl-dithieno[3,2-b:2′,3′-d]thiophene-4,4-dioxide (7). The different reactivities of 4 and 7 towards bromination are analyzed in the light of the results of ab initio B3LYP/6-31G^∗ calculations on both compounds.     

Synthesis and complexing property of four-bridged crownopaddlanes

A new series of crown compounds crownopaddlanes 3a-c bearing three cyclobutane rings were prepared by means of intramolecular [2+2] photocycloaddition of styrene derivatives. The yield of crownopaddlane 3b possessing five ethereal oxygen atoms was remarkably high 52% with the addition of sodium borofluoride in the photoreaction system. As this template effect suggests, 3b showed extraordinarily high Na⁺-selectivity with high efficiency on the liquid-liquid extraction of alkali metal picrates, though 3a having four ethereal oxygen atoms did not extracted any cations in this system. The high Na⁺-selectivity of 3b was further clarified by the equilibrium stability constants (log K_a) for Na⁺ (5.85) and K⁺ (2.91) in acetonitrile solution. The complexation of 3b to Na⁺ cation was also examined by X-ray crystallography. Crownopaddlane 3c bearing six ethereal oxygen atoms also efficiently and selectively extracted alkali metal cations, compared with conventional 18-crown-6 derivatives.     

Synthesis, properties, and oxidizing function of 6-substituted 7,9-dimethylcyclohepta[b]pyrimido[5,4-d]pyrrole-8(7H),10(9H)-dionylium tetrafluoroborates

Uracil-annulated heteroazulenes, 6-substituted 7,9-dimethylcyclohepta[b]pyrimido[5,4-d]pyrrole-8(7H),10(9H)-dionylium tetrafluoroborates 7a,b·BF₄⁻, which are the isoelectronic compounds of 5-dezazaflavin, were synthesized. X-Ray crystal analysis and MO calculations were carried out to clarify the structural characteristics of 7a,b·BF₄⁻. The stability of cations 7a,b is expressed by the pK_R+ values which were determined spectrophotometrically to be 10.9 and 11.2, respectively. The electrochemical reduction of 7a,b exhibited high reduction potentials at −0.84 and −0.87 (V vs Ag/AgNO₃) upon cyclic voltammetry (CV). A good linear correlation between the pK_R+ values and reduction potentials (E1_red) of 7a,b·BF₄⁻ and reference compounds 4·BF₄⁻ and 5·BF₄⁻ was obtained. In a search of the reactivity, reactions of 7a,b·BF₄⁻ with some nucleophiles, hydride and diethylamine, were carried out to clarify that the introduction of nucleophiles to give regio-isomers is dependent on the nucleophile. The photo-induced oxidation reactions of 7a,b·BF₄⁻ toward some alcohols under aerobic conditions were carried out to give the corresponding carbonyl compounds in more than 100% yield [based on compounds 7a,b·BF₄⁻], suggesting the oxidizing function of 7a,b·BF₄⁻ toward alcohols in the autorecycling process.     

Synthesis and properties of 4,9-methanoundecafulvenes and their transformation to 3-substituted 7,12-methanocycloundeca[4,5]furo[2,3-d]pyrimidine-2,4(1H,3H)-diones: photo-induced autorecycling oxidizing reaction toward amines

The synthesis and properties of 4,9-methanoundecafulvene [5-(4,9-methanocycloundeca-2′,4′,6′,8′,10′-pentaenylidene)pyrimidine-2,4,6(1,3,5H)-trione] derivatives 8a,b were studied. Their structural characteristics were investigated on the basis of the ¹H and ¹³C NMR and UV-vis spectra. The rotational barrier (ΔG^‡) around the exocyclic double bond of 8a was found to be 12.55 kcal mol⁻¹ by the variable temperature ¹H NMR measurement. The electrochemical properties of 8a,b were also studied by CV measurement. Furthermore, the transformation of 8a,b to 3-substituted 7,12-methanocycloundeca[4,5]furo[2,3-d]pyrimidine-2,4(1H,3H)-diones 16a,b was accomplished by oxidative cyclization using DDQ and subsequent ring-opening and ring-closure. The structural details and chemical properties of 16a,b were clarified. Reaction of 16a with deuteride afforded C13-adduct 19 as the single product, and thus, the methano-bridge controls the nucleophilic attack to prefer endo-selectivity. The photo-induced oxidation reaction of 16a and a vinylogous compound, 3-methylcyclohepta[4,5]furo[2,3-d]pyrimidine-2,4(3H)-dione 2a, toward some amines under aerobic conditions were carried out to give the corresponding imines (isolated by converting to the corresponding 2,4-dinitrophenylhydrazones) with the recycling number of 6.1-64.0 (for 16a) and 2.7-17.2 (for 2a), respectively.     

Novel photo-induced oxidative cyclization of 1,3-dimethyl-5-(1-arylmethylidene)pyrimidine-2,4,6(1,3,5H)-triones: synthesis and properties of areno[5,6]pyrano[2,3-d]pyrimidine-2,4(1,3H)-dionylium ions and their photo-induced autorecycling oxidizing reaction toward some amines

Novel photo-induced oxidative cyclization was accomplished to synthesize areno[b]pyrimido[5,4-e]pyran-2,4(1,3H)-dionylium ions 13a-c⁺·ClO₄⁻. Furthermore, 13a-c⁺·BF₄⁻ and their phenyl-substituted derivatives 19a,b⁺·BF₄⁻ were alternatively synthesized by the reaction of salicylaldehyde and its naphthyl derivatives with barbituric acids and subsequent treatment with aq. HBF₄. Structural characteristics of 13a-c⁺ and 19a,b⁺ were clarified on inspection of the UV-vis and NMR spectral data as well as X-ray crystal analyses. The electrochemical properties were studied by the CV measurement. In a search for reactivity, reactions of 13a-c⁺·BF₄⁻ with some nucleophiles, hydride, benzylamine, and H₂O, were also carried out. The photo-induced autorecycling oxidation reactions of 13a-c⁺·BF₄⁻ toward some amines under aerobic conditions were carried out to give the corresponding imines (isolated by converting to the corresponding 2,4-dinitrophenylhydrazones) in 643-3600% yield (recycling number of 13a-c⁺·BF₄⁻: 6.4-36.0).     

Synthesis, characterization and in vitro DNA binding studies of tin(IV) complexes of tert-butyl 1-(2-hydroxy-1-phenylethylamino)-3-methyl-1-oxobutan-2-yl carbamate

Tin(IV) complexes 1(a and b) and 2(a and b) of valine derived peptide derivatives were synthesized and characterized on the basis of elemental analysis, IR, ¹H, ¹³C, ¹¹⁹Sn NMR, ESI-MS spectra and molar conductance measurements. The C-Sn-C angle was estimated from ^I3C and ¹H NMR data ¹J(¹¹⁹Sn, ^I3C) = 623 Hz; solution ²J(¹¹⁹Sn, ¹H) = 93.04 Hz to be 149.9°. In vitro binding studies of complexes 1 and 2 under physiological conditions at room temperature with CT-DNA were carried out employing UV-visible, fluorescence, circular dichroism and viscometric studies. The binding affinity of the complexes was quantified by calculating the K_b values and it follows the order 2a > 1a > 2b > 1b. To further examine the specific mode of binding, the interaction of complexes 2(a and b) were carried out with 5′GMP and 5′TMP by using absorption and NMR (¹H, ³¹P) spectroscopy. The supercoiled pBR322 plasmid DNA cleavage activity of the complexes was ascertained by gel electrophoresis assay. The complexes cleave supercoiled pBR322 plasmid DNA efficiently into its nicked form at micromolar concentrations.     

p-Sulfonatocalix[7]arene: synthesis, protolysis, and binding ability

Water-soluble p-sulfonatocalix[7]arene 1 has been synthesized in good yield through standard procedures and its conformational preferences have been investigated by Monte Carlo conformational searches. The acid-base properties of 1 were investigated by means of potentiometric titration, obtaining pK_a values in agreement with those reported for other p-sulfonatocalix[n]arene homologs. The binding ability of 1 toward organic quaternary ammonium cations such as Diquat (2), Paraquat (3), and Chlormequat (4) was investigated by means of ¹H NMR titrations in D₂O at pD=7.3, DOSY NMR measurements, and 2D ROESY NMR spectroscopy. Spectrofluorimetry proved to be a useful method for the determination of trace amounts of 2 and 3 in aqueous solution by using Acridine Orange bound to 1 as a chemical indicator.     

Click reactions of 2H-azaphosphirene chromium and molybdenum complexes and a surprisingly facile access to a 2H-1,4,2-diazaphosphole derivative

Ring expansion reactions of 2H-azaphosphirene chromium and molybdenum complexes 1a,b with dimethyl cyanamide, triflic acid, and, subsequently at ambient temperature, with triethylamine gave a mixture of the respective 2H-1,4,2-diazaphosphole complex 2a,b and the non-ligated heterocycle 3. If the deprotonation with NEt₃ was carried out at low temperature, the selective formation of complexes 2a,b was observed, which were isolated in excellent yields and fully characterized (including single-crystal X-ray crystallography). Experimental and computational results revealed that the P, Cr and P, Mo bonds of 2H-1,4,2-diazaphosphole complexes are significantly weakened upon N-protonation of the heterocyclic ligand. When mixtures of 1a,b, TfOH, and Me₂NCN were warmed to ambient temperature, the primarily formed N-protonated of 2H-1,4,2-diazaphosphole complexes 4a,b could be observed by ³¹P NMR spectroscopy. The latter underwent decomplexation to give the N-protonated free ligand 5, which could be isolated and characterized by multinuclear NMR experiments. The neutral non-ligated heterocycle 3 was isolated from a one-pot reaction of 1b with TfOH and Me₂NCN by adding NEt₃ to a solution of intermediately formed 5.     

Normal and abnormal carbene complexes derived from thiazole: Preparation and a preliminary investigation of their relative catalytic performance

Readily prepared 2-, 4- and 5-bromo-3-methyl thiazolium triflates react by oxidative substitution with M(PPh₃)₄ (M = Ni or Pd) to furnish five of the expected normal and abnormal cationic thiazolylidene complexes (1a, 1b, 2a, 2b, and 3b). Carbene complex formation is accompanied by a ca. 40 ppm downfield shift of the α-N carbene carbons in Pd complexes 1 and 2 in their ¹³C NMR spectra but the chemical shift of C(carbene) in the abnormal3b (δ 135.7) is particularly low. Crystal and molecular structures of complexes 1a, 2b, and 3b all indicate a square planar arrangement of the ligands around the central metal atoms. The new complexes catalyse Suzuki-Miyaura aryl coupling.     

Copper(I) and silver(I) complexes of 1,5-methylene- and diethylmethylene-bridged bis(oxazoline) ligands. In situ Cu(II)-catalyzed oxidation of methylene bridge

Silver(I) and copper(I) complexes of C₂-symmetric bis(oxazoline) ligands were studied by UV, NMR, IR, EPR and ES-MS spectroscopies. The stability constants of the Ag-1a and Ag-1b complexes with 1:1 and 1:2 stoichiometries in acetonitrile were determined by NMR spectrometric titrations. The evidence of tetrahedral coordination for complex (Ag(1a)₂(⁺ was obtained from the complexation induced shifts (CIS) and NOEs. Mass spectra revealed the Cu(II) mediated oxidation of methylene bridge in copper complexes of 1a and 1b, which was in accordance with the UV, NMR, IR and EPR findings. The efficiency of Cu(I) complexes of methylene-bridged 1,5-bis(oxazoline)s 1 as chiral catalysts in stereoselective cyclopropanation of styrene with ethyl diazoacetate, was compared to that of the dialkylmethylene-bridged 1,5-bis(oxazoline)s 2.     

Synthesis, characterization and anti-Trypanosoma cruzi evaluation of ferrocenyl and cyrhetrenyl imines derived from 5-nitrofurane

A series of new cyrhetrenyl and ferrocenylimines complexes derived from 5-nitrofurane were designed, synthesized and characterized. The ¹H and ¹³C NMR spectra indicate that these compounds adopt an anti-(E) conformation in solution, and confirmed for 1b by the X-ray crystal crystallography. The electronic effects of cyrhetrenyl (1b) and ferrocenyl (1a) bound directly to nitrogen have been correlated with the chemical shift of the iminic carbon. The trypanocidal activity (Tulahuen strain of Trypanosoma cruzi) of these compounds has been studied with respect to the substituent on the nitrogen atom of the 5-nitrofurfurylideneamino pharmacophore. Even though all the resulting derivatives were less active than Nifurtimox, the cyrhetrenyl complex (1b), compared with ferrocenyl (1a) or purely organic (4a and 4b) analogues, was more efficient as antichagasic agent. This result is likely due to the enhanced lipophilic character of the molecules or from a possible synergy between the cyrhetrenyl and 5-nitrofurane groups.