Synthetic applications of aryl radical building blocks for cyclisation onto azoles

2-(2-Bromophenyl)ethyl groups have been used as building blocks in radical cyclisation reactions onto azoles to synthesise tri- and tetra-cyclic heterocycles. 2-(2-Bromophenyl)ethyl methanesulfonate was used to alkylate azoles (imidazoles, pyrroles, indoles and pyrazoles) for the synthesis of the radical precursors. Cyclisations of the intermediate aryl radicals yield new 6-membered rings attached to the azoles. The aryl radicals undergo intramolecular homolytic aromatic substitution onto the azole rings. Tributylgermanium hydride has been used with success to replace the toxic and troublesome tributyltin hydride. Initial studies show that the protocol can be used on solid phase resins. The molecular and crystal structures of methyl 5,6-dihydroimidazo[5,1-a]iso-quinoline-1-carboxylate and methyl 5,6-dihydroimidazo[2,1-a]isoquinoline-3-carboxylate were determined by X-ray crystallography.     

Photoswitchable organocatalysis in acylation of alcohol using dithienylethene-linked azoles

Three novel dithienylethenes bearing azole derivatives were synthesized and found to undergo reversible photocyclization of the dithienylethene units upon alternate irradiation with UV and visible light. Among them, the dithienylethene-linked imidazole and N-phenylimidazole exhibited a relatively high organocatalytic activity for the acylation of 2-decanol with acetic anhydride, and the catalytic activity of the dithienylethene-linked imidazole could be switched by reversible photoinduced cyclization/cycloreversion of the dithienylethene unit.     

The influence of aza-substitution on azole aromaticity

A homogeneous set of values for the aromaticity indices ASE (Aromatic Stabilisation Energy), HOMA (Harmonic Oscillator Model of Aromaticity) and NICS(1) (Nucleus-Independent Chemical Shift) for azoles has been investigated using multiple linear regression analysis. Statistically-significant relationships were found between the aromaticity indices and the number of nitrogen atoms at positions 2/5 and 3/4 of the ring. Aza-derivatives of pyrrole, furan and thiophene all gave similar relationships. For all three indices aza-substitution at positions 2 and/or 5 increases aromaticity. However, aza-substitution at positions 3 and/or 4 decreases classical aromaticity (ASE and HOMA) but increases magnetic aromaticity (NICS(1)). These indices appear to be measuring different properties of the azoles. The influence of aza-substitution on these different aspects of aromaticity is tentatively rationalized in terms of either bond length equalization or uniformity of π electron distribution.     

气相色谱-正化学源-质谱联用技术测定葡萄和葡萄酒中多种唑类杀菌剂的残留量

建立了可用于葡萄和葡萄酒中20种唑类杀菌剂残留量的分散型固相萃取-气相色谱-正化学离子源质谱分析方法.葡萄和葡萄酒样品分别用乙腈(含1%冰醋酸)和乙酸乙酯提取,分散型固相萃取法净化,由气相色谱-正化学离子源质谱分时段选择离子监测技术进行测定与确证,外标法定量.20种农药在50～1000 μg/L范围内线性均良好; 所有农药的方法定量限(LOQ)均低于10 μg/kg;在3个添加水平(10, 20和40 μg/kg)下,所有农药的回收率均处于71.2%～102.2%之间, RSD≤10.6%.     

Efficient synthesis of new 3-heteroaryl-1-functionalized 1H-indazoles

The efficient synthesis of novel 3-heteroaryl N-1-functionalized indazoles, via palladium cross-coupling reactions of ethyl (3-iodo-1H-indazol-1-yl)acetate with 2- and 3-pyrrolylboronic acids, 2-, 4- and 5-thiazolylstannanes, and other heteroarylmetallated derivatives are reported.     

Determination of azoles in sewage sludge from Spanish wastewater treatment plants by liquid chromatography-tandem mass spectrometry

A simple and rapid analytical method for the determination of 16 azoles in sewage sludge has been developed and validated. The method was based on ultrasound-assisted extraction followed by dispersive solid-phase extraction cleanup and liquid chromatography-electrospray tandem mass spectrometric detection. The azoles were selected by their intensive usage as biocides (tebuconazole, propiconazole, cyproconazole and thiabendazole), antimycotic pharmaceuticals (ketoconazole, econazole, fluconazole and clotrimazole) or fungicides in agriculture (difenoconazole, flusilazole, hexaconazole, prochloraz, bromuconazole, epoxiconazole and triticonazole). The recoveries of these compounds through the method were between 71.9 and 115.8%, with relative standard deviations lower than 20%. Detection limits were in the range of 0.5-5.0 ng/g. The developed method was applied to the analysis of azoles in sewage sludge samples collected from 19 Spanish wastewater treatment plants. Although azoles used as biocides or agriculture fungicides were present in a few sludge samples, the pharmaceuticals ketoconazole, econazole and clotrimazole were present in all of the analyzed sludge samples, being ketoconazole the one found at the highest level, representing the 68.6% of the total azole content found in the 19 sludge samples studied.     

The reactivity of ferrocenylalkyl azoles under the conditions of electrospray ionization

Under the conditions of electrospray ionization of ferrocenylalkyl azoles FcCH(R)X (Fc-η⁵-C₅H₅Fe-η⁵-C₅H₄, R - H, Me, XH - 2-methyl imidazole, pirazole) the processes of oxidation, protonation, fragmentation and ferrocenylalkylation to form, molecular ions [М]⁺, protonated molecules [М+Н]⁺, ferrocenylalkyl cations [FсCHR]⁺ and bisferrocenylalkyl azole cations [(FcCHR)2X]⁺, respectively, take place. Using special experimental techniques (deuterated solvents, saturation of ionic source of an ESI mass-spectrometer by the vapors of solvents, the experiments under the “inverse” ESI conditions when the solvent is subjected to electrospray in the presence of ferrocenylalkyl derivative vapours) and quantum-chemical calculations at the level of the B3LYP/LanL2DZ theory the scheme of the formation of these ions in a gas phase according to the mechanism of “activating protonation” was suggested. it was found that all these ions are formed through the protonation stage, which is taking place mainly in a gas phase. The key stage is the exothermic process of the protonation of the initial compounds by hydroxonium ions giving rise to protonated [M+H]⁺ molecules which further oxidize and alkylate ferrocenylalkylazoles to form molecular radical cations and bisferrocenylalkyl azole ions [FcCH(Me)-X-CH(Me)Fc]⁺. The decomposition of protonated ions with the elimination of the azole molecule gives rise to ferrocenylalkyl cations [FсCHR]⁺ capable in turn of oxidizing and alkylating the initial compounds.     

Synthesis and Characterization of 3,5‐Diamino‐1,2,4‐triazolium Dinitramide

3,5‐Diamino‐1,2,4‐triazole ( 1 , guanozol) was protonated with diluted hydrochloric acid, nitric acid, as well as perchloric acid forming 3,5‐diamino‐1,2,4‐triazolium chloride hemihydrate ( 2 ), 3,5‐diamino‐1,2,4‐triazolium nitrate ( 3 ) and 3,5‐diamino‐1,2,4‐triazolium perchlorate ( 4 ), respectively. In a second step 4 reacted with potassium dinitramide forming 3,5‐diamino‐1,2,4‐triazolium dinitramide ( 5 ) and low soluble potassium perchlorate. Compounds 2 – 5 were characterized by low temperature single X‐ray diffraction, IR and Raman as well as multinuclear NMR spectroscopy, mass spectrometry and differential scanning calorimetry. The heats of formation of 1 – 5 were calculated by the CBS‐4M method to be 81.1 ( 1 ), 124.7 ( 2 ), –76.1 ( 3 ), –25.2 ( 4 ) and 138.7 ( 5 ) kJ·mol^–1. With these values as well as the X‐ray densities several detonation parameters were calculated using both computer codes EXPLO5.03 and EXPLO5.04. In addition, the sensitivities of 1 – 5 were determined by the BAM drophammer and friction tester as well as a small scale electrical discharge device.     

Preparation and biological evaluation of key fragments and open analogs of scleritodermin A

The synthesis of key fragments of scleritodermin A, their assembly, and their biological evaluation as cytotoxic and anthelmintic were performed. Highlights of the synthetic route include formation of the α-ketoamide linkage and use of stereocontrolled reactions. Open analogs of this natural product were obtained using a convergent strategy.