Raman spectroscopic and structural studies of indigo and its four 6,6'-dihalogeno analogues

The Raman and electron impact mass spectra of synthetic indigo and its four 6,6'-dihalogeno analogues are reported and discussed. The influence of varying the halogen on these Raman spectra is considered. Particular emphasis is laid on distinguishing indigo from 6,6'-dibromoindigo and differentiating between the dihalogenocompounds, so as to develop protocols for determining whether artefacts are coloured with dyes of marine or terrestrial origin and whether such artefacts are dyed with genuine "Tyrian Purple" or with dihalogenoindigo substitutes that do not contain bromine. The value of even low resolution electron impact mass spectrometry in a forensic context as a means of identifying authentic 6,6'-dibromoindigo and distinguishing it from its dihalogenoanalogues is emphasised     

3-Aminooxetanes: versatile 1,3-amphoteric molecules for intermolecular annulation reactions

Despite the versatility of amphoteric molecules, stable and easily accessible ones are still limitedly known. As a result, the discovery of new amphoteric reactivity remains highly desirable. Herein we introduce 3-aminooxetanes as a new family of stable and readily available 1,3-amphoteric molecules and systematically demonstrated their amphoteric reactivity toward polarized π-systems in a diverse range of intermolecular [3 + 2] annulations. These reactions not only enrich the reactivity of oxetanes, but also provide convergent access to valuable heterocycles.

Despite the versatility of amphoteric molecules, stable and easily accessible ones are still limitedly known.

Amphoteric molecules, which bear both nucleophilic and electrophilic sites with orthogonal reactivity, represent an attractive platform for the development of chemoselective transformations.¹ For example, isocyanides are well-established 1,1-amphoteric molecules, with the terminal carbon being both nucleophilic and electrophilic, and this feature has enabled their exceptional reactivity in numerous multi-component reactions.² In the past few decades, substantial effort has been devoted to the search for new amphoteric molecules.^1–5 Among them, 1,3-amphoteric molecules proved to be versatile. The Yudin and Beauchemin laboratories have independently developed two types of such molecules, α-aziridine aldehydes and amino isocyanates, respectively.^4,5 With an electrophilic carbon and a nucleophilic nitrogen in relative 1,3-positions, these molecules are particularly useful for the chemoselective synthesis of heterocycles with high bond-forming efficiency without protective groups (Fig. 1). However, such elegant amphoteric systems still remain scarce. Therefore, the development of new stable amphoteric molecules with easy access remains highly desirable.Open in a separate windowFig. 1Representative [1,3]-amphoteric molecules versus 3-aminooxetanes.In this context, herein we introduce 3-aminooxetanes as a new type of 1,3-amphoteric molecules and systematically demonstrate their reactivity in a range of [3 + 2] annulations, providing rapid access to diverse heterocycles. Notably, 3-aminooxetanes are bench-stable and either commercially available or easily accessible. However, their amphoteric reactivity has not been appreciated previously.Oxetane is a useful functional group in both drug discovery and organic synthesis.^6–9 Owing to the ring strain, it is prone to nucleophilic ring-opening, in which it serves as an electrophile (Scheme 1A).^6–8 We envisioned that, if a nucleophilic group is installed in the 3-position (e.g., amino group), such molecules should exhibit 1,3-amphoteric reactivity due to the presence of both nucleophilic and electrophilic sites (Scheme 1B). Importantly, the 1,3-relative position is crucial for inhibiting self-destructive intra- or intermolecular ring-opening (i.e. the 3-nucleophilic site attack on oxetane itself) due to high barriers. Thus, such orthogonality is beneficial to their stability. In contrast, the nucleophilic site is expected to react with an external polarized π bond (e.g., X = Y, Scheme 1B), which enables a better-positioned nucleophile (Y) to attack the oxetane and cyclize. Thus, a formal [3 + 2] annulation should be expected. Unlike the well-known S_N2 reactivity of oxetanes with simple bond formation, this amphoteric reactivity would greatly enrich the chemistry of oxetanes with multiple bond formations and provide expedient access to various heterocycles. In contrast to the conventional approaches that require presynthesis of advanced intermediates (e.g., intramolecular ring-opening),⁸ the exploitation of such amphoteric reactivity in an intermolecular convergent manner from simple substrates would be more practically useful. Moreover, more activation modes could be envisioned in addition to oxetane activation. In 2015, Kleij and coworkers reported an example of cyclization between 3-aminooxetane and CO₂ in 55% yield, which provided a pioneering precedent.¹⁰ However, a systematic study to fully reveal such amphoteric reactivity in a broad context remains unknown in the literature.Open in a separate windowScheme 1Typical oxetane reactivity and the new amphoteric reactivity.To test our hypothesis, we began with the commercially available 3-aminooxetanes 1a and 1b as the model substrates. Phenyl thioisocyanate 2a and CS₂ were initially employed as reaction partners, as they both have a polarized C S bond as well as a relatively strong sulfur nucleophilic motif. Moreover, the resulting desired products, iminothiazolidines and mercaptothiazolidines, are both heterocycles with important biological applications (Fig. 2).¹¹ To our delight, simple mixing these two types of reactants in DCM resulted in spontaneous reactions at room temperature without any catalyst. The corresponding [3 + 2] annulation products iminothiazolidine 3a and mercaptothiazolidine 4a were both formed with excellent efficiency (Scheme 2). It is worth mentioning that catalyst-free ring-opening of an oxetane ring is rarely known, particularly for intermolecular reactions.^6–9 In this case, the high efficiency is likely attributed to the suitable choice and perfect position of the in situ generated sulfur nucleophile.Open in a separate windowFig. 2Selected bioactive molecules containing iminothiazolidine and mercaptothiazolidine motifs.Open in a separate windowScheme 2Initial results between 3-aminooxetanes and thiocarbonyl compounds.The catalyst-free annulation protocol is general with respect to various 3-aminooxetanes and isothiocyanates. A range of iminothiazolidines and mercaptothiazolidines were synthesized with high efficiency under mild conditions (Scheme 3). Many of them were obtained in quantitative yield. Quaternary carbon centers could also be generated from 3-substituted 3-aminooxetanes (e.g., 3j). The structure of product 3b was unambiguously confirmed by X-ray crystallography.Open in a separate windowScheme 3Formal [3 + 2] annulation with isothiocyanates and CS₂. Reaction conditions: 1 (0.3–0.4 mmol), 2 (1.1 equiv.) or CS₂ (1.5 equiv.), DCM (2 mL), RT, 3 h for 3 and 36 h for 4. Yields are for the isolated products.With the initial success of thiocarbonyl partners, we next turned our attention to isocyanates, in which the carbonyl group serves as the [3 + 2] annulation motif. Compared with sulfur as the nucleophilic site in the above cases, the oxygen atom is less nucleophilic. As expected, initial tests of the reactivity by mixing 1b and 5a resulted in no desired annulation product 6a in the absence of a catalyst (Table 1, entry 1). Next, Brønsted acids, including TsOH and the super acid HNTf₂, were examined as catalysts, but with no success (entries 2 and 3). We then resorted to various Lewis acids, particularly those oxophilic ones, in hope of activating the oxetane unit. Unfortunately, many of them still remained ineffective (e.g., ZnCl₂, AuCl, and FeCl₃). However, to our delight, further screening of stronger Lewis acids helped identify Sc(OTf)₃, Zn(OTf)₂, and In(OTf)₃ to be effective at room temperature, leading to the desired iminooxazolidine product 6a in good yield (entries 7–9). Its structure was confirmed by X-ray crystallography. Nevertheless, aiming to search for a cheaper catalyst, we continued to optimize this reaction at a higher temperature using previous ineffective catalysts. Indeed, FeCl₃ was found to be effective at 80 °C (61% yield, entry 10), while Brønsted acid TsOH remained ineffective at this temperature (entry 11). Notably, decreasing the loading of FeCl₃ to 1 mol% led to a higher yield (89% yield, entry 12). However, further decreasing to 0.5 mol% resulted in slightly diminished efficiency (entry 13).Reaction conditions for annulation with isocyanates^a

Particle beam-mass spectrometric analysis of difluorophenyl triazole compounds using normal phase-HPLC

Normal phase liquid chromatography combined with particle beam mass spectrometry has been applied to the analysis of fluconazole, an anti-fungal agent, [2-(2,4-difluorophenyl)-1,3-bis(1H-1,2,4-triazol-1-yl)-propan-2-ol] and a related intermediate, UK-51060 [2-(2,4-difluorophenyl)-1-(1H-1,2,4-triazol-1-yl)-ethan-2-one]. Electron ionisation and chemical ionisation have been investigated in combination with quadrupole ion trap and magnetic sector mass spectrometers and the spectra obtained compared with those for direct probe analysis. A novel method for the introduction of the chemical ionisation reagent gas via the interface is described for particle beam-magnetic sector mass spectrometry. Multi-stage scan routines have been implemented on the ion trap for the selective storage of analyte species and removal of solvent ions. Detection limits for both spectrometers have been determined and are discussed in terms of interface geometry and analyte transport characteristics. Normal phase HPLC on silica provided a good separation of the intermediate from the later eluting fluconazole peak.     

Negative ion photoelectron spectroscopy of solvated electron cluster anions, (H2O) n − and (NH3) n −

The photodetachment spectra of (H₂O) _n ^=2?69/? and (NH₃) _n ^=41?1100/? have been recorded, and vertical detachment energies (VDEs) were obtained from the spectra. For both systems, the cluster anion VDEs increase smoothly with increasing sizes and most species plot linearly withn ^?1/3, extrapolating to a VDE (n=∞) value which is very close to the photoelectric threshold energy for the corresponding condensed phase solvated electron system. The linear extrapolation of this data to the analogous condensed phase property suggests that these cluster anions are gas phase counterparts to solvated electrons, i.e. they are embryonic forms of hydrated and ammoniated electrons which mature with increasing cluster size toward condensed phase solvated electrons.     

蛋白质-蛋白质相互作用界面统计分析

以作者开发的从蛋白质结合部位推导出其界面所具有的疏水性质和氢键性质的计算程序PP_SITE为基础,利用蛋白质结构数据库(PDB),对蛋白质-蛋白质相互作用界面进行了统计分析.从PDB中挑出非冗余的链间相互作用对,计算出这个数据集中所有链间界面的疏水和氢键相互作用特征.对得到的界面特征进行统计分析,寻找能够明显聚类的界面特征.结果表明，界面大小、氢键和疏水相互作用在界面所占比例以及疏水相互作用的集中程度可以作为分类的依据.     

Cu离子A位掺杂对LaSrCoO4复合氧化物氧化性能的影响

采用聚丙烯酰胺法制备了La1-xCuxSrCoO4(x=0.2-0.8)复合氧化物,考察了Cu离子掺杂量(x)对CO及C3H8氧化反应活性的影响,并运用XRD、IR、TPR和TPD等多种手段对复合氧化物催化剂进行了表征。结果表明,催化剂活性随x的变化而变化,Cu部分取代A位La能提高LaSrCoO4催化剂的CO及C3H8氧化反应活性,当x=0.4时La1-xCuxSrCoO4催化剂的晶格氧和Co3 含量较多,晶格氧的活动性较高,催化活性最佳。     

Intermolecular rhodium-catalyzed [2+2+2] carbocyclization reactions of 1,6-enynes with symmetrical and unsymmetrical alkynes

The crossed intermolecular rhodium-catalyzed [2+2+2] carbocyclization of carbon and heteroatom tethered 1,6-enynes can be accomplished with symmetrical and unsymmetrical alkynes, to afford the corresponding bicyclohexadienes in an efficient and highly selective manner.     

A novel class of amide-derived air-stable P,O-ligands for Suzuki cross-coupling at low catalyst loading

The benzamide-derived P,O-ligands efficiently promoted the Pd-catalyzed Suzuki cross-coupling reactions of aryl bromides with phenylboronic acid at 0.01 mol % of Pd loading at 60-80 °C to form biaryls in excellent yields. A sterically hindered arylboronic acid gave a quantitative yield of the coupling product at 110 °C with 1 mol % Pd.     

Selective Determination of Trace Mercury (II) after Preconcentration with 4-(2-Pyridylazo)-Resorcinol-Modified Nanometer-Sized SiO2 Particles from Sample Solutions

A rapid, selective method that utilize 4-(2-Pyridylazo)-resorcinol (PAR)-modified nanometer SiO₂ (nanometer SiO₂–PAR) as a new solid-phase extractant for preconcentration of trace mercury (II) has been developed. The adsorption property of nanometer SiO₂–PAR for metal ions was studied by selectively extracting different metal ions from aqueous solutions. The results revealed an excellent affinity of the nanometer SiO₂–PAR for mercury (II) in presence of interfering metal ions at pH 4. The main parameters of solid-phase extraction such as shaking time, elution and sample dilution effect were studied. The extractant shows rapid kinetic sorption, and the adsorption equilibrium of mercury (II) on nanometer SiO₂–PAR was achieved in less than 2 min. The adsorbed mercury (II) was easily eluted by 4 mL of 6 mol L⁻¹ HCl. The maximum preconcentration factor was 50. The maximum static adsorption capacity was 276 μmol g⁻¹ at pH 4. The detection limit (3σ) was 0.43 μg L⁻¹ for cold vapor atomic absorption spectrometry (CVAAS), and the relative standard deviation of the eight replicate determinations was 2.4% for the determination of 2.0 μg of Hg(II) in 100 mL water sample. The method was applied to the determination of trace mercury (II) in sample solutions with satisfactory results.     

Construction and validation of an automated spray-and-trap gas chromatograph for the determination of volatile organic compounds in aqueous samples

An automated spray-and-trap (ST) chromatographic system was constructed for fast and efficient extraction of volatile organic compounds (VOCs) in aqueous samples with the capability to be deployed in the field for unattended continuous monitoring of surface or ground water. This system was built upon a commercial gas chromatograph with full automation capability using self-developed hardware and software. For sample analysis, fine droplets of the aqueous solution were generated in the extraction chamber by pressure expansion of a clean air stream through a spray nozzle. A portion of the VOCs distributed into the gas phase was retained by a multi-sorbent micro-trap kept at ambient temperature. Flash heating of the sorbent trap desorbed the enriched VOCs onto the gas chromatography (GC) with flame ionization detection (FID) for hydrocarbons or electron-capture detection (ECD) for halocarbons. In order to validate the performance of the ST method. it was compared with a more conventional method, i.e., a purge-and-trap (PT), by analyzing a serious of standard solutions containing benzene, toluene, ethylene. and o-, m-xylenes. Using a purge-and-trap method as a reference for complete extraction, the ST method showed less sensitivity. Extraction recoveries are in consistent with Henry's law constants. To test response time the ST-GC-ECD was periodically switched between tap and underground waters. Negligible carry-over of halogenated species and reproducibility better than 2% relative standard deviation (R.S.D.) can be achieved regardless of large concentration difference between the two sources, thus demonstrating applicability of the ST system for on-site monitoring.