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41.
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43.
John T. W. Lai Frankie W. Lau Damon Robb Peter Westh Gerda Nielsen Christa Trandum Aase Hvidt Yoshikata Koga 《Journal of solution chemistry》1995,24(1):89-102
The excess partial molar enthalpies, the vapor pressures, and the densities of dimethylsulfoxide (DMSO)–H2O mixtures were measured and the excess partial molar Gibbs energies and the partial molar volumes were calculated for DMSO and for H2O. The values of the excess partial molar Gibbs energies for both DMSO and H2O are negative over the entire composition range. The results for the water-rich region indicated that the presence of DMSO enhances the hydrogen bond network of H2O. Unlike monohydric alcohols, however, the solute-solute interaction is repulsive in terms of the Gibbs energy. This was a result of the fact that the repulsion among solutes in terms of enthalpy surpassed the attraction in terms of entropy. The data in the DMSO-rich region suggest that DMSO molecules form clusters which protect H2O molecules from exposure to the nonpolar alkyl groups of DMSO. 相似文献
44.
8,15,23,30-Tetramethyl[2.1.2.1]metacyclophane,4, is synthesised. Variable temperature 1Hmr and 13Cmr spectra indicate that 4e is the most likely conformation and that at temperatures above 50°C the molecule is fluxional (ΔG≠323 = 15.4 kcal/mole). 相似文献
45.
贮氢材料电极循环寿命的定量预测定时放电半衰期法的应用韩剑文,袁满雪,周作祥,赖城明(南开大学化学系天津300071)关键词:贮氢电极,循环寿命,半衰期。前文 ̄[1]讨论了应用定终点电位放电半衰期法来预测贮氢材料电极循环寿命的问题。本文讨论如何采用定时... 相似文献
46.
The substituent effects on O-H and O-CH(3) bond dissociation energies for a series of 18 para-substituted phenols (p-XC(6)H(4)OH) and 11 para-substituted anisoles have been studied using the density functional method in order to understand the origin of these effects. The calculated substituent effects agree well with experimental measurements for phenols but are substantially larger than the reported values for anisoles. Both ground-state effect and radical effect contribute significantly to the overall substituent effect. An electron-donating group causes a destabilization in phenols or anisoles (ground-state effect) but a stabilization in the phenoxy radicals (radical effect), resulting in reduced O-R bond dissociation energy. An electron-withdrawing group has the opposite effect. In most cases, the radical effect is more important than the ground-state effect. There is a good correlation between the calculated radical effects and calculated variations in charge and spin density on the phenoxy oxygen. This supports the concept that both polar and spin delocalization effects influence the stability of the phenoxy radical. While almost every para-substituent causes a stabilization of the phenoxy radical by spin delocalization, electron-donating groups stabilize and electron-withdrawing groups destabilize the phenoxy radical by the polar effect. 相似文献
47.
Xiu‐Li Dong Zheng‐Yu Zhou Lai‐Jin Tian Gang Zhao 《International journal of quantum chemistry》2005,102(4):461-469
The hydrogen bonding complexes HO(H2O)n (n = 1–3) were completely investigated in the present study using DFT and MP2 methods at varied basis set levels from 6‐31++G(d,p) to 6‐311++G(2d,2p). For n = 1 two, for n = 2 two, and for n = 3 five reasonable geometries are considered. The optimized geometric parameters and interaction energies for various complexes at different levels are estimated. The infrared spectrum frequencies and IR intensities of the most stable structures are reported. Finally, thermochemistry studies are also carried out. The results indicate that the formation and the number of hydrogen bonding have played an important role in the structures and relative stabilities of different complexes. © 2004 Wiley Periodicals, Inc. Int J Quantum Chem, 2005 相似文献
48.
Mangiferin (2-beta-D-glucopyranosyl-1,3,6,7-tetrahydroxyxanthen-9-one) has been isolated from the herbal root of Anemarrhena asphodeloides Bung showing antioxidative, antiviral, and anticancer effect. An in vivo microdialysis sampling method coupled to microbore high-performance liquid chromatography (HPLC) was employed for continuous monitoring of free mangiferin in rat blood. Microdialysis probes were inserted into the jugular vein/right atrium and brain striatum of Sprague-Dawley rats, and mangiferin at doses of 10, 30 or 100 mg/kg were then administered via the femoral vein. Dialysates were collected every 10 min and injected directly into a microbore HPLC system. Mangiferin was separated by a reversed-phase C18 microbore column (150 x 1 mm) from dialysate within 10 min. The mobile phase consisted of acetonitrile-0.05% phosphoric acid-tetrahydrofuran (10:75:15, v/v/v) with a flow-rate of 0.05 ml/min. The wavelength of the UV detector was set at 257 nm. The limit of quantification for mangiferin was 0.05 microg/ml and in vivo recovery of mangiferin at concentrations of 1, 5 and 10 microg/ml was in range of 37.7-39.8%. The results indicate that the pharmacokinetics of mangiferin at doses of 10-30 mg/kg reveals a linear relation, while doses of 30-100 mg/kg show a nonlinear pharmacokinetic phenomenon. Mangiferin was undetectable in brain dialysate. The proposed method provides a technique for rapid and sensitive analysis of free mangiferin in rat blood and further application in pharmacokinetic study. Furthermore, the metabolites of mangiferin in the rat bile were confirmed by LC electrospray ionization (ESI) tandem mass spectrometry (MS-MS). 相似文献
49.
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 SN2 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 isocyanatesa
Open in a separate windowaReaction scale: 1b (0.1 mmol), 5a (0.1 mmol), catalyst (10 mol%), toluene (1 mL).bYield based on analysis of the 1H NMR spectra of the crude reaction mixture using trichloroethylene as an internal reference. For all the entries, the urea product from simple amine addition to isocyanate 5a accounts for the mass balance.cRun at 80 °C.dIsolated yield.While there are multiple effective catalysts, FeCl3 was selected for the scope study in view of its low price. Various substituted 3-aminooxetanes and isocyanates were subjected to this annulation protocol (Scheme 4). The corresponding iminooxazolidine products were all obtained in good to excellent yields. Isocyanates containing an electron-donating or electron-withdrawing group were both suitable reaction partners. Remarkably, a 1.5 mmol scale reaction of 6a also worked efficiently.Open in a separate windowScheme 4Formal [3 + 2] annulation between 3-aminooxetanes and isocyanates. Reaction scale: 1 (0.3 mmol), 5 (0.3 mmol), FeCl3 (1 mol%), toluene (2 mL).Although (thio)isocyanates and CS2 have been successfully utilized in the formal [3 + 2] annulation with 3-aminooxetanes, these partners are relatively reactive. We were curious about whether the C O bond in relatively inert molecules could react in a similar manner. For example, the C O bond in CO2 is both thermodynamically and kinetically inert relative to typical organic carbonyl groups. However, as a cheap, abundant and green one-carbon source, CO2 has been a subject of persistent investigations owing to its versatility in various transformations leading to valuable materials.12 Specifically, if CO2 could be employed as a partner for the [3 + 2] annulation with 3-aminooxetanes, it would represent an attractive synthesis of oxazolidinones, a well-known heterocycle with applications in both organic synthesis and medicinal chemistry.13 In this context, we next studied the possibility of utilizing CO2 in our annulation.As expected, the reaction between 1b and CO2 at 1 atmospheric pressure did not proceed without a catalyst (Table 2, entry 1). Next, we examined representative Lewis acids, such as Sc(OTf)3, In(OTf)3 and FeCl3. Among them, Sc(OTf)3 exhibited the highest catalytic activity at room temperature (22% yield, entry 2). The reaction efficiency could be improved at 80 °C (65% yield, entry 6), but no further improvement could be made at a higher temperature or with other solvents. Next, we resorted to organic nitrogen bases, as they were known as effective activators of CO2.14 While Et3N and DABCO were completely ineffective for the reaction in MeCN at 80 °C, fortunately, TMG, TBD, and DBU were competent for the desired process (entries 7–11). Among them, DBU exhibited the best performance, leading to the desired product 7a in 89% yield (entry 11). It is worth noting that the polar solvent MeCN was found to be crucial for the base-catalyzed reactivity. Less polar solvents, such as toluene, DCE or THF, completely shut down the reaction. We believe that effective stabilization of certain polar intermediates involved here is critically beneficial to decreasing the reaction barrier. Finally, unlike the previous Lewis acid-catalyzed annulation with isocyanates, this base-catalyzed [3 + 2] annulation with CO2 proceeds via a different activation mode (i.e., to activate CO2 rather than oxetane). We believe that expansion of possible activation modes in this type of amphoteric reactivity will enrich the chemistry of oxetanes.Reaction conditions for annulation with CO2a
Open in a separate windowaReaction scale: 1b (0.1 mmol), CO2 (1 atm), solvent (0.5 mL). Yields based on analysis of the 1H NMR spectra of the crude reaction mixture using CH2Br2 as an internal standard.We next examined the scope of this CO2-fixation process. Unfortunately, at a larger scale (0.5 mmol), the same condition (entry 11, Table 2) could not lead to complete conversion within 12 h. Therefore, further optimization aiming to accelerate the reaction was performed. Indeed, a higher concentration (1.0 M) resulted in a higher rate without affecting the yield. As shown in Scheme 5, a wide variety of 3-aminooxetanes were smoothly converted to the corresponding oxazolidinones in high yields. Both electron-donating and electron-withdrawing substituents on the N-benzyl group did not affect the efficiency. Heterocycle-based N-benzyl or N-allylic substituents are all suitable substrates. However, for regular alkyl substituents, such as homobenzyl (7h) or n-butyl (7j), the stronger base catalyst TBD was needed to achieve good efficiency. Furthermore, this reaction can tolerate steric hindrance in the 3-position of the oxetane (7k), where a quaternary carbon center could be incorporated. However, increasing the size of the N-substituent, such as the secondary alkyl groups in 7i and 7l, did influence the reactivity, thus requiring a higher temperature (100 °C). This process exhibited good compatibility with diverse functional groups, such as ethers, pyridines, aryl halides, olefins, silyl-protected alcohols, and phthalimides. Finally, this protocol is also capable of generating various oxazolidinones embedded in a different structural context, such as chiral oxazaolidinone 7l, bis(oxazolidinone) 7m, and polyheterocycle-fused oxazolidinone 7o.Open in a separate windowScheme 5Formal [3 + 2] annulation between 3-aminooxetanes and CO2. aReaction scale: 1 (0.5 mmol), CO2 (1 atm), DBU (10 mol%), MeCN (0.5 mL). Isolated yield. bRun with TBD as the catalyst. cRun with DMF as solvent at 100 °C.In summary, 3-aminooxetanes have been systematically demonstrated, for the first time, as versatile 1,3-amphoteric molecules. They are a new addition to the limited family of amphoteric molecules. Though previously unappreciated, these molecules exhibited various advantages over the related known 1,3-amphotric molecules (e.g., α-aziridine aldehydes and amino isocyanates), including easy access and extraordinary stability. The perfect position of the nucleophilic nitrogen together with the orthogonal electrophilic carbon allowed them to participate in a diverse range of intermolecular formal [3 + 2] annulations with polarized π-systems, leading to rapid access to various valuable nitrogen heterocycles. Different types of polarized double bonds, from reactive (thio)isocyanates to inert CO2, all participated efficiently in these highly selective annulations with or without a suitable catalyst. Furthermore, the involvement of more functional groups in such amphoteric reactivity allowed manifold activation modes, thereby greatly enriching the reactivity of the already versatile oxetane unit to a new dimension. These reactions, proceeding in an intermolecular convergent manner from readily available substrates, provide expedient access to various valuable nitrogen heterocycles, thus being complementary to those traditional methods that either required multiple steps or less available substrates. More studies on the 1,3-amphoteric reactivity of 3-oxetanes, particularly those with other partners as well as their asymmetric variants, are ongoing in our laboratory. 相似文献
Entry | Catalyst | Yieldb (%) |
---|---|---|
1 | — | 0 |
2 | TsOH·H2O | 0 |
3 | HNTf2 | 0 |
4 | ZnCl2 | 0 |
5 | AuCl | 0 |
6 | FeCl3 | 0 |
7 | Sc(OTf)3 | 74 |
8 | Zn(OTf)2 | 78 |
9 | In(OTf)3 | 90 |
10 | FeCl3c | 61 |
11 | TsOH·H2Oc | 0 |
12 | FeCl3c (1 mol%) | 89(84)d |
13 | FeCl3c (0.5 mol%) | 85 |
Entry | Catalyst | T | Conv. (%) | Yield (%) |
---|---|---|---|---|
1 | — | RT | 0 | 0 |
2 | Sc(OTf)3 | RT | 48 | 22 |
3 | In(OTf)3 | RT | 33 | 9 |
4 | Zn(OTf)2 | RT | 7 | 0 |
5 | Sc(OTf)3 | 60 °C | 100 | 61 |
6 | Sc(OTf)3 | 80 °C | 100 | 65 |
7 | Et3N | 80 °C | 0 | 0 |
8 | DABCO | 80 °C | 5 | 0 |
9 | TMG | 80 °C | 72 | 54 |
10 | TBD | 80 °C | 100 | 88 |
11 | DBU | 80 °C | 100 | 89 |
50.
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. 相似文献