Synthesis and Crystal Structure of N-(5-Phenylseleno)pentyl Succinimide

N-(5-phenylseleno)pentyl succinimide 1, C15H19NO2Se Mr = 324.27, was prepared by treating BrCH25SePh with potassium succinimide. Its crystal structure has been determined by X-ray single-crystal diffraction. The crystal of 1 belongs to monoclinic system, space group P21/c with the crystal cell parameters: a = 18.018(6), b = 5.980(2), c = 14.682(5)A, β = 109.977(6)°, V = 1486.7(9)A3, Z = 4, Dc = 1.449 g/cm3, μMoKα = 2.523 mm-1, F(000) = 664,the final R = 0.0302 and wR = 0.0666 for 2623 independent observed reflections with I>2σ(I). Structure analyses revealed that there exist strong nonclassical hydrogen bonds C-H…O.     

N-(1-萘基)琥珀酰亚胺玻璃态的晶化

采用X射线粉末衍射(XRD)和差示扫描量热分析(DSC)方法, 跟踪研究了N-(1-萘基)琥珀酰亚胺的液氮淬冷样品在室温(25 益)即在玻璃化转变温度以下的冷结晶行为. DSC和XRD的结果一致表明, 其冷结晶动力学曲线与熔融结晶完全不同, 呈现出“快-慢-快的三阶段增长趋势, 这一结果可以用低密度界面区成核和体积收缩效应给予解释.     

非对称氮杂环丙烷的亲核开环反应及其区域选择性

本文系统地总结了各类亲核试剂对非对称氮杂环丙烷(吖丙啶)的亲核开环反应及开环的区域选择性.氮杂环丙烷亲核开环的区域选择性是一种空间效应和电子效应平衡的结果,非芳基和非烯基取代的氮杂环丙烷的亲核开环通常发生在氮杂环丙烷取代少的碳原子上,空间效应起主导作用;而芳基和烯基取代的氮杂环丙烷的亲核开环通常发生在氮杂环丙烷芳甲位和烯丙位的碳原子上,电子效应起主导作用,烯基取代的氮杂环丙烷的亲核开环还可以发生在烯基的β-碳原子上;分子内的亲核开环反应主要受成环时环大小的控制,成环时的倾向是五元环>六元环>七元环.对于亲核试剂,一般的亲核试剂也同时受电子效应和空间效应的影响; 而亲核性强的亲核试剂通常只受空间效应的影响.容易生成稳定自由基的亲核试剂容易发生单电子转移机理的开环反应,生成相当于亲核试剂进攻氮杂环丙烷中取代多的碳原子得到的开环产物.     

Electronic and chelation effects on the unusual C2-methylation of N-(para-substituted)phenylaziridines with lithium organocuprates

Density functional theory calculations with the B3LYP functional were performed for the title ring‐opening reaction to understand the intrinsic activating and directing effects of the N‐substituents, as well as the electron donating effect of the para‐substituted (Y = Cl, H, Me) phenyl group at the more hindered benzylic C2 atom. The N‐tosyl group (i.e., N‐Tos) or the N‐(2‐pyridyl)sulfonyl group (i.e., N‐Py) was introduced to activate the ring nitrogen atom (N1) and the para‐substituted (Y = Cl, H, Me) phenyl group for the activation of the C2 atom. Conformational searches and geometry optimizations were performed for the N‐(para‐substituted)phenylaziridines ( 1 ～ 6 ). Calculations indicate that the aziridine 6 (i.e., Py/Me) has the most elongated C2? N1 bond intrinsically due to the electronic activating effects, implying the aziridine 6 to be the most potent candidate for the more‐hindered C2 opening. Transition states (TSs) were investigated for the prospective ring‐opening paths (I～IV), considering the types of intermolecular push–pull interactions between the N‐activated phenylaziridines and the cuprate. The N‐Py group provides an unique C2‐favored TS along the path IV, which the N‐Tos group cannot afford, due to the less charge transfer from the nucleophilic CH of the cuprate into the electrophilic C2 atom. Furthermore, the e‐donating effect of the para‐substituents (Y = Cl, H, Me) enhances the C2 opening for the path IV. This study enables us to understand the unusual ring‐opening phenomena in terms of electronic and directing effects and hence may serve as a tool to design substrates for highly regioselective ring openings. © 2011 Wiley Periodicals, Inc. J Comput Chem, 2011     

Bis(oxiranes) Containing Cyclooctane Core: Synthesis and Reactivity towards NaN3

Reactions of oxirane ring opening provide a powerful tool for regio- and stereoselective synthesis of polyfunctional and heterocyclic compounds, widely used in organic chemistry and drug design. Cyclooctane, alongside other medium-sized rings, is of interest as a novel molecular platform for the construction of target-oriented leads. Additionally, cyclooctane derivatives are well known to be prone to transannular reactions, which makes them a promising object in the search for novel approaches to polycyclic structures. In the present work, a series of cyclooctanediones was studied in Corey-Chaykovsky reactions, and novel spirocyclic bis(oxiranes) containing cyclooctane core, namely, 1,5-dioxadispiro[2.0.2.6]dodecane and 1,8-dioxadispiro[2.3.2.3]dodecane, were synthesized. Ring opening of the obtained bis(oxiranes) upon treatment with sodium azide was investigated, and it was found that the reaction path is determined by the reciprocal orientation of oxygen atoms in the oxirane moieties. Diastereomers of the bis(oxiranes) with cis-orientation underwent independent ring opening, supplying corresponding diazidodiols, while in the case of stereoisomers with trans-orientation, domino-like reactions occurred, including intramolecular nucleophilic attack and the formation of a novel three- or six-membered O-containing ring. Summarily, a straightforward approach to polyfunctional compounds containing cyclooctane or oxabicyclo[3.3.1]nonane cores, employing bis(oxiranes), was elaborated.     

用(R)-(+)-缩水甘油的亲核开环反应制备手性连二醇

以D-甘露醇为原料合成(R)-(+)-缩水甘油1。该环氧化合物的亲核开环反应为高立体选择性地(93%-96%e.e.)制备各种手性连二醇提供了一条简便途径。     

Reactions of 2(3)-ethoxycarbonyl-5,6,7,8-tetrafluorochromones with methylamine

2-Ethoxycarbonyl-5,6,7,8-tetrafluorochromone reacts with methylamine differently, depending on the solvent nature and the amount of the amine: in DMSO and MeCN, the fluorine atom at the C(7) atom is initially replaced and then the C(2) and/or C(9) are attacked, while in ethanol, the reaction involves the C(2) atom with opening of the pyrone ring. The reaction of 3-ethoxycarbonyl-5,6,7,8-tetrafluoro-2-methylchromone with methylamine results, regardless of the solvent, in opening of the chromone ring and the formation of intermediate ethyl 3-(3,4,5,6-tetrafluoro-2-hydroxyphenyl)-2-(1-methylamino)ethylidene-3-oxopropionate, which undergoes intramolecular cyclization to give 5,6,7,8-tetrafluoro-3-(1-methyl-amino)ethylidene-3,4-dihydro-2H-benzopyran-2,4-dione. Dedicated to Academician N. S. Zefirov on the occasion of his 70th birthday. Published in Russian in Izvestiya Akademii Nauk. Seriya Khimicheskaya, No. 9, pp. 2093–2098, September, 2005.     

Taming the Reactivity of Phosphiranium Salts: Site-Selective C-Centered Ring Opening for Direct Synthesis of Phosphinoethylamines

Advances in the field of phosphorus chemistry are documented, by revealing the synthetic utility of previously underutilized quaternary phosphiranium salts (QPrS) as three-chain-atom electrophilic building blocks. Notably, control of their challenging C-centered electrophilicity is disclosed with an expedient synthesis of tertiary β-anilino phosphines as a proof-of-concept.     

Synthesis,Molecular Docking,and Preclinical Evaluation of a New Succinimide Derivative for Cardioprotective,Hepatoprotective and Lipid-Lowering Effects

Cardiac and hepatotoxicities are major concerns in the development of new drugs. Better alternatives to other treatments are being sought to protect these vital organs from the toxicities of these pharmaceuticals. In this regard, a preclinical study is designed to investigate the histopathological effects of a new succinimide derivative (Comp-1) on myocardial and liver tissues, and the biochemical effects on selected cardiac biomarkers, hepatic enzymes, and lipid profiles. For this, an initially lethal/toxic dose was determined, followed by a grouping of selected albino rats into five groups (each group had n = 6). The control group received daily oral saline for 8 days. The 5-FU (5-Fluorouracil) group received oral saline daily for 8 days, added with the administration of a single dose of 5-FU (150 mg/kg I.P.) on day 5 of the study. The atenolol group received oral atenolol (20 mg/kg) for 8 days and 5-FU (150 mg/kg I.P.) on day 5 of the protocol. Similarly, two groups of rats treated with test compound (Comp-1) were administered with 5 mg/kg I.P. and 10 mg/kg I.P. for 8 days, followed by 5-FU (150 mg/kg I.P.) on day 5. Toxicity induced by 5-FU was manifested by increases in the serum creatinine kinase myocardial band (CK-MB), troponin I (cTnI) and lactate dehydrogenase (LDH), lipid profile, and selected liver enzymes, including ALP (alkaline phosphatase), ALT (alanine transaminase), AST (aspartate aminotransferase), BT (bilirubin total), and BD (direct bilirubin). These biomarkers were highly significantly decreased after the administration of the mentioned doses of the test compound (5 mg/kg and 10 mg/kg). Similarly, histological examination revealed cardiac and hepatic tissue toxicity by 5-FU. However, those toxic effects were also significantly recovered/improved after the administration of Comp-1 at the said doses. This derivative showed dose-dependent effects and was most effective at a dose of 10 mg/kg body weight. Binding energy data computed via docking simulations revealed that our compound interacts toward the human beta2-adrenergic G protein-coupled receptor (S = −7.89 kcal/mol) with a slight stronger affinity than the calcium channel T-type (S = −7.07 kcal/mol). In conclusion, the histological and biochemical results showed that the test compound (Comp-1) had prominent cardioprotective, hepatoprotective, and lipolytic effects against 5-FU-induced toxicity in the subjected animal model.     

Taming the Reactivity of Phosphiranium Salts: Site‐Selective C‐Centered Ring Opening for Direct Synthesis of Phosphinoethylamines

Advances in the field of phosphorus chemistry are documented, by revealing the synthetic utility of previously underutilized quaternary phosphiranium salts (QPrS) as three‐chain‐atom electrophilic building blocks. Notably, control of their challenging C‐centered electrophilicity is disclosed with an expedient synthesis of tertiary β‐anilino phosphines as a proof‐of‐concept.     

Synthesis and reactivity of 3-(2-chloroalkyl)-2,2-dihaloaziridines

3-(2-Chloroalkyl)-2,2-dihaloaziridines were synthesized via cycloaddition of dihalocarbenes to the CN double bond of β-chloroimines. Under the action of Lewis acids or HCl, N-C³ bond cleavage occurred, giving rise to N-substituted 2,4-dichloro-3,3-dimethylbutanamides, which were further converted to 3-chloropyrrolidin-2-ones under alkaline conditions. When 2,2-dichloro-3-(2-chloro-1,1-dimethylethyl)-1-phenylaziridine was reacted with sodium methoxide, aziridine ring opening with N-C² bond cleavage took place, leading to methyl 4-chloro-3,3-dimethyl-2-(phenylamino)butanoate.     

Remarkable reactions of cyclooctatetraene diiron-bridging carbyne complexes with amino and amido compounds: nucleophilic addition to and breaking of the cyclooctatetraene ring

The reactions of the cationic, diiron-bridging carbyne complexes [Fe(2)(mu-CAr)(CO)(4)(eta(8)-C(8)H(8))]BF(4) (1, Ar=C(6)H(5); 2, Ar=p-CH(3)C(6)H(4); 3, Ar=p-CF(3)C(6)H(4)) with LiN(C(6)H(5))(2) in THF at low temperature gave novel N-nucleophilic-addition products, namely, the neutral, diiron-bridging carbyne complexes [Fe(2)(mu-CAr)(CO)(4)(eta(7)-C(8)H(8)N(C(6)H(5))(2))] (4, Ar=C(6)H(5); 5, Ar=p-CH(3)C(6)H(4); 6, Ar=p-CF(3)C(6)H(4))). Cationic bridging carbyne complexes 1-3 react with (C(2)H(5))(2)NH, (iC(3)H(7))(2)NH, and (C(6)H(11))(2)NH under the same conditions with ring cleavage of the COT ligand to produce the novel diiron-bridging carbene inner salts [Fe(2)[mu-C(Ar)C(8)H(8)NR(2)](CO)(4)] (7, Ar=C(6)H(5), R=C(2)H(5); 8, Ar=p-CH(3)C(6)H(4), R=C(2)H(5); 9, Ar=p-CF(3)C(6)H(4), R=C(2)H(5); 10, Ar=C(6)H(5), R=iC(3)H(7); 11, Ar=p-CH(3)C(6)H(4), R=iC(3)H(7); 12, Ar=p-CF(3)C(6)H(4), R=iC(3)H(7); 13, Ar=C(6)H(5), R=C(6)H(11); 14, Ar=p-CH(3)C(6)H(4), R=C(6)H(11), 15, Ar=p-CF(3)C(6)H(4), R=C(6)H(11)). Piperidine reacts similarly with cationic carbyne complex 3 to afford the corresponding bridging carbene inner salt [Fe(2)[mu-C(Ar)C(8)H(8)N(CH(2))(5)](CO)(4)] (16). Compound 9 was transformed into a new diiron-bridging carbene inner salt 17, the trans isomer of 9, by heating in benzene. Unexpectedly, the reaction of C(6)H(5)NH(2) with 2 gave a novel COT iron-carbene complex [Fe(2)[=C(C(6)H(4)CH(3)-p)NHC(6)H(5)](mu-CO)(CO)(3)(eta(8)-C(8)H(8))] (18). However, the analogous reactions of 2-naphthylamine with 2 and of p-CF(3)C(6)H(4)NH(2) with 3 produce novel chelated iron-carbene complexes [Fe(2)[=C(C(6)H(4)CH(3)-p)NC(10)H(7)](CO)(4)(eta(2):eta(3):eta(2)-C(8)H(9))] (19) and [Fe(2)[=C(C(6)H(4)CF(3)-p)NC(6)H(4)CF(3)-p](CO)(4)(eta(2):eta(3):eta(2)-C(8)H(9))] (20), respectively. Compound 18 can also be transformed into the analogous chelated iron-carbene complex [Fe(2)[=C(C(6)H(4)CH(3)-p)NC(6)H(5)](CO)(4)(eta(2):eta(3):eta(2)-C(8)H(9))] (21). The structures of complexes 6, 9, 15, 17, 18, and 21 have been established by X-ray diffraction studies.     

Selective Synthesis of Monofluorinated Compounds Applying Amine/HF Reagents

For nucleophilic monofluorination, amine/HF reagents such as Et₃N⋅3HF, Pyr⋅9HF (Olah's reagent) and similar combinations belong to the most frequently used fluoride sources, whereupon the selectivity of these reagents can be very different depending of its acidity, the nucleophilicity of the fluoride equivalent, and the structure of the particular substrate. These reagents can be used safely in ordinary chemistry laboratories for nucleophilic substitution reactions by fluoride at sp³-hybridized carbon centers. For ring opening reactions of epoxides, the regio- and stereoselectivity is very much depending of the nature of the epoxide and the acidity of the HF reagent favoring either S_N1 or S_N2 type reactions. Similarly, the outcome of halofluorination and similar reactions with sulfur or seleno electrophiles can be controlled by the particular combination of the electrophile and the fluoride source. Examples for the application of these reaction types for the synthesis of fluorine-containing analogues of natural products or biologically relevant compounds are in the focus of this personal account.     

Synthesis of Poly(lactide)s with Modified Thermal and Mechanical Properties

The use of poly(lactide)‐based materials is, in part, limited by their physical and mechanical properties. This article reviews the methods that have been employed to enable enhancement of the materials properties through synthetic manipulation of the polymer structure including block copolymer synthesis and modification of the lactide monomer structure, focusing on the application of ring‐opening polymerization. In turn the effect of these structural modifications on the properties of the resultant materials are reported.

     

Synthesis and characterization of four-armed poly(1,3-dioxepane) tetraol

A new four-armed poly(1,3-dioxepane) tetraol was prepared by cationic ring-opening polymerization of 1,3-dioxepane (DOP) in the presence of 6,6-bis(5-hydroxyl-2-oxapentyl)-4,8-dioxaundecanediol-1,11 (THA) with triflic acid(I) as initiator. The structure of the poly(DOP) tetraol obtained was characterized by ¹H and ¹³C NMR spectra. The molecular weights of the obtained tetraols were controlled by the mole ratio of DOP consumed to initial THA, and it was found that each macromolecule contains only one THA unit on the average. GPC studies showed that the cyclic oligomers in the products were negligible. © 1999 John Wiley & Sons, Inc. J Polym Sci A: Polym Chem 37: 2347–2353, 1999     

Synthesis,functionalization and crosslinking reactions of poly(silylenemethylene)s

Novel poly(silylenemethylene)s have been prepared by the ring‐opening polymerization of 1,3‐disilacyclobutanes followed by a protodesilylation reaction with triflic acid. The silicon–aryl bond cleavage could be controlled by using different leaving groups, for instance phenyl‐ and para‐anisyl substituents. The reactions of the triflate derivatives with organomagnesium compounds, LiAlH₄, amines or alcohols gave functional substituted poly(silylenemethylene)s. Hydrosilylation reactions or reductive coupling with potassium–graphite led to organosilicon network‐polymers, which may serve as suitable precursors for silicon carbide and Si/C/N‐based materials. The structures of the polymers were identified by nuclear magnetic resonance spectroscopy (²⁹Si, ¹³C, ¹H). Copyright © 1999 John Wiley & Sons, Ltd.     

Reaction of N-Nitro-benzotriazole with Nucleophiles

N-Nitro-benzotriazole 1 reacts with various C-nucleophiles 2 in tetrahydrofuran at room temperature to afford o-nitramidophenylazo-compounds 3a–f and o-nitramidophenyl hydrazones 3g–l, respectively. Reaction of 1 with sodium azide in aqueous acetonitrile gives a reactive 2-azidophenylnitramide intermediate 4 which is trapped by Cu-catalyzed 1,3-dipolar cycloadition with phenyl acetylene to afford 1-o-nitramidophenyl-4-phenyl-1,2,3-triazole 5. Reaction of 1 with trimethylsilylcyanide affords 3-amino-benzo[e][1,2,4]triazine 6.