Synthesis of Novel Spiro Tetrahydrothiapyrano-Isoxazolines and Pyrazolines

Cis 2,6-Diphenyltetrahydrothiapyranone (1) was subjected to Wittig reaction to generate exocyclic double bond (2a-c). Cycloaddition of nitrile oxides and nitrile imines to the latter led to a novel spiro tetrahydrothiapyranoisoxazolines (3a-f) and spiro tetrahydrothiapyranopyrazolines (4a-f)     

Understanding the reactivity and regioselectivity of [3 + 2] cycloaddition reactions between substituted nitrile oxides and methyl acrylate. A molecular electron density theory study

The [3 + 2] cycloaddition (32CA) reactions of three nitrile oxides (NOs) (R‐CNO; R = Ph, CO₂Me, and Br) with methyl acrylate (MA) have been theoretically studied within the molecular electron density theory. Topological analysis of the electron localization function of these NOs permits to establish that they will participate in zw‐type 32CA reactions. Analysis of the conceptual DFT indices indicates that these zw‐type 32CA reactions will have a low polar character as a consequence of the relatively low electrophilic character of MA and the low nucleophilic character of NOs, in agreement with the global electron density transfer computed at the corresponding TSs. The activation enthalpies associated with these 32CA reactions range from 8.2 to 12.7 kcal·mol^?1. The presence of the bromide atom provokes the larger acceleration. While the 32CA reaction involving the CO₂Me substituted NO is highly ortho regioselective, the other two reactions are poorly ortho regioselective. A bonding evolution theory study of the more favorable ortho regiosiomeric channel associated with the 32CA reaction involving the Br substituted NO indicates that this reaction is associated to a nonconcerted two‐stage one‐step mechanism, in which the activation energy is mainly related to the initial rupture of the C? N triple bond of the NO.     

1,3-Dipolar cycloaddition of nitrile oxides to N-vinylcarbazole: Regioselective formation of 5-(9-carbazolyl)-Δ2-isoxazolines

Aryl substituted nitrile oxides undergo 3 + 2 cycloaddition to N-vinyl carbazole to afford only one regioisomer, i.e., 3-aryl substituted 5-(9-carbazolyl)-Δ²-isoxazolines III in good yield.     

Stereoselective Synthesis of Masked Amino-polyols via Osmylation of 4,5-Dihydro-5-vinylisoxazoles

Variously substituted 4,5-dihydro-5-vinylisoxazoles, obtained by regio- and stereospecific cycloaddition of nitrile oxides to dienes, undergo smooth OsO₄-catalyzed cis-hydroxylation to give amino-polyol precursors. The reaction is ‘anti’-selective, the diastereoisomeric ratios ranging from 73:27 up to ≥ 99:1. Thus, the cycloaddition/osmylation sequence allows the control of the relative configuration of up to four contiguous asymmetric centers. A sulfoxide-mediated approach to enantiomerically pure compounds is also described.     

1,3‐Dipolar cycloaddition reaction: Synthesis of novel 5,6‐dehydronorcantharidin derivatives of substituted aromatic amines with potential antitumor activities

Twelve novel compounds were synthesized by the [3+2] 1,3‐dipolar cycloaddition reaction of 5,6‐dehydronorcantharidin derivatives of substituted aromatic amines with nitrile oxides. The structure and the configuration of all compounds were confirmed by ¹H NMR, IR, MS, ¹H‐¹HCOSY, and NOESY spectral data. Their anti‐tumor activities are under way.     

Synthesis of New Bis‐1,2,4‐Oxadiazoline Derivatives via 1,3‐Dipolar Cycloaddition Reaction

A series of novel bis‐oxadiazoline derivatives 4 was synthesized via 1,3‐dipolar cycloaddition reaction of bis‐aldimines 3 , and nitrile oxides generated in situ from various benzohydroximinoyl chlorides in the presence of Et₃N. The target products were confirmed by IR, ¹H‐NMR, and mass spectrometry.     

Synthesis of functional polyethylene <Emphasis Type="Italic">via</Emphasis> copolymerization of ethylene and substituted allene using bis(<Emphasis Type="Italic">β</Emphasis>-enaminoketonato)titanium catalysts

Novel copolymerization of ethylene with substituted allenes（CH₂=C = CH—R,1:R = n-butyl,2:R =n-octyl） using bis（β-enaminoketonato）titanium catalysts[PhN = C（R₂）CHC（R₁）O]₂TiCl₂（1a:R₁ = CF₃,R₂ = CH₃;1b:R₁ = Ph,R₂ = CF₃） has been investigated.In the presence of modified methylaluminoxane,these catalysts can copolymerize ethylene with substituted allenes,affording copolymers with unimodal molecular weight distributions and homogeneous compositions.By varying the reaction conditions,the comonomer incorporation can be tuned in the range of 0-3.6 mol%.¹H-NMR spectra reveal that the copolymerization proceeds through 1,2-insertion fashion of allene comonomer exclusively,and the regioselective nature maintains under various reaction conditions.The retained intra-chain double bond can be converted into the epoxy group under mild conditions.     

Phosphorylformonitrile oxides as spin traps for carbon-centered free radicals: co-formation with radicals in the generation of nitrile oxides from <Emphasis Type="Italic">C</Emphasis>-phosphorylformohydroximoyl halides in the presence of alcohols or ethers

One-electron oxidation of the oximes R₂P(=O)C(=NOH)X (X = Cl or Br) generates the nitrile oxides R₂P(=O)C⁺=NO⁻, which serve as spin traps for unstable carbon-centered radicals.The latter are generated upon addition of PbO₂ to a mixture of formohydroximoyl halide with an alcohol or an ether of the general formula R¹OCHR²R³ under the action of atomic chlorine (bromine) released during the generation of nitrile oxide. This gives rise to new, more persistent C phosphoryliminoxyls R₂P(=O)C(=NO^·)C(OR¹)R²R³ (R¹, R², R³ = H, Alk). When primary alcohols (R¹ = R² = H) are used, acyl radicals generated at the initial step of the reaction are also trapped by nitrile oxides to give C-acyl-C phosphoryl iminoxyl radicals R₂P(O)C(=NO^·)C(=O)R³. Hyperfine coupling constants for more than 20 C-phosphoryl-iminoxyls existing in solutions as mixtures of Z- and E-isomers were determined.The effect of the structure of the primary radical (length of the carbon chain, degree of branching, the presence of a ring, and its size) on the radiospectroscopic characteristics of new C-phosphoryliminoxyl radicals was studied.__________Published in Russian in Izvestiya Akademii Nauk. Seriya Khimicheskaya, No. 2, pp. 336–341, February, 2005.     

Multicomponent one pot synthesis of C-glucosides of 1-azaindolizines

Abstract

A protocol based on Groebke-Blackburn-Bienayame (GBB) multicomponent reaction has been developed for efficient and atom economical synthesis of C-glucosides of 1-azaindolizine, i.e. 2-(β-D-glucopyranosyl)-3-N-alkylamino-1-azaindolizine. Thus, a series of fourteen novel 2-(β-D-glucopyranosyl)-3-N-alkylamino-1-azaindolizines have been synthesized in moderate to good yields by reaction of a perbenzylated β-C-glucopyranosyl aldehyde with differently substituted 2-aminopyridines and alkyl isocyanides using InCl₃ as acid catalyst. All synthesized β-C-glucosides were unambiguously characterized with the help of spectroscopic (IR, ¹H-NMR, ¹³C-NMR and mass spectra) data analysis.     

二茂铁四唑和二茂铁甲醛缩3-取代丙二醇衍生物的合成

以甲酰基二茂铁6为原料, 通过与NH₄OH•HCl的缩合反应得到二茂铁肟7, 再经脱水剂脱水得到二茂铁腈8, 最后在(n-C₄H₉)₃SnCl的作用下与NaN₃反应生成新化合物二茂铁四唑(9). 以甲酰基二茂铁为原料, 在对甲苯磺酸(PTSA)的催化作用下与原甲酸三甲酯反应生成二甲基二茂铁缩醛(10), 然后与(R)-(－)-3-氯-1,2-丙二醇反应得到新的二茂铁缩醛衍生物12, 12再与NaN₃发生取代反应得到新的二茂铁缩醛衍生物13. 而新的二茂铁缩醛衍生物15的合成则是先由(R)-(－)-3-氯-1,2-丙二醇与CH₃OH在NaOH的作用下生成(R)-(－)-1-甲氧基-2,3-丙二醇(14), 再由14与二甲基二茂铁缩醛(10)反应得到的. 所合成的新化合物都用MS, ¹H NMR和IR谱确证了它们的结构.     

An efficient preparation of β‐dimethylaminovinyl sulfone and sulfoximide,and investigation of their reactivity as dipolarophiles

A simple reaction affording (E)‐1‐dimethylamino‐2‐phenylsulfonylethylene, and S‐((E)‐2‐(N',N'‐dimethylamino)ethenyl)‐S‐phenyl‐N‐(p‐tolylsulfonyl) sulfoximide in high yields is described. A reversal in regioselectivity was observed when the β‐dimethylaminovinyl sulfone was employed as a dipolarophile in cycloadditions with nitrile oxides. The sulfone gives rise mainly to 4‐substituted isoxazoles, after elimination of dimethyl amine. In comparison, phenyl vinyl sulfone cycloadds to give 5‐substituted isoxazolines. Although not showing comparable dipolarophilic activity in reactions with nitrile oxides and nitrile imides, the β‐dimethylaminovinyl sulfoximide was easily converted to S‐((E)‐(3‐ethoxycarbonyl)prop‐2‐enyl)‐S‐phenyl‐N‐(p‐tolylsulfonyl) sulfoximide. This allylic sulfoximide cycloadds in good yield to both benzonitrile oxide and diphenylnitrile imide, but no stereoselectivity was observed in the process; and only modest regioselectivity was detected in the case of benzonitrile oxide.     

Diastereoselective Synthesis and Antifungal Activity of Glycosyl Isoxazolines

Abstract

Glycosyl nitrile oxides, generated in situ by reaction of glycosyl oximes (3a, 3b, 4) with N‐chlorosuccinimide and DBU, on 1,3‐dipolar cycloaddition with substituted alkenes resulted in glycosyl isoxazolines (5, 7–28) in diastereoselective manner. The extent of diastereoselection varies with the nature of substituents both in sugar and alkenes. The compounds synthesized were screened in vitro against many fungi wherein two of the compounds (12, 23) showed significant inhibition against Sporothrix schenckii, Trychophyton mentagrophytes, and Cryptococcus neoformans with MIC of 12.5 and 6.25 µg/mL, respectively.     

1,3-Dipolar cycloaddition reactions of 2-phenyl-4-arylidene-5(4H)-oxazolones with nitrile oxides

Stable nitrile oxides are added stereospecifically and regioselectively to the carbon carbon double bond of 2-phenyl-4-arylidene-5(4H)-oxazolones resulting spiro-derivatives 3, 5 . The spectral properties of the reaction products are discussed. The cycloadducts give several substituted isoxazolines via an opening of the oxazolone ring with nucleophilic reagents.     

Thermolysis of furoxans annulated with five-membered carbocycles in the presence of dipolarophiles

The conditions for the thermolysis of furoxans annulated with differently strained five-membered carbocycles (cyclopentafuroxan 1, norbornenofuroxan 2, and acenaphthofuroxan 3) to bis(nitrile oxides) in the presence of various dipolarophiles (diethyl acetylenedicarboxylate, benzoylformonitrile, and ethoxycarbonylformonitrile) were optimized. It was found that the reactivities of the above furoxans as sources of bis(nitrile oxides) decrease in the order 2 > 1 > 3. Among the furoxans studied, only norbornenofuroxan 2 can be recommended as a possible cross-linking reagent for polymers. The formation of di-N-oxides of 3,4-bis(cyanopropyl)-, 3,4-bis(cyanocyclopentyl)-, and 3,4-bis(cyanonaphthyl)furoxans was detected. They resulted from intermolecular cyclodimerization of bis(nitrile oxides) initially formed in the thermolysis of furoxans 1–3. Dedicated to Academician V. A. Tartakovsky on the occasion of his 75th birthday. Published in Russian in Izvestiya Akademii Nauk. Seriya Khimicheskaya, No. 8, pp. 1521–1528, August, 2007.     

Sol–Gel Approach to Sr<Subscript>2</Subscript>CeO<Subscript>4</Subscript> Phosphor from Single Alkoxide Precursors

Syntheses and characterizations of sol–gel precursors of Sr₂CeO₄ were carried out. Each molecular precursor, [Sr₂Ce(OCH₂CH₂OCH₃)₈] (1), [Sr₂Ce(OⁱPr)₈] (2) and [Sr₂Ce₂(OⁱPr)₁₂(ⁱPrOH)₄] (3) was prepared from mixtures of Sr complexes and cerium(IV) alkoxides. The molecular structure of 3 showed that [CeO₆] octahedra are connected with distorted [SrO₆] octahedra by sharing edges with oxo bridges. X-ray powder diffraction patterns and spectrofluorometry were used to determine the evolution of structure from the precursor molecules to the luminescent oxides. The luminescent strontium cerium oxides were derived at relatively mild reaction conditions (700 °C for 1 h), and complete conversion was observed at 1000 °C for 1 h from these precursors. Comparing the spectra of the oxides derived from 2 and 3, the emission intensity of the oxide derived from 2 is much stronger.     

四个基于间苯二(取代水杨醛酰腙)的有机锡配合物的溶剂热合成、结构和荧光性能

采用间苯二（取代水杨醛酰腙）（H₄L）与R₃²SnOH溶剂热反应,或间苯二甲酰肼、3-叔丁基水杨醛和三环己基氢氧化锡一锅溶剂热法反应,合成了4个新的有机锡配合物（SnR²）₂L（1~4）,其中,H₄L=m-Ph（CONH—N=CH（o-OH） PhR¹）₂;R¹=NEt₂,R²=Ph（1）;R¹=3,5-di-tert-butyl=3,5-t-2Bu,R²=Ph（2）;R¹=3,5-t-2Bu,R²=Cy（3）;R¹=3-tert-butyl=3-t-Bu,R²=Cy（4）。经元素分析、红外光谱和（¹H、¹³C、¹¹9Sn）核磁共振谱表征,并用X射线衍射方法确证配合物1~4的结构。配体H₄L的2个取代水杨醛酰腙链向内取向并与锡原子配位形成3个内向E型配合物1~3,取代水杨醛酰腙链向外取向并与锡原子配位形成外向E型配合物4。配合物1、2和4属于三斜晶系P1空间群,配合物3属于单斜晶系P2₁/c空间群。中心锡与配位原子构成畸形双角三锥构型。配体、配合物-三氯甲烷溶液的荧光性能表明,当具有弱荧光的配体m-Ph（CONH—N=CH（o-OH） PhNEt₂）₂（H₄L¹）和无荧光的配体m-Ph（CONH—N=CH（o-OH） Ph（3,5-t-2Bu））₂（H₄L²）分别与苯基锡、环己基锡配位后,配合物-三氯甲烷溶液发出强荧光。     

Synthesis,Characterization, and In Vitro Antimicrobial Activity of Methyleneamine‐Linked Bis‐heterocycles

A new class of methyleneamine‐linked bis‐heterocycles that exhibit antimicrobial activity was synthesized. Bromination of 1 followed by condensation with thiourea gave 3 . The reaction of 3 with propargyl bromide in dry toluene under inert atmosphere led to the formation of 4 . Its subsequent reaction with different nitrile oxides using CuSO₄.5H₂O–sodiumascorbate system in a 2:1 mixture of water and tert‐butyl alcohol yielded the title compounds 6a , 6b , 6c , 6d , 6e , 6f , 6g , 6h , 6i , 6j , 6k , 6l in good yields. The identities of these compounds were confirmed following elemental analysis, IR, ¹H, ¹³C NMR, and mass spectral studies. All the title compounds exhibited pronounced in vitro antibacterial and antifungal activities.     

Diphenylphosphinoderivate von Malein- und Fumarsäureestern: Darstellung,Eigenschaften, Kristall- und Molekülstrukturen

The reaction between 2,3-dichloromaleic acid dialkylester (alkyl=CH₃ and C₂H₅) and diphenyl(trimethylsilyl)phosphine, leading to diphenylphosphine substituted esters of maleic and fumaric acid has been studied. With a molar ratio 1:1 of the components 2-chloro-3-diphenylphosphinomaleic acid dimethylester (3) and-diethylester are obtained as colourless crystalline compounds. From a 1:2 reaction however only bis(diphenylphosphino)fumaric acid dimethylester (colourless crystals) and-diethylester (yellow) can be crystallized, the latter in a partially oxydized form. The presence of bis(diphenylphosphino)maleic acid diester in the oily part of the reaction products has been proved by its chelating with Ni²⁺ and Pd²⁺ to complexes of the compositionMeCl₂·(PP). Pure bis(diphenylphosphino)maleic acid dimethylester (4) could be synthesized by alcoholysis and following methylation of bis (diphenylphosphino)maleic anhydrid. Contrary to this easily chelating and air stable compound the corresponding fumaric acid diesters give no complexes with the metals examined as far and are very sensitive towards oxygen. This sensitivity decreases strongly after oxydation to 2-diphenylphosphino-3-diphenylphosphorylfumaric acid diester, the diethylester of which could be crystallized in pure form.Characteristic vibration bands, uv/vis-absorption and³¹P-nmr peaks are discussed.The result of X-ray diffraction data of3 and4 are reported and conformation, bond lengthes and bond angles of these molecules are given.     

Cycloaddition Reactions of Benzonorbornadiene and Homonorbornadiene: New Isoxazoline and Pyridazine Derivatives

Ten new isoxazoline derivatives were synthesized from the reactions of benzonorbornadiene and homonorbornadiene derivatives with nitrile oxides formed from benzaldehyde and 4‐substituted benzaldehyde. Two new pyridazine derivatives were also synthesized from the reaction of the homonorbornadiene derivatives with 3,6‐di (2‐pyridyl)‐s‐tetrazine. It was seen that all cycloaddition reactions were realized as exo selectivity. Finally, γ‐Gauche effect in the isoxazoline derivatives was discussed.     

二-吡啶氧基-轴向取代-四-α-(3-戊氧基)锡(IV)酞菁的合成与表征

以3-硝基邻苯二甲腈为起始原料, 与正戊醇反应合成3-戊氧基邻苯二甲腈(1), 然后在高温溶剂1-氯萘中经缩聚反应合成二氯-轴向取代-四-α-(3-戊氧基)锡酞菁(2), 2进一步与2-羟基吡啶在N,N-二甲基甲酰胺中合成二-吡啶氧基-轴向取代-四-α-(3-戊氧基)锡酞菁配合物3, 同时对相关化合物分别进行了元素分析, IR, ¹H NMR, UV/Vis, 荧光和质谱表征.