1,3,4,5,7,8-六硝基八氢化二咪唑[4,5-b∶4',5'-e]吡嗪-2,6-(1H,3H)-N,N'-二亚硝胺反应中间体的量子化学研究

应用密度泛函理论,在B3PW91/6-31G++(d,p)水平下,分析了合成1,3,4,5,7,8-六硝基八氢化二咪唑[4,5-b∶4',5'-e]吡嗪-2,6-(1H,3H)-N,N'-二亚硝胺(ONIP)时可能产生的不同数量硝基取代的中间产物,并分析了在相同数量的硝基取代时,中间产物可能具有的同分异构体的热力学选择性,确认了热力学选择下的反应历程.比较了4~8个硝基取代中间产物的结构性能数据,计算结果表明,超过四硝基取代后,特别是六硝基中间产物,具有良好的爆轰性能,同时稳定性远超ONIP,并且更易于合成.     

The Crystal Structures of Pyrazine-2,6-Dicarboxylic Acid DihydRAte and Hexaaquamagnesium(II) Pyrazine-2,6-Dicarboxylate

The crystals of the pyrazine-2,6-dicarboxylic acid dihydrate [C 4 H 2 N 2 (COOH) 2 ]·2H 2 O or H 2 (2,6-PZDC)] crystallize in the monoclinic system, space group C2/m. Their structure is composed of planar layers in which the acid and the water molecules interact via a network of hydrogen bonds. The layers are also hydrogen bonded. Hexaaquamagnesium(II) pyrazine-2,6-dicarboxylate [Mg(H 2 O) 6 ] 2+ [C 4 H 2 N 2 (COO) 2 ] 2 m crystallizes in the monoclinic system, space group P2 1 / n . The magnesium(II) cation is surrounded by six water molecules located at the apices of an almost regular octahedron with the mean Mg-O bond distance of 2.068 Å. The 2,6-PZDC anions are planar and are acceptors in a network of hydrogen bonds donated by the coordinated water molecules.     

Halogenated 3-pyridylketones

The oxidation of 2,6-dichloro-3-benzylpyridines and bis(2,6-dichloro-3-pyridyl)methanes, respectively, was accomplished using chromic trioxide in a highly acidic medium. The synthesis of several phenyl-3-(2,6-dichloropyridyl)ketones and of bis(2,6-dichloro-3-pyridyl)ketone are reported.     

A comparison of sensitized Ln(III) emission using pyridine- and pyrazine-2,6-dicarboxylates

The synthesis, X-ray structure, solution stability, and photophysical properties of Eu(III) complexes with pyrazine-2,6-dicarboxylic acid (H(2)PYZ) are reported, and compared to structurally analogous complexes with pyridine-2,6-dicarboxylic acid (H(2)DPA). The [Eu(PYZ)(3)](3-) complex demonstrates highly efficient metal-centered Eu(III) luminescence in the solid state (Φ(total) ～ 60.9%). In aqueous solution, moderate stability is retained at pH 7.4 (pEu ～ 10.5), although hydrolysis of the complex anion becomes competitive below mM concentrations, and the observed luminescence intensity from the Eu(III) metal ion is reduced as a result. A complete evaluation of the thermodynamic solution stability has allowed the observed differences in the solution behaviour luminescence properties of these complexes to be rationalized. An analysis of their luminescence behaviour in the solid state has also allowed a direct comparison of the sensitisation behaviour for these isostructural compounds.     

1-(2,6-二氯苯基)-2-吲哚酮及相关物质的HPLC分离分析

 应用高效液相色谱方法研究了以2,6二氯苯酚和苯胺为起始原料合成药物中间体1(2,6二氯苯基)2吲哚酮(DCI)过程中,DCI及相关物质在不同色谱条件下的分离情况。结果表明,以CLCCN(150mm×6.0mmi.d.,7μm)为分离柱,以MeOHH2O(体积比为6∶4)为流动相,在流速为1mLmin的情况下,DCI及相关物质可以达到基线分离。建立了快速准确测定DCI纯度和检验杂质种类的高效液相色谱分析方法,方法准确可靠。对两个精品和两个粗品分别进行测定,结果表明精品中的杂质主要为N(2,6二氯二苯胺基)氯乙酰胺,粗品中的杂质主要为N(2,6二氯二苯胺基)氯乙酰胺和2,6二氯二苯胺。     

2,6-双(3-甲基-1H-吡唑基)-4-氨基吡啶的合成与表征

以2,6-二溴吡啶为起始原料,经过氧化、硝化、还原、亲核取代等四步合成了新型时间分辨荧光免疫分析双功能螯合剂中间体2,6-双(3-甲基-1H-吡唑基)-4-氨基吡啶.化合物结构通过DSC,IR,气质联用色谱(GC-MS),1H NMR和元素分析等确证,对合成条件进行了探讨.     

Synthesis of 6-Amino-5-R2-7-(6-R1-4-oxo-3,4-dihydro-2-quinazolyl)-5H-pyrrolo[2,3-b]pyrazine-2,3-dicarbonitriles

It has been found that malonodinitrile and 2-(6-R¹-oxo-3,4-dihydro-2-quinazolyl)acetonitrile in the presence of triethylamine undergo hetarylation by 5,6-dichloro-2,3-pyrazinedicarbonitrile at the active methylene group to give the triethylammonium salt of 2-(3-chloro-5,6-dicyano-2-pyrazinyl)malononitrile or 5-chloro-6-cyano(6-R¹-4-oxo-1,2,3,4-tetrahydro-2-quinazolylidene)methyl-2,3-pyrazinedicarbonitriles. Reaction of these with primary amines leads to annelation of the pyrrole ring at the pyrazine [b] edge to give 6-amino-5-R-5H-pyrrolo[2,3-b]pyrazine-2,3,7-tricarbonitriles and 6-amino-5-R²-7-(6-R¹-4-oxo-3,4-dihydro-2-quinazolyl)-5H-pyrrolo[2,3-b]pyrazine-2,3-dicarbonitriles respectively.     

Condensation of 4-Tert-butyl-2,6-dimethylbenzenesulfonamide with Glyoxal and Reaction Features: A New Process for Symmetric and Asymmetric Aromatic Sulfones

The synthesis of substituted aza- and oxaazaisowurtzitanes via direct condensation is challenging. The selection of starting ammonia derivatives is very limited. The important step in developing alternative synthetic routes to these compounds is a detailed study on their formation process. Here, we explored an acid-catalyzed condensation between 4-tert-butyl-2,6-dimethylbenzenesulfonamide and glyoxal in aqueous H₂SO₄, aqueous acetonitrile and acetone, and established some new processes hindering the condensation. In particular, an irreversible rearrangement of the condensation intermediate was found to proceed and be accompanied by the 1,2-hydride shift and by the formation of symmetric disulfanes and sulfanes. It has been shown for the first time that aldehydes may act as a reducing agent when disulfanes are generated from aromatic sulfonamides, as is experimentally proved. The condensation between 4-tert-butyl-2,6-dimethylbenzenesulfonamide and formaldehyde resulted in 1,3,5-tris((4-(tert-butyl)-2,6-dimethylphenyl)sulfonyl)-1,3,5-triazinane. It was examined if diimine could be synthesized from 4-tert-butyl-2,6-dimethylbenzenesulfonamide and glyoxal by the most common synthetic procedures for structurally similar imines. It has been discovered for the first time that the Friedel–Crafts reaction takes place between sulfonamide and the aromatic compound. A new synthetic strategy has been suggested herein that can reduce the stages in the synthesis of in-demand organic compounds of symmetric and asymmetric aromatic sulfones via the Brønsted acid-catalyzed Friedel–Crafts reaction, starting from aromatic sulfonamides and arenes activated towards an electrophilic attack.     

Mild and Efficient Synthesis of 1-（6-Chloroquinoxalin-2-yl）-2- [4-（trifluoromethyl）-2,6-dinitrophenyl] Hydrazine Derivatives by Microwave Irradiation

Some 1-（6-chloroquinoxalin-2-yl）-2-[4-（trifluoromethyl）-2,6-dinitrophenyl] hydrazine derivatives have been synthesized via both conventional and microwave assisted organic synthesis（MAOS） methods. The MAOS method is more effective on synthesizing these compounds than the conventional method in regard to the higher chemical yields of products（76%-98%） and the shorter reaction time（1-15 min）.     

The Crystal Structures of Two Calcium(II) Complexes with Pyrazine- 2,6-Dicarboxylate and Water Ligands

The structure of catena-{bis[(μ-aqua)(diaqua)(pyrazine-2,6-dicarboxylato-O,N-μ-O')](calcium(II)} consists of dimeric units composed of two calcium(II) ions, two ligand molecules and six water molecules. The calcium ions are bridged by two bidentate oxygen atoms, each donated by one carboxylic group of the ligand. The Ca(II) ion is also coordinated by one oxygen atom of the second carboxylate group and the hetero-ring nitrogen atom belonging to the same ligand molecule. Both calcium ions in a dimer are bridged to the Ca(II) ions in adjacent dimers by a pair of water molecules forming infinite molecular ribbons. In addition, each Ca(II) ion is coordinated by three water molecules; one of them is used for bridging the adjacent dimer. The coordination polyhedron around the Ca(II) ion is a pentagonal bipyramid with two apices above and one apex below the equatorial plane. The same molecular pattern is observed in the structure of catena-{bis[(μ-aqua)(diaqua)(pyrazine-2,6-dicarboxylato-O,N-μ-O')](calcium(II)} dihydrate which, in addition, contains two solvation water molecules per unit cell. In both compounds the molecular ribbons are held together by extended systems of hydrogen bonds.     

Reaction of 5-(3,4-dimethoxyphenyl)pyrazine-2,3-dicarbonitrile with alkyl radicals

The reaction of 5-(3,4-dimethoxyphenyl)pyrazine-2,3-dicarbonitrile (Ib) with alkyl radicals gives addition products at the C(6)-position of the pyrazine ring as the intermediates which collapse into substitution products, 6-alkyl-5-(3,4-dimethoxyphenylpyrazine-2,3-dicarbonitrile (II), under oxidative conditions. Under non-oxidative conditions the intermediate is converted into dihydropyrazine derivatives, 6-alkyl-(3,4-dimethoxy-phenyl)-5,6-dihydropyrazine-2,3-dicarbonitrile (III), and 3,6-disubstituted pyrazine derivatives, 3,6-dialkyl-5-(3,4-dimethoxyphenyl)pyrazine-2-carbonitrile (IV) and 3-acyl-6-alkyl-5-(3,4-dimethoxyphenyl)pyrazine-2-carbonitrile (V).     

Enantiocontrolled synthesis of 2,6-disubstituted piperidines by desymmetrization of meso-eta-(3,4,5)-dihydropyridinylmolybdenum complexes. application to the total synthesis of (-)-dihydropinidine and (-)-andrachcinidine

A conceptually new approach to the enantiocontrolled synthesis of 2,6-disubstituted piperidines was achieved by desymmetrization of meso-2,6-dimethoxy-eta-(3,4,5)-dihydropyridinylmolybdenum complexes. After protection of the piperidine nitrogen as a urethane derived from (+)- or (-)-trans-2-(alpha-cumyl)cyclohexyl (TCC), a sequential, one-pot methoxide abstraction/nucleophilic addition/methoxide abstraction/nucleophilic addition generated good yields of 2,6-disubstituted-eta-(3,4,5)-dihydropyridinylmolybdenum complexes. This sequence proceeds by way of a highly diastereoselective methoxide abstraction (>40:1). High yielding protodemetalation and N-deprotection provided a simple and enantiocontrolled synthetic entry to a variety of 2,6-disubstituted piperidines. This new method was used for the total synthesis of (-)-dihydropinidine and (-)-andrachcinidine.     

Synthesis and structural characterization of a tetracopper(I) complex of 2,6-(bis(3- dimethylamino)-propyliminomethyl)-4- methylthiophenolate

The compound 2,6-diformyl-4-methylphenyl (1) has been made by hydrolysis of S-(2,6- diformyl-4-methylphenyl)dimethylthiocarbamate followed by oxidation with I₂. Condensation of 1 with 4 equiv. of 3-dimethylaminopropylamine and subsequent reduction with Na/benzophenone results in the sodium salt of the Schiff base binucleating ligand 2,6-(bis(3-dimethylamino)-propyliminomethyl)-4-methyl-thiophenolate (2, NaL). The ligand (L) binds 2 eq of Cu(I) and crystallizes from MeCN solution to give an air sensitive tetracopper(I) complex with the formula [Cu₄L₂(MeCN)](PF₆)₂ (3)·0.5 MeCN·0.25 MeOH as determined by X-ray crystallography. The complex contains three distorted trigonal planar and one distorted tetrahedral Cu¹ centers with Cu---S bond lengths short for their respective coordination geometries. In DMSO solution, ¹H NMR spectra of 3 reflect free ligand symmetry suggesting dissociation into dimers. Cyclic voltammetry of 3 in MeCN reveals one irreversible oxidation at 110 mV (vs SCE).     

Synthetic study of carbapenem antibiotics I. (±)-2-cyclopropyl-6-(1′-hydroxyethyl)-1-carbapen-2-em-3-carboxylic acid

A synthetic scheme extensively utilizing silylation-desilylation reactions to achieve the total synthesis of 2,6-substituted carbapenem antibiotics from readily available azetidinones is reported. An epimeric pair of new 2,6-substituted carbapenems, (±)-2-cyclopropyl-6-(1′-hydroxyethyl)-1-carbapen-2-em-3-carboxylic acids were synthesized.     

2-[4-(2,6-二氟苯基)噻唑-2-基]-3-羟基丙烯腈衍生物的合成及生物活性

为了寻找生物活性良好的噻唑基丙烯腈类化合物, 利用2-[4-(2,6-二氟苯基)噻唑-2-基]乙腈(3)分别与取代氯甲酸酯4和取代苯基异氰酸酯6在碱存在下反应, 合成了8个2-[4-(2,6-二氟苯基)噻唑-2-基]-3-羟基-3-烃氧基丙烯腈化合物5和7个2-[4-(2,6-二氟苯基)噻唑-2-基]-3-羟基-3-取代苯胺基丙烯腈化合物7, 均为首次报道的丙烯腈类化合物. 化合物结构经1H NMR, IR, MS和元素分析表征. 初步生物活性测定结果表明, 在试验浓度下, 目标化合物均具有一定的杀虫和抑菌活性, 其中化合物5f和5h在100 mg/L浓度下对炭疽病菌的抑制率达95%; 化合物5g和7d在250 mg/L浓度下对棉红蜘蛛的致死率达85%.     

Electrochemical polymerization of 2,6-pyridinediamine and characterization of the resulting polymer

Electrochemical synthesis of poly(2,6-pyridinediamine)(PPa) in aqueous sodium hydroxide solution has been carried out by using cyclic voltammetry for the first time.The scanning electron microscopy(SEM) revealed the interpenetrating network structure of the as-prepared PPa film,which makes it possible that anions can be doped into the polymer in the oxidation process, and vice versa in the reduction process.The results from FT-IR spectrum provided a possible polymerization mechanism of 2,6- pyridinediamine.     

Synthesis and characterization of a compact tricyclic resorcinol from (+)- and (−)-3-pinanol

Resorcinol derivatives are important building blocks in the synthesis of natural products and pharmaceutical compounds including cannabinoids. Here we describe the synthesis and the structural characterization of a key resorcinol which carries a fully restricted bridged bicyclic group. We also report a potential mechanism for the acid catalyzed condensation of (+)- or (−)-3-pinanol with 2,6-dimethoxyphenol. The synthesized resorcinol facilitates the development of novel conformationally restricted cannabinoid analogs.     

SmI2-induced cyclization of (E)- and (Z)-β-alkoxyvinyl sulfones with aldehydes

SmI₂-induced reaction of (E)- and (Z)-β-alkoxyvinyl sulfones onto an aldehyde function afforded 2,6-syn-2,3-trans- and 2,6-syn-2,3-cis-tetrahydropyran-3-ols, respectively, via stereoselective cyclization. This reaction was applied to the synthesis of 2-methyl-tetrahydropyran, corresponding to the N-ring of gymnocin-A, and 2-exo-methylene-tetrahydropyran, a key intermediate for convergent synthesis of polycyclic ethers based on the Suzuki–Miyaura reaction.     

Highly enantioenriched tetrahydropyridines from chiral organosilanes: application to the synthesis of quinolizidine alkaloid (-)-217A

The tetrahydropyridine and piperidine subunits are widely found in biologically active molecules and natural products. Alhough considerable synthetic efforts have been made to reach these systems, there are few direct methods available for the preparation of enantionenriched tetrahydropyridines. A Lewis acid-promoted intramolecular imine crotylation is described and results in direct access to enantioenriched 2,6-cis- and 2,6-trans-3-trans-trisubstituted tetrahydropyridines with high diastereoselectivity. An example of the application of this methodology was demonstrated in an expedient total synthesis of (-)-quinolizidine 217A. The absolute stereochemistry of this natural product was established by the total synthesis.     

Synthesis of 2,6-di(pyrazol-1-yl)-4-bromomethylpyridine, and its conversion to other 2,6-di(pyrazol-1-yl)pyridines substituted at the pyridine ring

Two routes to 2,6-di(pyrazol-1-yl)-4-hydroxymethylpyridine (1) from 2,6-dihydroxy-isonicotinic acid, in four and six steps, are reported. Reaction of 1 with 48% HBr yields 2,6-di(pyrazol-1-yl)-4-bromomethylpyridine (2), which is a powerful precursor to a range of new tridentate ligands for transition metals functionalised at the pyridine ring. As a proof of principle, we describe the further elaboration of 2 to give two 2,6-di(pyrazol-1-yl)pyridines bearing nucleobase substituents, and the back-to-back ligand 1,2-bis[2,6-di(pyrazol-1-yl)pyrid-4-yl]ethane. Crystal structures of two of these new derivatives are presented.