2-Dicyanomethylidene-3-ethoxymethylidene-2,3-dihydroindole in the synthesis of fused tri- and tetracyclic systems

The reactions of 2-dicyanomethylidene-3-ethoxymethylidene-2,3-dihydroindole with hydrazine hydrate and phenylhydrazine afforded 2,3-diamino-4-cyanopyrido[4,3-b]indole and 3-amino-2-anilino-4-cyanopyrido[4,3-b]indole, respectively, and the reactions of the latter compounds with dimethylformamide diethyl acetal were studied. The reactions of 2,3-diamino-4-cyanopyrido[4,3-b]indole with benzaldehyde, ethyl acetoacetate, and acetylacetone were investigated. First representatives of new heterocyclic systems, viz., [1,2,4]triazolo[1’,5’:1,6]-pyrido[4,3-b]indole and pyrazolo[1’,5’:1,2]pyrido[4,3-b]indole, were synthesized. The structure of ethyl 6-cyano-5-[(E)-(dimethylamino)methylideneamino]-2-methyl-7H-pyrazolo-[1’,5’:1,2]pyrido[4,3-b]indole-1-carboxylate was established by X-ray diffraction.     

Synthesis and selected properties of N-substituted pyrrolo[2,1-c]-1,3-diazacycloalkano[1,2-a]pyrazinones

The reactions of methyl α-(2-formyl-1H-pyrrol-1-yl)carboxylates with N-substituted aliphatic 1,2-, 1,3-, and 1,4-diamines afford new pyrrole-containing heterocyclic systems: 1,2,3,10b-tetrahydroimidazo[1,2-a]pyrrolo[2,1-c]pyrazin-5(6H)-ones, 1,3,4,11b-tetrahydro-2H-pyrrolo[2′,1′:3,4]pyrazino[1,2-a]pyrimidin-6(7H)-ones, and 1,2,3,4,5,12b-hexahydro-pyrrolo[2′,1′:3,4]pyrazino[1,2-a][1,3]diazepin-7(8H)-ones. The reduction of these compounds with different reagents was studied.     

Stable azomethine imines having a 3,4-dihydroisoquinoline fragment and their cycloaddition to <Emphasis Type="Italic">N</Emphasis>-arylmaleimides

Aroylation of 5,6,8,8a,13,14,16,16a-octahydro[1,2,4,5]tetrazino[6,1-a:3,4-a′]diisoquinoline or 1,3,4,8b-tetrahydro[1,2]diazireno[3,1-a]isoquinoline, as well as reactions of 2-(2-bromoethyl)benzaldehyde with aroylhydrazines followed by treatment with triethylamine, led to the formation of stable azomethine imines, aroyl(3,4-dihydroisoquinolinium-2-yl)azanides. 1,3-Dipolar cycloaddition of the latter to N-mesitylmaleimide was stereoselective: the ratio of the trans- and cis-adducts was ∼(3–7): 1, the former prevailing. The reactions with N-arylmaleimides having no ortho-substituents in the aryl group gave the corresponding cis-adducts as the major products [trans/cis ratio ∼1: (2.5–10)].     

Condensed isoquinolines. 34.* Transformations of 4H-thieno-[3',2':5,6]- and 4H-thieno[2',3':5,6]pyrimido-[1,2-<Emphasis Type="Italic">b</Emphasis>]isoquinolines

Syntheses are given for previously unreported 4-chloro derivatives of 4H-thieno[3′,2′:5,6]- and 4H-thieno[2′,3′:5,6]pyrimido[1,2-b]isoquinolines and the reactions of these compounds with N- and S-nucleophiles were studied. The spectral characteristics and biological activity of the positional isomers were compared. The electron spectra most clearly reflect the differences related to the position of the sulfur atom in these quasiaromatic systems. *For Communication 33, see [1]. Translated from Khimiya Geterotsiklicheskikh Soedinenii, No. 4, pp. 619–630, April, 2009.     

Heterocyclization of 3-(R-amino)-3-methylthio-1-phenylpropenones and 5-benzoyl-6-methylthio-1,2-dihydropyridin-2-ones with 1,2- and 1,3-dinucleophilic reagents

The interaction of 3-(R-amino)-3-methylthio-1-phenylpropenones and 1-alkyl-5-benzoyl-3-ethoxy-carbonyl-6-methylthio-1,2-dihydropyridin-2-ones with N,N- and N,C-1,2- and 1,3-dinucleophiles proceeded regioselectively by [3 + 2] and [3 + 3] cyclocondensation with the formation of derivatives of pyrazole, benzimidazo[1,2-a]-pyridine, benzimidazo[1,2-a]pyrimidine, imidazo[1,2-a]pyrimidine, [1,2,4]triazolo[4,3-b]pyridazine, and 6,7-dihydro-2H-pyrazolo[3,4-b]pyridine. The regioselectivity of the reactions carried out was analyzed.     

Reactions of 5-nitrospiro[benzimidazole-2,1′-cyclohexane] 1,3-dioxide with nucleophiles

Reactions of 5-nitrospiro[benzimidazole-2,1′-cyclohexane] 1,3-dioxide with aliphatic amines and sodium hydroxide resulted in removal of one N-oxide oxygen atom and formation of 4-alkylamino- or 4-hydroxy-substituted 5-nitrospiro[benzimidazole-2,1′-cyclohexane] 1-oxides, respectively. The title compound reacted with ammonia and methylamine in the presence of MnO₂ with conservation of both N-oxide moieties, and the products were 4-amino- and 4-methylamino-5-nitrospiro[benzimidazole-2,1′-cyclohexane] 1,3-dioxides. The reactions with aromatic amines were accompanied by removal of both N-oxide oxygen atoms with formation of N-aryl-5-nitrospiro[benzimidazole-2,1′-cyclohexane]-4-amines. In the reactions of 5-nitrospiro-[benzimidazole-2,1′-cyclohexane] 1,3-dioxide with sodium azide and aromatic amine hydrochlorides nucleophilic replacement of the 5-nitro group by azido or arylamino occurred, in the first case both N-oxide fragments being conserved. The reactions with aromatic amine hydrochlorides afforded N-aryl-5-nitrospiro[benzimidazole-2,1′-cyclohexan]-4-amine 1-oxides. Treatment of 5-nitrospiro[benzimidazole-2,1′-cyclohexane] 1,3-dioxide with sodium cyanide led to the formation of 5-oxo-3,5-dihydrospiro[benzimidazole-2,1′-cyclohexane]-4-carbonitrile 1-oxide.     

A new era for organic synthesis—highlights of the recent progress

The major progress in organic synthesis since 2005 is briefly surveyed in two parts. The first part deals with some of the most impressive advances in the synthetic methodology, which includes: (1) metal-mediated synthetic reactions, with an emphasis on the olefin metathesis and gold-mediated reactions; (2) free radical-based organic synthesis; (3) synthetic transformations performed in a “one-pot” manner involving either tandem reactions or multicomponent reactions; (4) asymmetric reactions catalyzed by metal and organo-catalysts. The major advances in total synthesis of some complex natural products with significant biological activities are presented in the second part, with detailed illustrations of ten selected molecules, including dragmacidin F, abyssomicin C, 11-acetoxy-4-deoxyasbestinin D, pentacycloanammoxic acid, UCS1025A, (−)-merrilactone A, nigellamine A₂, (+)-saxitoxin, and Tamiflu (an artificially designed natural product-like molecule). An array of complicated structures of the natural products synthesized over the last two years is also listed to serve as a convenient lead to the original literature for the prospective interested readers. Translated from Progress in Chemistry, 2007, 19(1): 6–34 [译自: 化学 进展]     

Two-fragment α-adrenolytics

Dialkyl β-(2-aroxyethylamino)ethylphosphonates,N-[β-(2-methoxyphenoxy)ethyl]-N′-[β-(diethoxyphosphoryl)ethyl]-α,ω-diaminoalkanes, and diethyl β-(N-arylpiperazino)ethyl-phosphonates were synthesized by the reactions of dialkyl vinylphosphonates with β-aroxyethylamines,N-[β-(2-methoxyphenoxy)ethyl]-α,ω-diaminoalkanes, andN-aryl-piperazines, respectively. The compounds synthesized exhibit hypotensive and α-adrenolytic activities. Translated fromIzvestiya Akademii Nauk. Seriya Khimicheskaya, No. 5, pp. 987–991, May 1999.     

Domino reactions in the synthesis of benzothieno[2,3-c]pyridines. New one-pot method of preparing 2-([1]benzothieno-[2,3-c]pyridin-1-yl)benzoic acids and 8,13b-dihydro[1]benzothieno[2',3':3,4]pyrido-[2,1-a]isoindol-5(7?H)-ones

A series of previously unknown 2-([1]benzothieno[2,3-c]pyridin-1-yl)benzoic acids and 8,13b-dihydro-[1]benzothieno[2',3':3,4]pyrido[2,1-a]isoindol-5(7 H)-ones has been synthesized using domino reactions, taking place at the cyclization of 2-[3-oxo-4-(phenylsulfanyl)butyl]-1,3-isoindolinediones in polyphosphoric acid.     

Design and Synthesis of New Chiral Calix[4]arenes as Liquid Phase Extraction Agents for α-Amino Acid Methylesters and Chiral α-Amines

The article describes the synthesis and extraction properties of new (S)-(-)-1-phenylethylamine substituted p-tert-butylcalix[4]arene/calix[4]arene. These compounds have been synthesized via nucleophilic substitution reactions involving 5,11,17,23-tetra-tert-butyl-25,26,27,28-tetra(2-hydroxyethoxy)calix[4]arene (4a), or 5,11,17,23-tetra-H-25,26,27,28-tetra(2-hydroxyethoxy)calix[4]arene (4b) with (S)-(-)-1-phenylethylamine in dry THF. The extraction properties of ligands 5a and 5b towards the some selected α-amino acid methylesters and chiral α-amines are also reported. It has been observed that receptor 5a was an excellent ionophore for α-amino acid methylesters/α-amines and good extractant than 5b. However, both of the ligands did not display any selectivity towards the configurations of this species. in final form: 17 January 2005     

2-[3-(Trifluoromethyl)phenyl]furo[3,2-b]pyrroles: synthesis and reactions

The synthesis and reactions of methyl 2-[3-(trifluoromethyl)phenyl]-4H-furo[3,2-b]pyrrole-5-carboxylate (1a) are described. Upon reaction with methyl iodide, benzyl chloride, or acetic anhydride, this compound gave N-substituted products 1b-d. By hydrolysis of compounds 1a-c, the corresponding acids 2a-c were formed, or by reaction with hydrazine-hydrate, the corresponding carbohydrazides 3a-c were formed. By heating 2-[3-(trifluoromethyl)phenly]-4H-furo[3,2-b]pyrrole-5-carboxylic acid (2a) in acetic anhydride, 4-acetyl-2-[3-(trifluoromethyl)phenyl]furo[3,2-b]pyrrole (4) was formed. By hydrolysis of 4, 2-[3-(trifluoromethyl)phenyl]-4H-furo[3,2-b]pyrrole (5a) was formed, and reactions with methyl iodide or benzyl chloride gave N-substituted products 5b-c. The reaction of 4 with dimethyl butynedioate gave substituted benzo[b]furan 6. Compound 3a reacted with triethyl orthoesters giving 7a-c, which afforded with phosphorus (V) sulphide the corresponding thiones 8a-c. The thiones 8a-c reacted with hydrazine hydrate to form hydrazine derivatives 9a-c. The reaction of triethyl orthoformiate with compounds 9a-c led to furo[2′,3′: 4,5]pyrrolo[1,2-d][1,2,4]triazolo[3,4-f][1,2,4]triazines 10a-c. Hydrazones 11a-c were formed from 3a-c and 5-[3-(trifluoromethyl)phenyl]furan-2-carboxaldehyde. The effect of microwave irradiation on some condensation reactions was compared with “classical” conditions. The results showed that microwave irradiation shortens the reaction time while affording comparable yields.     

Do oxidations of α-diols by bis(hydrogenperiodato)argentate(III) proceed according to different rate laws?

Oxidation of α-diols, namely ethylene glycol, 1,2-propanediol, and 1,2-butanediol, by [Ag(HIO₆)₂]⁵⁻ is kinetically first-order with respect to the Ag(III) complex. The dependence of observed first-order rate constants k _obs on [α-diol] can generally be expressed by: k _obs = k _x[α-diol] + k _y[α-diol]². Our experimental results demonstrate that the different rate laws derived in the oxidation reactions of ethylene glycol (J. H. Shan et al. Chin. J. Chem. 24:478, 2006) and 1,2-butanediol (J. H. Shan et al. Transition Met. Chem. 30:651, 2005) by the Ag(III) complex are probably not correct. In turn, the reaction mechanisms based on these rate laws should probably be treated with caution.     

Ruthenium(III) – catalyzed oxidative cleavage of <Emphasis Type="Italic">p</Emphasis>-aminoazobenzene by chloramine-B in alkaline medium and uncatalyzed reaction in acid medium: spectrophotometric kinetic and mechanistic study

p-Aminoazobenzene (PAAB) is one of the important monoazo dyes and its oxidation kinetic study is of much use in understanding the mechanistic profile of PAAB in redox reactions. Consequently, the kinetics of oxidation of PAAB by sodium N-chlorobenzenesulfonamide or chloramine-B (CAB) in HClO₄ medium and in NaOH medium catalyzed by ruthenium(III) chloride (Ru^III) have been investigated at 298 K. U.v.–vis spectrophotometry was used as a basic analytical approach in this study. Under an identical set of experimental conditions, the reactions of PAAB–CAB in HClO₄ medium were facile, but the reactions became too slow to be studied in alkaline medium and hence ruthenium(III) chloride has been used as a catalyst in alkaline medium. The stoichiometry (1:2) and oxidation products (nitrosobenzene and p-nitrosoaniline) are the same in both media, but the kinetic and mechanistic patterns were found to be different. The experimental rate laws obtained are: − d[CAB]/dt = k [CAB]₀ [PAAB]₀ [H⁺] in acid medium and − d[CAB]₀/dt = k [CAB]₀ [PAAB]₀[OH⁻] ^x [Ru^III] ^y in alkaline medium, where x and y are less than unity. The reaction was examined with reference to changes in (a) concentration of benzenesulfonamide, (b) concentration of added neutral salts, (c) ionic strength, (d) dielectric permitivity and (e) solvent isotope effect. The reaction was also studied at different temperatures and the overall activation parameters have been evaluated. The oxidation reaction fails to induce the polymerization of added acrylonitrile. C₆H₄SO₂NHCl and C₆H₄SO₂NCl⁻ have been postulated as the reactive oxidizing species in acidic and alkaline media, respectively. It was found that the reactions are nearly 20 times faster in acid medium in comparison with alkaline medium. It was also observed that ruthenium(III) was an efficient catalyst for the facile oxidation of PAAB by CAB in alkaline medium by making the reaction go twelve-fold faster than the uncatalyzed reactions. The catalytic constant (K _C) has been calculated at different temperatures and the values of activation parameters with respect to ruthenium(III) have also been evaluated in alkaline medium. The observed results have been explained by plausible mechanisms and the relative rate laws have been deduced.     

Synthesis and complex-forming properties of thiazolyl-containing organophosphorus complexone

Alkaline hydrolysis of the previously prepared ethyl 2-methyl-2-[diethylamido-N-(4′-phenylthiazolyl-2-amido)phosphono]glycidate and 2-phenyl-2-[diethylamido-N-(4-phenylthiazolyl-2-amido)phosphono]glycidate accompanied by decarboxylation in situ of the obtained glycidic acids furnished 2-[diethylamido-(4′-phenylthiazolyl-2′-amido)phosphono]propionic and 2-phenyl-2-[diethylamido-(4′-phenylthiazolyl-2′-amido)phosphono]acetic aldehydes. The qualitative and quantitative evaluation of complex-forming ability of the compounds obtained with respect to transition metal ions was carried out. For identification of copper complex the evaluation of the stability constants of copper, cobalt, nickel, and zinc complexes was performed. Thermodynamic parameters of complex formation reactions were calculated. Correlation dependences between the physicochemical properties of metal ions and thermodynamic characteristics of complex formation with the organophosphorus ligands obtained were established.     

Transition structures and exo/endo stereoselectivities of concerted [6 + 4] cycloadditions with density functional theory

Density functional theory transition structures were located for three concerted [6 + 4] cycloaddition reactions involving cis-hexatriene and butadiene, cyclopentadiene and cycloheptatriene, and cyclopentadiene and tropone. Geometries, energies, and entropies were computed at the Becke3LYP/6-31G* level. The activation energy of the concerted [6 + 4] cycloaddition of hexatriene and butadiene is 33.3 kcal/mol, about 8 kcal/mol above the activation energy of the butadiene plus ethylene [4 + 2] cycloaddition. The endo concerted [6 + 4] transition state is 1.1 kcal/mol higher than the exo. The [6 + 4] reaction of cyclopentadiene and cycloheptatriene has a barrier of 25.9 kcal/mol, while the cyclopentadiene–tropone barrier drops to 20.7 kcal/mol. Received: 3 December 1998 / Accepted: 18 February 1999 / Published online: 7 June 1999     

Preparation and catalytic performance of monolayer-dispersed Pd/Ni bimetallic catalysts for hydrogenation

Pd/Ni bimetallic catalysts were prepared by replacement reactions, characterized by X-ray diffraction, CO chemisorption and H₂ temperature-programmed desorption, and evaluated for hydrogenation of cyclohexene, styrene and acetone. The results show that Pd atoms are monolayer-dispersed on the Ni surface in these Pd/Ni catalysts. Consequently, Pd/Ni catalysts are much more active than Pd/Ni and Pd/c-Al₂O₃ with the same Pd loading prepared by the conventional impregnation method. __________ Translated from Chinese Journal of Catalysis, 2007, 28(8): 676–680 [译自: 催化学报]     

Synthesis of fused uracils: pyrano[2,3-d]pyrimidines and 1,4-bis(pyrano[2,3-d]pyrimidinyl)benzenes by domino Knoevenagel/Diels-Alder reactions

Abstract  

Knoevenagel condensation of barbituric acids with aromatic aldehydes containing one or two formyl groups was carried out. 5-Arylidenebarbituric acids underwent smooth hetero-Diels-Alder (HDA) reactions with enol ethers to afford cis and trans diastereoisomers of pyrano[2,3-d]pyrimidine-2,4-diones and 5,5′-(1,4-phenylene)bis[2H-pyrano[2,3-d]pyrimidine-2,4(3H)-dione] derivatives in excellent yields (75–88 %). Syntheses were realized by Knoevenagel condensation and HDA reaction in four different reaction conditions: Knoevenagel condensation in water and Diels-Alder reaction in methylene chloride solution, Knoevenagel condensation in water and Diels-Alder reaction without solvent, three-component one-pot reaction in methylene chloride solution, or three-component one-pot reaction in water. All reactions were carried out without catalyst at room temperature. The reactions of malononitrile with Knoevenagel condensation products of barbituric acids and heteroaromatic aldehydes or terephthalaldehyde were examined and did not provide corresponding pyranopyrimidines.     

Synthesis and characterization of calixarene-based poly(ε-caprolactone) stars catalyzed by yttrium complex

Two calixarene derivatives (2a, 2b) have been synthesized and used as macro-initiators to prepare star-shaped poly(ε-caprolactone)s (SPCLs) via controlled ringopening polymerization of ε-caprolactone in the presence of yttrium tris(2,6-di-tert-butyl-4-methylphenolate) [Y(DBMP)₃]. The molecular weight of SPCLs was characterized by end group ¹H-NMR analyses and size-exclusion chromatography (SEC). The results indicate that SPCLs based on a calix[4]arene derivative (2a) are well-defined four-arm star polymers with reasonably narrow molecular weight distributions in the given molecular weight range, while SPCLs based on a calix[6]arene derivative (2b) are star polymers with not so defined structures. Differential scanning calorimetry (DSC) analyses suggest that the maximal melting point, the crystallization temperature and the degree of crystallinity of SPCLs increases with the increasing molecular weight and are lower than those of the liner poly(ε-caprolactone) (LPCL) counterpart. Furthermore, polarized optical microscopy (POM) indicates that SPCL exhibits irregular spherulites with poor morphology and slower crystallization rate, whereas LPCL shows fast crystallization rate and good spherulitic morphology. __________ Translated from Acta Polymerica Sinica, 2007, 10: 967–973 [译自:高分子学报]     

Mobile protons versus mobile radicals: Gas-phase unimolecular chemistry of radical cations of cysteine-containing peptides

A combination of electrospray ionization (ESI), multistage, and high-resolution mass spectrometry experiments are used to examine the gas-phase fragmentation reactions of radical cations of cysteine containing di- and tripeptides. Two different chemical methods were used to form initial populations of radical cations in which the radical sites were located at different positions: (1) sulfur-centered cysteinyl radicals via bond homolysis of protonated S-nitrosocysteine containing peptides; and (2) α-carbon backbone-centered radicals via Siu’s sequence of reactions (J. Am. Chem. Soc. 2008, 130, 7862). Comparison of the fragmentation reactions of these regiospecifically generated radicals suggests that hydrogen atom transfer (HAT) between the α C-H of adjacent residues and the cysteinyl radical can occur. In addition, using accurate mass measurements, deuterium labeling, and comparison with an authentic sample, a novel loss of part of the N-terminal cysteine residue was shown to give rise to the protonated, truncated N-formyl peptide (an even-electron x_n ion). DFT calculations were performed on the radical cation [GCG]^.+ to examine: the relative stabilities of isomers with different radical and protonation sites; the barriers associated with radical migration between four possible radical sites, [G.CG]⁺, [GC.G]⁺, [GCG.]⁺, and [GC(S.)G]⁺; and for dissociation from these sites to yield b₂-type ions.     

Diaziridine ring expansion in 6-aryl-1,5-diazabicyclo[3.1.0]hexanes upon reactions with activated olefins in ionic liquids

Reactions of 1,3-diphenylpropen-2-one and α-nitrostyrenes with azomethine imines, generated from 6-aryl-1,5-diazabicyclo[3.1.0]hexanes on catalysis with Et2O•BF3 in ionic liquids, were found to proceed with high regio- and stereoselectivity to afford the products of the diaziridine ring expansion, viz., [3-aryl-2-phenyltetrahydro-1H,5H-pyrazolo[1,2-a]pyrazol- 1-yl](phenyl)methanones, 1,3-diaryl-2-nitrotetrahydro-1H,5H-pyrazolo[1,2-a]pyrazoles and 5-aryl-6-(3-nitrophenyl)-2,3-dihydro-1H-pyrazolo[1,2-a]pyrazolium tetrafluoroborates (hexafluorophosphates). The reactions discovered are new, more simple methods for the syn- thesis of bicyclic structures.