Conversion of 4-amino-4H-1,2,4-triazole to 1,3-bis(1H-azol-l-yl)-2-aryl-2-propanols and 1-phenacyl-4-[(benzoyl or 4-toluenesulfonyl)-imino]-(1H-1,2,4-triazolium) Ylides

A series of 1,3-bis(1H-azol-1-yl)-2-aryl-2-propanols 17 were synthesized in an one-pot procedure by reacting l-aryl-2-(1H-1,2,4-triazol-l-yl)- or l-aryl-2-(1H-imidazol-l-yl)ethanones with dimethylsulfoxonium methide in the presence of either 1,2,4-triazole or imidazole. The aromatic groups in 17 were either 4-bromo-, 4-chloro-, 2,4-dichloro- or 2,4-difluorophenyl. 4-Amino-4H-1,2,4-triazole was acylated with either benzoyl or 4-toluene-sulfonyl chloride to afford [4-(benzoyl or 4-toluenesulfonyl)amino]4H-1,2,4-triazole. Subsequent alkylations with 4-bromo- or 4-chlorophenacyl bromide produced 1-(4-bromo- or 4-chlorophenacyl)-4-[(benzoyl- or 4-toluenesulfonyl)amino]-1H-1,2,4-triazolium bromides. Neutralizations of these salts provided the corresponding ylides.     

Synthesis and E/Z configuration determination of novel derivatives of 3-aryl-2-(benzothiazol-2'-ylthio) acrylonitrile, 3-(benzothiazol-2'-ylthio)-4-(furan-2'-yl)-3-buten-2-one and 2-(1-(furan-2'-yl)-3'-oxobut-1'-en-2-ylthio)-3-phenylquinazolin-4(3H)-one

Knoevenagel condensation of 2-(benzothiazol-2-ylthio) acetonitrile (2) with either furan-2-carbaldehyde or thiophene-2-carbaldehydes leads to E-isomers 4a-b exclusively, while the condensation of the compound 2 with benzaldehyde or para-substituted benzaldehydes with an electron-donating group afforded E/Z mixtures 4c-e with preferentially formation of the E-isomer. Condensation of furan-2-carbaldehyde (3a) with either 1-(benzothiazol-2'-ylthio) propan-2-one (5) or 2-(2'-oxo propylthio)-3-phenyl-quinazolin-4(3H)-one (9) leads exclusively to the Z-isomers of 6 and 10, respectively. The structures of the newly synthesized compounds were elucidated by elemental analyses, 1H-NMR and 13C-NMR spectra, COSY, HSQC, HMBC, NOE, MS and X-ray crystallographic investigations.     

Controlled copper-mediated chlorination of phenol rings under mild conditions

The very unusual case of copper-mediated chlorination of phenol rings under mild conditions at room temperature is reported. Reaction of the ligand 1,7-bis(2-hydroxyphenyl)-2,6-diaza-4-hydroxylheptane (H3L1) with CuCl2 in acetonitrile leads to either the formation of a tetranuclear copper(II) complex [Cu4(HL3)2(mu-Cl)2Cl2](CH3CN) (1) or a linear trinuclear complex [Cu3(HL1)2Cl2(CH3CN)2](CH3CN)2 (2), depending on the reaction conditions. Both compounds have been fully characterized, including the determination of their 3D structures by X-ray diffraction. The unprecedented tetranuclear compound 1 is constituted of a dichlorido-bridged dimer of di-mu-phenoxido-dinuclear species, whereas the trinuclear complex 2 presents a linear array of copper(II) ions, held together through di-mu-phenoxido bridges of the central and external ions. The magnetic susceptibility of the two compounds was investigated, revealing either very strong (J<-500 cm-1) or strong (J value around -370(1) cm-1) antiferromagnetic dominant interactions among the CuII ions for 1 and 2, respectively. The tetranuclear complex 1 is obtained, under dry conditions, through the in situ formation of ligand HL3 (H3L3=1,7-bis(2-hydroxy-5-chlorophenyl)-2,6-diaza-4-hydroxylheptane) by oxidative chlorination of (HL1)2-. In the presence of traces of water, 1 is partially hydroxylated at the ortho position of one of the phenyl rings. The use of trimethylorthoformate as the dehydrating agent prevents the formation of hydroxylated ligands. Several partly chlorinated/hydroxylated products (identified as H3L2) have also been obtained through slight variations of the synthetic procedures (presence or absence of water and/or triethylamine in the reaction mixtures). These partially chlorinated and/or hydroxylated coordination species are mutually isomorphous to either 1 or 2. Several "modified" ligands have been isolated and characterized by 1H NMR and MS, after reaction with sodium sulfide of the complexes formed.     

Reactions of chloromethoxy-substituted 3-(2-acetoxyethyl)-1-hydroxytriaz-1-ene 2-oxides with 1-alkoxy-3-(2-hydroxyethyl)triaz-1-ene 2-oxide alkali salts

Reactions of 1-alkoxy-3-(2-hydroxyethyl)triaz-1-ene 2-oxides and 1-chloromethoxytriaz1-ene 2-oxides with chloromethoxy derivatives of 3-alkyl-3-(2-acetoxyethyl)- and 3,3-bis(2-acetoxyethyl)-1-hydroxytriaz-1-ene 2-oxides result in very complex product mixtures with the major product comprising the starting salt fragments linked by a methylene bridge. In these products, the central methylene group bridges either two oxygen atoms or two nitrogen atoms, or one oxygen and one nitrogen atom. The synthesized compounds contain from two to four 2-hydroxyethyl moieties.     

A practical large scale chemical synthesis of chiral glycines

(R)- and (S)-[2-²H]glycine of high chiral purity were synthesized in large quantities in ≈ 40% overall yield from readily available starting materials via a totally chemical procedure. Reduction of either [1-²H]-furfural or [1-²H]-4-methoxybenzaldehyde with either (+) or (-)-B-isopinocampheyl-9-borabicyclo[3.3.1]nonane gave chiral arylmethyl alcohols which were converted into their respective phthaloyl amino derivatives of the opposite configuration at the methylene carbon via the Mitsunobu reaction. The aromatic groups were oxidatively unmasked to give their corresponding glycine derivatives by either ozone or ruthenium tetraoxide oxidation.     

Triazino-1,2,4-[4,5-a] indoles. V. Etude du dioxo-1,4 tetrahydro-1,2,3,4 triazino-1,2,4-[4,5-a] indole

1,4-Dioxo - 1,2,3,4- tetrahydro- 1,2,4- triazino[4,5-a] indole (1) was synthesized either by cyclising the N-carbethoxyhydraxizide of indole-2 carboxylic acid (4) or by alkaline rearrangement of 2-(2-indolyl)-5-oxadiazolone (6). The methylation reactions of the dilactam 1 were achieved with dimethyl sulfate or diazo-methane and afforded mixtures of O-methylated and N-methylated derivatives which were isolated and the structure of which were asigned. The tautomerism of dilactam 1 was studied using O-and N-methylated derivatives. The lactim-lactam structure 1a pre-ponderated in solution.     

Fast stereoselective reactions in electrosprayed Co(II)/neurotransmitter nanodroplets

Collision induced dissociation (CID) of the m/z 479 ion, formed by ESI of Co(NO3)2-CH3OH solutions with either pure (1S,2S)-(+)-N-methylpseudoephedrine or its mixtures with (1S,2R)-(+)- or (1R,2S)-(-)-ephedrine, provides compelling evidence for fast, stereoselective reactions in Co(II)/neurotrasmitter(s) aggregates during solvent evaporation of the ESI droplets.     

A common carbanion intermediate in the recombination and proton-catalysed disproportionation of the carboxyl radical anion, CO2*-, in aqueous solution

The carboxyl radical anion, CO2*- was produced by the reactions of OH radicals with either CO or formic acid in aqueous solution. The pKa(*CO2H) was determined by pulse radiolysis with conductometric detection at pH approximately equals 2.3. The bimolecular decay rate constant of CO2*- (2k approximately equals 1.4 x 10(9) dm3mol(-1)s(-1)) was found to be independent of pH in the range 3-8 at constant ionic strength. The yields of the products of the bimolecular decay of the carboxyl radicals, CO2 and the oxalate anion were found to depend strongly on the pH of the solution with an inflection point at pH 3.8. This pH dependence is explained by assuming a head-to-tail recombination of the CO2*- radicals followed by either rearrangement to oxalate or a protonation of the adduct, which subsequently leads to the formation of CO2 and formate. The recombination of CO2*- to give oxalate directly is estimated to have a contribution of <25%.     

Le probleme de la conjugaison a travers un atome de silicium π-lie dans les systemes sila-2 butadieniques

The chemical behaviour of sila-2 butadienes, formed as transient intermediates either by thermolysis or by photolysis of various 1-vinylsilacyclobutanes, was studied with respect to hydroxylated compounds of different pKa values Two mechanisms can explain the nature of the products obtained on the co-thermolysis of the cyclic compounds with phenol, one with 1-silacyclobut-1-ene intermediate and the other involving an allylic silicenium cation. In both hypothetical mechanisms, the 2-silabutadienes behave as a conjugated system since they lead either to (2+2) cycloaddition or to (1,2)- and (1,4)-electrophilic addition. This evidence for a conjugation phenomenon through a silicon atom is supported by the calculation of the delocalisation energies of butadiene and 2-silabutadiene.     

Complete assignments 1H and 13C NMR spectral data of four anabaseine derivatives

The anabaseine derivatives 6-methoxy-7-hydroxy-1-(pyridin-3-yl)-3,4-dihydroisoquinoline, 6,7-dimethoxy-1-(pyridin-3-yl)-1,2,3,4-tetrahydroisoquinoline and 6,7-dimethoxy-1-(piperidin-3-yl)-1,2,3,4-tetrahydroisoquino- line were prepared either by demethylation with HBr or by reduction with different reagents, NaBH4 and H2/PtO2 from 6,7-dimethoxy-1-(pyridin-3-yl)-3,4-dihydroisoquinoline, as starting material. The structures have been fully assigned by the combination of one- and two-dimensional experiments.     

Amine-induced rearrangements of 2-bromo-1-(1H-indol-3-yl)-2-methyl-1-propanones: A new route to α-substituted indole-3-acetamides, β-substituted tryptamines, α-substituted indole-3-acetic acids and indole β-aminoketones

The reaction of 2-bromo-1-(1H-indol-3-yl)-2-methyl-1-propanone ( 1 ) and 2-bromo-1-(1-methyl-1H-indol-3-yl)-2-methyl-1-propanone ( 2 ) with primary amines proceeds in good yields to produce rearranged amides by a proposed pseudo-Favorskii mechanism. These amides in turn can either be reduced to produce β-substituted tryptamines or hydrolyzed to produce substituted indole-3-acetic acids. When the reaction is carried out using bulky primary or secondary amines, β-aminoketones are produced by elimination of hydrogen bromide followed by Michael addition. When hindered secondary amines or tertiary amines are used, elimination to the α,β-unsaturated ketones occurs.     

Preparation of 4-hydroxy-3-substituted, 2H-1-benzopyran-2-ones and 2H-1-benzothiopyran-2-ones from carboxylic esters and methyl salicylates or methyl thiosalicylate

C(α)-Carboxylic acid esters were treated with excess lithium diisopropylamide, condensed with methyl salicylates or methyl thiosalicylate, followed by acid cyclization to either 4-hydroxy-3-substituted, 2H-1-benzopyran-2-ones (coumarins), or 2H-1-benzothiopyran-2-ones (thiocoumarins).     

Kinetics of the reaction between the antioxidant Trolox and the free radical DPPH in semi-aqueous solution

Reaction of the free-radical diphenylpicrylhydrazyl (DPPH(.)) with Trolox (TrOH) was investigated in buffered hydroalcoholic media by using a stopped-flow system. DPPH was reduced to the hydrazine analogue DPPH-H with a measured stoichiometry of about 2. DPPH-H was characterized by an acid-base equilibrium (pKa = 8.6). Time-resolved absorption spectra recorded with an excess of either TrOH or DPPH indicated that no significant amount of the TrO radical was accumulated. The TrO radical formed in a first step further reacted quickly with DPPH(.). For 1 : 1 ethanol-buffer mixtures at pH 7.4, the bimolecular rate constants of the first and second steps were 1.1 x 10(4) M(-1) s(-1) and 2 x 10(6) M(-1) s(-1), respectively. A significant increase of the measured rate constant was observed for ethanol-buffer solutions as compared to ethanol. The rate was also increased at higher pH. A deuterium isotopic effect of 2.9 was measured. These data are discussed with regards to mechanisms involving either electron or proton exchange as rate determining steps in the reaction of DPPH with Trolox. The importance of solvent acidity control in investigation of antioxidant properties is outlined.     

A novel entry toward 2-imino-1,3-thiazolidines and 2-imino-1,3-thiazolines by ring transformation of 2-(thiocyanomethyl)aziridines

A new, efficient, and straightforward synthesis of 3-arylmethyl-4-chloromethyl-2-imino-1,3-thiazolidines and 2-(N-acylimino)-3-arylmethyl-4-chloromethyl-1,3-thiazolidines has been developed by ring transformation of 1-arylmethyl-2-(thiocyanomethyl)aziridines upon treatment with a catalytic amount of titanium(IV) chloride in dichloromethane. The latter 2-(thiocyanomethyl)aziridines were prepared in high yields from 1-arylmethyl-2-(bromomethyl)aziridines by reaction with potassium thiocyanate in DMF. The 2-imino-1,3-thiazolidines and 2-(N-acylimino)-1,3-thiazolidines thus obtained can be easily interconverted, either by treatment with an acid chloride and a base in ether toward 2-(N-acylimino)thiazolidines or by treatment with potassium carbonate in methanol toward N-deprotected 2-iminothiazolidines. Dehydrohalogenation of 2-(N-acylimino)-3-arylmethyl-4-chloromethyl-1,3-thiazolidines by means of potassium tert-butoxide in DMSO afforded 2-(N-acylimino)-4-methyl-2,3-dihydro-1,3-thiazolines in good yields.     

Synthesis of 4,5-dihydro-4-phenyl-3H-1,3,4-benzotriazepines

Several 4,5-dihydro-4-phenyl-3H-1,3,4-benzotriazepines were synthesized by conversion of 1-[(2-nitrophenyl)methyl]-1-phenylhydrazine to either 1-[(2-aminophenyl)methyl]-1-phenylhydrazine or 1-[(2-aminophenyl)-methyl]-2-methyl-1-phenylhydrazine. Ring closure of these intermediates with triethyl orthoacetate or triethyl orthopropionate gave the title compounds in overall yields of 40-60%.     

Ag(I)-based tectons for the construction of helical and meso-helical hydrogen-bonded coordination networks

The new ligand 4-(3-(2-pyridyl)pyrazol-1-ylmethyl)benzoic acid (L) has been prepared and characterized. This bifunctional ligand incorporates both a chelating region, with two nitrogen donors, suitable for chelating to soft transition metal ions, and a self-complementary hydrogen-bonding region which can facilitate intermolecular association of ligands or ligand-based complexes. X-ray structural analysis of the ligand shows it to adopt a one-dimensional helical polymeric structure, with adjacent ligands hydrogen bonded to each other. Reaction of L with silver(I) salts (AgOTf (1, 1.1.5H(2)O), AgNO(3) (2), AgPF6 (3.CH(3)OH), and AgClO(4) (4.CH(3)OH)) results in the formation of complexes with 2:1 stoichiometries. X-ray structural analysis of these complexes shows that, in each case, one-dimensional chain structures are obtained where chiral AgL(2) tectons are hydrogen bonded together, either directly or mediated by anions or solvent. Structures with either helical or meso-helical structures are observed.     

Cyclohexadienone diazeniumdiolates from nitric oxide addition to phenolates

Sterically hindered phenols react with nitric oxide under basic condititons to give either cyclohexadienone diazeniumdiolates or oximates. Phenols with 2,6-di-tert-butyl and 4-methyl (butylated hydroxy toluene, BHT), 4-ethyl, or 4-methoxy methylene substituents yield the corresponding 2,6-di-tert-butyl-2, 5-cyclohexadienone-4-alkyl-4-diazeniumdiolate salts (4-methyl 1a, 4-ethyl 3a, 4-methoxymethylene 5a). Phenols with 2,6-di-tert-butyl and 4-methylene (2,6-di-tert-butylphenol) substituents yield 4-methoxymethylenediazeniumdiolate (5a) together with 2, 6-di-tert-butyl benzoquinone oximate (6a), while phenols with 2, 6-di-tert-butyl and 4-methylenedimethylamino or hydrogen substituents yield exclusively 2,6-di-tert-butyl benzoquinone oximate (6a). Alkylation of the silver salts of 1a, or treating the O(2)-protonated diazeniumdiolate with diazomethane, both yield mixtures of O(1)- and O(2)-methylated isomers. All the compounds exhibit exothermic thermal decomposition except the quinuclidinium (1e, 3e, 5e) and triethylenediammonium (1f) salts which decompose endothermically. Three of the compounds namely "O(2)-protonated" (Z)-1-[4-(2, 6-di-tert-butyl-4-methyl-cyclohexadienonyl)]diazen-1-ium+ ++-1, 2-diolinic acid (1b), O(2)-methyl (Z)-1-[4-(2, 6-di-tert-butyl-4-methyl-cyclohexadienonyl)]diazen-1-ium+ ++-1,2-diolate (1c), and "O(2)-protonated" (Z)-1-[4-(2, 6-di-tert-butyl-4-methoxymethylenecyclohexadienonyl)]diazen- 1-ium-1, 2-diolinic acid (5b) were characterized by single-crystal X-ray diffraction studies. The diazeniumdiolate framework in all the structures is coplanar with considerable pi-bonding delocalized over the O-N-N-O framework.     

Synthése,stéréochimie,et réactivité thermique de (N-méthylidenealkylamino)-2 aziridines

1-Alkyl-2-(N-methylidenealkylamino)aziridines are obtained by the reaction of primary amines with either α-chloroacraldehyde or α-chlorocrotonaldehyde. Structural assignments are made by nmr spectroscopy. The thermal rearrangement of 1-alkyl-2-(N-methylidenealkylamino)-3-methylaziridines to pyrroles is described.     

Pyrrolo[1,2-d]triazines-1,2,4 III. Etude de la dioxo-1,4 tetrahydro-1,2,3,4 pyrrolo[1,2-d]triazine-1,2,4

1,4-Dioxo-1,2,3,4-tetrahydro-l,2,4-pyrrolo[l,2-～-1,2,4-triazine (1) was synthesized either by cyclising the N-carbethoxyhydrazide of pyrrole-2-carboxylic acid (2) or by alkaline rearrangement of 2-(2-pyrrolyl>5-oxadi- azolone (3). The methylation reactions of the dilactam 1 were achieved with dimethyl sulfate or diazomethane and afforded mixtures of U-methylated and N-methylated derivatives which were isolated by gas chromatography and the structures of which were assigned using ir and ¹H nmr spectra.     

Iodine-induced reaction cascades for the rapid construction of variously substituted benzothiophenes

[reaction: see text] Readily accessible propynols with a 2-thioxyphenyl substituent selectively undergo 5-exo-iodocyclization followed by tandem rearrangement and elimination or substitution processes to give selective access to either 2-acyl- or 2-(1-iodoalkeny)-benzo[b]thiophene systems.