Synthesis of 2"-bromo-8-methylspiro(4H-3,1-benzooxazine-4,1"-cyclopentan)-2(1H)-one and 2-amino-2"-bromo-8-methylspiro(4H-3,1-benzooxazine-4,1"-cyclopentane) from 6-(cyclopent-1-enyl)-2-methylaniline

The reaction of 6-(cyclopent-1-enyl)-N-ethoxycarbonyl-2-methylaniline with Br₂ or its reaction with NH₃ followed by the reaction with Br₂ afforded 2"-bromo-8-methylspiro(4H-3,1-benzooxazine-4,1"-cyclopentan)-2(1H)-one and 2-amino-2"-bromo-8-methylspiro(4H-3,1-benzooxazine-4,1"-cyclopentane), respectively.     

Solvation of uranyl(II), europium(III) and europium(II) cations in "basic" room-temperature ionic liquids: a theoretical study

We report a molecular dynamics study of the solvation of UO2(2+), Eu3+ and Eu2+ ions in two "basic" (Lewis acidity) room-temperature ionic liquids (IL) composed of the 1-ethyl-3-methylimidazolium cation (EMI+) and a mixture of AlCl4- and Cl- anions, in which the Cl-/AlCl4- ratio is about 1 and 3, respectively. The study reveals the importance of the [UO2Cl4]2- species, which spontaneously form during most simulations, and that the first solvation shell of europium is filled with Cl- and AlCl4- ions embedded in a cationic EMI+ shell. The stability of the [UO2Cl4]2- and [Eu(III)Cl6]3- complexes is supported by quantum mechanical calculations, according to which the uranyl and europium cations intrinsically prefer Cl- to the AlCl4- ion. In the gas phase, however, [Eu(III)Cl6]3- and [Eu(II)Cl6]4- complexes are predicted to be metastable and to lose two to three Cl- ions. This contrasts with the results of simulations of complexes in ILs, in which the "solvation" of the europium complexes increases with the number of coordinated chlorides, leading to an equilibrium between different chloro species. The behavior of the hydrated [Eu(OH2)8]3+ complex is considered in the basic liquids; the complex exchanges H2O molecules with Cl- ions to form mixed [EuCl3(OH2)4] and [EuCl4(OH2)3]- complexes. The results of the simulations allow us to better understand the microscopic nature and solvation of lanthanide and actinide complexes in "basic" ionic liquids.     

Metastable one-dimensional AgCl(1)-(x)I(x) solid-solution wurzite "tunnel" crystals formed within single-walled carbon nanotubes

High-resolution transmission electron microscopy and spatially resolved electron loss spectroscopy have revealed that a eutectic mixture of AgCl and AgI crystallizes within single walled carbon nanotubes (SWNTs) as metastable AgCl(1-)(x)I(x) 1D solid solution crystals. The incorporated halide crystals form wurzite "tunnel" structures with locally varying Cl:I ratios and reduced Ag coordination.     

The spin-orbit and rotational constants for the N2 C" 5Pi(ui) (v = 3) state

The spin-orbit (A = -16.4 cm(-1)) and rotational (B = 1.017 cm(-1)) constants for the N2 C" 5Pi(ui)(v = 3) level are determined by a fit to rotational lines in the C" 5Pi(u)-A' 5Sigma(g)+(3-1) band that terminate in J'Omega' = 3(3), 4(3), 3(2), and 4(2) levels of the C" state. The C"-state spin-orbit constant is consistent with semi-empirical estimates, based on spin-orbit constants observed in several other electronic states of N2 and the atomic spin-orbit coupling constant, zeta(N 2p). The C"-A' bands exhibit the unusual feature of oppositely degraded sub-band heads, Omega' = 3 (red) and Omega' = 1, 0, and -1 (blue). The unusually wide range of B(Omega)eff values, from 0.85 cm(-1) (Omega = 3) to 1.28 cm(-1) (Omega = -1) for C" 5Pi(v = 3) should be diagnostically useful for Omega'-assignments. The C" 5Pi(v = 3) level lies 14257.17 and 90599 cm(-1) above A' 5Sigma(g)+(v = 1) and X 1Sigma(g)+(v = 0), respectively, and Re(C" 5Pi) = 1.50 A.     

Synthesis and reactivity of dimeric Ar'TlTlAr' and trimeric (Ar"T1)3 (Ar', Ar" = bulky terphenyl group) thallium(I) derivatives: Tl(I)-Tl(I) bonding in species ligated by monodentate ligands

The synthesis and characterization of three new organothallium(I) compounds are reported. Reaction of (Ar'Li)(2) (Ar' = C(6)H(3)-2,6-(C(6)H(3)-2,6-Pr(i)(2))(2)) and Ar"Li (Ar" = C(6)H(3)-2,6-(C(6)H(3)-2,6-Me(2))(2)) with TlCl in Et(2)O afforded (Ar'Tl)(2) (1) and (Ar' 'Tl)(3) (2). The "dithallene" 1 is the heaviest group 13 dimetallene and features a planar, trans-bent structure with Ar'Tl-Tl = 119.74(14) degrees and Tl-Tl = 3.0936(8) A. Compound 2 is the first structurally characterized neutral, three-membered ring species of formula c-(MR)(3) (M = Al-Tl; R = organo group). The Tl(3) ring has Tl-Tl distances in the range ca. 3.21-3.37 A as well as pyramidal Tl geometries. The Tl-Tl bonds in 1 and 2 are outside the range (2.88-2.97 A) of Tl-Tl single bonds in R(2)TlTlR(2) compounds. The weak Tl-Tl bonding in 1 and 2 leads to their dissociation into Ar'Tl and Ar' 'Tl monomers in hexane. The Ar'Tl monomer behaves as a Lewis base and readily forms a 1:1 donor-acceptor complex with B(C(6)F(5))(3) to give Ar'TlB(C(6)F(5))(3), 3. Adduct 3 features an almost linear thallium C(ipso)-Tl-B angle of 174.358(7) degrees and a Tl-B distance of 2.311(2) A, which indicates strong association. Treatment of 1 with a variety of reagents resulted in no reactions. The lower reactivity of 1 is in accord with the reluctance of Tl(I) to undergo oxidation to Tl(III) due to the unreactive character of the 6s(2) electrons.     

Characterization and identification of a "mystery" oil spill from Quebec (1999)

This paper describes a case study in which advanced chemical fingerprinting and data interpretation techniques were used to characterize the chemical compositions and determine the source of an unknown spilled oil from Quebec. On 28 February 1999, significant amounts of oil was reported on the river banks of St. Laurence River in front of a company named "Thermex" (in a town - Beauharnois, Quebec, about 50 km northwest of Montreal). The spilled oil was suspected to be released from a nearby factory. In response to this specific site investigation needs, a tiered analytical approach using GC-MS and GC-flame ionization detection was applied. A variety of diagnostic ratios of "source-specific marker" compounds, in particular isomers of biomarkers and alkylated series of polycyclic aromatic hydrocarbons within the same alkylation groups, were determined and analyzed. The hydrocarbon analysis results reveal the following: (1) the spilled oil is very "specific", and is significantly different from most crude oils in chemical composition; (2) the oil in samples come from the same source, however, the spill sample 2569 was identified to contain a small amount (approximately 10%) of diesel; (3) the spilled oil was relatively "fresh", its chemical composition has not undergone significant alteration yet; (4) the spilled oil showed unusually high concentration of the US Environmental Protection Agency priority polycyclic aromatic hydrocarbons (PAHs). The "Pyrogenic Index" values were determined to be as high as 0.11-0.13, significantly higher than crude oils (<0.010) and heavy Bunker type fuels (0.015-0.060). This indicates significant contribution of PAH composition from pyrogenic components; (5) biomarkers were also detected, but their concentrations were unusually low in comparison to most crude oils.     

Reactions of 1-(3"-Amino)- and 1-(3"-Acetamido)propylsilatranes with Cobalt(II) Chloride and Dicobalt Octacarbonyl

1-(3"-Amino)propylsilatrane (I) and 1-(3"-acetamido)propylsilatrane (II) react with anhydrous cobalt(II) chloride to give dichlorobis[1-(3"-amino)propylsilatrane]cobalt(II) {Co[NH₂CH₂CH₂CH₂Si(OCH₂CH₂)₃N]₂Cl₂} (III) and dichlorobis[1-(3"-acetamido)propylsilatrane]cobalt(II) {Co[CH₃C(O)NHCH₂CH₂CH₂Si(OCH₂CH₂)₃N]₂Cl₂} (IV). Being unstable, compound IV transforms into an imidic acid derivative. Reactions of silatranes I and II with dicobalt octacarbonyl afford hexakis[1-(3"-aminoamido)propylsilatrane]cobalt(II) bis(tetracarbonylcobaltate) {Co[NH₂CH₂CH₂CH₂Si(OCH₂CH₂)₃N]_4.8[HC(O)NHCH₂CH₂CH₂Si(OCH₂CH₂)₃N]_1.2}[Co(CO)₄]₂ (V) and hexakis[1-(3"-acetamido)propylsilatrane]cobalt(II) bis(tetracarbonylcobaltate) {Co[CH₃C(O)NHCH₂CH₂CH₂Si(OCH₂CH₂)₃N]₆}[Co(CO)₄]₂ (VI), respectively. In acetonitrile, tetracarbonylcobaltate anions of compound VI are oxidized with atmospheric oxygen and moisture to cobalt hydroxocarbonate, giving a carbonate gel (VII).     

"Switching on" the properties of single-molecule magnetism in triangular manganese(III) complexes

The reaction between oxide-centered, triangular [MnIII3O(O2CR)6(py)3](ClO4) (R = Me (1), Et (2), Ph (3)) compounds and methyl 2-pyridyl ketone oxime (mpkoH) affords a new family of Mn/carboxylato/oximato complexes, [MnIII3O(O2CR)3(mpko)3](ClO4) [R = Me (4), Et (5), and Ph (6)]. As in 1-3, the cations of 4-6 contain an [MnIII3(mu3-O)]7+ triangular core, but with each Mn2 edge now bridged by an eta1:eta1:mu-RCO2- and an eta1:eta1:eta1:mu-mpko- group. The tridentate binding mode of the latter causes a buckling of the formerly planar [MnIII3(mu3-O)]7+ core, resulting in a relative twisting of the three MnIII octahedra and the central O2- ion now lying approximately 0.3 A above the Mn3 plane. This structural distortion leads to ferromagnetic exchange interactions within the molecule and a resulting S = 6 ground state. Fits of dc magnetization data for 4-6 collected in the 1.8-10.0 K and 10-70 kG ranges confirmed S = 6 ground states, and gave the following D and g values: -0.34 cm(-1) and 1.92 for 4, -0.34 cm(-1) and 1.93 for 5, and -0.35 cm(-1) and 1.99 for 6, where D is the axial zero-field splitting (anisotropy) parameter. Complexes 4-6 all exhibit frequency-dependent out-of-phase (chi" M) ac susceptibility signals suggesting them possibly to be single-molecule magnets (SMMs). Relaxation rate vs T data for complex 4 down to 1.8 K obtained from the chi" M vs T studies were supplemented with rate vs T data measured to 0.04 K via magnetization vs time decay studies, and these were used to construct Arrhenius plots from which was obtained the effective barrier to relaxation (Ueff) of 10.9 K. Magnetization vs dc field sweeps on single-crystals of 4.3CH2Cl2 displayed hysteresis loops exhibiting steps due to quantum tunneling of magnetization (QTM). The loops were essentially temperature-independent below approximately 0.3 K, indicating only ground-state QTM between the lowest-lying Ms = +/-6 levels. Complexes 4-6 are thus confirmed as the first triangular SMMs. High-frequency EPR spectra of single crystals of 4.3CH2Cl2 have provided precise spin Hamiltonian parameters, giving D = -0.3 cm(-1), B40 = -3 x 10(-5) cm(-1), and g = 2.00. The spectra also suggest a significant transverse anisotropy of E > or = 0.015 cm(-1). The combined work demonstrates the feasibility that structural distortions of a magnetic core imposed by peripheral ligands can "switch on" the properties of an SMM.     

Computational analysis of aza analogues of [2',5'-bis-O-(tert-butyldimethylsilyl)-beta-D-ribofuranose]-3'-spiro-5"-(4"-amino-1",2"-oxathiole-2",2"-dioxide) (TSAO) as HIV-1 reverse transcriptase inhibitors: relevance of conformational properties on the inhibitory activity

We have carried out a theoretical analysis of aza analogues of [2',5'-bis-O-(tert-butyldimethylsilyl)-beta-D-ribofuranosyl]-3'-spiro-5"-(4"-amino-1",2"-oxathiole-2",2"-dioxide) by a variety of computational tools, aimed to account for the effect of the endocyclic amino moiety N-2" on the inhibitory activity against HIV-1. Docking studies suggest that compounds substituted at the N-3 and N-2' ' positions present the same binding mode to the [2',5'-bis-O-(tert-butyldimethylsilyl)-beta-D-ribofuranosyl]-3'-spiro-5"-(4"-amino-1",2"-oxathiole-2",2"-dioxide)thymine prototype, where the endocyclic amino group remains mostly exposed to the solvent. A careful conformational analysis performed through different theoretical levels, from molecular mechanics to high-level quantum mechanical calculations, provides a rationalization based on conformational preferences, which appears as strongly determined by the substitution at N-2", and on electrostatic effects from the bulk water.     

Synthesis of stereoarray isotope labeled (SAIL) lysine via the "head-to-tail" conversion of SAIL glutamic acid

A stereoarray isotope labeled (SAIL) lysine, (2S,3R,4R,5S,6R)-[3,4,5,6-(2)H(4);1,2,3,4,5,6-(13)C(6);2,6-(15)N(2)]lysine, was synthesized by the "head-to-tail" conversion of SAIL-Glu, (2S,3S,4R)-[3,4-(2)H(2);1,2,3,4,5-(13)C(5);2-(15)N]glutamic acid, with high stereospecificities for all five chiral centers. With the SAIL-Lys in hand, the unambiguous simultaneous stereospecific assignments were able to be established for each of the prochiral protons within the four methylene groups of the Lys side chains in proteins.     

Unique "cradled barbell" complex between a secondary diammonium ion and bis(m-phenylene)-32-crown-10

[formula: see text] The complexation between N,N'-dibenzyl(m-xylylene)diammonium bis(hexafluorophosphate) (2) and bis(m-phenylene)-32-crown-10 (5) was shown to occur in solution by nuclear magnetic resonance with 1:1 stoichiometry and a Ka value of 189 +/- 19 M-1. A crystal structure of 2:5 revealed a unique 1:1 "exo" or "cradled barbell" complex, instead of the expected pseudorotaxane. This unexpected result illustrates that caution be used in interpreting the results from these types of complexes in the solution and "gas" phases on the basis of crystal structures.     

An unprecedented "linear-bent" isomerism in tri-nuclear Cu(2)(II)Zn(II) complexes with a salen type di-Schiff base ligand

Two new trinuclear hetero-metallic copper(ii)-zinc(ii) complexes [(CuL)(2)Zn(N(3))(2)] ( and ) have been synthesized using [CuL] as a so-called "metalloligand" (where H(2)L = N,N'-bis(salicylidene)-1,3-propanediamine) and structurally characterized. Complexes and have the same molecular formula but crystallize in different crystal systems (triclinic for and monoclinic for ) with space group P1[combining macron] for and P2(1)/c for . is an angular trinuclear species, in which two terminal four-coordinate square planar "metalloligand" [CuL] are coordinated to a central Zn(ii) through double phenoxido bridges. The Zn(ii) is in a six-coordinate distorted octahedral environment being bonded additionally to two mutually cis nitrogen atoms of terminal azide ions. In complex , in addition to the double phenoxido bridge, the two terminal Cu(ii) ions are linked to the central Zn(ii) via a μ(-l,l) azido bridge giving rise to a square pyramidal environment around the Cu(ii) ions and consequently the structure becomes linear. These two species can be considered as "linear-bent" isomers. EPR spectra and ESI mass spectra show that the two isomers are identical in solution. The DFT calculation reveals that the energy of is 7.06 kcal mol(-1) higher than that of . The existence of both isomers in the solid state suggests that crystal packing interactions in are more efficient and probably compensate for the difference in energy.     

Reactivity of the "yl"-bond in uranyl(VI) complexes. 1. Rates and mechanisms for the exchange between the trans-dioxo oxygen atoms in (UO2)2(OH)2 2+ and mononuclear UO2(OH)n 2-n complexes with solvent water

The stoichiometric mechanism, rate constant, and activation parameters for the exchange of the "yl"-oxygen atoms in the dioxo uranium(VI) ion with solvent water have been studied using 17O NMR spectroscopy. The experimental rate equation, (-->)v= k(2obs)[UO2(2+)]tot2/[H+]2, is consistent with a mechanism where the first step is a rapid equilibrium 2U(17)O2(2+) + 2H2O<==>(U(17)O2)2(OH)2(2+) + 2H+, followed by the rate-determining step (U(17)O2)2(OH)2(2+) + H2O<==>(UO2)2*(OH)2(2+) + H2(17)O, where the back reaction can be neglected because the (17)O enrichment in the water is much lower than in the uranyl ion. This mechanism results in the following rate equation (-->)v= d[(UO2)2(OH)2(2+)]/dt = k(2,2)[(UO2)2(OH)2(2+)] = k(2,2*)beta(2,2)[UO2(2+)]2/[H + ]2; with k(2,2) = (1.88 +/- 0.22) x 10(4) h(-1), corresponding to a half-life of 0.13 s, and the activation parameters DeltaH++ = 119 +/- 13 kJ mol-1 and DeltaS++ = 81 +/- 44 J mol(-1) K(-1). *Beta(2,)2 is the equilibrium constant for the reaction 2UO2(2+) + 2H2O<==>(UO2)2(OH)2(2+) + 2H+. The experimental data show that there is no measurable exchange of the "yl"-oxygen in UO2(2+), UO2(OH)+, and UO2(OH)4(2-)/ UO2(OH)5(3-), indicating that "yl"-exchange only takes place in polynuclear hydroxide complexes. There is no "yl"-exchange in the ternary complex (UO2)2(mu-OH)2(F)2(oxalate)2(4-), indicating that it is also necessary to have coordinated water in the first coordination sphere of the binuclear complex, for exchange to take place. The very large increase in lability of the "yl"-bonds in (UO2)2(OH)2(2+) as compared to those of the other species is presumably a result of proton transfer from coordinated water to the "yl"-oxygen, followed by a rapid exchange of the resulting OH group with the water solvent. "Yl"-exchange through photochemical mediation is well-known for the uranyl(VI) aquo ion. We noted that there was no photochemical exchange in UO2(CO3)3(4-), whereas there was a slow exchange or photo reduction in the UO2(OH)4(2-) / UO2(OH)5(3-) system that eventually led to the appearance of a black precipitate, presumably UO2.     

Asymmetric total syntheses of (+)-3-(z)-laureatin and (+)-3-(z)-isolaureatin by "lone pair-lone pair interaction-controlled" isomerization

The first asymmetric total syntheses of the dihalogenated medium-sized dioxabicyclic marine natural products (+)-3-(Z)-isolaureatin (1) and (+)-3-(Z)-laureatin (2) have been accomplished. Notable features of the highly stereo-, regio-, and chemoselective syntheses of these alpha,alpha'-trans-oxocene natural products include an intramolecular amide enolate alkylation to construct the alpha,alpha'-cis-oxocene, novel "lone pair-lone pair interaction-controlled" epimerizations to the alpha,alpha'-trans-oxocenes, various strategies for stereoselective introduction of halogen atoms, and novel olefin cross-metatheses for construction of the (Z)-enyne systems.     

Synthesis of Gingerenone C and 5-Hydroxy-1-(4'-hydroxy- 3'-methoxyphenyl)-7-(4"-hydroxyphenyl)-3-heptanone

The two diarylheptanoids (E)-1-(4'-hydroxy-3'-methoxyphenyl)-7-(4"-hydroxyphenyl) hept-4-en-3-one 1 (Gingerenone C) and (±)-5-hydroxy-1-(4'-hydroxy-3'-methoxyphenyl)-7-(4"-hydroxyphenyl)-3-heptanone 2 were synthesized from vanillin 3 and 4-hydroxybenzaldehyde 9.     

"Dimers" and "trimers" of tetrahydroindenes and hexahydroazulenes, respectively generated from [2-(1-cycloalkenyl)ethynyl]carbene complexes (M = W, Cr) by cascade cyclization/cycloaddition reactions

A cascade of cyclization/cycloaddition reactions was triggered by addition of protic oxygen nucleophiles ROH 2 (RO = CH3CO2, PhCO2, PhO) to [2-(1-cyclohexenyl)ethynyl]carbene complexes 1b and 1c (M=W, Cr, respectively), affording highly strained "dimers" 11/11' and "trimers" 12 of the carbene ligand. The first reaction step involved the formation of 1-metalla1,3,5-hexatrienes 7, which readily gave tetrahydroindenes 8 by pi cyclization and extrusion of the metal unit. "Dimers" 11/11' were generated from tetrahydroindenes 8 by a highly exo selective [4+2] cycloaddition of compounds 1b and 1c to afford 1-metalla-1,3,5-hexatriene intermediates 9, and a spontaneous pi cyclization of the latter compounds involving the disengagement of the metal unit. Propenylidene cyclohexenes 13/13' were formed in "ene"-type side reactions to the pi cyclization of 1-metalla-1,3,5-hexatrienes 7, by loss of the metal unit. "Dimers" 11 were transformed into "trimers" 12 by a [4+2] cycloaddition and subsequent pi-cyclization of the resulting 1-metalla-1,3,5-hexatriene system. The course of the reaction was elucidated by means of model reactions with (2-phenylethynyl)carbene complex 14, in which 1-metalla-1,3,5-hexatriene intermediates 16 and 17 were isolated and characterized. Alkynyl benzene derivatives 19 were obtained by an unprecedented ring-expansion of a cyclopentadiene unit of "dimers" 11a and 11c, involving the insertion of a carbene carbon atom of compound 14 into a C=C bond. A reaction cascade leading to "dimers" 24/24' could also be triggered by treatment of compounds 2 with [2-(1-cycloheptenyl)ethynyl]carbene tungsten complex 1d.     

"Through-space" nuclear spin-spin J(PP) coupling in tetraphosphine ferrocenyl derivatives: a (31)P NMR and X-ray structure correlation study for coordination complexes

Herein, we report on (31)P(31)P solution-phase "through-space" nuclear spin-spin coupling constants (J(PP)) from a novel family of organometallic tetraphosphine nickel and palladium complexes. These J(PP) constants were accurately determined through NMR iterative simulation based on the second-order spectra obtained for the compounds. The corresponding solid-state X-ray structures of the complexes were determined, and the "through-space" P.P distances are reported. Due to the blocked conformation of the species in solution, a qualitative and semiquantitative experimental correlation is obtained, which links the geometric parameters and the intensity of the corresponding P.P coupling constant. The lone-pair overlap theory developed for (19)F(19)F and (15)N(19)F "through-space" couplings in organic compounds [J. Am. Chem. Soc. 1973, 95, 7747-7752; 2000, 122, 4108-4116] appears to be a reliable foundation on which to account for our results. Based on the reported observations, the lone-pair overlap model is extended to "through-space" (31)P(31)P coupling, and the model is broadened to encompass metal orbital contributions for coordination complexes. Some of the predictions and consequences of the proposed theory are discussed.     

Crystal structure of <Emphasis Type="Italic">tris</Emphasis>-(dipivaloylmethanato) (ethylendiamine)yttrium(III)

The structure of a mixed-ligand complex tris-(dipivaloylmethanato)(ethylendiamine)yttrium(III) [Y(en)(dpm)₃] is studied at 150(2) K by single crystal XRD. The crystallographic data for C₃₅H₆₅N₂O₆Y are as follows: space group P2₁/c, a = 10.3771(3) Å, b = 26.3566(8) Å, c = 14.8412(4) Å, β = 100.385(2)°, V = 3992.6(2) ų, Z = 4. The structure is molecular. The coordination environment of yttrium atoms is square antiprismatic; the Y–О distances are 2.2597(13)-2.3760(12) Å and Y–N distances are 2.5381(16) Å and 2.5499(17) Å.     

Bioactive diterpenoid containing a reversible "spring-loaded" (E,Z)-dieneone Michael acceptor

Three new briarane diterpenoids, briareolate esters L-N (1-3), have been isolated from a gorgonian Briareum asbestinum. Briareolate esters L (1) and M (2) are the first natural products possessing a 10-membered macrocyclic ring with a (E,Z)-dieneone and exhibit growth inhibition activity against both human embryonic stem cells (BG02) and a pancreatic cancer cell line (BxPC-3). Briareolate ester L (1) was found to contain a "spring-loaded" (E,Z)-dieneone Michael acceptor group that can form a reversible covalent bond to model sulfur-based nucleophiles.     

The application of "click chemistry" for the decoration of 2(1H)-pyrazinone scaffold: generation of templates

The "click chemistry" approach has been explored on the 2-(1H)-pyrazinone scaffold for the generation of pharmacologically interesting heterocyclic moieties. Huisgen 1,3-dipolar cycloaddition has been evaluated as the key step for the construction of the 1,2,3-triazole ring at the C-3 position of 2-(1H)-pyrazinones. Two different pathways have been successfully evaluated: (1) via C-C or C-O linkage of the acetylenic part to the C-3 position of the 2-(1H)-pyrazinone scaffold or (2) via azide introduction in the C-3 position. The subsequent application of "click chemistry" resulted in the formation of hitherto unknown skeletons. Microwave irradiation has successfully been applied in different steps of the sequence.