Cycloaddition of Chlorosulfonyl Isocyanate to 2H-Azirines: Formation of [2+2+2] Cycloadducts

Chlorosulfonyl isocyanata (CSI) reacts with 2H-azirines 1 a-c at -78°C to form [2+2+2] cycloadducts 3a-c and 4a-c. The tricyclic aziridine derivatives 4a-c undergo CSI extrusion reactions and subsequent oxidation to the corresponding pyrazines 5a-c. Structural identifications of 3a-c and 4a-c are based on ir, nmr and mass spectral data.     

13C NMR spectra of alkyl- and phenylpyrazines and their N-oxides

The ¹³C chemical shifts of 37 pyrazines, including their N-oxides, are reported. Substituent effects of methyl, phenyl and N-oxide groups on the chemical shifts were examined. To comprehend these effects, the chemical shifts were compared with charge densities calculated by the CNDO/2 method and a good correlation was obtained. ¹³C, ¹H coupling constants of some pyrazines were also determined and assigned. These data enable us to assign the ¹³C NMR spectra of substituted pyrazines and to understand the effects of N-oxidation on the pyrazine nuclei.     

Synthesis of alkyl-5H-cyclopenta[b]pyrazines (author's transl)]

Synthesis of alkyl-5H-cyclopenta[b]pyrazines. Alkyl-5H-cyclopenta[b]-pyrazines (sometimes together with 5-alkylidene-5H-6,7-dihydrocyclopenta[b]pyrazines) are prepared by thermal degradation of 5-acetoxy-5H-6,7-dihydrocyclopenta[b]pyrazines; these are obtained by treatment of alkyl-5H-6,7-dihydrocyclopenta[b]pyrazine N-oxides with acetic anhydride. Cyclopenta[b]pyrazines which are potentially present in roasted food flavors possess interesting organoleptic properties.     

Identification of alkyl-5H-6,7-dihydrocyclopenta[b]pyrazines in roasted meat flavor. Model reaction used as basis for natural product formation and new synthesis (author's transl)]

Identification of alkyl-5H-6,7-dihydrococyclopenta[b]pyrazines in roasted meat flavor. Model reaction used as basis for natural product formation and new synthesis. Seven alkyl-5H-6,7-dihydrocyclopenta[b]pyrazines have been identified in a roasted meat aroma obtained by thermolysis of the hydrosoluble flavor precursors of raw meat. Formation of these heterocyclics by condensation of hydroxycyclopentenones with aliphatic α-dicarbonyl compounds in the presence of ammonia has been confirmed by a model reaction. Alkyl-5H-cyclopenta[b]pyrazines and dicyclopenta [b,e]pyrazines are also obtained from this reaction, but have not yet been identified in roasted flavors. Preparation of the intermediates of the model reaction enabled development of an economical synthesis of 2,3,5-trimethyl-5H-6,7-dihydrocyclopenta[b]pyrazine.     

Aza-2-dienes-1,3. Partie 5. Préparation de N-aminoimidazoles, 3H-pyrroles,triazolo[1,2,4][1,5-a]pyrazines et imidazo[1,2-a]pyrazines

2-Aza-1,3-dienes. Access to N-Aminoimidazoles, 3H-Pyrroles, [1,2,4]Triazolo[1,5-a]pyrazines, or Imidazo[1,2-a]pyrazines Nucleophilic attack of 5-(dialkylamino)-2-aza-1,3-diene-1,1-dicarbonitriles (or their 1-methoxycarbonyl analogous) by hydrazines or hydrazdes gives substituted N-aminoimidazoles, [1,2,4]triazolo-[1,5-a]pyrazines, or α-dihydrazino derivatives. With α-amino esters (or analogous), imidazo[1,2-a]pyrazines are produced. Addtion of cyanide anions occurs also with formation of substituted 3H-pyrroles. Structures and rationalisation of this nucleophilic attack are discussed.     

Synthesis and characterization of a nickel metavanadate complex: Ni(pz)(V2O6) (pz = pyrazine)

A nickel metavanadate complex Ni(pz)(V₂O₆) (pz =?pyrazine) (1) was hydrothermally synthesized and characterized by elemental analysis, IR spectroscopy and thermal analysis. The complex was also investigated by single crystal X-ray diffraction analysis. The three-dimensional extended structure in the crystal is constructed by corner sharing {VO₃}_n chains running along the b axis and two types of {Ni(pz)}_n chains oriented in [0?1?1] and [0?1??1] directions, respectively. Ni is coordinated by two N atoms from two pyrazines and four O atoms from three metavanadates in a distorted octahedral geometry. The variable-temperature magnetic susceptibility of 1 was measured. The magnetic coupling parameter indicates an antiferromagnetic interaction within the {Ni(pz)}_n chain.     

Efficient synthesis of some novel furo[3,2-e]pyrazolo[3,4-b]pyrazines and related heterocycles

A series of novel 6-functionalized-5-amino-3-methyl-1-phenyl-1H-furo[3,2-e]pyrazolo[3,4-b]pyrazines (4a–c) was synthesized by the reaction of 3-methyl-6-oxo-1-phenyl-6,7-dihydro-1H-pyrazolo[3,4-b]pyrazine-5-carbonitrile (2) with α-halocarbonyl compounds such as: diethyl 2-bromomalonate, phenacyl bromide and chloroacetone. Cyclocondensation of the amino benzoyl 4b with diethyl malonate yielded the oxopyridine carboxylate derivative 5. Also, the starting intermediate amino ester compound 4a was allowed to react with ethanol amine to afford the hydroxyethyl caboxamide derivative 6. Furthermore, hydrazinolysis of the amino ester 4a afforded the corresponding amino carbohydrazide 7 which was used as a versatile precursor for synthesis of other heterocyclic compounds attached or fused to the furopyrazolopyrazine moiety. The chemical structures of the newly synthesized compounds were confirmed on the basis of elemental and spectral analyses containing FT-IR, ¹H NMR, ¹³C NMR, and mass spectrometry hoping these molecules should allow us to investigate their pharmacological activities in the future study.     

Dipyrrolo[1,2-a:2',1'-c]pyrazines. 8. Electrophilic Substitution in Dipyrrolo[1,2-a:2',1'-c]pyrazines and 5,6-Dihydrodipyrrolo[1,2-a:2',1'-c]pyrazines. Acylation of Dipyrrolo[1,2-a:2',1'-c]pyrazines

Esters, nitriles, and amides of dipyrrolo[1,2-a:2',1'-c]pyrazines have been synthesized by the acylation of dipyrrolo[1,2-a:2',1'-c]pyrazines and 5,6-dihydrodipyrrolo[1,2-a:2',1'-c]pyrazines with trichloroacetic acid chloride, p-tosyl isocyanate, and isocyanatophosphoric acid dichloride (Kirsanov isocyanate).     

Pyrazines. 2ème communication [1]. II. Synthèse de dihydro-6,7-5H-cyclopenta[b]pyrazines alkylées

Alkyl-5H-6,7-dihydrocyclopenta[b]pyrazines are prepared by condensation of cyclopentenolones with alkylenediamines or of aliphatic α-diketones with 1,2-diaminocyclo pentanes. Products so obtained were dehydrogenated using palladium on activated charcoal, or copper chromite. NMR. and mass spectra are given for 21 bicyclic pyrazines and intermediates, and their IR. spectra are compared.     

Catalyst-free synthesis of N-rich heterocycles via multi-component reactions

Efficient and straightforward methods for the synthesis of 5-substituted 1H-tetrazoles via multi-component reaction of α-dicarbonyl compounds, 2,3-diaminomaleonitrile and sodium azide without any catalyst has been reported. These general protocols provide a wide variety of N-rich heterocyclic compounds (1H-tetrazole-5-yl) pyrazines and di(1H-tetrazole-5-yl) pyrazines, in good to excellent yields.     

Sampling and Analysis of Odorous Compounds in Water Treatment Plants

Abstract

The following analytical method has been used to identify some odorous compounds in the air of the water treatment plant Werdholzli, Zurich: sampling of contaminated air with the help of activated carbon, desorption by the solvents carbon disulphide and methylene chloride, separation of the carbon disulfide extract into a polar and a nonpolar fraction by adsorption column chromatography on silica. Hereafter gaschromatographic analysis of the polar fraction on glass capillary column (Ucon HB 5100); detection and identification were achieved by flame ionisation, thermoionic nitrogen selective detector and computerized mass spectrometry (Finnigan 3200 F, data system 6110).

The results show the presence of sulfur compounds: thiophenes, thiazoles; nitrogen compounds: pyrazines; oxygen compounds: phenols, alcohols and some unsatured hydrocarbons. The malodorous compounds were sulfur and nitrogen compounds in the range of 0.01-0.1 ppm.     

Carbon-13 NMR spectra of monosubstituted pyrazines

Carbon-13 NMR chemical shifts and one-bond carbon–hydrogen coupling constants have been obtained at 15·09 MHz. The trends in the carbon chemical shifts obtained for the pyrazines parallel those of monosubstituted benzenes and 2-substituted pyridines, except for the direct effect of substitution where the pyrazines resemble pyridines not benzenes. The substituent effects on the ¹³C NMR spectra are generally quite similar to those in the ¹H NMR spectra. The ¹³C NMR spectrum of the tautomeric hydroxypyrazine has been compared with the ¹³C NMR spectra of 2-, 3- and 4-hydroxypyridines. Hydroxy compounds that can exist as a cyclic amide show a large meta substituent effect on the chemical carbon shift.     

Regioselectivity in the amination of azines: Reaction of pyrazine derivatives with <Emphasis Type="Italic">O</Emphasis>-mesitylenesulfonylhydroxylamine

Treatment of 2-X-substituted pyrazines [X = H, Me, Et, Pr, i-Pr, t-Bu, MeCH(OH), H₂N, AcNH] with O-mesitylenesulfonylhydroxylamine gave the corresponding 2-X- and 3-X-(1-amino)pyrazin-1-ium mesitylenesulfonates. 2-Alkylpyrazines (X = Me, Et, Pr, i-Pr) displayed a correlation between the logarithms of the concentration ratio of 2- and 3-substituted cations and substituent steric constants. Wider series of substituted pyrazines [X = H, Me, Et, Pr, i-Pr, MeCH(OH), H₂N, AcNH] conformed to a multiparameter correlation between the logarithms of the concentration ratio of 2- and 3-substituted cations, on the one hand, and substituent constants σ_I, σ_R^o, and E _s^o, on the other. The obtained data on the regioselectivity of amination of pyrazines were interpreted in terms of DFT/PBE/3Z quantum-chemical calculations.     

Base strengths and polarographic behaviour of a number of pyrazine derivatives

The _pK₁ and _pK₂ values and the Polarographic half-wave reduction potentials for a series of methyl substituted pyrazines are reported, together with the reduction potentials of several of their N-alkyl derivatives. There is a linear inverse relationship between _pK₁ and E_1/2 for the pyrazines.     

Liquid Chromatographic Behavior of Nitrogen Compounds

Abstract

Chromatographic behavior of nitrogen compounds differed from others. The column efficiency was poor for the compounds and sometimes solutes were not eluted out from a column. Therefore, the elution volume of alkylamines, anilines, pyridines, pyrazines, quinolines and aminopolyaromatic hydrocarbons was measured on a methacrylate gel and octadecyl bonded silica gels in pH controlled acetonitrile/water mixtures. The solvent effect on the dissociation constant differs from that obtained for aromatic acids. The values in acetonitrile/water mixtures are smaller than those obtained in 100% water. The linear relation between log P and log k′ values is obtained in eluents of pH 7 where the retention of these compounds is maximized. Some hydrophobic fragmental constants are proposed from this result. Prediction of retention time of these compounds from their log P values can be done in the individual groups on octadecyl bonded silica gels in pH controlled acetonitrile/water mixtures.     

Acylation of 3,4-Dihydropyrrolo[1,2-a]pyrazines

The direction of trifluoroacetylation with trifluoroacetic anhydride of 3,4-dihydropyrrolo[1,2-a]pyrazines containing an alkyl or aralkyl substituent in position 1 depends on both the structure of the 3,4-dihydropyrrolo[1,2-a]pyrazine starting materials and on the ratio of reagent:substrate. It may lead to both mono- and disubstituted products. Trifluoroacetylation of 1-methyl-3,4-dihydropyrrolo[1,2-a]pyrazines occurs at the methyl group. Acetylation of 3,4-dihydropyrrolo[1,2-a]pyrazines leads only to N-acetyl-substituted reaction products.     

Reaction of tetrachloropyrazine with active methylene compounds

When tetrachloropyrazine was allowed to react with the anions formed from diethyl malonate and malonitrile, the normal alkylation took place. When the anions from ethyl acetoacetate and N,N-diethylacetoacetamide were used, alkylation was followed by enolization and ring formation to give furo [2,3-b] pyrazines. The structure proof and reaction of the furo [2,3-b] pyrazines are discussed.     

Sur l'arǒme de viande de bœuf grillée III. Pyrrolo [1,2-a]pyrazines,identification et synthèse

Synthesis of alkylpyrrolo[1,2-a]pyrazines, roasted meat flavor constituents Seven alkylpyrrolo[1,2-a]pyrazines have been identified for the first time in a roasted meat aroma obtained by thermolysis of the hydrosoluble flavor precursors of raw meat. Identification of individual components was done by capillary gas chromatography/mass spectroscopy coupling. The structure of these nitrogen heterocyclic compounds was for some time in doubt because of the similarity of the MS. with those of other diazaindene and diazanaphthalene derivatives such as benzimidazoles, indazoles, cyclopenta [b]pyrazines and dihydroquinoxalines. The structure of these new flavor components was completely elucidated in some cases by interpretation of NMR. spectra, the others being deduced by analogy. Hypotheses are formulated concerning the formation of this skeleton by a non-enzymatic browning reaction between carbohydrates and amino acids. Four different schemes have been adopted to synthesize substituted isomers selectively.     

Novel approach to the synthesis of perhydropyrazino[1,2-a]pyrazine derivatives from amino alcohols

2,4,7-Trisubstituted hydrogenated pyrazino[1,2-a]pyrazines as potential β-turn mimetics were prepared for the first time in a stereoselective synthesis from hexahydro[1,2,3]triazolo[1,5-a]pyrazines.