Use of temporary tethers in the intramolecular [2+2] photocycloaddition reactions of tetrahydrophthalimide derivatives: a new approach to complex tricyclic lactones

The intramolecular [2+2] photocycloaddition reactions of a series of alkenols tethered to ethanolamine, l-(+)-valinol and R-(−)-2-phenylglycinol derived 3,4,5,6-tetrahydrophthalimides via a carbonate or silicon linkage have been examined. These [2+2] photocycloadditions gave the corresponding cyclobutanes in high yield with complete endo control in all cases and with diastereoselectivities as high as 8:1 with the chiral tethers. The cleavage of the temporary tethers by either desilylation or hydrolysis provided the endo diols. Cleavage of the ethanolamine linkage by reduction/hydrolysis precipitated an acid-catalysed fragmentation/ring expansion sequence to generate complex tricyclic lactones.     

Stabilization of even-electron ions in 4-amino-substituted cytosines. Appearance of the strong ortho effect between an aryl substituent and the pyrimidinyl ring

The mass fragmentation of 4-arylaminocytosine derivatives was investigated and it was found that the ortho effect is mainly responsible for the strong stabilization of even-electron ions formed during fragmentation. The ortho effect in this class of compounds completely eliminates other possible fragmentation patterns. This effect disappears when the aryl substituent is separated from the 4-amino group of the cytosine moiety by a methylene group.     

Synthesis of ferrocene-grafted poly(p-phenylene-ethynylenes) and control of electrochemical behaviors of their thin films

New ferrocene-coated poly(p-phenylene-ethynylenes) (PPEs) with end capping groups of protected thiol were prepared by a palladium-catalyzed Sonogashira coupling reaction. Ferrocene groups were covalently attached to polymers A and B through ethylene oxide tethers and to polymer C through methylene tethers. Polymers A and B are soluble in common solvents such as tetrahydrofuran (THF), chloroform, methylene chloride, acetone, dimethylformamide (DMF), and dimethyl sulfoxide (DMSO), and polymer C is soluble in toluene, THF, chloroform, and methylene chloride. Polymers A-C display low quantum yield, caused by electron-transfer quenching of ferrocene groups as electron donors. The polymer thin films were prepared through incubation of gold electrodes in THF solutions containing the polymers for 2 days. Ferrocene in thin films of polymers A and B display significantly faster electron-transfer rate than that of polymer C. Hydrophilic ethylene oxide side chains of polymers A and B decrease formal potential of tethered ferrocene groups because of electron-donating effect from ethylene oxide side chains, which stabilizes the ferrocenium ion and leads to a cathodic shift of the redox wave.     

Peptide Dimethylation: Fragmentation Control via Distancing the Dimethylamino Group

Direct reductive methylation of peptides is a common method for quantitative proteomics. It is an active derivatization technique; with participation of the dimethylamino group, the derivatized peptides preferentially release intense a₁ ions. The advantageous generation of a₁ ions for quantitative proteomic profiling, however, is not desirable for targeted proteomic quantitation using multiple reaction monitoring mass spectrometry; this mass spectrometric method prefers the derivatizing group to stay with the intact peptide ions and multiple fragments as passive mass tags. This work investigated collisional fragmentation of peptides whose amine groups were derivatized with five linear ω-dimethylamino acids, from 2-(dimethylamino)-acetic acid to 6-(dimethylamino)-hexanoic acid. Tandem mass spectra of the derivatized tryptic peptides revealed different preferential breakdown pathways. Together with energy resolved mass spectrometry, it was found that shutting down the active participation of the terminal dimethylamino group in fragmentation of derivatized peptides is possible. However, it took a separation of five methylene groups between the terminal dimethylamino group and the amide formed upon peptide derivatization. For the first time, the gas-phase fragmentation of peptides derivatized with linear ω-dimethylamino acids of systematically increasing alkyl chain lengths is reported. Figure

?     

Synthesis and Characterization of Novel Quaternary Ammonium RAFT Agents

Synthesis of three new cationic thio compounds suitable to control free‐radical polymerization according to the reversible addition fragmentation chain transfer (RAFT) process (reversible addition fragmentation transfer) is presented. Among them, two bear a quaternary ammonium group in the R group [i.e., N,N‐dimethyl‐N‐(4‐(((phenylcarbonothionyl)thio)methyl)benzyl)ethanammonium bromide and N‐(4‐((((dodecylthio) carbonothioyl)thio)methyl)benzyl)‐N,N‐dimethylethanammonium bromide, a dithioester and a trithiocarbonate, respectively]. The synthesis of a trithiocarbonate bearing an ammonium group in the Z group [i.e., 2‐((11‐((benzylthio)carbonothioyl)thio)undecanoyl)oxy)‐N,N,N‐trimethylammonium iodide] is also presented. Another three thio compounds, namely 1,4‐phenylenebis(methylene)dibenzenecarbodithioate, didodecyl‐1,4‐phenylenebis(methylene)bistrithiocarbonate, and 11‐(((benzylthio)carbonothioyl)thio)undecanoic acid, identified as other potentially interesting mono‐or difunctional RAFT agents, which were obtained as side products or intermediates, were isolated and fully characterized.     

Identification of monoacylglycerol regio-isomers by gas chromatography–mass spectrometry

Monoacylglycerols (MAGs) are lipids found in trace amounts in plants and animal tissues. While they are widely used in various industrial applications, accurate determination of the regio-specific distribution is hindered by the lack of stable, commercially available standards. Indeed, unsaturated β-MAG (or Sn-2 MAG) readily undergoes isomerization into α-MAG (acyl chain is attached to the Sn-1 or the Sn-3 position). In the present study, we describe structural elucidation of α- and β-regio-isomers of monopalmitoyl-glycerol (MAG C16:0) as model compounds in their silylated forms using gas chromatography–mass spectrometry (GC–MS) with electronic impact (EI) ionization. MS fragmentation of α-MAG C16:0 is characterized by the loss of methylene(trimethylsilyl)oxonium (103 amu) and the consecutive loss of acyl chain yielding a fragment ion at m/z 205. The fragmentation pattern of β-MAG C16:0 shows a series of diagnostic fragments at m/z 218, 203, 191 and 103 that are not formed from the α-isomer and hereby enable reliable distinction of these regio-isomers. Possible fragmentation scenarios are postulated to explain the formation of these marker ions, which were also applied to characterize the regio-isomer composition of a complex mixture of MAG sample containing n-3 long-chain polyunsaturated fatty acids.     

Copper(I)-catalyzed [2 + 2] photocycloadditions with tethered linkers: synthesis of syn-photodimers of dicyclopentadienes.

Cu(I)-catalyzed intramolecular photocycloadditions of diesters made of endo-dicyclopentadiene derivatives linked by the ester bonds with tethers are highly regio- and stereoselective and complete within hours, and the tethers can be easily cleaved afterward upon reduction with LiAlH4-Irradiation of the diesters afforded a 1:1 mixture of the heretofore unknown exo-cis-exo dimer, originating from the (R,S/S,R) diastereomer of the diester and the exo-trans-exo, deriving from the (R,R/S,S) diastereomer. The intermolecular photodimerization yielded, instead, only exo-trans-exo isomers and side products after irradiation for several days. The role of the tether's length and structure on the course of the photocycloadditions was investigated, and it was observed that short tethers introduce considerable strain in the products' framework. Adamantyl-containing tethers provided the shortest reaction times and highest yields. X-ray diffraction analysis of an exo-cis-exo stereoisomer containing adamantane in the tether exhibited an unusually close approach between H atoms on the methylene bridges and a long C-C distance in the cyclobutane ring. A rearrangement induced by X-ray irradiation was observed in this molecule.     

Syntheses and rearrangements of ketene mercaptals derived from some active methylene compounds and carbon disulphide

By use of the ion pair extraction technique, tetrabutylammonium salts of diethyl malonate, methyl cyanoacetate or malodinitrile were reacted with carbon disulphide giving salts of dithioacids (or of the tautomeric gem-mercapto thiolates) and of ketene mercaptals. Ketene methyl allyl mercaptals derived from diethyl malonate or methyl cyanoacetate rearranged at room temp to dithioesters by S → C allyl migration. The corresponding methyl crotyl derivatives gave equilibrium mixtures of the ketene mercaptals and the dithioesters, each of which were shown to undergo S → C and C → S rearrangements, respectively, with inversion of the crotyl group. Contrary to this the ketene dicrotyl mercaptals rearranged during distillation (at about 150°) with retention of the crotyl group. Methyl [(methylthio, crotylthio)methylene] cyanoacetate underwent fragmentation at 170° to MeSSMe, MeScrotyl, MeS(1-methylallyl) and the “desaurin”: 2,4-bis-(carbomethoxy-cyan-methylen)-1,3-dithiocyclobutan. Similarly bis(allylthio)methylene malodinitrile yielded diallyl sulphide.     

Fragmentation of conjugate bases of esters derived from multifunctional alcohols including triacylglycerols

Enolate anions of esters from 1,2 and 1,3 diols undergo an internal nucleophilic substitution reaction that produces a β-ketoester and an alkoxide ion within the molecular species. These intermediate ions undergo two competitive fragmentation pathways. The first pathway corresponds to a second nucleophilic substitution of the ketoester by the alkoxide that yields a neutral cyclic ether and the β-ketoacid carboxylate. The latter then loses carbon dioxide and produces the enolate anion of the corresponding ketone. The second proposed pathway is stepwise: it starts with a proton transfer from the methylene group between the two carbonyls to the alkoxide anion that produces an alcohol and the enolate ion of the β-ketoester inside the molecular species. The latter undergoes cleavage of the ester bond induced by the negative charge to yield an ion-dipole complex composed of a neutral acylketene and an alkoxide ion. The direct dissociation of this ion-dipole complex competes with an internal proton exchange to yield a new complex that consists of an alcohol molecule and the anion of the acylketene, which can also dissociate. The fragmentation pathway that leads to the ketone enolate is sensitive to the relative positions (1,2 or 1,3) of the esters on the molecular backbone. This position-sensitive reaction is useful for the assignment of the primary and secondary positions in triacylglycerols, even in mixtures, as shown by some examples.     

Mannich Condensation of 3,3,5-Trimethylcyclohexanone and Its Oxime

Mannich condensation of 3,3,5-trimethylcyclohexanone with paraformaldehyde and dimethylamine or benzylamine hydrochloride involves both activated methylene group in the initial ketone to give compounds with equatorial aminomethyl substituent. The major isomer is that formed by addition at the less sterically hindered carbon atom. Likewise, Mannich condensation of the E and Z isomers of 3,3,5-trimethylcyclohexanone oxime react at both methylene groups, and the addition of aminomethyl fragment occurs preferentially at that methylene group which is located more closely to the oxime hydroxy group.     

Symmetry allowed π4s+π2s additions silacyclopentadienes

π⁴s+π²s cycloaddition of hexaphenylsilacyclopentadiene with ethyl acrylate gives rise to a bicyclosilaheptene derivative. High resolution NMR studies have shown that the ester group in this adduct is in the endo position and that the ester methylene protons are magnetically inequivalent. Similar cycloadditions of hexaphenylsilacyclopentadiene, 1,1-dimethyl-2,3,4,5-tetraphenylsilacyclopentadiene, 1-methyl-1,2,3,4,5-pentaphenylsilacyclopentadiene, and 1-methyl-1-vinyl-2,3,4,5-tetra-phenylsilacyclopentadiene with dienophiles like acrylonitrile, maleic anhydride and dibenzoylacetylene have been carried out. The stereochemistry of these adducts has been deduced on the basis of NMR studies. Mass spectral fragmentation studies of some of the silabicycloheptenes have been carried out.     

An efficient synthesis of 2-amino-3-cyano-2-pyrrolin-4-ones, via the corresponding open chain tautomers (aminoacetylmalononitriles)

Malononitrile has been found to be acylated effectively using N-protected glycines by simultaneous activation of an amino acid carbonyl group and a malononitrile methylene group using carbonyl diimidazole (CDI). The corresponding aminoacetonitriles were isolated as enols and/or as their tautomeric forms, 2-amino-3-cyano-2-pyrrolin-4-ones.     

Porphyrinogen fragmentation profiles by ultra‐high‐performance liquid chromatography/electrospray ionisation tandem mass spectrometry

An ultra‐high‐performance liquid chromatography/electrospray ionisation tandem mass spectrometry system is described for the separation and characterisation of uroporphyrinogen, heptacarboxylic acid porphyrinogen, hexacarboxylic acid porphyrinogen, pentacarboxylic acid porphyrinogen and coproporphyrinogen. The separation was carried out on a 100 mm × 2.1 mm Thermo‐Hypersil BDS column (2.4 µm average particle size) by gradient elution with a mixture of acetonitrile, methanol and 1 mol/L aqueous ammonium acetate buffer, pH 5.16, as eluent. The fragmentation pattern of each compound was established by collision‐induced dissociation tandem mass spectrometry. The most characteristic fragmentation was ring opening at one of the four methylene bridges of the protonated porphyrinogen molecule followed by further cleavages of methylene bridges linking the four pyrrole rings at various points to give product ions with methylenepyrrolenine, methylene‐dipyrrolenine and methylene‐tripyrrolenine structures. Copyright © 2011 John Wiley & Sons, Ltd.     

Synthesis and olfactory properties of unnatural derivatives of lilac aldehydes

Lilac aldehydes are considered as principal olfactory molecules of lilac flowers. We have designed, prepared and evaluated two sets of their unnatural racemic analogues as pure diastereomers. While the synthesis of gem-dimethyl homologues starts from geranyl acetate, the preparation of methylene derivatives commences from linalyl acetate. The key Lewis and/or Brønsted acid catalysed cyclisation furnishes easily separable cis-/trans-tetrahydrofuranyl esters as common advanced intermediates. The subsequent functional group transformations lead to target aldehydes, alcohols, nitriles and olefins. Unlike the homologues possessing similar herbal scents, methylene derivatives exhibit woody and/or flowery odours. In the latter case, the sensory evaluation suggests the importance of relative stereochemistry and/or type of functional group on the odour character of respective compounds.     

Conformation of ATP and ADP Molecules in Aqueous Solutions Determined by High-Energy X-ray Diffraction

High-energy X-ray diffraction measurements were carried out at 26 °C for aqueous 1.0, 2.0 and 2.05 mol% disodium adenosine 5′-triphosphate (ATP) and 2.0 and 2.05 mol% disodium adenosine 5′-diphosphate (ADP) solutions in order to obtain direct experimental information on the intramolecular conformations of ATP and ADP molecules in aqueous solutions. Observed interference terms were analyzed in terms of the intramolecular geometry of the ATP and ADP molecules. Dihedral angles between adenine and the ribose group (t ₁), ribose-ring and methylene group of ribose (t ₂), and the methylene group of ribose and triphosphate (or diphosphate) group (t ₃), were determined through the least-squares fitting procedure of the observed interference term.     

Mass spectrometry of dinucleotide analogues containing 6-azauracil moiety

The mass fragmentation of three dinucleotide analogues in which D -ribose phosphodiester linkages were replaced by a three methylene unit chain has been investigated. The fragmentation pathways were proposed on the basis of high resolution data and metastable transitions. These compounds demonstrated a unique fragmentation with the formation of the fragment ion containing nitrogen at the end of the C₃H₆ chain.     

Direct mass spectrometry of polymers. XIV. Thermal fragmentation processes in poly-schiff bases

The thermal fragmentation processes in poly-Schiff bases have been investigated by direct pyrolysis–mass spectrometry. The mass spectral data show that the thermal fragmentation occurring in the polymers under investigation is characterized by hydrogen transfer reactions. In the case of a totally aromatic poly-Schiff base (polymer I ), the thermal fragmentation process involves hydrogen transfer irom the methyne group with formation of fragments bearing nitrile and/or phenyl end groups. In the case of aromatic-aliphatic poly-Schiff bases (polymers II–IV ), the hydrogen transfer process occurs from the aliphatic methylene groups. The latter process involves a lower energy and therefore occurs at lower temperatures with respect to the totally aromatic polymer I , with formation of thermal fragments bearing olefin and/or imine end groups. Beside these fragments, several thermal fragmentation compounds are also evolved by multiple hydrogen transfer reactions.     

Spectrometrie de masse,problemes de structure et de stereochimie—CCVII Fragmentations des Ethers Insatures

In connection with work on computerized mass spectral interpretation of organic com-pounds, the behavior of three groups of unsaturated ethers was examined: allylic, substituted allylic and unsaturated ethers with 2 or 3 methylene groups between the oxygen atom and the double bond. A total of 36 compounds (11 labelled) were prepared and mechanistic rationalizations presented. The allylic ethers isomerized to vinylic ethers after ionization. No double bond migration was observed, however, before or after electron-impact of allylic and homoallylic ethers or ethers with 3 methylene groups between the oxygen atom and the double bond. The allylic ethers with seven carbon atoms in the saturated chain lost a saturated alcohol molecule [R' + C₃H₆OH] by a uni-directional quadruple hydrogen transfer prior to fragmentation.     

Synthesis of chlorophyll-a derivatives possessing (un)substituted 13-exo-methylene moiety and their optical properties

Chlorophyll-a derivatives possessing an un/mono/disubstituted methylene moiety at the 13¹-position were prepared by (un)substituted methylation of the 13-carbonyl group and successive dehydration. Substitution of the 13¹-oxo to the methylene group slightly blue-shifted electronic absorption and emission bands in a solution and decreased chemical stability to give an oxidation product cleaved at the E-ring. Further mono/disubstitution at the methylene terminal increased wavelengths of absorption and emission maxima as well as oxidative tolerance.     

Chemical transformations of tetracyclo[3.3.1.1<Superscript>3,7</Superscript>.0<Superscript>1,3</Superscript>]decane (1,3-dehydroadamantane): III. Reactions of 1,3-dehydroadamantane with isothiocyanates

1,3-Dehydroadamantane reacted with phenyl isothiocyanate at 120–130°C under solvent-free conditions to give 4-(adamantan-1-yl)phenyl isothiocyanate. The selectivity of its reactions with benzyl and phenethyl isothiocyanates in which the isothiocyanato group is separated from the benzene ring by methylene or ethylene bridge was lower, and adamantylation of the para position of the benzene ring was accompanied by adamantylation of the methylene groups.