Search

Ketones with bulky aromatic, heteroaromatic and ferrocene substituents react with acetylene in the presence of a KOH/DMSO super-base suspension (90 °C, 15 min) to give polysubstituted furans in up to 86 % isolated yields in a one-pot fashion. This assembly of the furan scaffold involves a domino sequence in which one molecule of ketone reacts with two molecules of acetylene., (© 2015 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.)

1-Vinylpyrrole-2-carbaldehydes react with acetylene at atmospheric pressure in a NaOH/EtOH/DMSO system at 7-10 °C to afford 2-(1-hydroxypropyn-2-yl)-1-vinylpyrroles in 53-94% yield. Thus, the first base-mediated direct ethynylation of pyrrolecarbaldehydes with free acetylene under modified conditions of the Favorsky reaction has been implemented to pave an expedient route to important biomolecules containing a pyrrole ring.

Acetylene reacts with methylaryl(hetaryl)ketones in the presence of 6.5 mol % KOH in DMSO to give diastereoselectively in single operationally functionalized cyclopentenes. This domino cyclization involving two molecules of acetylene and two molecules of ketone proceeds with the formation of four C-C bonds. The complementary assembly of the cyclopentenes with similar functionalities from acetylenes and 1,5-diketones has been developed.

A facile one-pot synthesis of 3-trifluoromethylated piperazin-2-ones has been achieved by the treatment of trifluoromethyl 2-bromo enones with N,N'-disubstituted ethylenediamines in trifluoroethanol. The mechanism of this unexpected reaction is discussed in terms of multistep processes involving formation of captodative aminoenone as a key intermediate. The unique influence of trifluoromethyl group on the reaction path was demonstrated.

Comparative analysis of the (1)Н and (13)С NMR data for a series of the E and Z-1-styrylpyrroles, E and Z-1-(1-propenyl)pyrroles, 1-vinylpyrroles and styrene suggests that the conjugation between the unsaturated fragments in the former compounds is reduced. This is the result of the mutual influence of the donor p-π and π-π conjugation having opposite directions. According to the NMR data combined with the density functional theory calculations, the Z isomer of 1-styrylpyrrole has essentially a nonplanar structure because of the steric hindrance. However, the E isomer of 1-styrylpyrrole is also an out-of-plane structure despite the absence of a sterical barrier for the planar one. Deviation of the E isomer from the planar structure seems to be caused by an electronic hindrance produced by a mutual influence of the p-π and π-π conjugation. The structure of the E isomer of the 2-substituted 1-styrylpyrroles is similar to that of the 2-substituted 1-vinylpyrroles. The steric effects in the Z isomer of the 2-substituted 1-styrylpyrroles result in the large increase of the dihedral angle between planes of the pyrrole ring and double bond., (Copyright © 2013 John Wiley & Sons, Ltd.)

1-Substituted imidazoles undergo exceptionally facile stereoselective ring opening under the influence of electron-deficient acetylenes and water (equimolar ratio of the reactants) in MeCN at 45-60 °C without any catalysts to afford functionalized (Z,Z)-1,4-diaza-2,5-dienes, (Z,Z)-propenylaminoethenylformamides, in up to 80% yields. The reaction is rationalized to proceed in a tandem manner via zwitterionic vinyl carbanions formed by nucleophilic addition of imidazole to the triple bond. The carbanionic center is then quenched with water followed by the rearrangement of the intermediate 2-hydroxy-3-alkenylimidazolines.

The sequential reaction of ketones with arylacetylenes and hydroxylamine in the presence of KOBu(t)/DMSO followed by the treatment of the reaction mixture with H(2)O and KOH leads to Δ(2)-isoxazolines in up to 88% yield.

A wide variety of β,γ-unsaturated ketones of E configuration have been obtained in good to excellent yields via KO(t)Bu/DMSO promoted α-vinylation of aliphatic, cycloaliphatic, and alkyl aromatic (heteroaromatic) ketones with diverse arylacetylenes.

In the (13) C NMR spectra of methylglyoxal bisdimethylhydrazone, the (13) C-5 signal is shifted to higher frequencies, while the (13) C-6 signal is shifted to lower frequencies on going from the EE to ZE isomer following the trend found previously. Surprisingly, the (1) H-6 chemical shift and (1) J(C-6,H-6) coupling constant are noticeably larger in the ZE isomer than in the EE isomer, although the configuration around the -CH═N- bond does not change. This paradox can be rationalized by the C-H⋯N intramolecular hydrogen bond in the ZE isomer, which is found from the quantum-chemical calculations including Bader's quantum theory of atoms in molecules analysis. This hydrogen bond results in the increase of δ((1) H-6) and (1) J(C-6,H-6) parameters. The effect of the C-H⋯N hydrogen bond on the (1) H shielding and one-bond (13) C-(1) H coupling complicates the configurational assignment of the considered compound because of these spectral parameters. The (1) H, (13) C and (15) N chemical shifts of the 2- and 8-(CH(3) )(2) N groups attached to the -C(CH(3) )═N- and -CH═N- moieties, respectively, reveal pronounced difference. The ab initio calculations show that the 8-(CH(3) )(2) N group conjugate effectively with the π-framework, and the 2-(CH(3) )(2) N group twisted out from the plane of the backbone and loses conjugation. As a result, the degree of charge transfer from the N-2- and N-8- nitrogen lone pairs to the π-framework varies, which affects the (1) H, (13) C and (15) N shieldings., (Copyright © 2012 John Wiley & Sons, Ltd.)

N-Vinylpyrroles and -indoles bearing electron-withdrawing substituents at the pyrrole ring are mercurated, with 1 equivalent of Hg(OAc)(2) in dry MeCN (20-80 °C), regioselectively at the vinyl group (yields are almost quantitative), while their congeners without electron-withdrawing functions are mercurated both at the N-vinyl group and the pyrrole ring.

The (1)H NMR spectra of semiquinalate cobalt complex have been analyzed in a wide range of temperatures. It has been established that the intramolecular exchange requires the obligatory presence of a paramagnetic structure containing non-compensated electron spin localized on the carbon atom of the ligand aromatic ring, the cobalt atom being trivalent. The presence of such a structure leads to the appearance of satellite signals in the NMR spectra because of the superfine interactions., (Copyright © 2012 John Wiley & Sons, Ltd.)

A general efficient route to hitherto inaccessible symmetric and asymmetric meso-CF(3)-BODIPY dyes has been developed. The key stages include the reduction of available 2-trifluoroacetylpyrroles to the corresponding alcohols which are further condensed with pyrroles. The method allows the BODIPY with 3(5)aryl(hetaryl) and 3,5-diaryl(hetaryl) substituents to be readily assembled. The BODIPY dyes synthesized fluoresce (Φ(f) = 0.56-1.00) in the 560-680 nm region.

The (1)H, (13)C and (15)N NMR studies have shown that the E and Z isomers of pyrrole-2-carbaldehyde oxime adopt preferable conformation with the syn orientation of the oxime group with respect to the pyrrole ring. The syn conformation of E and Z isomers of pyrrole-2-carbaldehyde oxime is stabilized by the N-H...N and N-H...O intramolecular hydrogen bonds, respectively. The N-H...N hydrogen bond in the E isomer causes the high-frequency shift of the bridge proton signal by about 1 ppm and increase the (1)J(N, H) coupling by approximately 3 Hz. The bridge proton shows further deshielding and higher increase of the (1)J(N, H) coupling constant due to the strengthening of the N-H...O hydrogen bond in the Z isomer. The MP2 calculations indicate that the syn conformation of E and Z isomers is by approximately 3.5 kcal/mol energetically less favorable than the anti conformation. The calculations of (1)H shielding and (1)J(N, H) coupling in the syn and anti conformations allow the contribution to these constants from the N-H...N and N-H...O hydrogen bondings to be estimated. The NBO analysis suggests that the N-H...N hydrogen bond in the E isomer is a pure electrostatic interaction while the charge transfer from the oxygen lone pair to the antibonding orbital of the N-H bond through the N-H...O hydrogen bond occurs in the Z isomer., (2010 John Wiley & Sons, Ltd.)

In the series of diaminoenones, large high-frequency shifts of the (1)H NMR of the N-H group in the cis-position relative to the carbonyl group suggests strong N-H...O intramolecular hydrogen bonding comprising a six-membered chelate ring. The N-H...O hydrogen bond causes an increase of the (1)J(N,H) coupling constant by 2-4 Hz and high-frequency shift of the (15)N signal by 9-10 ppm despite of the lengthening of the relevant N-H bond. These experimental trends are substantiated by gauge-independent atomic orbital and density functional theory calculations of the shielding and coupling constants in the 3,3-bis(isopropylamino)-1-(aryl)prop-2-en-1-one (12) for conformations with the Z- and E-orientations of the carbonyl group relative to the N-H group. The effects of the N-H...O hydrogen-bond on the NMR parameters are analyzed with the atoms-in-molecules (AIM) and natural bond orbital (NBO) methods. The AIM method indicates a weakening of the N-H...O hydrogen bond as compared with that of 1,1-di(pyrrol-2-yl)-2-formylethene (13) where N-H...O hydrogen bridge establishes a seven-membered chelate ring, and the corresponding (1)J(N,H) coupling constant decreases. The NBO method reveals that the LP(O) --> sigma*(N-H) hyperconjugative interaction is weakened on going from the six-membered chelate ring to the seven-membered one due to a more bent hydrogen bond in the former case. A dominating effect of the N-H bond rehybridization, owing to an electrostatic term in the hydrogen bonding, seems to provide an increase of the (1)J(N,H) value as a consequence of the N-H...O hydrogen bonding in the studied diaminoenones., (2010 John Wiley & Sons, Ltd.)

The reaction of beta-halogeno-beta-polyfluoromethylstyrenes with N,N- or N,O-binucleophiles leads to unexpected fragmentation products (imidazolines) or to heterocyclization giving CF(3)-substituted imidazolidines (N,N-) and oxazolidines (N,O-) depending on aryl substituent. The scope and the reaction mechanism are discussed.

Alkylaryl- and alkylheteroarylketones, including those with condensed aromatic moieties, are readily vinylated with arylacetylenes (KOH/DMSO, 100 degrees C, 1 h) to give regio- and stereoselectively the (E)-beta-gamma-ethylenic ketones ((E)-3-buten-1-ones) in 61-84% yields and with approximately 100% stereoselectivity. This vinylation represents a new C(sp(3))-C(sp(2)) bond-forming reaction of high synthetic potential.

An unexpected facile domino reaction of alpha,beta-acetylenic gamma-hydroxy nitriles with arenecarboxylic acids (Et(3)N, MeCN, 20-25 degrees C, 48 h) affords 4-cyano-3(2H)-furanones in 67-86% yield. The reaction is triggered by the addition of an arenecarboxylic acid to a triple bond, followed by the domino reaction sequence: intramolecular transesterification-enol formation and Claisen condensation of the ketoacetonitrile tautomer with ester functional group.

In the (1)H and (13)C NMR spectra of 1-(2-selenophenyl)-1-alkanone oximes, the (1)H, the (13)C-3 and (13)C-5 signals of the selenophene ring are shifted by 0.1-0.4, 2.5-3.0 and 5.5-6.0 ppm, respectively, to higher frequencies, whereas those of the (13)C-1, (13)C-2 and (13)C-4 carbons are shifted by 4-5, approximately 11 and approximately 1.7 ppm to lower frequencies on going from the E to Z isomer. The (15)N chemical shift of the oximic nitrogen is larger by 13-16 ppm in the E isomer relative to the Z isomer. An extraordinarily large difference (above 90 ppm) between the (77)Se resonance positions is revealed in the studied oxime isomers, the (77)Se peak being shifted to higher frequencies in the Z isomer. The trends in the changes of the measured chemical shifts are well reproduced by the GIAO calculations of the (1)H, (13)C, (15)N and (77)Se shielding constants in the energy-favorable conformation with the syn orientation of the-C=N-O-H group relative to the selenophene ring.

In the acetylenic aldehyde oximes with substituents containing silicon and germanium, the (13)C NMR signal of the C-2 carbon of triple bond is shifted by 3.5 ppm to lower frequency and that of the C-3 carbon is moved by 7 ppm to higher frequency on going from E to Z isomer. A greater low-frequency effect of 5.5 ppm on the C-2 carbon signal and a greater high-frequency effect of 11 ppm on the C-3 carbon signal are observed in the analogous acetylenic ketone oximes. The carbon chemical shift of the C=N bond is larger by 4 ppm in E isomer relative to Z isomer for the aldehyde and ketone oximes. The (29)Si chemical shifts in the silicon containing acetylenic aldehyde and ketone oximes are almost the same for the diverse isomers. The trends in changes of the measured chemical shifts are well reproduced by the gauge-including atomic orbital (GIAO) calculations of the (13)C and (29)Si shielding constants., (2009 John Wiley & Sons, Ltd.)

2-(Benzo[b]thiophene-3-yl)-1-vinylpyrrole has been synthesized directly from 3-acetylbenzo[b]thiophene oxime and acetylene (flow system, KOH-DMSO, 120 degrees C, 5 h) in 68% yield. Devinylation of the synthesized pyrrole (Hg(OAc)(2), NaBH(4), 50 degrees C) led to the corresponding 2-(benzo[b]thiophene-3-yl)pyrrole in 63% yield. Trifluoroacetylation of both the pyrroles with trifluoroacetic anhydride (80 degrees C, 1 h) gave the corresponding 5-trifluoroacetyl pyrroles in 97% and 76% yields, respectively. 2-(Benzo[b]thiophene-3-yl)pyrrole was reacted subsequently with mesityl aldehyde, 2,3-dichloro-5,6-dicyano-1,4-benzoquinone (DDQ), and BF(3)OEt(2) to afford 4,4-difluoro-3,5-di(benzo[b]thiophene-3-yl)-8-mesityl-4-bora-3a,4a-diaza-s-indacene, a representative of the novel BODIPY fluorophore family (BODIPY = 4,4-difluoro-4-bora-3a,4a-diaza-s-indacene), in 34% overall yield. The synthesized pyrroles exhibit promising optical properties (absorption and emission spectra, nonlinear optical (NLO) features), superior to existing analogues. The BODIPY fluorophore displays an intense red-shifted fluorescence emission in CH(2)Cl(2) (625 nm, 0.84 fluorescence quantum yield) that is fully preserved in the solid state.

Theoretical energy-based conformational analysis of bis(2-phenethyl)vinylphosphine and related phosphine oxide, sulfide and selenide synthesized from available secondary phosphine chalcogenides and vinyl sulfoxides is performed at the MP2/6-311G** level to study stereochemical behavior of their (31)P-(1)H spin-spin coupling constants measured experimentally and calculated at different levels of theory. All four title compounds are shown to exist in the equilibrium mixture of two conformers: major planar s-cis and minor orthogonal ones, while (31)P-(1) H spin-spin coupling constants under study are found to demonstrate marked stereochemical dependences with respect to the geometry of the coupling pathways, and to the internal rotation of the vinyl group around the P(X)-C bonds (X = LP, O, S and Se), opening a new guide in the conformational studies of unsaturated phosphines and phosphine chalcogenides., (Copyright (c) 2009 John Wiley & Sons, Ltd.)

According to the (1)H, (13)C and (15)N NMR spectroscopic data and DFT calculations, the E-isomer of 1-vinylpyrrole-2-carbaldehyde adopts preferable conformation with the anti-orientation of the vinyl group relative to the carbaldehyde oxime group and with the syn-arrangement of the carbaldehyde oxime group with reference to the pyrrole ring. This conformation is stabilized by the C-H...N intramolecular hydrogen bond between the alpha-hydrogen of the vinyl group and the oxime group nitrogen, which causes a pronounced high-frequency shift of the alpha-hydrogen signal in (1)H NMR (approximately 0.5 ppm) and an increase in the corresponding one-bond (13)C-(1)H coupling constant (ca 4 Hz). In the Z-isomer, the carbaldehyde oxime group turns to the anti-position with respect to the pyrrole ring. The C-H...O intramolecular hydrogen bond between the H-3 hydrogen of the pyrrole ring and the oxime group oxygen is realized in this case. Due to such hydrogen bonding, the H-3 hydrogen resonance is shifted to a higher frequency by about 1 ppm and the one-bond (13)C-(1)H coupling constant for this proton increases by approximately 5 Hz., (2008 John Wiley & Sons, Ltd.)

First examples of direct vinylation of 1-substituted imidazoles at the 2-position of the imidazole nucleus are described. 1-Substituted imidazoles 1a-e are C(2)-vinylated with 3-phenyl-2-propynenitrile (2) at room temperature without catalyst and solvent to afford 3-(1-organyl-1H-imidazol-2-yl)-3-phenyl-2-propenenitriles 3a-e, mainly (c.a. 95%) as (Z)-isomers, in 56-88% yield. The reaction is likely to involve the zwitterionic intermediates, which prototropically isomerizes to imidazole carbene and eventually undergoes the selective 3,2-shift of the functionalized vinyl substituent.

The N-H...X (X = N,O,S) intramolecular hydrogen bond in the series of 2(2'-heteroaryl)pyrroles and their trifluoroacetyl derivatives is examined by the (1)H, (13)C, (15)N spectroscopy and density functional theory (DFT) calculations. The influence of the hydrogen bond on coupling and shielding constants is considered. It is shown that the N-H...N intramolecular hydrogen bond causes a larger increase in the absolute size of the (1)J(N,H) coupling constant and a larger deshielding of the bridge proton than the N-H...O hydrogen bond. The effect of the N-H...S interaction on the (1)J(N,H) coupling constant and the shielding of the bridge proton is small. The NMR parameter changes in the series of the 2(2'-heteroaryl)pyrroles due to N-H...X hydrogen bond and the series of the 1-vinyl-2-(2'-heteroaryl)-pyrroles due to C-H...X hydrogen bond have the same order. The proximity of the nitrogen, oxygen or sulfur lone pair to the F...H hydrogen bridge quenches the trans-hydrogen bond spin-spin couplings (1h)J(F,H-1) and (2h)J(F,N)., (2008 John Wiley & Sons, Ltd.)

According to the (1)H, (13)C and (15)N NMR spectroscopic data and DFT calculations, bifurcated N--H...N and N--H...O intramolecular hydrogen bond is shown to be present in 2-trifluoroacetyl-5-(2'-pyridyl)-pyrrole. This bifurcated hydrogen bond causes an increase in the absolute size of the (1)J(N,H) coupling constant by about 6 Hz, and the deshielding of the bridge proton by 2 ppm. DFT calculations show that the influence of the N--H...N and N--H...O intramolecular hydrogen bonds on the (1)J(N,H) coupling and proton shielding is almost additive, although the components of the bifurcated hydrogen bond slightly weaken each other. In 2-trifluoroacetyl-5-(2'-pyridyl)-pyrrole, the coupling constants involving the fluorine and the N--H covalent bond nuclei depend dramatically on the spatial position of the pyridine ring. The pyridine ring rotation operates as a quantum switch controlling the spin information transfer between the (19)F and (15)N nuclei, as well as the proton., (Copyright (c) 2007 John Wiley & Sons, Ltd.)

Dynamic NMR of 1-(methylsulfonyl)-3,5-bis(trifluoromethylsulfonyl)-1,3,5-triazinane reveals the existence of three conformers and two dynamic processes: ring inversion and rotation about the N-S bond, both processes having DeltaG(++) = 13.5 kcal/mol. An unprecedented large reverse Perlin effect (J(CHax) > J(CHeq)) was found experimentally and calculated theoretically.

According to the (1)H, (13)C and (15)N NMR spectroscopic data and ab initio calculations, the strong N--H...O intramolecular hydrogen bond in the Z-isomers of 2-(2-acylethenyl)pyrroles causes the decrease in the absolute size of the (1)J(N,H) coupling constant by 2 Hz in CDCl(3) and by 4.5 Hz in DMSO-d(6), the deshielding of the proton and nitrogen by 5-6 and 15 ppm, respectively, and the lengthening of the N--H link by 0.025 A. The N--H...N intramolecular hydrogen bond in the 2(2'-pyridyl)pyrrole leads to the increase of the (1)J(N,H) coupling constant by 3 Hz, the deshielding of the proton by 1.5 ppm and the lengthening of the N--H link by 0.004 A. The C--H...N intramolecular hydrogen bond in the 1-vinyl-2-(2'-pyridyl)-pyrrole results in the increase of the (1)J(C,H) coupling constant by 5 Hz, the deshielding of the proton by 1 ppm and the shortening of the C--H link by 0.003 A. Different behavior of the coupling constants and length of the covalent links under the hydrogen bond influence originate from the different nature of the hydrogen bonding (predominantly covalent or electrostatic), which depends in turn on the geometry of the hydrogen bridge. The Fermi-contact mechanism only is responsible for the increase of the coupling constant in the case of the predominantly electrostatic hydrogen bonding, whereas both Fermi-contact and paramagnetic spin-orbital mechanisms bring about the decrease of coupling constant in the case of the predominantly covalent hydrogen bonding.

Experiments aboard "Spacelab-D1" and "Cosmos-1887" revealed an adverse effect of space flight on Carausius morosus embryos. The main influencing factor for stick insect eggs turned out to be microgravity, while the contribution of HZE particles of cosmic radiation was relatively low. Flight experiments indicated an increased vulnerability of stick insect eggs to microgravity at intermediate stages of development, that could support the "convection" hypothesis.

A number of experiments have been carried out in space flight using Protozoans, cell cultures, plants, flat worms, insects and amphibians. No qualitative, strictly unfavorable effects of microgravity could be detected. Microgravity may only slightly stimulate or inhibit some biological processes.

Among the biological problems that arise in long duration spaceflights, the effects of weightlessness and ionizing radiation appear to be the two main risk factors. Eggs of the stick insect Carausius morosus were exposed to spaceflight conditions during the 12.56 day Biosatellite mission Cosmos 1887. Five different ages were used, representing different sensitivities to radiation and different capacities for regeneration. During spaceflight the eggs continued their development. Already, in the Spacelab D1 mission in 1985, it has been shown that microgravity leads to a reduced hatching rate of eggs exposed during the early steps of development. When the eggs were hit by a heavy ion, a further but not significant reduction of the hatching rate was observed. Hatching was normal for eggs which were exposed on a 1 g reference centrifuge in space. Heavy ion hits caused body anomalies. The combined action of heavy ions and microgravity resulted in an unexpectedly high rate of anomalies. In the experiment on Cosmos 1887 these results were confirmed. Studies on the embryonic development before hatching showed no major difference between flight and ground control specimen, neither in speed of development nor in morphological anomalies. Hatching therefore seems to be the critical point in insect ontogenesis.

Eggs of Carausius morosus were exposed to spaceflight conditions in two spaceflight missions, the German 7 day Spacelab Mission D1 and the Soviet 12.56 day Biosatellite Mission "COSMOS 1887". During spaceflight the eggs continued their development. Eggs of five different ages representing different sensitivity to radiation and different capacity to regeneration were used to investigate the influence of cosmic radiation and/or microgravity on insect development. Using the Biostack concept--eggs in monolayers sandwiched between nuclear track detectors--and the 1 g reference centrifuge of BIORACK in D1 we were able to separate effects of heavy ions of the cosmic radiation from microgravity effects and also from combined effects of these two factors in space. After retrieval, hatching rates, embryonic and larval growth kinetics and anomaly frequencies were determined. Microgravity leads to a reduced hatching rate of eggs exposed in the early stages of development. Hatching was normal in eggs which were exposed on the 1 g reference centrifuge. Hits by heavy ions caused body anomalies. The combined action of heavy ions and microgravity resulted in an unexpectedly high frequency of anomalies. These results obtained from the Spacelab Mission D1, were confirmed in an experiment onboard of COSMOS 1887. In addition to the previous analysis, embryonic development before hatching was followed which showed no major difference between flight and the ground control specimens. Since a reconfirmation of reduced hatching rates was observed in COSMOS 1887, too, the above results suggest some microgravity induced functional impairment of the hatching activity, rather than blockage in embryonic development.