Olefinic Double Bond Research Articles

E, E, E-1-(4-Arylamino-4-oxo-2-butenoyl)-3,5-bis(arylidene)-4-piperidones: A topographical study of some novel potent cytotoxins

A series of E, E, E-3,5-bis(arylidene)-1-(4-arylamino-4-oxo-2-butenoyl)-4-piperidones 4 (phenylidene) and 5 (4-nitrophenylidene) were prepared in order to explore the structural features of the N-acyl group which affects the cytotoxic potency. Evaluation toward human Molt 4/C8 and CEM T-lymphocytes revealed that many of the IC 50 figures were submicromolar and lower than melphalan. Marked inhibitory potencies toward murine leukemia L1210 cells were also noted. When evaluated against a panel of human tumor cell lines, three representative compounds in series 4 displayed selective toxicity to leukemia and colon cancer cell lines and were significantly more potent than the reference drug melphalan. Molecular modeling of representative compounds in both series 4 and the analogs, in which the configuration of the olefinic double bond was changed from E to Z (series 3), revealed that the torsion angles of the arylidene aryl rings and locations of the terminal arylaminocarbonyl groups may have contributed to the greater cytotoxic properties displayed in 3. Compounds 4c (3,4-dichlorophenylamino), d (4-methylphenylamino) and 5c (3,4-dichlorophenylamino), d (4-methylphenylamino) inhibited the activity of human N-myristoyltransferase by approximately 50% at concentrations of 50–100 μM. The compounds in series 4 and 5 were well tolerated in a short-term toxicity study in mice.

Efficient ring-opening metathesis polymerization of norbornene by vanadium-alkylidenes generated in situ from V(NAr)Cl 2(L) (L: ketimide, aryloxo)

Ring-opening metathesis polymerization (ROMP) of norbornene (NBE) using a catalyst system consisting of V(N-2,6-Me 2C 6H 3)Cl 2(N = C t Bu 2) ( 1a), MeMgBr, and PMe 3 proceeded at a remarkable rate, and the catalytic activities (TON values, TON = turnover number) were low when MeLi or AlMe 3 was used in place of MeMgBr. The activities increased upon increasing the polymerization temperature, and were dependent upon the molar ratio(s) of the catalyst component(s) employed. The resultant polymers prepared at 25 °C under the optimized conditions possessed high molecular weights with unimodal molecular weight distributions ( M n = 1.31–1.66 × 10 6, M w/ M n = 1.40–1.59), and contained a mixture of cis/ trans olefinic double bonds. The effects of anionic donor ligands (L) and substituents on the arylimido ligands on the activity in the ROMP using V(NAr)Cl 2(L) [Ar = 2,6-Me 2C 6H 3 ( 1), 2,6- i Pr 2C 6H 3 ( 2); L = N = C t Bu 2 ( a), N = C(CH 2SiMe 3) t Bu ( b), O-2,6-Me 2C 6H 3 ( c), O-2,6- i Pr 2C 6H 3 ( d), O-2,6- t Bu 2-4-MeC 6H 2 ( e)]-MeMgBr-PMe 3 were explored; both 1a and 1c showed the remarkable activities, and the observed trends were similar to those observed in ethylene polymerization using V(NAr)Cl 2(L)-MAO catalyst systems.

A water soluble nanostructured platinum (0) metal catalyst from platinum carbonyl molecular clusters: Synthesis, characterization and application in the selective hydrogenations of olefins, ketones and aldehydes

High nuclearity platinum carbonyl cluster anions (Chini's clusters) have been used as precursors to prepare a platinum nanocatalyst. The ionic polyelectrolyte poly(diallyldimethylammonium chloride) has been used as the support material for anchoring [Pt 30(CO) 60] 2− via ion-pairing and subsequent stabilization of the nanoparticles. The polymer-supported material has been studied by spectroscopy (NIR, 13C NMR, and IR) and TEM before and after its use as a water soluble hydrogenation catalyst. The nanocatalyst is found to be effective for the chemoselective hydrogenation of olefinic, aldehydic and ketonic double bonds. For most of the substrates isolation of the product and reuse of the catalyst are extremely easy due to the automatic phase separation of the products from the catalyst. The spectral features of the fresh catalyst show retention of the carbonyl ligands and molecular identity of the parent cluster, but after use the carbonyl ligands appear to be lost. TEM of the supported material before and after use as a catalyst shows the presence of platinum nanoparticles with majority (≥70%) of the particles in the range of 2–6 nm. Smaller particles are dominant in the used catalyst and this observation is rationalized on the basis of the known reactivity of Chini's clusters with dihydrogen.

A new route to Vitamin E key-intermediates by olefin cross-metathesis

The ruthenium-catalyzed olefin cross-metathesis has been successfully applied to the synthesis of derivatives of phytyltrimethylhydroquinone. These products, containing a trisubstituted olefinic double bond, are useful intermediates for an alternative route to α-tocopheryl acetate (Vitamin E acetate). Using the second generation Grubbs’ catalyst RuCl 2(C 21H 26N 2)(CHPh)PCy 3 (Cy = cyclohexyl) and Hoveyda–Grubbs’ catalyst RuCl 2(C 21H 26N 2){CH-C 6H 4(O-iPr)-2}, the reactions were performed with various C-allylated and O-allylated derivatives of trimethylhydroquinone-1-acetate as substrates. 2,6,10,14-Tetramethylpentadec-1-ene and derivatives of phytol were employed as olefin partners for the cross-metathesis reactions. The Vitamin E precursors could be prepared in up to 83% isolated yields as mixtures of E and Z stereoisomers.

Ion Exchange Resin Catalyzed Selective Oxidation of Sulfides to Sulfoxides Using Hydrogen Peroxide

An efficient method for the selective oxidation of sulfides to sulfoxides under mild and environmentally safe conditions is achieved using hydrogen peroxide in the presence of Amberlyst 15 and Amberlite IR-400 at room temperature. This procedure can be applied for dialkyl and diaryl sulfides with a variety of functional groups. Functional groups such as hydroxyl, methoxy, amino, aldehyde, and olefinic double bonds remain intact.

Isomers and conformers of two push–pull hydrazines studied by NMR and vibrational spectroscopy and by ab initio calculations

The isomers and conformers of two push–pull hydrazines: 3- N, N-dimethylhydrazino-2-acetyl propenenitrile [(H 3C) 2N NH CH C(CN)(COCH 3)] (DMHAP) and 3- N, N-dimethylhydrazino-2-methylsulfonyl propenenitrile [(H 3C) 2N NH CH C(CN)(SO 2CH 3)] (DMHSP) have been studied experimentally by NMR and vibrational spectroscopy and theoretically by the ab initio calculations at MP2 level in 6-31G** basis set. The IR and Raman spectra of both compounds as a solid and solute in various solvents have been recorded. The NMR spectra were obtained in chloroform and DMSO at room temperature. Both compounds have been prepared by the same way. NMR spectra revealed that DMHAP was prepared as a pure Z-isomer whereas in the case of DMHSP a pure E-isomer was obtained. Due to the low barrier for both compounds practically free isomerisation process occurred in the solutions but in opposite directions. Whereas DMHAP exists in the solid state and in the less polar solvent as Z-isomer, in more polar solvents the appearance of next two conformers of E-isomer was observed. On the contrary DMHSP exists in the solid state and in the more polar solvent as E-isomer only but in less polar solvent the presence of Z-isomer was observed as well. Conformational possibilities of both studied compounds are given by the rotation of dimethylhydrazino group with its anti- or syn-orientation towards the olefinic double bond. Moreover, by the rotation of the acetyl group with Z- and E-orientation of carbonyl bond towards olefinic double bond can occur in DMHAP. Vibrational and NMR spectra revealed the existence of single conformer with intramolecular hydrogen bond for Z-isomer in less polar solvent and next two conformers for E-isomer of DMHAP with Z-orientation of acetyl group and anti and syn orientation of dimethylhydrazine group in more polar solvents. For E-isomer of DMHSP two conformers with anti or syn orientations of dimethylhydrazino group have been also confirmed by NMR spectra in more polar solvents. Additionally the third DMHSP conformer with anti orientation of dimethylhydrazino group originating from Z-isomer was detected in less polar solvents. These experimental findings have been supported by ab initio calculations with solvent effect inclusion.

Mechanistic and Structural Studies of Apoform, Binary, and Ternary Complexes of the Arabidopsis Alkenal Double Bond Reductase At5g16970

In this study, we determined the crystal structures of the apoform, binary, and ternary complexes of the Arabidopsis alkenal double bond reductase encoded by At5g16970. This protein, one of 11 homologues in Arabidopsis thaliana, is most closely related to the Pinus taeda phenylpropenal double bond reductase, involved in, for example, heartwood formation. Both enzymes also have essential roles in plant defense, and can function by catalyzing the reduction of the 7-8-double bond of phenylpropanal substrates, such as p-coumaryl and coniferyl aldehydes in vitro. At5g16970 is also capable of reducing toxic substrates with the same alkenal functionality, such as 4-hydroxy-(2E)-nonenal. The overall fold of At5g16970 is similar to that of the zinc-independent medium chain dehydrogenase/reductase superfamily, the members of which have two domains and are dimeric in nature, i.e. in contrast to their original classification as being zinc-containing oxidoreductases. As provisionally anticipated from the kinetic data, the shape of the binding pocket can readily accommodate p-coumaryl aldehyde, coniferyl aldehyde, 4-hydroxy-(2E)-nonenal, and 2-alkenals. However, the enzyme kinetic data among these potential substrates differ, favoring p-coumaryl aldehyde. Tyr-260 is provisionally proposed to function as a general acid/base for hydride transfer. A catalytic mechanism for this reduction, and its applicability to related important detoxification mammalian proteins, is also proposed.

Atomic contributions to bond dissociation energies in aliphatic hydrocarbons

This paper explores the atomic contributions to the electronic vibrationless bond dissociation enthalpy (BDE) at 0 K of the central C-C bond in straight-chain alkanes (C(n)H(2n+2)) and trans-alkenes (C(n)H(2n)) with an even number of carbon atoms, where n=2, 4, 6, 8. This is achieved using the partitioning of the total molecular energy according to the quantum theory of atoms in molecules by comparing the atomic energies in the intact molecule and its dissociation products. The study is conducted at the MP2(full)6-311++G(d,p) level of theory. It is found that the bulk of the electronic energy necessary to sever a single C-C bond is not supplied by these two carbon atoms (the alpha-carbons) but instead by the atoms directly bonded to them. Thus, the burden of the electronic part of the BDE is primarily carried by the two hydrogens attached to each of the alpha-carbons and by the beta-carbons. The effect drops off rapidly with distance along the hydrocarbon chain. The situation is more complex in the case of the double bond in alkenes, since here the burden is shared between the alpha-carbons as well as the atoms directly bonded to them, namely, again the alpha-hydrogens and the beta-carbons. These observations may lead to a better understanding of the bond dissociation process and should be taken into account when locally dense basis sets are introduced to improve the accuracy of BDE calculations.

(Z)-2-(Cyclohexylidene)-1-azabicyclo[2.2.2]octan-3-one

The reaction of cyclo­hexa­necarboxaldehyde with 1-aza­bicylo[2.2.2]octan-3-one in methano­lic KOH afforded the title compound, C14H21NO. The cyclo­hexane ring adopts a chair conformation and the olefinic double bond has Z geometry.

1-(4-Methylphenylsulfonyl)-5-nitro-2-[(E)-prop-1-enyl]-1H-benzimidazole

In the title compound, C17H15N3O4S, the p-tolyl­sulfonyl group is perpendicular to the benzimidazole fragment, and the propenyl group has a trans configuration about the olefinic double bond. The mol­ecule is stablized by intra­molecular π–π inter­actions.

Preparation of trialkyl-substituted olefins by ruthenium catalyzed cross-metathesis

A summary of the application of ruthenium catalyzed olefin cross-metathesis towards the synthesis of selected natural compounds is given. Recent examples for the preparation of intermediates on the way to tocopherols (vitamin E) are discussed. This group of biologically most important fat-soluble antioxidants is synthetically available by various routes, for which key-building blocks containing trialkyl-substituted olefinic double bonds can now be prepared efficiently (isolated yields up to 83%). The results presented may be of interest for the area of syntheses of isoprenoid natural products in general.

Metathesis of halogenated olefins: A computational study of ruthenium alkylidene mediated reaction pathways

The cross-metathesis reaction pathways of norbornene (NB) with ethylene ( 2a), trans-1,2-difluoro-ethylene ( 2b) and trans-1,2-dichloro-ethylene ( 2c) using (1,3-diphenyl-4,5-dihydroimidazol-2-ylidene) (PCy 3)CI 2Ru CHPh ( I) have been studied at B3LYP/LACVP * level of theory. The calculations show that the Gibbs free activation energy of the metathesis reaction is strongly dependent on the volume of halogene substituents. The calculated Gibbs free activation energies for cross-metathesis of NB with 2a, 2b and 2c are of 10.2, 17.3 and 25.1 kcal/mol, respectively. Strong binding in transition states results in large deformation energies increasing energy barrier. Calculation shows that steric hindrance caused by the atoms directly linked to the olefin double bond is the most important factor influencing the activation energy of the metathesis reaction.

Unimolecular dissociation of protonated trans‐1,4‐diphenyl‐2‐butene‐1,4‐dione in the gas phase: rearrangement versus simple cleavage

Fragmentation mechanisms of trans-1,4-diphenyl-2-butene-1,4-dione were studied using a variety of mass spectrometric techniques. The major fragmentation pathways occur by various rearrangements by loss of H(2)O, CO, H(2)O and CO, and CO(2). The other fragmentation pathways via simple alpha cleavages were also observed but accounted for the minor dissociation channels in both a two-dimensional (2-D) linear ion trap and a quadrupole time-of-flight (Q-TOF) mass spectrometer. The elimination of CO(2) (rather than CH(3)CHO or C(3)H(8)), which was confirmed by an exact mass measurement using the Q-TOF instrument, represented a major fragmentation pathway in the 2-D linear ion trap mass spectrometer. However, the elimination of H(2)O and CO becomes more competitive in the beam-type Q-TOF instrument. The loss of CO is observed in both the MS(2) experiment of m/z 237 and the MS(3) experiment of m/z 219 but via the different transition states. The data suggest that the olefinic double bond in protonated trans-1,4-diphenyl-2-butene-1,4-dione plays a key role in stabilizing the rearrangement transition states and increasing the bond dissociation (cleavage) energy to give favorable rearrangement fragmentation pathways.

A General Process for the Haloamidation of Olefins. Scope and Mechanism

A methodology is described for the addition of a bromine atom and an amide nitrogen in a trans sense to an olefinic double bond. The process, which is illustrated by numerous examples, involves the use of an N-bromoamide and a Lewis acid as a source of Br+ which reacts with the olefin. The amide group is derived from a nitrile and a water molecule which serve as nucleophiles for the overall three-component reaction. The bromoamidation is general for a broad range of olefins and nitriles. This reaction pathway provides access not only to vicinal bromoamides but also to N-acyl aziridines and oxazolines. From these, many types of amines and amino alcohols can be prepared. Examples are provided which delineate diastereo- and regioselectivity preferences. An analogous chloroamidation reaction is also described.

Metal-Catalyzed Cycloisomerization of Enyne Functionalities via a 1,3-Alkylidene Migration

We report a new metal-catalyzed 6-endo-dig cyclization of cis-4,6-dien-1-yn-3-ols, which produces substituted benzene and naphthalene derivatives with structural reorganization. In this process, we observe a 1,3-alkylidene migration via cleavage of the olefin double bond of the starting substrates. The ease and reliability of this cyclization are manifested by its compatibility with a wide array of diverse substrates and several pi-alkyne activators, including PtCl2, Zn(OTf)2, AuCl, and AuCl3.

Polymerization of 1,5-Hexadiene by Half-Titanocenes−MAO Catalyst Systems: Factors Affecting the Selectivity for the Favored Repeated 1,2-Insertion

Polymerization of 1,5-hexadiene (HD) by Cp*TiCl2(OAr) (1, Ar = 2,6-iPr2C6H3), [Me2Si(C5Me4)(NtBu)]TiCl2 (2), [Me2Si(Ind)2]ZrCl2 (3), and Cp2ZrCl2 (4) was explored in the presence of methylaluminoxane (MAO). Both 1 and 3 exhibited the remarkable catalytic activities, and the resultant poly(HD)s were insoluble and possessed a sole glass transition temperature. On the basis of the DSC thermograms, 13C CPMAS spectra, and the dynamic mechanical analysis (DMA) results, it turned out that 1 favored repeated 1,2-insertion rather than cyclization, affording a polymer-containing olefinic double bond (butenyl group) in the side chain with uniform distribution, whereas the polymerization by metallocenes (3, 4) favored cyclization. Linked half-titanocene 2 showed lower catalytic activities with favored repeated insertion, affording high molecular weight poly(HD)s which possessed internal olefinic double bonds. (tBuC5H4)TiCl2(OAr) (5) exhibited lower catalytic activities and favored the repeated insertion; the Cp*-keti...

Synthesis and biological evaluation of acyclic triaryl ( Z)-olefins possessing a 3,5-di- tert-butyl-4-hydroxyphenyl pharmacophore: Dual inhibitors of cyclooxygenases and lipoxygenases

A new class of regioisomeric acyclic triaryl ( Z)-olefins possessing a 3,5-di- tert-butyl-4-hydroxyphenyl (DTBHP) 5-lipoxygenase (5-LOX) pharmacophore that is vicinal to a para-methanesulfonylphenyl cyclooxygenase-2 (COX-2) pharmacophore were designed for evaluation as selective COX-2 and/or 5-LOX inhibitors. The target compounds were synthesized via a highly stereoselective McMurry olefination cross-coupling reaction. This key synthetic step afforded a ( Z):( E) olefinic mixture with a predominance for the ( Z)-olefin stereoisomer. Structure–activity studies for the ( Z)-1-(3,5-di- tert-butyl-4-hydroxyphenyl)-2-(4-methanesulfonylphenyl)-1-phenylalk-1-ene regioisomers showed that COX-1 inhibition decreased, COX-2 inhibition increased, and the COX-2 selectivity index (SI) increased as the chain length of the alkyl substituent attached to the olefinic double bond was increased (Et → n-butyl → n-heptyl). In this group of compounds, inhibition of both 5-LOX and 15-LOX was dependent upon the length of the alkyl substituent with the hex-1-ene compound 9c having a n-butyl substituent exhibiting potent inhibition of both 5-LOX (IC 50 = 0.3 μM) and 15-LOX (IC 50 = 0.8 μM) relative to the inactive (IC 50 > 10 μM) Et and n-heptyl analogs. Compound 9c is of particular interest since it also exhibits a dual inhibitory activity against the COX (COX-1 IC 50 = 3.0 μM, and COX-2 IC 50 = 0.36 μM, COX-2 SI = 8.3) isozymes. A comparison of the relative inhibitory activities of the two groups of regioisomers investigated shows that the regioisomers in which the alkyl substituent is attached to the same olefinic carbon atom (C-2) as the para-methanesulfonylphenyl moiety generally exhibit a greater potency with respect to COX-2 inhibition. The 4-hydroxy substituent in the 3,5-di- tert-butyl-4-hydroxyphenyl moiety is essential for COX and LOX inhibition since 3,5-di- tert-butyl-4-acetoxyphenyl derivatives were inactive inhibitors. These structure–activity data indicate acyclic triaryl ( Z)-olefins constitute a suitable template for the design of dual COX-2/LOX inhibitors.

Mechanism of catalytic asymmetric hydrogenation of 2-formyl-1-methylene-1,2,3,4-tetrahydroisoquinoline using Ru(CH3COO)2[(S)-binap

The mechanism of the asymmetric hydrogenation of 2-acyl-1-alkylidene-1,2,3,4-tetrahydroisoquinolines, the first reported reaction with the Noyori–Takaya Ru(CH3COO)2(binap) complex, has been investigated by means of deuterium labeling, kinetics, and NMR analysis. A series of experiments has revealed that (1) a monohydride-unsaturated mechanism operates involving the initial formation of RuH followed by reaction with the enamide substrate, (2) the hydride transfer from RuH to the olefinic double bond is endothermic and reversible, and (3) the rate is determined in the hydrogenolysis step. This view is consistent with that of proposed for the BINAP–Ru catalyzed Kagan reaction.

Synthesis of Isoxazolino Norbornene Derivatives Containing Sugar Residues by 1,3-Dipolar Cycloaddition and Their Application to the Synthesis of Neoglycopolymers by Living Ring-Opening Metathesis Polymerization

The in situ generation and subsequent cycloaddition of glycosyl nitrile oxides to norbornadiene (NBD) afforded monomeric isoxazolino norbomenes bearing xylose, glucose, and mannose residues in high yields. Ring-opening metathesis polymerization (ROMP) of the norbomene derivatives containing acetyl-protected sugar residues initiated by Ru(CHPh)(Cl) 2 (PCy 3 ) 2 (1) and Mo(CHCMe2Ph)(N-2,6-'Pr2C6H3)(O t Bu)2 (3) proceeded in a living manner with quantitative initiation, affording polymers with narrow molecular weight distributions (M w / M n = 1.11-1.35). The living nature of this polymerization by 1 was further demonstrated by the preparation of diblock copolymers in a precise manner by the sequential polymerization of norbomene and its carbohydrate derivatives. Polymers bearing multiple sugar units bearing free sugars were prepared by the deacetylation of the glycopolymers under basic conditions, and olefinic double bonds in these ROMP polymers were hydrogenated exclusively by p-toluenesulfonhydrazide in chlorobenzene without cleavage of the sugar functionality.

Methoxy-Substituted Stilbenes, Styrenes, and 1-Arylpropenes: Photophysical Properties and Photoadditions of Alcohols

The photochemistry of trans-stilbene and four methoxy-substituted stilbene derivatives has been investigated in a variety of solvents. The fluorescence of all five trans isomers was quenched by 2,2,2-trifluoroethanol (TFE). Upon irradiation of the five substrates in TFE, the products derived from photoaddition of the solvent were detected. Nuclear magnetic resonance spectroscopy of the products formed by irradiation in TFE-OD indicated that the proton and nucleophile are attached to two adjacent atoms of the original alkene double bond. Irradiation of the corresponding methoxy-substituted styrenes and trans-1-arylpropenes in TFE produced the analogous solvent adducts. The photoaddition of TFE proceeded with the general order of reactivity: styrenes > trans-1-arylpropenes > trans-stilbenes. Transient carbocation intermediates were observed following laser flash photolysis of the stilbenes in 1,1,1,3,3,3-hexafluoro-2-propanol (HFIP). The results are consistent with a mechanism that involves photoprotonation of the substrates by TFE or HFIP, followed by nucleophilic trapping of short-lived carbocation intermediates. Compared to the other stilbene derivatives, trans-3,5-dimethoxystilbene displayed a large quantum yield of fluorescence and a low quantum yield of trans-cis isomerization in polar organic solvents. The unique photophysical properties of trans-3,5-dimethoxystilbene are attributed to formation of a highly polarized charge-transfer excited state (mu(e) = 13.2 D).