Showing papers on "Double bond published in 1998"

The 16,17-double bond is needed for irreversible inhibition of human cytochrome p45017alpha by abiraterone (17-(3-pyridyl)androsta-5, 16-dien-3beta-ol) and related steroidal inhibitors.

Abstract: Abiraterone (17-(3-pyridyl)androsta-5,16-dien-3beta-ol, 1) is a potent inhibitor (IC50 4 nM for hydroxylase) of human cytochrome P45017alpha. To assist in studies of the role of the 16,17-double bond in its mechanism of action, the novel 17alpha-(4-pyridyl)androst-5-en-3beta-ol (5) and 17beta-(3-pyridyl)-16,17alpha-epoxy-5alpha-androst-3beta-ol (6) were synthesized. 3beta-Acetoxyetienic acid was converted in three steps into 5 via photolysis of the thiohydroxamic ester 8. Oxidation of an appropriate 16,17-unsaturated precursor (21) with CrO3-pyridine afforded the acetate (23) of 6. Inhibition of the enzyme by 1, the similarly potent 5,6-reduced analogue 19 (IC50 5 nM), and the 4, 16-dien-3-one 26 (IC50 3 nM) and by the less potent (IC50 13 nM) 3,5, 16-triene 25 is slow to occur but is enhanced by preincubation of the inhibitor with the enzyme. Inhibition following preincubation with these compounds is not lessened by dialysis for 24 h, implying irreversible binding to the enzyme. In contrast under these conditions the still potent (IC50 27 nM) 17alpha-(4-pyridyl)androst-5-en-3beta-ol (5) showed partial reversal after 5 h of dialysis and complete reversal of inhibition after 24 h. This behavior was also shown by the less potent 16,17-reduced 3-pyridyl compounds 3 and 24. Further, in contrast to the compounds (1, 19, 25, 26) with the 16,17-double bond, the inhibition of the enzymic reaction was not enhanced by preincubation either with 5 or with the 17beta-pyridyl analogues 3, 4, and 24 which also lack this structural feature. The results show that the 16,17-double bond is necessary for irreversible binding of these pyridyl steroids to cytochrome P45017alpha. However oxidation to an epoxide is probably not involved since epoxide 6 was only a moderately potent inhibitor (IC50 260 nM).

High modulus polymers and composites from plant oils

Abstract: The liquid resins described herein are derived from plant and animal oil triglycerides by suitably functionalizing the triglyceride with chemical groups that render it polymerizable. The triglyceride molecular structure is a combination of various triesters of fatty acids linked together with glycerol. The fatty acid residues are linear carboxylic acids containing from about 4 to about 30 carbon atoms, but preferably from about 14 to about 22 carbons and from about zero to about 4, or preferably from about 2 to 3 carbon-carbon double bonds. As obtained in nature, these double bonds are predominantly in the cis (Z) configuration and, in the case of polyunsaturated acids, not conjugated. The fatty acids derived from triglycerides include, but are not limited to the following: Lauric (C12:0), i.e., 12 carbon atoms long containing zero C=C double bonds, Myristic (C14:0), Palmitic (C16:0), Stearic (C18:0), Oleic (C18:1), Linoleic (C18:2), Linolenic (C18:3), Eicosanoic (C20:0), cis-11-Eicosanoic (C20:1), Docosanoic (C22:0) and cis-13-Docosanoic (C22:1). Typical plant oil triglycerides used for the purpose of this invention contain about 10-20 % saturated, about 20-30 % mono-unsaturated, about 40-60 % di-unsaturated, and about 5-15 % tri-unsaturated fatty acid residues, but other distributions, both narrow and broad, of fatty acid residues can also be used for the thermoset and plastic resins described in this invention.

A New and Highly Efficient Asymmetric Route to Cyclic α-Amino Phosphonates: The First Catalytic Enantioselective Hydrophosphonylation of Cyclic Imines Catalyzed by Chiral Heterobimetallic Lanthanoid Complexes

Abstract: The catalytic and enantioselective hydrophosphonylation of cyclic imines is described for the first time. In addition, we have uncovered a new and highly efficient asymmetric approach to cyclic α-amino phosphonates using thiazolines as the imine model component. The desired pharmaceutically interesting phosphonates 5a−e could be synthesized by a heterobimetallic (R)-LnPB-catalyzed (Ln = lanthanoid metal, P = potassium, B = (R)=binaphthol) hydrophosphonylation of the CN double bond with up to 98% enantiomeric excess and up to 98% chemical yield. Using other types of organometallic catalysts (titanium(IV) complexes), the reaction proceeds with modest enantioselectivity. A detailed investigation concerning the dependence of enantioselectivity and chemical yield, respectively, on a series of reaction parameters (e.g., lanthanoid and alkali metal, solvent, reaction temperature, pressure, and catalytic amount) is reported. An optimized catalytic lanthanoid system “(R)-YbPB (5 mol %)/50 °C/48 h/THF−toluene (1:7)...

Zeolite titanium beta as a selective catalyst in the epoxidation of bulky alkenes

Abstract: The catalytic potential of aluminum-free zeolite titanium beta (Ti-beta) is demonstrated by its facile catalysis of the epoxidation of alkenes with aqueous hydrogen peroxide. The Ti-beta catalyst is compared with TS-1, Ti,Al-beta and Ti-MCM-41 in the epoxidation of 1-octene and norbornene. The advantage of the larger pore size of Ti-beta is illustrated by the facile epoxidation of norbornene in which TS-1 displayed no activity. Rate differences in the epoxidation of terminal or internal alkenes are very small for Ti-beta, indicating that the Ti-site is rather spacious. The catalytic properties of Ti-beta were further investigated in the epoxidation of bulky alkenes such as cyclohexenes, cyclic terpenes and allylic alcohols. Ti-beta was found to catalyze the epoxidation of a wide variety of alkenes with aqueous hydrogen peroxide. In the epoxidation of linear alkenes two trends were observed. The lower alkenes were epoxidized fastest and the internal alkenes were slightly faster than the alkenes with a terminal double bond. The reactivity of methylenecyclohexane is about twice that of 1-methylcyclohexene. Based on electronic effects of substituents the reverse order would be expected, which suggests that here steric effects at the titanium site can play a dominant role in determining reactivity. Pronounced electronic effects were observed to be more important in the epoxidation of allylic alcohols: more highly substituted allylic alcohols are more reactive, whereas the reactivity of the substrates bearing a terminal, unsubstituted double bound is over an order of lower magnitude.

Synthesis, structure, and reactivity of the first kinetically stabilized silanethione

Abstract: Diaryltetrathiasilolanes 2a,b, bearing bulky aryl groups such as 2,4,6-tris[bis(trimethylsilyl)methyl]phenyl (Tbt), mesityl (Mes), and 2,4,6-triisopropylphenyl (Tip), were obtained by thermal reaction of dihydrosilane 3a with elemental sulfur, reaction of highly hindered disilene 4 with sulfur, or reduction of dibromosilane 6 followed by addition of sulfur. The molecular structure of 2a was determined by X-ray crystallographic analysis. Desulfurization of 2a at −78 °C afforded a silicon−sulfur double bond compound (silanethione 7a). Although the formation of 7a was confirmed by various trapping reactions, 7a dimerized at room temperature to give 1,3,2,4-dithiadisiletane 8, whose molecular structure was determined by X-ray crystallographic analysis. Desulfurization of 2b afforded the first stable silanethione, Tbt(Tip)SiS (7b), as yellow crystals, which were thermally stable under inert gas up to its melting point (185−189 °C) and showed λmax (n→π*) at 396 nm and νSiS (Raman) at 724 cm-1. The chemical shif...

Living olefin polymerization processes

Abstract: Processes for the living polymerization of olefin monomers with terminal carbon-carbon double bonds are disclosed. The processes employ initiators that include a metal atom and a ligand having two group 15 atoms and a group 16 atom or three group 15 atoms. The ligand is bonded to the metal atom through two anionic or covalent bonds and a dative bond. The initiators are particularly stable under reaction conditions in the absence of olefin monomer. The processes provide polymers having low polydispersities, especially block copolymers having low polydispersities. It is an additional advantage of these processes that, during block copolymer synthesis, a relatively small amount of homopolymer is formed.

Theoretical Study of the Mechanism of Zeolite-Catalyzed Isomerization Reactions of Linear Butenes

Abstract: Density functional theory is used to study the mechanism of double-bond isomerization and skeletal isomerization of linear butenes catalyzed by a protonated zeolite, which is simulated by a cluster consisting of two Si and one Al tetrahedra. The study includes complete geometry optimization and characterization of reactants, products, reaction intermediates and transition states, and calculation of the activation energies for the different processes involved. It is shown that the double bond isomerization proceeds by a concerted mechanism which does not involve the formation of either ionic or covalent alkoxy intermediates. According to this concerted mechanism, in one step the acid OH group of the zeolite protonates the double bond of adsorbed but-1-ene and the basic neighboring O atom of the cluster abstracts a hydrogen from the olefin, restoring the zeolite active site and yielding adsorbed but-2-ene. However, the mechanism of skeletal isomerization of linear butenes consists of three elementary steps:...

Photochemical Rearrangement of Enediynes: Is a "Photo-Bergman" Cyclization a Possibility?

Abstract: The enediynes 1 and 2 were photolyzed in 2-propanol to yield products akin to those analogous to a thermal Bergman cyclization mechanism. In addition, products resulting from photoreduction of one of the triple bonds of the enediyne functionality are also formed. The product distributions and yields were found to be dependent on the substituents on the triple bonds and on the nature of the double bond; in particular, phenyl substituents on the triple bonds eliminated the photoreduction products, and overall yields were higher when the double bond of the enediyne was of aromatic character. Triplet sensitization studies and laser flash photolysis experiments point toward radical mechanisms taking place during formation of both classes of products, with the photoreduction products forming from the excited triplet state and the cyclized naphthyl products forming from either the singlet or the triplet states. For the cyclization reaction, a substituted 1,4-dehydronaphthalene biradical species, structurally ide...

Non-volatile phenylglyoxalic esters

Abstract: Compounds of formula (I) in which R1 and R2 independently of one another are, for example, a group of formula (II); R3, R4, R5, R6 and R7 independently of one another are, for example, hydrogen, C1-C12alkyl, OR8, SR9, NR10R11, halogen or phenyl; R8, R9, R10, R11 independently of one another are, for example, hydrogen or C1-C12alkyl; R12 is, for example, C1-C8alkyl; R13 is, for example, C1-C12alkyl; R14 is, for example, hydrogen; Y is C1-C12alkylene, C4-C8alkenylene, C4-C8alkynylene or cyclohexylene, or is phenylene or C4-C40alkylene interrupted one or more times by -O-, -S- or -NR15-, or Y is a group of the formula (III), (IV), (V), (VI), (VII), (VIII), (IX), (X) or (XI); Y1 is as defined for Y with the exception of formula (V); R15 is hydrogen, C1-C12alkyl or phenyl; and R16 is hydrogen, CH2OH or C1-C4alkyl; and mixtures of these compounds with further photoinitiators are suitable for photopolymerizing compounds having ethylenically unsaturated double bonds.

The formation of heteroleptic carbene homologues by ligand exchange : synthesis of the first plumbanediyl dimer

Abstract: Double bond—yes or no? The centrosymmetic trans-bent dimers 1 and 2 crystallize from a mixture of the corresponding monomeric carbene analogues Rf2Sn/Sn(SiR3)2 or Rf2Sn/Pb(SiR3)2. The question whether the plumbanediyl dimer 2 contains a double bond and therefore becomes the last member of the series of ethene homologues R4E2 (E = Si, Ge, Pb) remains open. R = SiMe3, Rf = 2,4,6-(CF3)3C6H2.

Hydrocyanation processes and multidentate phosphite ligand and nickel catalyst compositions therefor

Abstract: A process for hydrocyanation of an aliphatic monoethylenically unsaturated compound, in which the ethylenic double bond is not conjugated to any other unsaturated group in the molecule, or a monoethylenically unsaturated compound in which the ethylenic double bond is conjugated to an ester group, which process uses a catalyst composition comprising a zero-valent nickel and a multidentate phosphite ligand in the presence of a Lewis acid promoter.

Oxidative crosslinking of alkyd resins studied with mass spectrometry and NMR using model compounds

Abstract: The crosslinking of alkyd resins has been studied using ethyl linoleate and methyl ricinoate as model compounds. With quantitative13C NMR it was established that ether- and peroxy-crosslinks were formed in roughly equal amounts. Double bonds reacted to give epoxides, endoperoxides, and β-scission into aldehydes. Using SIMS it was established that dimers through pentamers were formed having included several oxygen atoms. After reduction of peroxide (crosslinks) with stannous chloride, the higher oxygen homologues decreased. In the NMR spectrum of the reduced material, peroxide and epoxide signals completely disappeared. High resolution electrospray ionization mass spectra (ESI-MS) yielded evidence regarding the crosslink mechanism. The non-conjugated linoleic acid was found to crosslink by combination of radicals: dimers were having masses 2(M-1). The conjugated linoleic acid crosslinked by addition of radicals to the double bond and disproportionation, yielding masses 2M as well. (M = mass of ethyl linoleate or methyl ricinoate, respectively, including several oxygen atoms.) EIS-MS of oligomers after isotopic exchange enabled estimation of OH and OOH groups.

An Infrared Spectroscopic Study of Acetone and Mesityl Oxide Adsorption on Acid Catalyst

Abstract: The interactions between the acetone carbonyl and the carbonyl and double bond of mesityl oxide and the Bronsted and Lewis acid sites of acid catalysts have been studied by Fourier Transform infrared (FTIR) spectroscopy. The acetone carbonyl interactions with bridging acidic OH and with bridging weakly acidic OH can be distinguished from one another semiquantitatively. This was substantiated by a quasi one-to-one relation between the number of bridging OH in a cluster Si−nAl containing only one Al and the number of strongly hydrogen-bonded acetone. The distinction between Bronsted and Lewis sites is not easy with acetone, while it is with mesityl oxide. The system acetone−mesityl oxide adsorbed an acid catalysts is rather unique, since the reagent and the reaction product of the condensation reaction are qualitatively and quantitatively detectable by FTIR spectroscopy. The quantitative determination of the coverage of the acid sites by the reagent and the reaction product was a prerequisite to the study o...

Diiodotetrasupersilylcyclotetrasilene (tBu3Si)4Si4I2—A Molecule Containing an Unsaturated Si4 Ring

Abstract: The red-orange tetrasilacyclobutene 1 (R*=SitBu3 ) is formed quantitatively by the reaction of tetrasilatetrahedrane 2 and iodine. Surprisingly, water and methanol do not react with 1 with addition to the Si-Si double bond, but instead with replacement of the silicon-bound iodine atoms with oxygen or the methoxy group, respectively. The substitutions possibly proceed by dissociative activation via intermediate 3.

Conformations of Chiral α,β-Unsaturated Sulfoxides and Their Complexes with Lewis Acids. An ab Initio Study

Abstract: The rotational potential energy surface (PES) of methyl vinyl sulfoxide (1) was calculated at MP2/6-31+G*, B3LYP/6-311+G*, B3LYP/3-21G(*), MP2/3-21G(*), PM3, and AM1. All ab initio methods gave two conformations: one with the S−O bond (a) syncoplanar to the carbon−carbon double bond and one with the lone pair in plane (b); the first one is preferred by 1.7 kcal mol-1. The energy difference is strongly basis set dependent: B3LYP/6-311+G* offers the best compromise. Semiempirical methods give a qualitatively different rotational PES. Whereas the effect methyl group in the E-position is small, Z-substitution leads to destabilization of conformation a through sterical interaction, so that conformation b is preferred by 0.4 kcal mol-1. Electron-withdrawing substituents such as ester or keto groups in the α-position destabilize conformations c and d where the lone pair is syncoplanar to the CC double bond, so that the syncoplanar orientation of the S−O bond is favored by ca. 5 kcal mol-1, depending on the sub...

The Transition Metal ION Chemistry of Linked Macrocyclic Ligands

Abstract: Publisher Summary This chapter discusses the transition metal ion chemistry of linked macrocyclic ligands. Linked macrocyclic systems are capable of simultaneously binding two or more metal ions, thus yielding the prospect of generating unusual electronic, catalytic, and/or redox properties (associated with the proximity of the metal centers). Heterometallic complexes are also a possibility and if rigid spacers are employed then the distance between metal centers can be tuned. Steric interaction between the methyl substituents surrounding the double bond linkage joining the rings results in this link being quite strained. As a consequence, the respective double bonds in the dimer are almost completely localized. The visible spectra of each of the new (dinuclear) complexes confirmed the presence of a square planar coordination environment for the Ni (II) ions. A small yield of the linked cyclam derivative was identified as a minor product in the Ni(II) template synthesis of cyclam.

High-Level Computational Study of the Stereoelectronic Effects of Substituents on Alkene Epoxidations with Peroxyformic Acid

Abstract: The epoxidations of propene and isobutene with peroxyformic acid proceed by a concerted pathway via slightly unsymmetrical transition structures where the differences in the bond distances between the double-bond carbons and the spiro oxygen are only 0.021 and 0.044 A at the QCISD/6-31G* level. In contrast, the more polarizable nature of the carbon−carbon double bond of α,β-unsaturated systems results in an unsymmetrical transition structure for the epoxidation of 1,3-butadiene with an order of magnitude difference in the carbon−oxygen bond distances of 0.305 A at the QCISD/6-31G* level. A highly unsymmetrical transition structure has been also found at this level for the epoxidation of acrylonitrile. Notwithstanding the difference in the extent of asymmetry of the transition structures, both epoxidations of methyl-substituted alkenes and such α,β-unsaturated systems as 1,3-butadiene and acrylonitrile with peroxyformic acid follow a concerted asynchronous pathway. An unsymmetrical transition structure for...

Efficient Preparation of Functionalized (E,Z) Dienes Using Acetylene as the Building Block

Abstract: Received March 10, 1998 (E,Z)-Diene structures spread widely in the scope of not only important bioactive natural products,1 but also useful chemicals applicable in the perfume industry and other fields.2 The characteristic (E,Z) double-bond configuration of the molecules, which is usually responsible for the special functions,3 meanwhile poses great challenges for their stereoselective synthesis. The advent solutions mainly reside in the range of Wittig-type olefination4 or transitionmetal-mediated coupling reactions of deliberately functionalized precursors.5 While the methods of both classes have been successfully used in a good number of laboratory syntheses, their intrinsic drawback of low atom economy causing poor mass conversion greatly limited their application in large-scale preparations. A naive retrosynthetic analysis suggests that two acetylene molecules can be added together to form the (E,Z) double bonds, provided the addition reaction occurs in a stereoselective manner. Indeed, from the well-documented organometallic elementary reactions, we could infer that a tandem addition incorporating two molecules of acetylene may lead to (E,Z)-conjugated diene structure (Scheme 1). In this sequence, the stereochemical requirements of trans-addition and cis-insertion (carbometalation) helped to establish the otherwise hard-to-access conjugate (E,Z) doublebond configuration. Despite the extreme efficiency this sequence may bring about, there was only one precedent in the literature realizing such a concept: The Pd-catalyzed cotrimerization reaction of acetylene and allyl chloride developed by Kaneda et al.,6 but the reaction gave in low yield a mixture of codimer and cotrimer and the stereochemistry of the cotrimer was not established (Scheme 2). Recently, we have developed the facile synthesis of γ,δunsaturated carbonyl compounds in which a halide-assisted protonolysis efficiently recycles Pd(II)-catalytic species,7 thus effecting the tandem addition reaction of halide, an alkyne, and an R,â-unsaturated carbonyl. In this context, we attempted the reaction of acetylene with R,â-unsaturated electron-deficient alkenes in the presence of palladium catalyst to explore the possibility of developing new methods for (E,Z)-diene synthesis. Acrolein was first selected to react with acetylene under the catalysis of Pd(OAc)2. We first used acrolein as solvent to avoid the excessive polymerization of acetylene. When acetylene was passed through a mixture of acrolein 1 (20 mL), HOAc (50 mmol), Pd(OAc)2 (0.5 mmol), and LiBr (5 mmol) at 15 °C for 2 h, rapid formation of palladium black was observed. The reaction afforded the expected dienal 2a together with the R,â-unsaturated trienal 3a in 220% and 80% yield, respectively (yields are calculated on the basis of Pd(OAc)2) (Scheme 3).8 Pure 2a could be purified carefully by column chromatography. The geometry of the two double bonds in 2a was established by the coupling constants in 1H NMR between related vinylic protons. Thus, J(H6-H7) of 14 Hz and J(H4-H5) of 11 Hz manifest the (6E) and (4Z) double bonds, respectively. Further evidence from NOESY studies of the chloro derivative 2b unambiguously shows the (E,Z)-configuration of the molecule.9 The formation of 2a and 3a could be explained by Scheme 4, which also rationalizes the stereoselectivity. First, transhalopalladation of acetylene gives the (E)-vinylpalladium intermediate 4, which is inserted by a second molecule of acetylene to form (E,Z)-dienylpalladium 5; after the insertion of acrolein, the (2-oxoalkyl)palladium intermediate undergoes protonolysis (path a) or â-hydride elimination (path b) to afford 2a or 3a, respectively. Our previous studies reveal that excess coordinating halide inhibits â-H elimination and facilitates protonolysis in acidic conditions.7 A number of reaction conditions were screened. The results were summarized in Table 1. Preliminary results showed that polar solvents, high acetylene and halide concentration, and low temperature favor the yield of 2a. In most cases, using HOAc as a solvent and passing acetylene rapidly into the reaction mixture, 2a was isolated as the main product after chromatography (entries 3-5, Table 1). A codimerization byproduct of acetylene and acrolein,10 which could be removed after purification, could be detected in some cases by 1H NMR spectra. We found that the LiBr-Pd(OAc)2 ratio has a great impact on the reaction: when the LiBr-Pd(OAc)2 ratio was in(1) (a) Lalonde, R. T.; Wong, C. F.; Hofstead, S. J.; Morris, C. D.; Gardner, L. C. J. Chem. Ecol. 1980, 6, 35. (b) Baker, R.; Bradshaw, J. W. S. In Aliphatic and Related Natural Product Chemistry; Gunstone, F. D., Ed.; Specialist Periodical Report; Royal Society of Chemistry: London, 1983; Vol. 3. (2) Goldbach, M.; Jakel, E.; Schneider, M. P. J. Chem. Soc., Chem. Commun. 1987, 1434. (3) (a) Bergmann E. D. In Pesticide Chemistry, Vol. 1, Insecticides; Tahori, A. S., Ed.; Gordon and Breach: New York, 1972; p 1. (b) Rossi, R.; Carpita, A.; Quirici, M. G.; Gaudenzi, M. L. Tetrahedron 1982, 35, 631. (c) Stille, J. K.; Simpson, J. H. J. Am. Chem. Soc. 1987, 109, 2138. (4) Crombie, L.; Fisher, D. Tetrahedron Lett. 1985, 26, 2481. (5) Alami, M.; Gueugnot, S.; Domingues, E.; Linstrumelle, G. Tetrahedron 1995, 51, 1209. (6) Kaneda, K.; Uchiyama, T.; Fujuwara, Y.; Imanaka, T.; Taranash, S. J. Org. Chem. 1979, 44, 55. (7) (a) Wang, Z.; Lu, X. Chem. Commun. 1996, 535. (b) Wang, Z.; Lu, X. J. Org. Chem. 1996, 61, 2254. (8) The ratio of 2a to 3a was determined by the 1H NMR spectra of the product mixture. The presence of the trienal product 3a was further supported by GC-MS analysis and UV spectra. (9) There is a strong NOE effect between H6 and H3 and no cross-peak between H5 and H3. Scheme 1