Search

We have prepared and characterized new examples of 5-substituted-1-aza-4,6-dioxabicyclo[3.3.0]octanes (bicyclic amide acetals) and examples of the new heterocyclic system, 5-substituted-1-aza-4-oxa-6-thiabicyclo[3.3.0]octanes (bicyclic amide monothioacetals). Detailed analysis of NMR coupling constants and X-ray structure determination for an example of each class of compound established the stereochemistry and conformation of these ring systems. Key words: bicyclic amide acetals, preparation, coupling constants, X-ray structure.

The 2-siloxysubstituted 2-alkenylcyclopropanecarboxylic acids 10-14 were converted into the corresponding carbonyl azides by treatment with DPPA (diphenyl phosphorazidate) and triethylamine. On heating to 80 [degrees]C these intermediates smoothly furnished azepinone derivatives 19-25 in moderate to good overall yields, which are the result of a sequence of Curtius reaction to cyclopropylisocyanates, [3,3]-sigmatropic rearrangement, and a final proton shift. The primary products may undergo desilylation (to afford azepin-2,5-diones such as 23) or double bond migration (to compound 25). Cyclopropanecarboxylic acids cis-32, cis-34, and cis-35, which bear no 2-siloxy group, similarly provided azepinone derivatives 36-38 in good yields. No influence of the 2-siloxy substituent on the reaction course and rates could be observed in these qualitative studies, which was confirmed by DFT calculations with model compounds 39-42 showing similar reaction barriers for rearrangements of cyclopropylisocyanates with or without a 2-hydroxy group. Key words: vinyl cyclopropanes, carbonylazides, [3.3]-sigmatropic rearrangements, azepinones.

Byline: D.J. Klein (1), O. Ivanciuc (2) Keywords: index C(G); degeneracy; cyclomatic Abstract: A new graph-theoretic cyclicity index C(G) is defined, being motivated in terms of mathematical concepts from the theory of electrical networks. This 'global bond excess conductance' index C(G) then is investigated, with a number of theorems as well as some discussion and numerical investigation. It is found that C(G) typically has less degeneracy than the standard cyclomatic number and has some intuitively appealing features. Author Affiliation: (1) Texas A&amp M University at Galveston, Galveston, TX, 77553-1675, USA (2) Human Biological Chemistry &amp Genetics, University of Texas Medical Branch, Galveston, TX, 77555, USA Article History: Registration Date: 08/10/2004

Results show that borane adducts reveal 'frozen' envelope conformations in solution with BR(sub)3 groups occupying equatorial positions. The H(sup)delta- ....(sup)delta+H contacts in solution are similar to those found in solid state as indicated by the relaxation studies.

The authors review the concept of antiaromaticity in cyclic conjugated organic molecules. The major studies on the cationic, anionic and free radical conjugated cyclic hydrocarbons that do not contain the Huckel pi-electrons have been summarized and discussed.

Results demonstrate that the structural framework of hexamethylenebis(acetamide) (HMBA) involves transfer of anions facilitating octahedrally coordinated 'node' points of HMBA-linked cations and the highly charged counteranions of suitable size and shape in the framework 'voids'.

Research describes the synthesis of tricyclic hybrid cannabinoids using Trost's metallo-ene reaction and a cation-olefin cyclization. Data indicate that cyclization forms the nonaromatic rings with the proper stereochemistry.

The synthesis of oligonucleotides incorporating a cyclouridylic acid derivative, pc3-2'-O-methyluridine, in which the 2'-position is masked with a methyl group at the 5'-terminal site, is described. Results indicate that the cyclic structure significantly contributes to the thermal stabilization of the oligomer duplexes.

A study investigated enzyme activation by cyclodextrins by examining their effect on the serine protease subtilisin suspended in organic solvents and, in particular, on the reaction rates and enzyme enantioselectivity. After finding that the additive methyl-beta-cyclodextrin is very efficient in enhancing enzyme performance, an analysis was conducted on the influence of this additive on enzyme structure and rigidity under different conditions, which led to new mechanistic insights. Experimental findings are presented.

A study extended an X-ray diffraction technique to include the X-ray structure analysis of a 2-benzyl-5-benzylidenecyclopentanone monomer crystal at temperatures ranging from 132 K to 324 K. Chromatographic analysis was independently conducted to confirm the accuracy of the monomer/dimer composition as determined by X-ray diffraction. The reaction rate constant of 2-benzyl-5-benzylidenecyclopentanone photodimerization exhibited a maximum value at equivalent to 200K and an Arrhenius-type decrease under this threshold temperature. Other findings are presented.

A study investigated the geometry dependence of computed rotation angles for a variety of carbocyclic and heterocyclic organic molecules. It was demonstrated that computed optical rotation angles are very sensitive to geometry and that proper geometry sampling is required for reliable prediction of observed rotations. It was also shown that static-field methods are limited to near-resonant absorption and that twisted chains remote from the chiral centers have a profound effect on the rotation angle.

The partitioning of Ca(II), Sr(II), and Ba(II) in solvent extraction systems comprising di-n-octylphosphoric acid (HDOP) and individual stereoisomers of dicyclohexano-18-crown-6 (DCH18C6) in toluene has been investigated at 23(2) [degrees] C. Results of vapor pressure osmometric experiments, continuous variation studies, single- and double-extractant dependencies, and acid dependencies have been used to determine the stoichiometries of the extracted complexes. Extraction of Ca(II) by HDOP alone affords Ca[(H[(DOP).sub.2]).sub.2][multiplied by]HDOP as the extracted species, and no synergism is observed in the presence of DCH18C6, presumably due to the strong complexation of Ca(II) with HDOP and the strained complexes this cation forms with DCH18C6. In the absence of DCH18C6, Sr(II) and Ba(II) are extracted as the M[(H[(DOP).sub.2]).sub.2][multiplied by]2HDOP (M = Sr or Ba) complexes. Upon addition of DCH18C6, the extracted complexes are formulated as M(DCH18C6)[(H[(DOP).sub.2]).sub.2] (M = Sr or Ba), with Ba(II) showing greater synergistic effects than Sr(II). The effectiveness of the DCH18C6 stereoisomers as synergists decreases in the following order: cis-syn-cis > cis-anti-cis > cis-trans > trans-syn-trans > trans-anti-trans. This sequence has been explained by correlating the logarithm of the synergistic adduct formation constants with the ligand strain energies of the DCH18C6 stereoisomers calculated using molecular mechanics methods. Those stereoisomers having the largest strain energies afford the lowest extraction and synergistic adduct formation constants.

Free jet millimeter wave absorption and molecular beam Fourier transform microwave spectroscopy are used in studying the ground-state rotational spectrum of the tetrahydrothiophene***water complex (C4H8S***H2O). It has been determined that the water subunit lies in the CSC bisector plane, being hydrogen-bonded to the sulfur atom of THT. This phenomenon results from the interaction between the electrophilic region of the proton donor and the nucleophilic regions in the acceptor molecule.

Six macrocyclic bis(indolyl)maleimides 1-6 have been prepared as potential fluorine-NMR probes for structural analysis of the catalytic domain of protein kinase C (PKC). These compounds retain a strong resemblance for PKC as shown by low nanomolar IC50's. As long as they are measured by quantitative J correlation in the protein complex, the vicinal proton-fluorine coupling constants correlate to the local macrocycle conformation and can be applied to identify the bound conformation.

The molecular and electronic structures as well as the thermal stability of six-membered phosphazene and heterophosphazene rings have been studied through ab initio molecular orbital calculations at the MP2/6-31G level. Examined were the phosphazene ring (NPCL2)3, the carbophosphazene ring ((NCCl)(NPCl2)2), three thionylphosphazene rings ((NSOX)(NPCl2)2) (X = F, Cl) and ((NSOF)(NPF2)2) and their cations ((NPCl)), (NPCl2)2 (super +), (NC)(NPCl2)2(super +) and (NSO)(NPY2)2(super +) Y = F, Cl.

Radical cyclization in heterocycle synthesis was examined via stannyl cyclization of oxime ethers connected with aldehydes or ketones. The results revealed that treatment with tributyltin hydride in the presence of AIBN enables the stannyl radical addition-cyclization of oxime ethers connected with either an aldehyde or a ketone via a nitrogen atom. Moreover, the radical cyclization was shown to provide a method for preparing both bifunctionalized heterocyclic compounds and adjacently functionalized amino alcohols that carry two quaternary carbons.

The synthesis of potassium- and lithium-containing cyclic clusters has been carried out to study the influence of the alkali metal ion on the properties of the core of the clusters. Synthesizing the potassium clusters turned out to be a failure but lithium clusters were successfully derived. Results show that the metal ion in complexes 1 to 3 tunes the magnetism of the core. Its j value is related to the ionic radius of the guest ion which also determines the exact pattern at the bridging methoxide ligands.

Reaction of cyclohexyl isocyanide with dimethyl acetylenedicarboxylate (DMAD) was found to produce a mixture of compounds such as the cyclopenta[b]pyridine derivatives (14 and 19) and the azaspirononatriene derivative(13) and the azabicyclononatriene (16). Hydrogenation of 13 and 14 produced a mixture of tetrahydro derivatives, 22 and 23. The structures of 13, 14, 16, 19, 22 and 23 were determined unambiguously by X-ray crystallographic analysis.

The synthesis of functionalized enantiomerically pure cis- and trans-2-aminocyclohexanecarboxylic acid derivatives from 4-nitrocyclohexanes has been undertaken. These compounds have the beta-amino ester moiety in a conformationally restricted environment which is a distinct characteristic of peptidomimetics and beta-peptides. The synthetic procedure allows for the derivation of a large variety of cyclic beta-amino acid derivatives with different substituents.

The cycloisomerization of several unsaturated alkyl and aryl iodides by phenyllithium (PhLi) has been studied. Results indicate primary, secondary, tertiary or aryl iodides tethered to a suitable carbon-carbon pi-bond can be converted to cyclic isomers by stirring a solution of the iodide in the presence of a catalytic quantity of PhLi. The isomerization was observed to be dependent on the substrate and involves a three-step cascade mediated by a series of lithium-iodine exchange equilibria.

A series of cyclic ketones with better catalytic properties have been synthesized from the corresponding diacids. The derived ketones are highly effective in catalyzing the oxidation of olefins due to their steric and electronic effects as well as the ring strains. Ketone recovery is greater than 90% and product yield is excellent in the epoxidation of olefins and catalysis of alcohols. The synthesized ketones are robust, recyclable and environment-friendly catalysts that should find wide use in oxidation reactions.

The CH stretching overtone spectra of 1,3- and 1,4-cyclohexadiene were determined in the regions corresponding to Delta v = 2-6. Bands were assigned as overtones of the different nonequivalent CH bonds. Oscillation strengths were computed according to the harmonically coupled anharmonic oscillator local mode model, with ab initio dipole moment functions. The theoretical values were found to be consistent with experimental values of relative intensities within an overtone band.

The far-infrared spectrum of 1,4-disilacyclohexa-2,5-diene revealed a series of four closely spaced bands from 70.5 cm(super -1) due to ring-puckering vibration. Ring-puckering transitions were caused by a single minimum potential energy function, V(cm(super -1)) = 1.23 x 10000x(super 2) + 2.40 x 10000x(super 4), where x is the puckering coordinate. The molecule was found to be planar and less rigid than 1,4-cyclohexadiene.

The structures of phenylcyclopropane (1) and cumene (2) cation radicals were computed by applying both CASSCF and B3LYP computational techniques. Both techniques indicated that 1 adopts a delocalized, bisected structure and that the barrier to phenyl group rotation is quite large (11-14 kcal/mol). On the other hand, the spin and charge in 2 was largely localized in the phenyl ring and there was no strongly preferred ground state conformation.

Initial findings regarding the (4 + 2) cycloaddition of vinylallenes as a stereoselective pathway to tetrasubstituted exocyclic alkenes including very strained ones that are difficult to produce through other methods, are presented. The cycloaddition of several vinylallene with various dienophiles was studied. Results indicate the potential of the intermolecular Diels-Alder reaction of vinylallenes to selectively produce tetrasubstituted exocyclic double bonds on six-membered rings.

The synthesis of medium-ring lactones and ethers by electrophilic heteroatom cyclizations of linear precursors was studied. Findings indicated that medium-ring heterocyclic compounds such as lactones and lactams can be obtained by electrophilic cyclizations when two conditions are met. One condition is that a conformational limitation must be introduced in the chain to at least two vicinal atoms. The other requirement is that the reagent must be highly electrophilic with an unreactive counteranion.

The various methods which have been developed for the synthesis of cyclic oligosaccharides are reviewed. Two primary strategies for the synthesis of cyclic oligosaccharides are the cycloglycosylation of a long-chain linear oligosaccharide derivative with both donor and acceptor functions, and the polycondensation-cyclization or cyclooligomerization of an appropriately functionalized saccharide derivative, corresponding to the smallest repeating unit of a specific target cyclic oligosaccharide.

Techniques for the modification of cyclodextrins, particularly those in which the number and the exact locations of modifications are known and pure compounds with unambiguous structures are derived, are reviewed. Methods involved in primary face modification include monosubstitution at the 6-position of cyclodextrins, disubstitution at the 6-position of cyclodextrins and trisubsitution at the 6-position of cyclodextrins. Techniques involving secondary face modification include monosubstitution at the 2-position of cyclodextrins and disubstitution at the 2-position of cyclodextrins.

Several interesting catalysts can be synthesized using cyclodextrins that perform biomimetic chemistry. Such species can be regarded as artificial enzymes because cyclodextrin is employed to bind a substrate. Reactions involve simple cyclodextrins, cyclodextrins with catalytic or reactive groups, cyclodextrin trimers and tetramers, and noncatalytic biomimesis. The catalysts often have substrate specificity, for molecules that can bind into the cyclodextrin cavity.

Studies involving the mechanically-interlocked compounds of rotaxanes and catenanes which utilize cyclodextrins as one of their ring components are reviewed. The three mechanisms for the formation of rotaxanes are cyclodextrin-based pseudorotaxanes, rotaxanes with stoppers connected by coordinative or ionic bonds and cyclodextrin-containing (2)rotaxanes with covalently bound stoppers. Cyclodextrin-containing polyrotaxanes are either inclusion complexes of polymers with cyclodextrins, linear-chain cyclodextrin-based polyrotaxanes or side-chain cyclodextrin-based polyrotaxanes.

The complexation thermodynamics of cyclodextrins have been investigated utilizing various experimental methods with a large number of guest molecules. However, the accuracy of a large percentage of the thermodynamic data need to be validated. Some of factors which may affect the correlation between the thermodynamic quantities, and the structural and electronic characteristics of the guest molecules include hydrophobicity, the shape-matching and steric effects upon host-guest interaction, and the hydrogen-bonding capability of an aromatic hydroxyl group.

The structures of cyclodextrin complexes in the crystalline state are primarily determined by the intrinsic properties of the macrocycle and crystal packing. The cyclodextrin cavity is very much hydrophobic and has a positive charge. Hence, an anion is easily inserted into the cavity when it is complexed with ionic guests. X-ray structures show that monosubstitution of cyclodextrins have nothing to do with their macrocylic shape. However, methylation of the O-2, O-3 or O-6 hydroxyl groups of the cyclodextrin alters the physical characteristics of the cavity.

Computational chemistry with regards to cyclodextrins was reviewed. Both quantum-based methods and empirical force field techniques were utilized. Cyclodextrins appear to be simple because of their inherent symmetries. However, computational chemistry studies revealed several internal degrees of freedom which make structure prediction difficult. Quantum-based and force field techniques have also been employed to study the structure and dynamics of guest-host complexes.

Ab initio calculations and continuum dielectric methods have been employed to map out the lowest activation free-energy profiles for the alkaline hydrolysis of a five-membered cyclic phosphate, methyl ethylene phosphate (MEP), its acyclic analog, trimethyl phosphate (TMP), and its six-membered ring counterpart, methyl propylene phosphate (MPP). The rate-limiting step for the three reactions was found to be hydroxyl ion attack at the phosphorus atom of the triester. By performing constrained optimization along the reaction coordinate, defined as the phosphorus to incoming hydroxyl oxygen distance, and computing the solvation free energies of the resulting stationary points, the rate-limiting transition states have been relocated in solution. Dihedral ring constraints in the five-membered ring leading to a more solvent-exposed hydroxyl group and, thus, better solvation of the cyclic transition state compared to its acyclic counter-part was found to be the dominant factor governing the rate enhancement of cyclic MEP relative to acyclic TMP alkaline hydrolysis. However, both ground-state destabilization of MEP relative to MPP, due to ring strain, and transition-state stabilization of the five-membered cyclic phosphate transition state relative to its six-membered ring analog, due to the differential location of the transition states in solution, were found to contribute to the enhanced rates of alkaline hydrolysis of five-membered ring MEP compared to six-membered ring MPP.

An analysis of the process of synthesis and characterization of two innovative macrocycles of polyamine which incorporate the 2,9-phenathroline unit in their cyclic structure was presented. Electronic and nuclear magnetic resonance spectroscopies were utilized to determine the ligands synthesis and characterization. Results showed that the innovative macrocyclic ligands behave as ditopic receptors for Cu(II) and both ligands display different binding sites.

A study was conducted on the reactivity of a series of cyclic pentaoxyphosphoranes containing a sulfonyl group. P NMR monitoring of the reactions of the oxyphosphoranes with catechol and 4-nitrocatechol reveals the following order of reactivity: 7 > 8 > 6 > 2 > 5 > >> 1. The findings indicate that the looseness of P-O bonds is a key factor associated with reactivity for these cyclic oxyphosphoranes. Moreover, the order of reactivity for the hexacoordinated geometries parallels the extent of octahedral character: 8 > 6 > 2 > 5.

The photophysics of 9,9'-bianthryl were studied through fluorescence spectroscopy, nanosecond transient-absorption spectroscopy and semiempirical computations. Results provided a consistent picture of the solvent dependence of 9,9-bianthryl photophysics, whose main characteristic is the presence of two distinct deactivation pathways prevailing in the domains of low and high solvent polarity, respectively. Singlet-singlet absorption provided for the first time direct evidence for charge separation in polar solvents based on the equality of the measured decay kinetics with those of fluorescence decay.

The theoretical stability of several isomers of the lanthanum-carbon clusters LaC(sub x)+ was investigated. Included were linear isomers and various types of cyclic and graphitic structures. Geometries and energies of the suggested structures were computed through the B3LYP density functional technique. Cyclic isomers were found to be more stable than linear isomers over a broad range of cluster sizes. Two classes of cyclic isomers were seen which have a pattern of relative thermodynamic stability that correlates to the pattern of cluster intensities in the ion mobility studies of the LaC(sub x)+ clustering process.

A new form of the intermolecular potential that conforms with ab initio structures, interaction energies, interaction forces, intermolecular force constants and dipole derivatives of four different hydrogen-bonded structures of the formic acid dimer, was developed. The ab initio data were based on a scaled HF/6-311++G** force field in nonredundant coordinates and indicate a reassignment of some bands in the spectrum. The model considers charges, charge fluxes, atomic dipoles and van der Waals interactions, and can reproduce intermolecular force constants.

The bonding of pi-electron rich guests exhibiting pseudorotaxane-like geometries with cyclobis(paraquat-p-phenylene) was analyzed to determine the bonding properties of pi-electron deficient bipyrimidinium-based receptors. The binding efficiency of cyclobis(paraquat-p-phenylene) was mediated by edge-to-face T type interactions, hydrogen bonding and pi-pi stacking. The template-directed synthesis of cyclobis(paraquat-p-phenylene) was also enhanced by 1,5-bis(2-(2-methoxyethoxy)ethoxy)naphthalene due to high association binding constants.

The inclusion complex of benzoic acid and beta-cyclodextrins formed by alpha (1-4) linked units of alpha-D-glucopyranose was analyzed by nuclear resonance spectroscopy and molecular modeling. NMR analysis and experimental data on the beta-CD/benzoic acid complex indicated the presence of low association constants due to a fast equilibrium between the complexed and free substrates. Furthermore, NMR analysis indicated the presence of small spectral shifts in H2 and H4 due to the effects of complexation.

Nuclear magnetic resonance (NMR) spectroscopy was utilized to determine the kinetics of dimerization during flouride ion-mediated elimination of trimethylsilyl mesylate from 2-(trimethylsilyl)benzocyclobutenyl-1 mesylate. NMR analysis of benzocyclobutadiene dimerization did not detect the presence of transient intermediates during the transformation of the complex to 2-(trimethylsilyl)benzocyclobutenyl-1 mesylate. Furthermore, the dimerization mechanism involves the formation of a [4+2] dimer that led to the formation of a cyclooctatetraene dimer by ring opening.

The cycloaddition reactivity of bisketenes was analyzed during the reaction of O=C=C(SiMe3)CR=C=O (R = SiMe3 or Ph) with aldehydes. 2,5-Disubstituted 4-(trimethylsilyl)-4-cyclopentene-1,3-diones and 4-substituted 3-(trimethylsilyl)-5-methylene-2(5H)-furanones were formed by the reaction of the bisketenes with diazomethanes. The cycloaddition reactions of the bisketenes proceeded via multiple pathways due to net [2+2], [4+1] and [4+2] processes and tandem processes that led to the formation of spiro products.

The kinetics of aldol reactions of alpha-sulfinylcyclohexanones with different esters was analyzed during the reaction of lithium enolates derived from esters and lactones with 2-(p-tolylsulfinyl)cyclohexanones. The synthetic strategy was characterized by the evolution of the alpha-sulfinylcyclohexanones with complete control of the stereoselectivity in both the carbonyl and enolate prochiral centers. The formation of mixtures of two diastereoisomers depends on the equilibration of the enolates.

A method for the synthesis of optically pure cyclic lipoidal ammonium salts based on the generation of (R)- and (S)-1-pentadecyloxiranes is presented. The synthetic strategy involves the formation of the key intermediates via a four-step synthesis involving the asymmetric dihydroxylation of 1-pentadecene. The optically pure quarternary ammoniun salts are composed of a methyl group that is located on the phosphorus and the long alkyl chain that are cis to each other.

properties of the cyclobutane ring from new energetic nitramines were analyzed to determine its strain energy and the performance of the new energetic materials compared to hexahydro-1,3,5-trinitro-1,3,5-triazine. Analysis of a series of nitramines indicated the unusual thermal and hydrolytic stability of a nitrourea that is soluble in DMF and DMSO. Furthermore, the nitrourea can be utilized to produce 1,2,3,4-cyclobutanetetramine by hydrolysis in dilute sulfuric acid.

A method for the synthesis of 9-methylenetricyclo[4.3.0.03,8]non-4-ene was developed by the reduction of 9-methylenetricyclo[4.3.0.03,8]non-4ene-2-ol and modifications on the tricyclo[3.3.0.03,7]octane skeleton. The formation of the target compound is characterized by the Diels-Alder reaction of methyl ketone with 7,9-dioxa-8-phenylbicyclo[4.3.0]nona-2,4-diene. The products exhibited variable pi splitting due to the interaction of their double bonds with their central six-membered ring.