Heterocycles that contain nitrogen, such as piperidine, pyrrolidine and tropane, are widespread as natural product alkaloids and serve as templates for many bioactive drugs and drug candidates. The intent of this research is to the develop asymmetric syntheses of piperidine-containing syn and anti 1,3-amino alcohols as well as tropinone and tropane-containing derivatives using sulfinimines (N-sulfinyl imines) as precursors for acid-catalyzed cascade cyclizations. Chiral N-sulfinyl b-amino ketones derived from N-sulfinyl b-amino Weinreb amides, serve as novel and direct precursors to syn and anti N-sulfinyl 1,3-amino alcohols through stereoselective reductions. General reduction conditions have been developed for a variety of substrates. This methodology was applied to a concise formal synthesis of the piperidine-containing natural product, (-)-pinidinol, through an intramolecular cascade-cyclization of a masked-oxo N-sulfinyl 1,3-amino alcohol. Special conditions were found for the syn reduction of these substrates. Tropinones and tropanes are structural motifs which encompass many interesting bioactive natural products such as cocaine and scopolamine. The synthesis of these tropinone derivatives, using an asymmetric and intramolecular cascade reaction, allows for facile functionalization of one of the bridgehead carbons. This opens doors to novel derivatives of (-)-cocaine which can be used as potential addiction therapeutics or in new SAR studies of dopamine reuptake transporter blockers. Here a five-membered cyclic imine can be formed through the acid-catalyzed intramolecular cyclization of acyclic ketal-protected N-sulfinyl ketones. After reaction with an acylating agent, the tropinone nucleus can be formed through an intramolecular Mannich reaction of an N-acyl iminium ion. / Chemistry

Three 2, 5-dialkyl-1, 3, 4-triphenyl-2, 4-cyclopentadien-1-ols and 2, 5-di(t-butyl)-1, 3-diphenyl-2, 4-cyclopentadien-1-ol were prepared from their precursor ketones using phenyllithium and Grignard reagent. In general, the phenyllithium reagent produced products faster and in better yield and purity than the Grignard reagent. The alcohols were rearranged thermally to obtain the appropriate ketones and to obtain information about the relative rates of the rearrangement. The rearrangement of the three 2, 5-dialkyl-1, 3, 4-triphenyl-2, 4-cyclopentadien-1-ols were studied kinetically and the results compared with those obtained from similar studies on 1,2,3,4,5-pentaphenyl-2,4-cyclopentadien-1-ol. The alcohols all possessed energies of activation and enthalpies of activation which were essentially identical, these supporting earlier theory that no linear free energy relationship (LFER) exists in these rearrangements and that a purely concerted mechanism exists in these cases. The rate of reaction for 15,16,17—triphenylbicyclo[12.2.1] heptadeca-14,16-dien-1-ol was very much faster than any other studied alcohol. The difference in this rate is thought to be due to the severe steric restraints that are present in this alcohol. The entropy of activation for this strained alcohol was shown. to be much less than for the other alcohols. / Ph. D.

In order to investigate the details of hydrogen bonding and solution molecular conformation of complex alcohols in water, isobaric-isothermal Monte Carlo simulations were carried out on several systems. The solutes investigated were ethanol, ethylene glycol, 1,2-propylene glycol, 1,3-propylene glycol and glycerol. In addition, propane, which does not hydrogen bond but does form water hydrates, was simulated in aqueous solution. The complex alcohol-water systems are very nonideal in their behavior as a function of solute concentration down to very dilute solutions. The water model employed was TIP4P water¹ and the intermolecular potentials employed are of the Jorgensen type² in which the interactions between the molecules are represented by interaction sites usually located on nuclei. The interactions are represented by a sum of Coulomb and Lennard-Jones terms between all intermolecular pairs of sites. Intramolecular rotations in the solute are modeled by torsional potential energy functions taken from ethanol, 1-propanol and 2-propanol for C-O and C-C bond rotations. Quasi-component pair correlation functions were used to analyze the hydrogen bonding. Hydrogen bonds were classified as proton acceptor and proton donor bonds by analyzing the nearest neighbor pair correlation function between hydroxyl oxygen and hydrogen and between solvent-water hydrogen and oxygen. The results obtained for partial molar heats of solution are more negative than the experimental values by 3.0 to 14 kcal/mol. In solution, all solutes reached a contracted molecular geometry with the OH groups generally on one side of the molecule. There is a tendency for the solute OH groups to hydrogen bond with water, with more proton acceptor bonds than proton donor bonds. The water-solute binding energies correlate with experimental measurements of the water-binding properties of the solute. 1. Jorgensen, W.L. et al, J. Chem. Phys., 79, 926 (1983). 2. Jorgensen, W.L., J. Phys Chem., 87, 5304 (1983). / Ph. D.

A series of eight l-substituted-2,3,4,5-tetraphenyl-2,4-cyclopentadien-l-ols were efficiently synthesized by the addition of the appropriate organometallic reagent to tetracyclone. It was determined that the steric and electronic nature of the migrating groups played a predictable role in the [l,5]-sigmatropic rearrangement of these compounds. Electron donating groups increased the rate of migration whereas electron withdrawing substituents were responsible for slowing the migration. Likewise, smaller groups accelerated the rate while bulky groups deterred the migration. Consequently, the experimental evidence supports the originally proposed charge separated transition state. The Michael addition of potassium cyanide to tetracyclone afforded upon protonation a diastereomeric mixture of the cis (kinetic product) and the trans (thermodynamic product) 4-cyano-2,3,4,5-tetraphenyl-2-cyclopenten-l-ones. Finally an efficient synthesis of 2,3,4,5-tetraphenyl-2(1H)-pyridinone (90%) resulted from the acid promoted addition of sodium azide to tetracyclone. The presence of an intermediate bicyclic triazoline eliminated the Schmitt mechanism as a viable reaction pathway. / Ph. D.

The entire dissertation/thesis text is included in the research.pdf file; the official abstract appears in the short.pdf file (which also appears in the research.pdf); a non-technical general description, or public abstract, appears in the public.pdf file. Title from PDF of title page (University of Missouri--Columbia, viewed on April 6, 2010). Vita. Thesis advisor: Shivendra D. Shukla. "August 2008" Includes bibliographical references

Climate change is one of the biggest global threats of the 21st century. Fossil fuels constitute by far the most important energy source for transportation and the different governments are starting to take action to promote the use of cleaner fuels. Biomass-derived fuels are a promising alternative for diversifying fuel sources, reducing fossil fuel dependency and abating greenhouse gas emissions. The research interest has quickly shifted from first-generation biofuels, obtained from food commodities, to second-generation biofuels, produced from non-food resources. The subject of this PhD thesis is the production of second-generation biofuels via thermochemical conversion: biomass is first gasified to synthesis gas, a mixture of mainly H2 and CO; synthesis gas can then be catalytically converted to different fuels. This work summarizes six publications, which are focused on the synthesis gas conversion step. Two processes are principally examined in this summary. The first part of the PhD thesis is devoted to the synthesis of ethanol and higher alcohols, which can be used as fuel or fuel additives. The microemulsion technique is applied in the synthesis of molybdenum-based catalysts, achieving a yield enhancement. Methanol cofeeding is also studied as a way of boosting the production of longer alcohols, but a negative effect is obtained: the main outcome of methanol addition is an increase in methane production. The second part of the PhD thesis addresses wax hydroconversion, an essential upgrading step in the production of middle-distillate fuels via Fischer-Tropsch. Bifunctional catalysts consisting of noble metals supported on silica-alumina are considered. The deactivation of a platinum-based catalyst is investigated, sintering and coking being the main causes of decay. A comparison of platinum and palladium as catalyst metal function is also carried out, obtaining a fairly different catalytic performance of the materials in terms of conversion and selectivity, very likely due to dissimilar hydrogenation power of the metals. Finally, a kinetic model based on the Langmuir-Hinshelwood-Hougen-Watson formalism is proposed to describe the hydroconversion reactions, attaining a good fitting of the experimental data. / Klimatförändringarna är ett av de största globala hoten under det tjugoförsta århundradet. Fossila bränslen utgör den helt dominerande energikällan för transporter och många länder börjar stödja användning av renare bränslen. Bränslen baserade på biomassa är ett lovande alternativ för att diversifiera råvarorna, reducera beroendet av fossila råvaror och undvika växthusgaser. Forskningsintresset har snabbt skiftat från första generationens biobränslen som erhölls från mat-råvaror till andra generationens biobränslen producerade från icke ätbara-råvaror. Ämnet för denna doktorsavhandling är produktion av andra generationens biobränslen via termokemisk omvandling. Biomassa förgasas först till syntesgas, en blandning av i huvudsak vätgas och kolmoxid; syntesgasen kan sedan katalytiskt omvandlas till olika bränslen. Detta arbete sammanfattar sex publikationer som fokuserar på steget för syntesgasomvandling. Två processer är i huvudsak undersökta i denna sammanfattning. Den första delen av doktorsavhandlingen ägnas åt syntes av etanol och högre alkoholer som kan användas som bränsle eller bränsletillsatser. Mikroemulsionstekniken har använts vid framställningen av molybden-baserade katalysatorer, vilket gav en höjning av utbytet. Tillsatsen av metanol har också studerats som ett sätt att försöka få en högre koncentration av högre alkoholer, men en negativ effekt erhölls: huvudeffekten av metanoltillsatsen är en ökad metanproduktion. Den andra delen av doktorsavhandlingen handlar om vätebehandling av vaxer som ett viktigt upparbetningssteg vid framställning av mellandestillat från Fischer-Tropsch processen. Bifunktionella katalysatorer som består av ädelmetaller deponerade på silica-alumina valdes. Deaktiveringen av en platinabaserad katalysator undersöktes. Sintring och koksning var huvudorsakerna till deaktiveringen. En jämförelse mellan platina och palladium som funktionella metaller genomfördes också med resultatet att det var en ganska stor skillnad mellan materialens katalytiska egenskaper vilket gav olika omsättning och selektivitet, mycket sannolikt beroende på olika reaktionsmönster hos metallerna vid vätebehandling. Slutligen föreslås en kinetisk modell baserad på en Langmuir-Hinshelwood-Hougen-Watson modell för att beskriva reaktionerna vid vätebehandling. Denna modell ger en god anpassning till experimentella data. / El cambio climático es una de las mayores amenazas del siglo XXI. Los combustibles fósiles constituyen actualmente la fuente de energía más importante para el transporte, por lo que los diferentes gobiernos están empezando a tomar medidas para promover el uso de combustibles más limpios. Los combustibles derivados de biomasa son una alternativa prometedora para diversificar las fuentes de energía, reducir la dependencia de los combustibles fósiles y disminuir las emisiones de efecto invernadero. Los esfuerzos de los investigadores se han dirigido en los últimos años a los biocombustibles de segunda generación, producidos a partir de recursos no alimenticios. El tema de esta tesis de doctorado es la producción de biocombustibles de segunda generación mediante conversión termoquímica: en primer lugar, la biomasa se gasifica y convierte en gas de síntesis, una mezcla formada mayoritariamente por hidrógeno y monóxido de carbono; a continuación, el gas de síntesis puede transformarse en diversos biocombustibles. Este trabajo resume seis publicaciones, centradas en la etapa de conversión del gas de síntesis. Dos procesos se estudian con mayor detalle. En la primera parte de la tesis se investiga la producción de etanol y alcoholes largos, que pueden ser usados como combustible o como aditivos para combustible. La técnica de microemulsión se aplica en la síntesis de catalizadores basados en molibdeno, consiguiendo un incremento del rendimiento. Además, se introduce metanol en el sistema de reacción para intentar aumentar la producción de alcoholes más largos, pero los efectos obtenidos son negativos: la principal consecuencia es el incremento de la producción de metano. La segunda parte de la tesis estudia la hidroconversión de cera, una etapa esencial en la producción de destilados medios mediante Fischer-Tropsch. Los catalizadores estudiados son bifuncionales y consisten en metales nobles soportados en sílice-alúmina. La desactivación de un catalizador de platino se investiga, siendo la sinterización y la coquización las principales causas del problema. El uso de platino y paladio como componente metálico se compara, obteniendo resultados catalíticos bastante diferentes, tanto en conversión como en selectividad, probablemente debido a su diferente capacidad de hidrogenación. Finalmente, se propone un modelo cinético, basado en el formalismo de Langmuir-Hinshelwood-Hougen-Watson, que consigue un ajuste satisfactorio de los datos experimentales. / <p>QC 20160308</p>

The development and optimisation of conditions for oxidative Wacker-type cyclisations followed by establishing the reaction scope are reported. Building upon the achievements in the field of oxidative Wacker-type reactions that has recently gathered interest, hydroxylamines and hydrazines were converted to isoxazolidines and pyrazolidines respectively. Secondary hydroxylamines cyclised yielding syn-isoxazolidines with excellent diastereoselectivities, whereas secondary hydrazines cyclised yielding anti-pyrazolidines but still maintained a high level of diastereoselectivity. Additionally, an enantioselective variant was explored. Isoxazolidines were successfully transformed to the corresponding 1,3-amino alcohols, which were further converted to amino sugar derivatives.

<p>Allylic amines are important and fundamental building blocks due to their wide-spread occurrence in many natural products and the ability to further functionalize them by transformations on the double bond to generate a diverse range of compounds. Transition-metal catalyzed allylic substitution represents an attractive and efficient approach towards the synthesis of these allylic amines. However, limitations associated with the traditional methods developed for such allylic amination in terms of regiospecificity, atom economy and generality in these transformations, combined with the importance of allylic amination, prompted us to develop novel atom efficient and regiospecific methods for their synthesis.</p><p>A 1:1 mixture of AuCl[P(<italic>t</italic>-Bu)₂<italic>o</italic>-biphenyl] (5 mol %) and AgSbF₆ (5 mol %) catalyzed the intermolecular amination of underivatized allylic alcohols with 1-methyl-2-imidazolidinone and related nucleophiles. The first examples of intermolecular allylic amination was developed that in the case of gamma-unsubstituted and gamma-methyl-substituted allylic alcohols, occurred with high gamma-regioselectivity and <italic>syn</italic>-stereoselectivity.</p><p>A 1:1 mixture of AuCl[P(<italic>t</italic>-Bu)₂<italic>o</italic>-biphenyl] (5 mol %) and AgSbF₆ (5 mol %) also served as a very efficient catalytic system for the intramolecular amination of allylic alcohols with alkylamines to form substituted pyrrolidine and piperidine derivatives. The protocol was effective for a range of secondary as well as primary alkylamines as nucleophiles with different substitutions on the alkyl chain tethering the nucleophile to the allylic alcohol. The method was also extended towards the total synthesis of the naturally occurring alkaloid (S)-(+)-coniine in two steps from the starting (R,Z)-8-(N-benzylamino)-3-octen-2-ol. In addition, gold(I)-catalyzed cyclization of (R,Z)-8-(N-benzylamino)-3-octen-2-ol (96% ee) led to isolation of (R,E)-1-benzyl-2-(1-propenyl)piperidine in 99% yield and 96% ee that established the net syn-addition of the nucleophile with respect to the departing hydroxyl group.</p><p> A bis(gold) phosphine complex (S)-Au₂Cl₂(DTBM-MeOBIPHEP) (2.5 mol %) and AgClO₄ (5 mol %) catalyzed the intramolecular enantioselective dehydrative amination of allylic alcohols with carbamates to form the corresponding substituted pyrrolidines, piperidines, morpholines and piperazines in excellent yields and with up to 95% ee. This general and effective protocol tolerated a range of carbamates as well as sulfonamides as nucleophiles. Cyclization of chiral amino allylic alcohols that possessed a stereogenic homoallylic or hydroxy-bound carbon atom occurred with an overriding catalyst control of asymmetric induction. In addition, stereochemical analysis of the cyclization of a chiral non-racemic secondary allylic alcohol established the net syn-displacement of the hydroxy group by the carbamate nucleophile.</p><p>Alongside allylic amination, a cationic gold(I)-N-heteocyclic carbene complex catalyzed the intermolecular etherification (alkoxylation) of allylic alcohols in a regiospecific and syn-stereoselective fashion. The transformation was highly efficient to utilize unactivated primary and secondary alcohols as nucleophiles with different allylic alcohols to undergo regiospecific etherification. Employment of a chiral nonracemic secondary allylic alcohol, trans-5-(benzyloxy)pent-3-en-2-ol (98% ee) showed a high level of chirality transfer on reaction with n-butanol to the corresponding allylic ether, (2-butoxypent-3-en-1-yloxy)methylbenzene (97% ee) and established the net syn-addition of the alcohol nucleophile with respect to the departing hydroxyl group of the allylic alcohol.</p> / Dissertation

CHDS State/Local / This thesis examines the interoperability of federal law enforcement's Big Six investigative agencies, to include the Federal Bureau of Investigation, Immigration and Customs Enforcement, Drug Enforcement Administration, Alcohol Tobacco Firearms and Explosives, Internal Revenue Service-CID, and the United States Secret Service-Investigations. The main issue is whether, in the post-9/11 environment of transnational and terrorist criminal threats, the current administrative and jurisdictional configuration of the Big Six within three executive epartments with overlapping duties marginalizes the nation's investigative work-product. This discussion includes the establishment of metrics used to gauge the functionality of the Big Six and, thus, to determine whether Negative Characteristics are present that materially affect the "total" mission. Ultimately, the conclusion is drawn that the integration of the Big Six into a single agency, namely the FBI, would better serve the nation's federal investigative law enforcement needs. This leads into the next area of discussion, which is how to integrate the Big Six. Associated with both these topics is an analysis of what the federal investigative mission means and whether it should include a domestic intelligence product. / Special Agent, Department of Homeland Security, ICE

Submitted in fulfillment of the requirements of the degree of Master of Engineering, Durban University of Technology, Durban, South Africa, 2016. / Separation processes in the chemical process industries is dependent on the science of chemical thermodynamics. In the field of chemical separation process engineering, phase equilibrium is a primary area of interest. This is due to separation processes such as distillation and extraction which involves the contacting of different phases for effective separation. The focal point of this research project is the measurement and modeling of binary vapour-liquid equilibrium (VLE) phase data of systems containing ether-alcohol organic compounds. The VLE data were measured with the use of the modified apparatus of Raal and Mühlbauer, (1998). The systems of interest for this research arose from an industrial demand for VLE data for systems containing ether-alcohol organic compounds. This gave rise to the experimental VLE data isotherms being measured for the following binary systems: a) Methyl tert-butyl ether (1) + 1-pentanol (2) at 317.15 and 327.15 K b) Methyl tert-butyl ether (1) + 2, 2, 4-trimethylpentane (2) at 307.15, 317.15 and 327.15K c) 2, 2, 4-Trimethylpentane (1) + 1-pentanol (2) at 350.15, 360.15 and 370.15K d) Diisopropyl ether (1) + 2,2,4-trimethylpentane (2) at 320.15, 330.15 and 340.15K e) Diisopropyl ether (1) + 1-propanol (2) at 320.15, 330.15 and 340.15K f) Diisopropyl ether (1) + 2-butanol (2) at 320.15, 330.15 and 340.15K The data for all the measured binary systems investigated at these temperatures are currently not available in the open source literature found on the internet and in library text resources. The systems were not measured at the same temperatures because certain system isotherm temperatures correlate to a pressures above 1 bar. This pressure of 1 bar is the maximum operating pressure specification of the VLE apparatus used in this project. The experimental VLE data were correlated for model parameters for both the  and methods. For the method, the fugacity coefficients (vapour-phase non-idealities) were tabulated using the virial equation of state and the Hayden-O’Connell correlation (1975); chemical theory and the Nothnagel et al. (1973) correlation method. The activity coefficients (liquid phase non-idealities) were calculated using three local-composition based activity coefficients models: the Wilson (1964) model, the NRTL model (Renon and Prausnitz, 1968); and the UNIQUAC model (Abrams and Prausnitz, 1975). Regarding the direct method, the Soave-Redlich-Kwong (Redlich and Kwong, 1949) and Peng-Robinson (1976) equations of state ii were used with the temperature dependent alpha-function (α) of Mathias and Copeman (1983) with the Wong-Sandler (1992) mixing rule. Thermodynamic consistency testing, which presents an indication of the quality and reliability of the data, was also performed for all the experimental VLE data. All the systems measured showed good thermodynamic consistency for the point test of Van Ness et al. (1973) - the consistency test of choice for this research. This however, was based on the model chosen for the data regression of a particular system. Therefore, the combined method of VLE reduction produced the most favourable results for the NRTL and Wilson models. / M