Exam 2000

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Exam 2001 pdf

Exam questions and solutions in PDF

Exam 1998

Exam questions and solutions in LaTex

Exam 2001

Exam questions and solutions in LaTex

Exam 1998 pdf

Exam questions and solutions in PDF

Rhodium(I) catalyzed [2+2+2] cycloaddition reactions: experimental and theoretical studies

The [2+2+2] cycloaddition reaction involves the formation of three carbon-carbon bonds in one single step using alkynes, alkenes, nitriles, carbonyls and other unsaturated reagents as reactants. This is one of the most elegant methods for the construction of polycyclic aromatic compounds and heteroaromatic, which have important academic and industrial uses. The thesis is divided into ten chapters including six related publications. The first study based on the Wilkinson’s catalyst, RhCl(PPh3)3, compares the reaction mechanism of the [2+2+2] cycloaddition process of acetylene with the cycloaddition obtained for the model of the complex, RhCl(PH3)3. In an attempt to reduce computational costs in DFT studies, this research project aimed to substitute PPh3 ligands for PH3, despite the electronic and steric effects produced by PPh3 ligands being significantly different to those created by PH3 ones. In this first study, detailed theoretical calculations were performed to determine the reaction mechanism of the two complexes. Despite some differences being detected, it was found that modelling PPh3 by PH3 in the catalyst helps to reduce the computational cost significantly while at the same time providing qualitatively acceptable results. Taking into account the results obtained in this earlier study, the model of the Wilkinson’s catalyst, RhCl(PH3)3, was applied to study different [2+2+2] cycloaddition reactions with unsaturated systems conducted in the laboratory. Our research group found that in the case of totally closed systems, specifically 15- and 25-membered azamacrocycles can afford benzenic compounds, except in the case of 20-membered azamacrocycle (20-MAA) which was inactive with the Wilkinson’s catalyst. In this study, theoretical calculations allowed to determine the origin of the different reactivity of the 20-MAA, where it was found that the activation barrier of the oxidative addition of two alkynes is higher than those obtained for the 15- and 25-membered macrocycles. This barrier was attributed primarily to the interaction energy, which corresponds to the energy that is released when the two deformed reagents interact in the transition state. The main factor that helped to provide an explanation to the different reactivity observed was that the 20-MAA had a more stable and delocalized HOMO orbital in the oxidative addition step. Moreover, we observed that the formation of a strained ten-membered ring during the cycloaddition of 20-MAA presents significant steric hindrance. Furthermore, in Chapter 5, an electrochemical study is presented in collaboration with Prof. Anny Jutand from Paris. This work allowed studying the main steps of the catalytic cycle of the [2+2+2] cycloaddition reaction between diynes with a monoalkyne. First kinetic data were obtained of the [2+2+2] cycloaddition process catalyzed by the Wilkinson’s catalyst, where it was observed that the rate-determining step of the reaction can change depending on the structure of the starting reagents. In the case of the [2+2+2] cycloaddition reaction involving two alkynes and one alkene in the same molecule (enediynes), it is well known that the oxidative coupling may occur between two alkynes giving the corresponding metallacyclopentadiene, or between one alkyne and the alkene affording the metallacyclopentene complex. Wilkinson’s model was used in DFT calculations to analyze the different factors that may influence in the reaction mechanism. Here it was observed that the cyclic enediynes always prefer the oxidative coupling between two alkynes moieties, while the acyclic cases have different preferences depending on the linker and the substituents used in the alkynes. Moreover, the Wilkinson’s model was used to explain the experimental results achieved in Chapter 7 where the [2+2+2] cycloaddition reaction of enediynes is studied varying the position of the double bond in the starting reagent. It was observed that enediynes type yne-ene-yne preferred the standard [2+2+2] cycloaddition reaction, while enediynes type yne-yne-ene suffered β-hydride elimination followed a reductive elimination of Wilkinson’s catalyst giving cyclohexadiene compounds, which are isomers from those that would be obtained through standard [2+2+2] cycloaddition reactions. Finally, the last chapter of this thesis is based on the use of DFT calculations to determine the reaction mechanism when the macrocycles are treated with transition metals that are inactive to the [2+2+2] cycloaddition reaction, but which are thermally active leading to new polycyclic compounds. Thus, a domino process was described combining an ene reaction and a Diels-Alder cycloaddition.

Flavour characterization of fresh and processed pennywort (Centella asiatica L.) juices

The flavour characteristics of fresh and processed pennywort juices treated by pasteurization, sterilization and high pressure processing (HPP) were investigated by using solid-phase micro-extraction combined with gas chromatography-mass spectrometry. Sesquiterpene hydrocarbons comprised the major class of volatile components present and the juices had a characteristic smell due to the presence of volatile compounds including β-caryophyllene, humulene, E-β-farnesene, α-copaene, alloaromadendrene and β-elemene. All processing operations caused a reduction in the total volatile concentration, but HPP caused more volatile acyclic alcohols, aldehydes and oxygenated monoterpenoids to be retained than pasteurization and sterilization. Ketones were not present in fresh pennywort juice, but 2-butanone and 3-nonen-2-one were generated in all processed juices, and 2-nonanone and 2-hexanone were present in pasteurized and sterilized juices. Other chemical changes including isomerization were also reduced by HPP compared to pasteurization, and sterilization.

Notations and conventions in molecular spectroscopy: part 1. General spectroscopic notation

The field of Molecular Spectroscopy was surveyed in order to determine a set of conventions and symbols which are in common use in the spectroscopic literature. This document, which is Part I in a series, establishes the notations and conventions used for general spectroscopic notations and deals with quantum mechanics, quantum numbers (vibrational states, angular momentum and energy levels), spectroscopic transitions, and miscellaneous notations (e.g. spectroscopic terms). Further parts will follow, dealing inter alia with symmetry notation, permutation and permutation-inversion symmetry notation, vibration-rotation spectroscopy and electronic spectroscopy.

Notations and conventions in molecular spectroscopy: part 2. Symmetry notation

The field of Molecular Spectroscopy was surveyed in order to determine a set of conventions and symbols which are in common use in the spectroscopic literature. This document, which is Part 2 in a series, establishes the notations and conventions used for the description of symmetry in rigid molecules, using the Schoenflies notation. It deals firstly with the symmetry operators of the molecular point groups (also drawing attention to the difference between symmetry operators and elements). The conventions and notations of the molecular point groups are then established, followed by those of the representations of these groups as used in molecular spectroscopy. Further parts will follow, dealing inter alia with permutation and permutation-inversion symmetry notation, vibration-rotation spectroscopy and electronic spectroscopy.

Sequentially testing for a gene-drug interaction in a genomewide analysis

Assaying a large number of genetic markers from patients in clinical trials is now possible in order to tailor drugs with respect to efficacy. The statistical methodology for analysing such massive data sets is challenging. The most popular type of statistical analysis is to use a univariate test for each genetic marker, once all the data from a clinical study have been collected. This paper presents a sequential method for conducting an omnibus test for detecting gene-drug interactions across the genome, thus allowing informed decisions at the earliest opportunity and overcoming the multiple testing problems from conducting many univariate tests. We first propose an omnibus test for a fixed sample size. This test is based on combining F-statistics that test for an interaction between treatment and the individual single nucleotide polymorphism (SNP). As SNPs tend to be correlated, we use permutations to calculate a global p-value. We extend our omnibus test to the sequential case. In order to control the type I error rate, we propose a sequential method that uses permutations to obtain the stopping boundaries. The results of a simulation study show that the sequential permutation method is more powerful than alternative sequential methods that control the type I error rate, such as the inverse-normal method. The proposed method is flexible as we do not need to assume a mode of inheritance and can also adjust for confounding factors. An application to real clinical data illustrates that the method is computationally feasible for a large number of SNPs. Copyright (c) 2007 John Wiley & Sons, Ltd.

Quantum mechanics studies of the tautomers of dlhydrodiacetylformoin, an important Maillard intermediate and the synthesis of furaneol

Conformational analyses have been carried out on the acyclic and cyclic forms of dihydrodiacetylformoin, an important Maillard intermediate and precursor for furaneol. For the acyclic forms, the 2,5-dicarbonyl isomers have the lowest energy, while for the cyclic forms, the 3-carbonyl are favoured over the 4-carbonyl isomers. The likely path for cyclisation is investigated and it is shown that the favoured path is dependent upon the relative chiralities of the carbon atoms and in particular that the reaction proceeds more readily if C2 and C3 have different chiralities. After cyclisation, the reaction path to produce furaneol proceeds via the loss of a water molecule. This reaction has been studied with a model including two water molecules and a hydroxide anion and shows relatively low-energy barriers. (C) 2008 Published by Elsevier B.V.

The role of terminal tyrosine residues in the formation of tripeptide nanotubes: a crystallographic insight

Terminally protected acyclic tripeptides containing tyrosine residues at both termini self-assemble into nanotubes in crystals through various non-covalent interactions including intermolecular hydrogen bonds. The nanotube has an average internal diameter of 5 angstrom (0.5 nm) and the tubular ensemble is developed through the hydrogen-bonded phenolic-OH side chains of tyrosine (Tyr) residues [Org. Lett. 2004, 6, 4463]. We have synthesized and studied several tripeptides 3-6 to probe the role of tyrosine residues in nanotube structure formation. These peptides either have only one Tyr residue at N- or C-termini or they have one or two terminally located phenylalanine (Phe) residues. These tripeptides failed to form any kind of nanotubular structure in the solid state. Single crystal X-ray diffraction studies of these peptides 3-6 clearly demonstrate that substitution of any one of the terminal Tyr residues in the Boc-Tyr-X-Tyr-OMe (X=VaI or Ile) sequence disrupts the formation of the nanotubular structure indicating that the presence of two terminally located Tyr residues is vital for nanotube formation. (c) 2006 Elsevier Ltd. All rights reserved.

A new motif in the formation of peptide nanotubes: the crystallographic signature

Terminally protected acyclic tripeptides Boc-Tyr(1)-Val(2)-Tyr(3)-OMe 1 and Boc-Tyr(1)-lle(2)-Tyr(3)-OMe 2 self-assemble into nanotubes in crystals through various noncovalent interactions with an average internal diameter of 5 Angstrom (0.5 nm), and the tubular ensemble is developed through the hydrogen-bonded side chains of tyrosine residues. The inside of the hollow nanotubular structures is hydrophilic; however, no solvent molecules have been crystallographically detected.

Asymmetric ammonium ylid rearrangements: the effect of nitrogen asymmetry

[2,3]-Sigmatropic rearrangements of allylic ammonium ylids derived from glycinoylcamphorsultams are highly selective in terms of relative and absolute stereocontrol only when acyclic alkenes are present. When chiral esters of ylids derived from N-methyltetrahydro-pyridine ('NMTP') undergo rearrangement, the reactions show exclusive cis-stereoselectivity but the products are obtained with virtually no absolute stereocontrol. These observations support the notion that sigmatropic rearrangements of N-chiral ammonium ylids are controlled by nitrogen stereogenicity. (c) 2006 Elsevier Ltd. All rights reserved.

Asymmetric [2,3]-rearrangement of glycine-derived allyl ammonium ylids

The first examples of highly enantioselective [2,3]-sigmatropic rearrangements of acyclic allylic ammonium ylids are reported. Thus, a range of N-{2‘-[(N‘-allyl-N‘,N‘-dialkyl)ammonium]}acetyl camphor sultams undergo rearrangement at 0 °C in DME solution with high diastereofacial control (up to 99:1 dr) to give allylglycines in generally high yield. The power of the method has been demonstrated in a rapid and efficient synthesis of (R)-allyl glycine.