59 research outputs found

    Homoaromatics as intermediates in the substitution reactions of 1,2,4,5-tetrazines with ammonia and hydrazine

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    This thesis describes some nucleophilic substitution reactions between the red 1,2,4,5-tetrazines and hydrazine-hydrate or ammonia. Special attention was paid to the occurrence of the S N (ANRORC) mechanism in these substitution reactions. This mechanism comprises a sequence of reactions, involving the A ddition of a N ucleophile to a heteroaromatic species, followed by a R ing- O pening and R ing C losure reaction to the substitution product.σ-Adducts, namely 6-hydrazino- and 6-amino-3-aryl(alkyl)-1,6-dihydro-1,2,4,5-tetrazines, are formed upon addition of hydrazine or ammonia to 3-aryl(alkyl)-1,2,4,5-tetrazines. This is accompanied by a change in colour from red to yellow. These adducts can be observed by NMR spectroscopy. ln heteroaromatics in liquid ammonia, an upfield shift (Δδ) of 4-5 ppm is usually measured for the hydrogen atom, attached to the carbon atom to which addition takes place. An extra ordinary large upfield shift is observed however upon addition to 1,2,4,5-tetrazines; Δδ= ~ 8.5 ppm in hydrazine and Δδ= ~ 8.7 ppm in liquid ammonia (at 230 K, chapters 4 and 6).The fact that 3-aryl(alkyl)-1,2,4,5-tetrazines are converted into the 6-amino compounds by oxidation of the intermediate in liquid ammonia (chapter 2), indicates that an intermediary 1,6-dihydro-6-amino structure must exist. 1H NMR measurements at various temperatures of 1,6-dihydro-1,2,4,5-tetrazines as model compounds for these σ-adducts gave an explanation for the large up field shift (Δδ). 1,6-Dihydro-1,2,4,5-tetrazines and their conjugate acids and bases were found to be homoaromatic and they are present in the monohomotetrazole conformation. The hydrogens at the sp 3carbon atom have a different orientation towards the tetrazole ring. One (H A) is oriented above the aromatic ring, in the shielding regio; H Bis in the exo position, in the deshielding regio; thus resulting in a large difference in chemical shift. The homoaromatic species show a ring inversion. The kinetic parameters (ΔH, ΔS and ΔG) were determined by dynamic NMR measurements (chapter 3). Since a large substituent at C 6 of the homotetrazole (e.g. methyl or ethyl) is found exclusively in the exo position, the hydrogen of the above mentioned a-adducts is oriented above the ring current of the tetrazole ring, resulting in a chemical shift at high field.The charge of the tetrazole ring exerts an influence through space on H A, H Bis hardly influenced. This became obvious from δH Ain 1H NMR and JCH Ain 13C NMR (chapters 3 and 4).The homoaromatic σ-adducts in liquid ammonia and even in hydrazine- hydrate/ methanol are anionic species, as was primarily proven by a 13C NMR study (chapters 4 and 6). The driving force for the deprotonation is probably the larger resonance stabilization of the homoaromatic anion with respect to the neutral homoaromatic species.3-Alkyl(aryl)-1,2,4,5-tetrazines were found to undergo a Chichibabin hydrazination into 6-hydrazino-3-alkyl(aryl)-1,2,4,5-tetrazines on treatment with hydrazine-hydrate. The first step in this reaction sequence was the formation of a homoaromatic σ-adduct. Subsequently an open-chain intermediate was observed by NMR, on raising the temperature. Finally the hydrazino compound is formed by ring closure. This reaction sequence can be considered as an S N (ANRORC) process. With 15N-labelled hydrazine, only part of the label was found to be built in the 1,2,4,5-tetrazine ring of the 6-hydrazino compounds. This is the first example of a reaction in which both the hydrazino compound with the 15N-label in the ring and with the 15N-label in the exocyclic hydrazino group are formed according to the S N (ANRORC) mechanism (chapter 6).During the hydrazino-deamination and hydrazino-dehalogenation of 6-amino- and 6-halogeno-1,2,4,5-tetrazines only a part of the molecules was found to react according to the S N (ANRORC) process. The other part followed the alternative S N (AE), A ddition- E limination, pathway (chapters 5 and 6).The crystal structure of 6-ethyl-3-phenyl-1,6-dihydro-1,2,4,5-tetrazine was elucidated by X-ray structural analysis very recently. This analysis revealed that the molecule is in a boat-conformation. C 6 points upwards with a dihedral angle of 49.3° and C 3 with an angle of 26.7°. N 1 was found to be sp 2hybridized and the N(1)-N(2), N(2)-N(3), C(3)-N(4) and N(4)-N(5) bond distances were found to be between single- en double bond length, in agreement with the expected electron delocalization. Therefore we came to the conclusion that the crystal structure agrees with the homoaromatic character of the compound (chapter 7)

    Characterization of Poly(A)-Protein Complexes Isolated from Free and Membrane-Bound Polyribosomes of Ehrlich Ascites Tumor Cells

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    Proteins present in messenger ribonucleoprotein particles were labeled with [35S]-methionine in Ehrlich ascites tumor cells in which synthesis of new ribosomes was inhibited. Poly(A)-protein complexes were isolated from free and membrane-bound polyribosomes by sucrose gradient centrifugation and affinity chromatography on oligo(dT)-cellulose. Both classes of Poly(A)-protein particles contain a poly(A) chain of about 70 adenyl residues and a protein with a molecular weight of 76000 attached to it

    Structural reduction of carbon emissions through online education in Dutch Higher Education

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    Dutch institutions of Higher Education have to meet stringent requirements for energy efficiency andreducing carbon emissions imposed by the national government. The commute of students and staffgreatly contributes to the carbon footprint of a Higher Education Institution. International students inDutch Higher Education also have a substantial impact on the environment due to air travel. Theirnumber increases every year. The deployment and use of ICT can contribute substantially to thereduction of energy use and carbon emissions through decreasing mobility of students and staff byincreasing virtualization and digitalization of educational processes.This exploratory study examines the opportunities of online learning as a means to reduce the impactof students’ traveling on the carbon footprint. The research methodology consists of a systematicreview of literature and a series of interviews with experts of online learning and managers of energy,ICT and/or sustainability.An obstacle for decreasing the carbon footprint of a Higher Education Institution using online learningare differences in opinion as expressed by professionals, regarding the quality of this form ofeducation. Our research shows that those in favour of face-to-face education believe, that the socialprocesses are essential for high quality education. Proponents of online learning emphasize theopportunities by focusing on the advantages for individual students – i.e. giving students more controlover their own learning process. So far, only a minority have recognized that online learning can leadto decreased mobility and a reduction of carbon emissions
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