The thermal decompositions of a series of amide complexes of nickel(II) chloride have been studied. Thermochemical, kinetic, structure and solid-state stability correlations have been investigated. Complexes containing homologous amide ligands (L) of the form NiLCℓ₂, Ni₃L₂Cℓ₆, Ni₃LCℓ₆, NiL₂Cℓ₂(2H₂0) and ML₂Cℓ₂ (where M = Ni(II), Co(II) or Cu(II)) have been prepared. Chemical analysis, spectral and thermogravimetric measurements were used to characterize the complexes and their decomposition stoichiometries. Three sets of reactions were identified as yielding stable products in a single step: (i) NiLCℓ₂ (s) → NiCℓ₂ (s) + L (g) (ii) Ni₃LCℓ₆ (s) → 3NiCℓ₂ (s) + 2L (g) (iii) Ni₃LCℓ₆ (s) → 3NiCℓ₂ (s) + L (g) Characterization of the processes in the ML₂Cℓ₂ and NiL₂Cℓ₂(2H₂0) complexes was not straightforward. Reaction enthalpies (ΔH) were determined using DSC. The orders of the reaction onset temperatures (Tc), peak temperatures (Tmax) and ΔHL values for the NiCℓ₂ system were: N-methylacetamide < acetamide < N-methylformamide, suggesting the importance of steric hindrance of the methyl-substituent groups in the amide skeleton. In the Ni₃LCℓ₆, NiL₂Cℓ₂(2H₂0) and ML₂Cℓ₂ systems no simple orders could be deduced. The Te and Tmax sequences obtained from analogous metal(II) chloride complexes indicated that the copper(II) complexes were the least stable. The kinetics of the loss of L from NiLCℓ₂ complexes were investigated using isothermal TG, non-isothermal TG and DSC measurements. The contracting geometry models described the course of the decompositions in the most satisfactory manner. Apparent activation energies ( Ea) were estimated from Arrhenius plots of rate coefficients from: (i) an approximate zero-order relationship, (ii) the contracting-area (R2) and contracting-volume (R3) equations, (iii) a new empirical (B2) expression, (iv) the half-life ( 1/t₀.₅) and (v) the characteristic feature of the rate-time curve ( 1/tmax/2 ). The non-dependence of Ea on the rate equation used supports the reliability of the kinetic parameters. Non-isothermal experiments were analyzed by the Coats-Redfern, the modified BorchardtDaniels and the Kissinger methods. Arrhenius parameters were in keeping with results from the isothermal kinetic measurements. The values of Ea obtained for the NiLCℓ₂ system increased with an increase in basicity of the amide ligands. No straightforward correlation was found between Ea and Te, Tmax, ΔHL or spectral properties.

The metabolites of the basic tertiary arylaliphatic amine N,N,α-trimethyl-7-phenylbenzenepropanamine (RecipavrinR) from male Wistar rats were characterized by gas chromatography-mass spectrometry (GCMS). The work was undertaken in an attempt to determine the source of a novel metabolite, N-(1-methyl-3,3-diphenylpropyl) formamide. The formamide metabolite was isolated from the bile of recipavrin dosed rats only after hydrolysis with the enzyme β-glucuronidase, suggesting that it arose from a glucuronide conjugated precursor. Recipavrin was chosen for the study based on structural similarity to the narcotic analgesic methadone which was shown to give rise to a similar metabolite, 6-formamido-4,4-diphenyl-3-heptanone. The secondary formamide was not a plausible candidate for a β-glucuronidase liberated metabolite of recipavrin, suggesting that a labile aglycone was responsible for the GCMS observation of the formamide metabolite. Labile isomeric compounds, α-methyl-(N-methylene)-7-phenylbenzenepropanamine N-oxide, N-(α-methyl-7-phenylbenzenpropylidene) methylamine N-oxide, and 2-(4',4'-diphenyl-but-2'-yl) oxaziridine were synthesized as possible precursors of the formamide. N-hydroxy-a-methyl-7-phenylbenzenepropanamine, and N-hydroxy-N,α-dimethyl-7-phenylbenzenepropanamine were synthesized as candidates for labile β-glucuronidase liberated aglycone precursors of the nitrones. The biliary nonconjugated and conjugated metabolites of recipavrin were characterized in detail. In addition to the formamide, 15 different metabolites representing the N- dealkylation, oxidative deamination, N-oxidation and phenyl ring oxidation pathways were identified by GCMS. To determine if thermal decomposition of the methylene nitrone in the GC inlet was responsible for the GCMS observation of the formamide metabolite, liquid chromatography-mass spectrometry (LCMS) was used to show that the formamide and not the isomeric methylene nitrone was present in bile prior to GCMS analysis. Although the synthetic methylene nitrone was shown to degrade in the GC inlet to the formamide, the LCMS experiment ruled out the thermal generation of the biliary formamide from a nitrone precursor. The nonconjugated and conjugated metabolites of the recipavrin metabolite, norrecipavrin were characterized in detail by GCMS. Since the secondary formamide metabolite was observed in the β-glucuronidase hydrolyzed bile extract, norrecipavrin was implicated as an intermediate in the biotransformation of recipavrin to the formamide. The possibility of solvent mediated formylation or free radical oxidation of desalkyl metabolites to afford the formamides was ruled out. The methylene nitrone was shown to afford the formamide metabolite under simulated workup conditions. An alkali catalyzed Beckmann rearrangement of nitrone to amide was used to account for this transformation. The secondary hydroxylamine was shown to give rise to the methylene nitrone under simulated workup conditions. It was concluded that the oxidation of a β-glucuronidase liberated secondary hydroxylamine metabolite to the methylene nitrone followed by Beckmann rearrangement of the nitrone to the formamide was the probable source of the formamide observed by GCMS in extracts of bile from recipavrin dosed rats. The metabolism of N-methyl-N-(1-methyl-3,3- diphenylpropyl) formamide was investigated in detail to determine whether the carbinolamide, N-hydroxymethyl-N-(1-methyl-3,3-diphenylpropyl) formamide was involved in the genesis of the formamide metabolite of recipavrin. The above carbinolamide and N-(1-hydroxy-1-methyl-3,3-diphenylpropyl) formamide were identified by GCMS along with 16 other metabolites representing the metabolic pathways N-deformylation, N-dealkylation, N-oxidation and phenyl ring oxidation. The carbinolamides were not found in bile from recipavrin dosed rats, ruling out the possibility of a carbinolamide glucuronide precursor of the recipavrin formamide metabolite. This was the first report of the isolation of stable dealkylation intermediates of a high molecular weight formamide. The hepatotoxicity of the anticancer agent N-methyl formamide and the solvent dimethylformamide, suggests that the recipavrin formamides could also be metabolized to toxic carbinolamide or glutathione related metabolites. / Pharmaceutical Sciences, Faculty of / Graduate

It has been previously shown that benzenesulfonamide gives thiophenol and diphenyldisulfide upon Birch reduction. The sulfonamide group is easily reduced. Probably the electron deficient sulfur atom in sulfonamide can accommodate an electron easily. The present study involved the Birch reduction of benzenesulfonamide, N,N-dimethylbenzenesulfonamide, N,N-diisobutylbenzenesulfonamide and 2-mesitylenesulfonamide.

No description available.

The objective of this research was the development of new methods for the asymmetric synthesis of nitrogen containing compounds. As one part of this goal, 3,4-dihydroxyprolines and their derivatives were prepared from sulfinimines (N-sulfinyl imines). During this project new methods were developed for asymmetric hydroxylation and decarboxylation of 3-oxo-2-carboxylate pyrroldines. The application of this new methodology was realized by the total synthesis of the α- and β-glycosidases inhibitor (+)-lentginosine. It was also found that electrophiles regioselectively add to the 4-position of 3-oxo-2-carboxylate-5-substituted pyrrolidines. The addition is accomplished through lithium diisopropyl amide generation of the pyrrolidine dianion. This addition was also compatible with 3-oxo-2-phosophono-5-substituted pyrroldines. Furthermore air oxidation of these pyrrolidines give the corresponding pyrroles. This procedure represents the first general preparation procedure for 2-phonopyrroles, which have been examined as HIV protease inhibitors. A range of β-amino carbonyl compounds were prepared from N-sulfinyl β-amino Weinreb amides in a concise and efficient procedure. A general method for the preparation of a variety of β-amino carbonyl compounds arose from the addition of an assortment of organometallic reagents to the Weinreb amides. The N-sulfinl β-amino Weinreb amides are prepared by reaction of the potassium enolate of N-methoxy-N-methylacetamide with sulfinimines or lithium N,O-dimethylhydroxylamine with N-sulfinyl β-amino esters. / Chemistry

Diss. (sammanfattning) Stockholm : Karol. inst., 2003. / Härtill 5 uppsatser.

BDTBPMB has been proven to be an essential ligand in carbonylation chemistry. Its two tert-butyl groups and wide bite angle give it the ideal characteristics for this kind of chemistry, and leads to high activity and selectivity with use of its complexes. During this work the group of reactions where this ligand has been proven to be active has been extended with two new protocols for hydroxycarbonylation and aminocarbonylation. In the hydroxycarbonylation process, a large variety of unsaturated compounds were studied. Dioxane was found to be the ideal solvent, due to its properties in terms of coordinability, and miscibility with water. Using this solvent as the medium, a BDTBPMB complex of palladium was found to be highly active and selective under mild conditions. Initial attempts to address the aminocarbonylation of alkenes catalysed by the Pd/BDTBPMB system did not give high activity. This problem was overcome by the addition of an arylalcohol. Under those conditions, high selectivity and conversion was obtained in a wide variety of amides. However, attempts to address the aminocarbonylation of alkenes with ammonia gas to generate primary amides did not result in any conversion. The generation of these primary amides was obtained with transamidation of N-phenylnonamides which can be prepared by aminocarbonylation. Amides have been successfully hydrogenated to amines catalysed by a Ru/Triphos system. This system has been proven to be highly active in this reaction. High selectivities have been obtained in the generation of secondary amine. However, initial results of the hydrogenation of primary amides resulted in no formation of primary amines. A careful analysis of the mechanism of the formation of various products from the hydrogenation of primary amides allows the selective formation of primary amines by the ruthenium/Triphos system in the presence of ammonia. The possibility of the generation of primary amides in situ from acids under hydrogenation conditions, giving primary amines was explored with high conversion and moderate selectivities. To complete this work, a system based on a palladium complex for the decarboxylation of benzoic acids was developed. Usually, the decarboxylation reactions catalysed by copper require high temperatures. However, palladium complexes of highly electron donating ligands such as BDTBPMB or P([superscript]tBu)₃ were found to be highly active under milder conditions. This catalytic system was proven to be active in desulfonation reactions giving high conversion.

This thesis describes the chemistry developed during a study of novel transition metalcatalysed reactions for the synthesis of carboxylic acid derivatives. Chapter 2 describes a novel protocol for the synthesis of primary amides from alcohols in one-pot where a metal complex mediates two fundamentally different catalytic processes. An iridium catalyst has been shown to be effective for the selective rearrangement of aldoximes into primary amides. In addition, an iridium-catalysed oxidation of activated alcohols via hydrogen transfer has been developed using an alkene as formal oxidant. These reactions have been combined in a sequential process affording good yields for a range of benzylic alcohols. An improved system for the rearrangement of aldoximes into amides using a new ruthenium catalyst is described in Chapter 3. Through a systematic program of optimisation excellent selectivity was achieved for a wide range of substrates at markedly reduced catalyst loading. Chapter 4 describes the development of a ruthenium-catalysed elimination reaction for the conversion of oxime ethers into nitriles. The application of this reaction to tandem and sequential reactions has been explored, albeit with limited success. Also, a method for the ruthenium-catalysed oxidation of alcohols using an electron-deficient alkene as hydrogen acceptor is described, and its application to a tandem oxidation process with a nitrogen nucleophile demonstrated. As an extension of the concept presented in Chapter 4, tandem oxidation processes with oxygen nucleophiles are the subject of Chapter 5. This strategy has been used for the oxidation of primary alcohols to their corresponding methyl esters in one-pot, with good yields obtained for a range of substrates. The use of water as a nucleophile in such a process has also been examined.

A química de carboidratos têm sido um importante link entre a síntese orgânica, a biologia e a química medicinal devido ao papel fundamental que açúcares apresentam na glicobiologia. Neste contexto, a ligação amida glicosídica é uma importante conexão encontrada na natureza, sendo uma das formas de ligar um núcleo de carboidrato a outras biomoléculas e produtos naturais, como glicopeptídeos e N-glicosil amidas. Dessa forma, o desenvolvimento de métodos sintéticos para a introdução de núcleos de carboidratos em diferentes estruturas é fundamental. Tendo em vista o interesse do nosso grupo de pesquisa em desenvolver novas estratégias utilizando a química de selênio na funcionalização de derivados de carboidratos, o presente projeto descreve uma metodologia de síntese de N-glicosil amidas e de glicoconjugação via formação de ligação amida, envolvendo a reação entre selenocarboxilatos, gerados in situ, com azidas glicosídicas. Foi possível sintetizar com sucesso uma série de derivados de carboidratos, para uma variedade de substratos que incluíram: N-glicosil amidas furanosídicas (20 exemplos), piranosídicas (13 exemplos) e também N-glicoconjugados graxos (10 exemplos). A metodologia foi baseada na geração in situ de selenocarboxilatos de lítio, a partir de Se0/ LiEt3BH e derivados de ácidos carboxílicos, e suas reações com azidas derivadas de açúcares. Um aspecto importante deste protocolo é que a reação se inicia com selênio elementar e apresenta como subprodutos N2 e Se0. O isolamento e manipulação de espécies intermediárias reativas de selênio são evitadas durante o curso reacional, conferindo ao selenocarboxilato o status de reagente traceless. / Carbohydrate chemistry has been an important link between organic synthesis, biology and medicinal chemistry due to the fundamental roles that sugars play in glycobiology. In this context, the glycosyl amide linkage is an important connection found in nature, since it is one of the ways in which a sugar unit can be found attached to other biomolecules and natural products, such as N-glycosyl amides and glycopeptides that are known for possessing a wide range of bioactivities. Therefore, the development of synthetic methods for the introduction of sugar moieties into various different scaffolds is of paramount importance. In connection with our interest on the development of new strategies using selenium chemistry for the functionalization of carbohydrate derivatives, we describe herein an efficient synthesis of glycosyl amides and glycoconjugation methodology via amide bond-formation, enabled by the reaction of in situ generated selenocarboxylates with glycosyl azides. Carbohydrate-derived amides were successfully prepared in good yields for a broad range of substrates, including: furanosyl (20 examples), pyranosyl (13 examples) N-glycosil amides derivatives and also fatty acids glycoconjugates (10 examples). The methodology relied in the in situ generation of lithium selenocarboxylates, from Se/LiEt3BH and acyl chlorides or carboxylic acids and their reaction with sugar azides. A key aspect of the present protocol is that we start from elemental selenium and as by-products we have harmless gaseous nitrogen and elemental selenium. Isolation and handling of all reactive and sensitive seleniumcontaining intermediates is avoided, therefore assigning to the selenocarboxylate the status of a traceless reagent.

Reproduction de : Thèse doctorat : Physique-Chimie : Reims : 2006. / Titre provenant de l'écran titre. Bibliogr. f. 158-168.