Academic literature on the topic 'Amidine N-oxide'

The synthesis and crystal structures of bis(S-methylisothiouronium) (MSTUH)+, N,N′-bis((3- guanidinopropyl)piperazinium (PipeC3GuaH4)4+ and hexamidinium (HexaH2)2+ tetrachloro platinate(ll) salts ( called hereafter PtMSTU, PtPipeC3Gua and PtHexa respectively ) were investigated. These compounds contain the “amidine” function (- C(=NH)NH2 ) in which the H atoms supplied by the acid have become attached to the imino group of each terminal amidino function. Moreover, in PtPipeC3Gua, the nitrogen atoms of the chair-piperazine moiety are also protonated. The influence of tetrachloroplatinate(ll) counteranion ( versus sulfate, nitrate and diisethionate ) in the in vivo nitrite inhibition by the (MSTUH)+, (PipeC3GuaH4)4+ and (HexaH2)2+ cations was investigated. The three tetrachloroplatinate(ll) salts, unexpectedly, do not inhibit significantly the in vivo nitrite production in comparison with the other salts (sulfate, nitrate and diisethionate and their corresponding previous countercations) which exhibit NO synthase inhibition, especially bis(S-methylisothiouronium) sulfate, a selective and potent inducible NO synthase (iNOS) inhibitor commonly used as standard.

N-Methylated amides (N,4-dimethylbenzamide and N-methylcyclohexanecarboxamide) were systematically subjected to chemical transformations, namely, N-tosylation followed by nucleophilic substitution. The amide function was converted to the corresponding carboxylic acid, esters, amides, aldehyde, and ketone upon treatment with hydroxide, alkoxide, amine, diisobutylaluminium hydride and Grignard reagent, respectively. In these transformations, N-methyl-N-tosylcarboxamides behave like a Weinreb amide. Similarly, N-methyl-5-phenylisoxazole-3-carboxamide was converted into 3-functionalized isoxazole derivatives. Since the amide was prepared by the cycloaddition reaction of ethynylbenzene and N-methylcarbamoylnitrile oxide, the nitrile oxide served as the equivalent of the nitrile oxides bearing a variety of functional groups such as carboxy, alkoxycarbonyl, carbamoyl, acyl and formyl moieties.

A bi-macrocycle with an incorporated isophthalamide substructure was synthesized by double amide formation between an isophthaloyl dichloride and two equivalents of a bis(alkenyloxy)aniline, followed by ring-closing metathesis and hydrogenation. In contrast to many related isophthalamides, the concave host exhibits a better binding for oxides, such as DMSO or pyridine-N-oxide, than for halide anions. A general method for a quick estimation of the strength of binding derived from only a few data points is presented and gives an estimated K ass of pyridine-N-oxide of ca. 40 M−1, NMR titration confirms 25 M−1.

Sulfonamide drugs are well known antibacterial and antimicrobial molecules for pharmaceutical development. Building a library of suitable supramolecular synthons for the sulfonamide functional group and understanding their crystal structures with partner coformer molecules continues to be a challenge in crystal engineering. Although a few sulfonamide cocrystals with amides and N-oxides have been reported, the body of work on sulfonamide synthons is limited compared with those that have carboxylic acids and carboxamides. To address this structural gap, the present work is primarily focused on sulfonamide–lactam and sulfonamide–syn-amide synthons with drugs such as celecoxib, hydrochlorothiazide and furosemide. Furthermore, the electrostatic potential of previously reported cocrystals has been recalculated to show that the negative electrostatic potential on the lactam and syn-amide O atom is higher compared with the charge on carboxamide and pyridine N-oxide O atoms. The potential of sulfonamide molecules to form cocrystals with syn-amides and lactams are evaluated in terms of the electrostatic potential energy for the designed supramolecular synthons.

The title compound, [Ge2(C8H17N2)4O2], crystallizes with imposed twofold symmetry, which allows the monodentate amidinate ligands to be arranged in acisoidfashion. The independent Ge—O distances within the central Ge2O2ring, which is essentially planar (r.m.s. deviation = 0.039 Å), are 1.7797 (8) and 1.8568 (8) Å. The germanium centres adopt a distorted trigonal–bipyramidal geometry, being coordinated by the two O atoms and by one bidentate and one monodentate amidinate ligand (three N atoms). OneN-isopropyl group is disordered over two positions; these are mutually exclusive because of `collisions' between symmetry-equivalent methyl groups and thus each has 0.5 occupancy.

A series of novel [1,2,4]triazolo[4,3-c][1,3,5,2]triazaphosphinine-5-oxidederivatives 2a-h were synthesized by a reaction of N-alkyl/aryl-N'-(4H-1,2,4-triazol-3-yl) amidines with N,N-dimethylphosphoramic dichloride in the presence of triethylamine (TEA) in refluxing 1,4-dioxane. The structures of all the synthesized compounds have been established by NMR (1H, 13C, 31P) and IR spectroscopy, as well as by elemental analysis and mass spectral analysis. Bull. Chem. Soc. Ethiop. 2020, 34(1), 157-161. DOI: https://dx.doi.org/10.4314/bcse.v34i1.15

4-{4-[N-((3-Dimethylamino)propyl)amide]phenoxy} substituted zinc(ii) phthalocyanine (2) and its water-soluble sulfobetaine (3), betaine (4) and N-oxide (5) containing zwitterionic and cationic (6) derivatives were synthesized for the first time in this study.

Anion...π interactions are newly recognized weak supramolecular forces which are relevant to many types of electron-deficient aromatic substrates. Being less competitive with respect to conventional hydrogen bonding, anion...π interactions are only rarely considered as a crystal-structure-defining factor. Their significance dramatically increases for polyoxometalate (POM) species, which offer extended oxide surfaces for maintaining dense aromatic/inorganic stacks. The structures of tetrakis(caffeinium) μ12-silicato-tetracosa-μ2-oxido-dodecaoxidododecatungsten trihydrate, (C8H11N4O2)4[SiW12O40]·3H2O, (1), and tris(theobrominium) μ12-phosphato-tetracosa-μ2-oxido-dodecaoxidododecatungsten ethanol sesquisolvate, (C7H9N4O2)3[PW12O40]·1.5C2H5OH, (2), support the utility of anion...π interactions as a special kind of supramolecular synthon controlling the structures of ionic lattices. Both caffeinium [(HCaf)+ in (1)] and theobrominium cations [(HTbr)+ in (2)] reveal double stacking patterns at both axial sides of the aromatic frameworks, leading to the generation of anion...π...anion bridges. The latter provide the rare face-to-face linkage of the anions. In (1), every square face of the metal–oxide cuboctahedra accepts the interaction and the above bridges yield flat square nets, i.e. {(HCaf+)2[SiW12O40]4−} n . Two additional cations afford single stacks only and they terminate the connectivity. Salt (2) retains a two-dimensional (2D) motif of square nets, with anion...π...anion bridges involving two of the three (HTbr)+ cations. The remaining cations complete a fivefold anion...π environment of [PW12O40]3−, acting as terminal groups. This single anion...π interaction is influenced by the specific pairing of (HTbr)+ cations by double amide-to-amide hydrogen bonding. Nevertheless, invariable 2D patterns in (1) and (2) suggest the dominant role of anion...π interactions as the structure-governing factor, which is applicable to the construction of noncovalent linkages involving Keggin-type oxometalates.

Cette thèse a portée sur deux sujets différents. D’abord la synthèse des 1-silylalléneboranes a été étudiée, pour la première fois, à partir d’époxyde acétylénique et d’un silylborane. Cette méthode permet la préparation stéréosélective et stéréospécifique des allénylboranes via un mécanisme SNi anti. Par la suite, la propargylation des aldéhydes par l’intermédiaire de ces allènes a permis d’accéder de façon stéréosélective aux 2-alcynyldiols-1,3 correspondants. Un état de transition fermé à six chainants a été proposé pour cette dernière transformation qui procède via un mécanisme SE2’. L’étendu et les limites de ces deux réactions ont été explorés. Finalement, la réactivité électrophile et nucléophile des imidates issus de la condensation de 2-aminobenzimidazole sur une variété d’orthoesters a été étudiée comme voie de préparation des dimères N-benzimidazoliques. Nous avons également étudié la synthèse des dimères [1,2a]benzimidazolo-1,3,5,2-triazaphosphorine-2-oxydes via l’action d’hexaméthylphosphoramide sur les dimères N-benzimidazoliques, l’évaluation de l’activité anti-oxydante de ces nouveaux composés formés (dimères amidiniques et phosphoazotés) est en cours
This thesis has focused on two different topics. Firstly, the synthesis of 1-silylalleneborane was studied, for the first time, from acetylenic epoxide and a silylborane. This method allows the stereoselective and stereospecific preparation of allenylboranes through an anti SNi mechanism. Subsequently, propargylation of the aldehydes using allenes afforded stereoselective access to the corresponding 2-alkynyldiols-1,3. A six-member closed transition state has been proposed for this last transformation which proceeds via a SE2' type mechanism. The scope and limitations of these two reactions have been explored.Finally, the electrophilic and nucleophilic reactivity of imidates resulting from the condensation of 2-aminobenzimidazole on a variety of orthoesters was studied as a route for the preparation of N-benzimidazole dimers. We also studied the synthesis of [1,2a] benzimidazolo-1,3,5,2-triazaphosphorin-2-oxide dimers through the action of hexamethylphosphoramide on N-benzimidazole dimers, the evaluation of the antioxidant activity of these new compounds formed (amidic and phospho-nitrogen dimers) is in progress

The English translation of the chapters written in French is available in Appendix.
La motivation initiale de ce travail provient de l'importance que les composés de coordination ont dans notre vie quotidienne. Leurs propriétés les rendent attrayants pour un large éventail d'applications, dans des domaines allant de la catalyse et de la conversion et stockage de l'énergie solaire jusqu’au domaine des matériaux et des sciences de la vie. Poussée par l'évolution et le progrès général de notre société, la recherche en chimie de coordination moderne évolue vers la complexité au niveau moléculaire, où la Nature représente une source majeure d'inspiration, comme dans le cas de la photosynthèse artificielle et de la chimie métallo-supramoléculaire. Dans le même temps, l'étude des complexes de coordination nourrit la curiosité scientifique et les approches pluridisciplinaires ouvrent de nouveaux mondes fascinants, tout en repoussant les frontières de la connaissance à des niveaux sans précédent. En continuité avec l'étude et le développement de composés de coordination pour des applications spécifiques, le thème central de cette thèse est l'interaction Métal - Ligand et les moyens de la moduler par le design du ligand, afin de générer les propriétés nécessaires pour les applications ciblées. Le design de complexes de coordination est considéré comme un «ensemble de composants modulables» – le ligand: les groupes fonctionnels des atomes donneurs, les substituants et leurs effets électroniques et stériques, le type et la dimension du cycle chélate; l’ion métallique; l'environnement. Les ligands étudiés ici sont les oxydes d’amidines N,N’-disubstitués (AMOXs) (aussi appelés α-aminonitrones ou hydroxyamidines). L'influence du motif de substitution du ligand sur les propriétés des composés est étudiée pour des complexes bis(AMOX) de cobalt(II) et de zinc(II). Les bis(chélates) de cobalt(II) sont plan carré (bas spin) à l'état solide, mais présentent une isomérisation de la structure plan carré (bas spin) vers une structure tétraédrique (haut spin) en solution dans des solvants non-coordinants. L'équilibre d'isomérisation est fortement influencé par le motif de substitution sur le ligand, du fait d’une combinaison de facteurs stériques et électroniques. Une approche théorique (DFT/ TD-DFT) et expérimentale combinée a montré que, dans la famille des chélates bis(AMOX) de zinc(II), le gap optique peut être finement modulé pour de potentielles applications dans des dispositifs optoélectroniques par la modification spécifique des ligands. Un cas spécial de solvatomorphisme a été identifié: des modifications de la géométrie et de l’état de spin sont induites par la présence ou l’absence de liaisons hydrogènes dans un même composé de cobalt(II). L’influence de l'environnement est ainsi illustrée. Les interactions faibles sont les principaux facteurs responsables pour la stabilisation du système vers une combinaison spécifique géométrie - état de spin à l'état fondamental, de façon similaire au contrôle allostérique et aux interactions hôte-invité dans les systèmes biologiques. Des études préliminaires vers des systèmes supramoléculaires à base des ligands AMOX ont été effectuées (assemblées multimétalliques vers des matériaux fonctionnels et des systèmes photocatalytiques pour conversion d'énergie solaire, en particulier la photocatalyse pour la production de H2). J’espère que les résultats et les perspectives présentées dans cette thèse incitent à la poursuite de la chimie de coordination des AMOXs.
The underlying motivation for this work stems from the importance that coordination compounds play in our daily lives. Their properties make them suitable and attractive for a wide range of applications in fields going from catalysis and solar energy conversion/ storage to materials and life sciences. Driven by the general progress of our society, research in modern coordination chemistry evolves toward complexity at the molecular level, with Nature representing a major source of inspiration as shown by artificial photosynthesis and metallosupramolecular chemistry. At the same time, the study of coordination complexes nurtures scientific curiosity, and multidisciplinary approaches are opening fascinating new worlds, while pushing the frontiers of knowledge to unprecedented depths. In line with the study and the development of coordination compounds for specific applications, the central theme of this thesis is the Metal-Ligand interaction and how it can be modulated through ligand design to generate the properties targeted for particular applications. The design of coordination complexes is seen as a ‘collection of adjustable components’ (e.g. the ligand: the donor atoms and their functional groups, the type and the size of the chelating ring, the ring substituents and their electronic and steric effects; the metal-ion; the environment). The ligands under study are the N,N’-disubstituted amidine oxides (AMOXs) (also known as α-aminonitrones/ hydroxyamidines). The influence of the ligand substitution pattern on the properties of the compounds is investigated in series of cobalt(II) and zinc(II) bis(AMOX) complexes. The cobalt(II) bis(chelates) are square-planar (low spin) in the solid state, but show square-planar (low spin) to tetrahedral (high spin) isomerization in solution of non-coordinating solvents. The isomerization equilibrium is highly sensitive to the substitution pattern on the ligand due to a combination of steric and electronic influences. A combined experimental and theoretical approach [DFT and time dependent (TD-DFT)] has shown that in the family of zinc(II) bis(AMOX) chelates, by specific modification of the ligands, the optical band gap can be fine-tuned for potential applications in optoelectronic devices. A special case of hydrogen-bonding-induced geometry and spin change at a cobalt(II) centre within a same cobalt(II) bis(chelate) has been identified. It highlights the influence of the environment on the properties of the complex. Weak interactions are the main factors responsible for biasing the system toward a specific geometry – spin state combination in the ground state, in a similar fashion to allosteric control and host-guest interactions in biological systems. Preliminary studies were conducted toward AMOX-based supramolecular systems: multimetallic assemblies toward functional materials and photocatalytic systems for solar energy-conversion (in particular photocatalysis for H2 production). It is my hope that the above results and the perspectives presented in this work motivate further developments in AMOX coordination chemistry.

碩士
國立中興大學
化學系
87
According to the results of Curran and Kanemasa, the use of hydrogen bonding or magnesium ion in 1,3-dipolar cycloaddition reaction can direct the regioselectivity of nitrile oxides with alkenes. Furthurmore, the reaction can be accelerated by ultrasound and decreases the reaction time. We choice the imidazolidin-4-one (A) to be our model study which has the structure of allylic amine and allylic amide. Compound A should be abtained by acetalization of a-amino amide (B) and unsaturated aldehyde (C). First, 25 was synthesized which was easily becomed dark, and then changed to compound 27. 27 and trans-cinnamyalde-hyde react in acidic condition, but product 28 can't be isolated. Through the search of literature and changing the protecting group, we can synthesize 30 by reaction with 29 and trans-cinnamyaldehyde in nonacidic condition. 30 and carbethoxy-formo nitrile oxide and benzo nitrile oxide react in many different conditions, but it's a pity that cycloadduct 31 and 32 can't be isolated. In order to finding out the reason of the reaction's failure, we hope to synthesize compound 34. However, 34 was unstable, so we don't continue the research on the condition of this reaction. Alternatively, we use a simple allylic amine 35 as a model study. Surprisely, undesired compounds 36 and 37 were acquired. Therefore, N-allylic amides 40a, 40b and 40c having weaker nucleophilicity than 35 were studied. N-allylic amides 40a, 40b and 40c and nitrile oxides 41a, 41b and 41c personally react at rt for 50 h. The regioselectivities of 42/43 were between 93/7 to 35/65, and the yields were among 18 ~ 79 %. Compared with other results in literature, hydrogen bonding between acyclic 2°N-allylic amides and nitrile oxides don't strongly direct the regioselectivity. In order to shorten the reaction time, we accelerate the reaction by ultrasound. In accordance with 1H NMR following, the reaction time was 12 h. The yields reach the same quality as thermal reaction (16 ~ 80 %).

The Hajos-Parrish cyclization was a landmark in the asymmetric construction of polycarbocyclic natural products. Impressive at the time, the proline-mediated intramolecular aldol condensation proceeded with an ee that was low by modern standards. Ben Bradshaw and Josep Bonjoch of the Universitat de Barcelona optimized this protocol, then used it to prepare (J. Am. Chem. Soc. 2010, 132, 5966) the enone 3 en route to the Aspergillus alkaloid (-)-anominine 4. The optimized catalyst for the enantioselective Robinson annulation was the amide 5 . With 2.5 mol % of the catalyst, the reaction proceeded in 97% ee. With only 1 mol % of catalyst, the reaction could be taken to 96% yield while maintaining the ee at 94%. Conjugate addition proceeded across the open face of 3 to give, after selective protection, the monoketal 7. After methylenation and deprotection, oxidation with IBX delivered the enone 9. With the angular quaternary centers of the natural product in place, the molecule became increasingly congested. Attempted direct alkylation of 9 led mainly to O-methylation. A solution to this problem was found in condensation with the Eschenmoser salt, followed by N-oxide formation and elimination to give the tetraene 10. Selective reduction by the Ganem protocol followed by equilibration completed the net methylation. Under anhydrous conditions, the oxide derived from the allylic selenide 12 did not rearrange. On the addition of water, the rearrangement proceeded smoothly. Protection and hydroboration converted 13 into 14. The bulk of the folded molecule protected the exo methylene of 14, so hydrogenation followed by protection and oxidation delivered 15. Conjugate addition of indole to 15 set the stage for oxidation and bis-methylenation to give 17. Selective Ru-mediated cross-coupling with 18 followed by deprotection then completed the synthesis of (-)-anominine 4, which proved to be the enantiomer of the natural product.

The traditional Chinese pharmacopeia includes Gelsemium elegans benth, from which the alkaloid gelsemoxonine 3 was isolated. Erick M. Carreira of the Eidgenössische Technische Hochschule Zürich envisioned (J. Am. Chem. Soc. 2013, 135, 8500) that the unusual azetidine ring of 3 could be established by Brandi contraction of 1 to give 2. Following Brandi and Salaün (Eur. J. Org. Chem. 1999, 2725), the hemiketal 4 was carried onto the aldehyde 9. Condensation with nitromethane followed by dehydration gave the unsaturated nitrile oxide, which cyclized to 10. Epoxidation of 10 across the more open face gave an intermediate epoxide. Addition of 11 to the epoxide, promoted by InBr3, delivered 12 with good stereocontrol. CeCl3-mediated addition of 1-propynyl lithium completed the assembly of 1. A cyclopropanone could be seen as the addition product of carbon monoxide to an alkene. On exposure of 1 to acid, this formal addition was reversed, leading to the β-lactam 2. A computational study of this cleavage was recently reported (Eur. J. Org. Chem. 2011, 5608). Conceptually, one can imagine protonation activating the C–N bond for cleavage, leading to an intermediate such as 14, which then fragments to the acylium ion, leading to cyclization. It is unlikely that 14 would have any real lifetime. On warming with the Petasis reagent, the Boc-protected β-lactam was converted to the alkene 15. Hydroboration proceeded to give the alcohol 16 as a single diastereomer. Reduction followed by oxidation to 17 then set the stage for intramolecular aldol condensation to give 18. The last challenge was the diastereoselective assembly of the N-methoxyoxindole. To this end, oxidation and dehydration of 18 led to the bromo amide 20. As hoped, Heck reductive cyclization proceeded across the more open face of the alkene, leading to 21. Hydroxyl-directed hydrosilylation of the pendant alkyne to give the ethyl ketone then completed the synthesis of gelsemoxonine 3. Twice in this synthesis, advantage was taken of the preparation and reactivity of heteroatom-substituted alkenes. Dimethyl dioxirane, generated as a solution in acetone, was sufficiently water free that the epoxide derived from 10 could survive long enough to react in a bimolecular sense with the ketene silyl acetal 11.

Timothy F. Jamison at MIT developed (Org. Lett. 2013, 15, 710) a metal-free continuous-flow hydrogenation of alkene 1 using the protected hydroxylamine reagent 2 in the presence of free hydroxylamine. The reduction of nitroindole 4 to the corresponding aniline 5 using in situ-generated iron oxide nanocrystals in continuous flow was reported (Angew. Chem. Int. Ed. 2012, 51, 10190) by C. Oliver Kappe at the University of Graz. A flow method for the MPV reduction of ketone 6 to alcohol 7 was disclosed (Org. Lett. 2013, 15, 2278) by Steven V. Ley at the University of Cambridge. Corey R.J. Stephenson, now at the University of Michigan, developed (Chem. Commun. 2013, 49, 4352) a flow deoxygenation of alcohol 8 to yield 9 using visible light photoredox catalysis. Stephen L. Buchwald at MIT demonstrated (J. Am. Chem. Soc. 2012, 134, 12466) that arylated acetaldehyde 11 could be generated from aminopyridine 10 by diazonium formation and subsequent Meerwein arylation of ethyl vinyl ether in flow. The team of Takahide Fukuyama and Ilhyong Ryu at Osaka Prefecture University showed (Org. Lett. 2013, 15, 2794) that p-iodoanisole (12) could be converted to amide 13 via low-pressure carbonylation using carbon monoxide generated from mixing formic and sulfuric acids. The continuous-flow Sonogashira coupling of alkyne 14 to produce 15 using a Pd-Cu dual reactor was developed (Org. Lett. 2013, 15, 65) by Chi-Lik Ken Lee at Singapore Polytechnic. A tandem Sonogashira/cycloisomerization procedure to convert bromopyridine 16 to aminoindolizine 18 in flow was realized (Adv. Synth. Cat. 2012, 354, 2373) by Keith James at Scripps, La Jolla. A procedure for the Pauson-Khand reaction of alkene 19 to produce the bicycle 20 in a photochemical microreactor was reported (Org. Lett. 2013, 15, 2398) by Jun-ichi Yoshida at Kyoto University. Kevin I. Booker-Milburn at the University of Bristol discovered (Angew. Chem. Int. Ed. 2013, 52, 1499) that irradiation of N-butenylpyrrole 21 in flow produced the rearranged tricycle 22. Professor Jamison described (Angew. Chem. Int. Ed. 2013, 52, 4251) a unique peptide coupling involving the photochemical rearrangement of nitrone 23 to the hindered dipeptide 24 in continuous flow.