Synthetic Attempts Research Articles

Coordinating Tectons 4: Coordination Chemistry of the 4,5-Diazafluoren-9-yl Moiety as a Metallo-Ligand for Allenylidene Complexes

We describe how the 4,5-diazafluoren-9-yl moiety has been utilized in the construction of multinuclear complexes incorporating a ruthenium(II) allenylidene functionality. The coordination chemistry of diazafluorenyl-terminated allenylidene complexes is limited by the sensitivity (instability) of the allenylidene moiety under a variety of synthetic conditions. In contrast the κ2-N,N′-coordination of the diazafluorenyl propargylic alcohol (alkynol) to a metal center prior to allenylidene formation provides a facile route toward the synthesis of multinuclear allenylidene coordination complexes. Our synthetic attempts and successes are discussed in combination with spectroscopic and electronic characterization of the latter cases.

Asymmetric hydroformylation-initiated tandem sequences for syntheses of (+)-patulolide C, (-)-pyrenophorol, (+)-decarestrictine L, and (+)-prelog djerassi lactone.

Four different Rh-catalyzed asymmetric hydroformylation (AHF) tandem reactions have been developed in the context of the total syntheses of (+)-patulolide C, (-)-pyrenophorol, (+)-decarestrictine L, and (+)-Prelog-Djerassi lactone. A total synthesis of (+)-patulolide C has been accomplished in three steps utilizing a Rh(I)-catalyzed Z-selective anti-Markovnikov hydroacetoxylation of a known alkyne to give a Z-enol acetate with excellent selectivity. An AHF/intramolecular Wittig olefination cascade was utilized to set the C4-hydroxyl stereochemistry, E-olefin geometry, and form the macrolactone. In addition, both (-)-pyrenophorol and (+)-decarestrictine L have been synthesized from the enantiomeric (4R)- and (4S)-4-(tert-butyldimethylsiloxy)-1-pentyne in five and four steps, respectively. These syntheses feature Ru(II)-catalyzed Z-selective anti-Markovnikov hydroacetoxylation of terminal alkynes followed by AHF/Wittig olefination sequences to rapidly establish functionality and stereogenicity. A synthesis of (+)-Prelog-Djerassi lactone was accomplished in three isolations from the known 1-vinyl-4-methyl-2,6,7-trioxabicyclo[2.2.2]octane ortho ester. An AHF/crotylation tandem sequence has been developed to set the C2-C4 stereochemistry. An asymmetric hydrogenation was employed to set the C6 stereochemistry, resulting in an especially efficient enantioselective synthesis from achiral starting material. In summary, these syntheses have greatly improved efficiency in terms of atom-economy, catalytic stereoselective transformations, inexpensive reagents, step-counts, and overall yield when compared with previous synthetic attempts.

Revisiting the Synthesis of 4,6‐Difluorobenzofuroxan: A Study of Its Reactivity and Access to Fluorinated Quinoxaline Oxides

AbstractNew quinoxaline 1,4‐dioxide derivatives have been synthesized from novel fluorinated benzofuroxans such as 4‐fluorobenzofuroxan, which is prepared for the first time. Furthermore, the preparation 4,6‐difluorobenzofuroxan has been revisited because we were unable to reproduce the reported synthetic method. Several synthetic pathways have thus been investigated, and the optimal way to prepare this disubstituted benzofuroxan was from the 3,5‐difluoro‐2‐nitroaniline. The various synthetic attempts have allowed the isolation of interesting new compounds such as hydroxybenzotriazole‐like heterocycles or benzoquinone 2‐diazide. In the latter case, our study reveals some interesting features in the mechanism of their formation. The first structural elucidation of benzoquinone 2‐diazide through an X‐ray crystallographic study is also reported. This study has unambiguously shown that benzoquinone 2‐diazide can be involved in Diels–Alder reactions. The first case of a reaction involving a nitro‐substituted benzoquinone 2‐diazide and cyclopentadiene is also reported. To understand better the influence of the fluorine atoms on the reactivity of benzofuroxans and benzofurazans, a wide array of new fluorinated heterocycles were synthesized together with some already known compounds. This has enabled an extensive investigation of their electrophilic behavior to be undertaken through a theoretical and an electrochemical study. From these studies, it could be deduced that the replacement of nitro groups by fluorine atoms results in a significant decrease in the electrophilic character of benzofuroxan. Nevertheless, these compounds could undergo SNAr processes, leading to new functionalized heterocycles. The first examples of aromatic nucleophilic substitution of fluorine with these compounds are also described.

Mechanistic Insights into the Formation of Dodecanethiolate-Stabilized Magnetic Iridium Nanoparticles: Thiosulfate vs Thiol Ligands.

The synthesis of stable and isolable iridium nanoparticles with an average core size of ∼1.2 ± 0.3 nm was achieved by employing sodium S-dodecylthiosulfate as a ligand precursor during the modified Brust–Schiffrin reaction. Transmission electron microscopy (TEM) of the isolated Ir nanoparticles revealed a high degree of monodispersity. Further characterizations with 1H NMR, FT-IR, UV–vis spectroscopy, thermogravimetric analysis (TGA), and X-ray photoelectron spectroscopy (XPS) confirmed that the synthesized Ir nanoparticles are stabilized by dodecanethiolate ligands produced upon the adsorption/cleavage of S-dodecylthiosulfate on the growing Ir nanoparticle surface. By comparison, synthetic attempts employing dodecanethiol as a stabilizing ligand led to the formation of Ir-thiolate species (Ir(SR)3) as an intermediate and Ir-hydroxide species at the completion of reaction. Mechanistic investigations of these two reactions using S-dodecylthiosulfate and dodecanethiol provided deeper understandings on the novelty of thiosulfate ligands, which allow the successful formation of stable thiolate-capped Ir nanoparticles. Moreover, these Ir nanoparticles were shown to have strong magnetic properties.

Design and synthesis of the first triply twisted Möbius annulene.

As long as 50 years ago theoretical calculations predicted that Möbius annulenes with only one π surface and one edge would exhibit peculiar electronic properties and violate the Hückel rules. Numerous synthetic attempts notwithstanding, the first singly twisted Möbius annulene was not prepared until 2003. Here we present a general, rational strategy to synthesize triply or even more highly twisted cyclic π systems. We apply this strategy to the preparation of a triply twisted [24]dehydroannulene, the structure of which was confirmed by X-ray analysis. Our strategy is based on the topological transformation of 'twist' into 'writhe'. The advantage is twofold: the product exhibits a lower degree of strain and precursors can be designed that inherently include the writhe, which, after cyclization, ends up in the Möbius product. With our strategy, triply twisted systems are easier to prepare than their singly twisted counterparts.

Immobilization of Poly(1,1-dimethysilacyclobutane) by Means of Anionic Ring-Opening Polymerization on Organic Nanoparticles and Reinvestigation of Crystallization

In the present study, the synthesis of poly(1,1-dimethylsilacyclobutane) (PDMSB) by anionic ring opening polymerization (ROP) is reinvestigated, leading to narrowly distributed molar masses (polydispersities 1.04–1.15) in the range of 2.3 to 60 kg mol−1. Investigations of thermal behavior for low molar mass PDMSB revealed an untypical multiple peaks melting phenomenon, which at first glance, seems to be of the same origin as low molar mass poly(ethylene oxide)s. Small angle X-ray scattering (SAXS) and X-ray diffraction (XRD) measurements are done, proving the fast crystallization and subsequent recrystallization for investigated low molar mass samples. Synthetic attempts are expanded to the surface-initiated anionic ROP of 1,1-dimethylsilacyclobutane (DMSB) monomer from the surface of cross-linked polystyrene (PS) nanoparticles. Novel polycarbosilanes (PCS)/organic core/shell particles are obtained, which are investigated by using transmission electron microscopy (TEM) and dynamic light scattering (DLS) experiments. First insights into the crystallization behavior of surface-attached PDMSB chains reveal that crystallization seems to be hindered.

ChemInform Abstract: Synthesis and Molecular Structure of New Macro Acyclic Mannich Derivatives: Symmetrical and Unsymmetrical 2‐[(E)‐(Benzylideneamino)(aryl)methyl]cyclododecanone.

Abstract In an effort to provide a green synthetic route for heterocyclic scaffolds, new macro analogs of acyclic Mannich derivatives have been synthesized in good yields in a one-pot, efficient fashion. The acyclic symmetrical and unsymmetrical 2-[(E)-(benzylideneamino)(aryl)methyl]cyclododecanones have been synthesized by condensation of cyclododecanone, aromatic aldehyde, and ammonium acetate in ethanolic media. By infrared, NMR, and mass spectral analyses, their structures were determined. Examination of crystal structure of a p-Cl and o-Br analogs reveals the minimum energy [3333] square conformation of cyclododecanone ring. In the crystal, molecules aggregate in dimeric subunits formed by C-Cl … π and C-H..π interactions. The reported one-pot, multichain reaction of macrocycles is the first synthetic attempt of acyclic compounds in this type of Mannich reaction involving ketones containing active methylene groups. Supplemental materials are available for this article. Go to the publisher's online ed...

Synthesis and Molecular Structure of New Macro Acyclic Mannich Derivatives: Symmetrical and Unsymmetrical 2-[(E)-(Benzylideneamino)(aryl)methyl]cyclododecanone

In an effort to provide a green synthetic route for heterocyclic scaffolds, new macro analogs of acyclic Mannich derivatives have been synthesized in good yields in a one-pot, efficient fashion. The acyclic symmetrical and unsymmetrical 2-[(E)-(benzylideneamino)(aryl)methyl]cyclododecanones have been synthesized by condensation of cyclododecanone, aromatic aldehyde, and ammonium acetate in ethanolic media. By infrared, NMR, and mass spectral analyses, their structures were determined. Examination of crystal structure of a p-Cl and o-Br analogs reveals the minimum energy [3333] square conformation of cyclododecanone ring. In the crystal, molecules aggregate in dimeric subunits formed by C-Cl … π and C-H..π interactions. The reported one-pot, multichain reaction of macrocycles is the first synthetic attempt of acyclic compounds in this type of Mannich reaction involving ketones containing active methylene groups. Supplemental materials are available for this article. Go to the publisher's online edition of Synthetic Communications® to view the free supplemental file.

Optically switchable organic field-effect transistors based on photoresponsive gold nanoparticles blended with poly(3-hexylthiophene)

Interface tailoring represents a route for integrating complex functions in systems and materials. Although it is ubiquitous in biological systems--e.g., in membranes--synthetic attempts have not yet reached the same level of sophistication. Here, we report on the fabrication of an organic field-effect transistor featuring dual-gate response. Alongside the electric control through the gate electrode, we incorporated photoresponsive nanostructures in the polymeric semiconductor via blending, thereby providing optical switching ability to the device. In particular, we mixed poly(3-hexylthiophene) with gold nanoparticles (AuNP) coated with a chemisorbed azobenzene-based self-assembled monolayer, acting as traps for the charges in the device. The light-induced isomerization between the trans and cis states of the azobenzene molecules coating the AuNP induces a variation of the tunneling barrier, which controls the efficiency of the charge trapping/detrapping process within the semiconducting film. Our approach offers unique solutions to digital commuting between optical and electric signals.

Pyrrolic macrocycles with stabilized triplet states: Metal-centered and ligand-centered separation of unpaired electrons

Two groups of cationic macrocycles with contrasting behaviors have been investigated. The boron group has singlet states well below triplet states. This is the standard behavior for most macrocycles without transition metals. The aluminum group has triplet states stabilized through metal-centered and macrocycle-centered separation of unpaired electrons. The cationic boron subphthalocyanine (1B) has a triplet state whose unpaired electrons are delocalized in the conjugated ring. This is not surprising because a conjugated macrocycle can act as an electron buffer for multiple electrons. On the other hand, coexistence of metal-centered and ligand-centered distributions of unpaired electrons leads to the stabilized triplet state of 1Al. Results from the spin density, natural bond orbital (NBO) charges, and electron localization function (ELF) indicate distinguishable electron distributions between 1B and 1Al. The metal-centered unpaired electron in the triplet state of 1Al leads to the longer Al–N bond length and smaller N–Al–N bond angle compared with these in its singlet state. Consistent with this, the TDDFT study suggests a significant energy relaxation after the first vertical singlet-to-triplet transition. The ligand-centered unpaired electron in the triplet state of 1Al leads to the odd number of π electrons in the macrocycle. NICS values of this macrocycle are distinguishable from these of an aromatic or an antiaromatic macrocycle. The two highest singly occupied orbitals in the triplet state of 1Al are almost degenerate, spatially separated, and have little overlap. This rationalizes its stabilized triplet state. The stabilization mechanism of an unpaired electron at the tetrahedral corner above the central aluminum can also be rationalized by considering the spatial requirement in the valence shell electron pair repulsion (VSEPR) model. The metal-centered and ligand-centered separation of unpaired electrons also leads to stabilized triplet states in some other cationic macrocycles. It is hoped that this theoretical study will stimulate more synthetic attempts to access the experimentally unknown 1Al and more interest in the experimentally known 1B.

Synthetic Approaches to Natural Antioxidant Benzastatin E, F and G Analogues

For synthesis of benzastatin E, F and G analogues, the indole-2-carbaldehydes with or without substituents at C-5 position were prepared as key intermediates. Several synthetic attempts to achieve benzastatin E-G analogues were suggested using the indole-2-carbaldehyde intermediates.

A THEOLOGIAN'S TYPOLOGY FOR SCIENCE AND RELIGION

Abstract: A 1991 article by psychologist John D. Carter offers an underdeveloped insight that typologies for relating science and religion might be fruitfully formulated in discipline‐specific perspectives. This essay thus covers a specifically theological perspective only briefly outlined in Carter, and it expands four models that theologians have used to relate religion and science. This essay renames these models and expands their implications, especially for addressing the behavioral sciences. (1) The contrarian model generally opposes science, (2) the apologetic makes theology congenial to science, (3) the correlational holds both disciplines in tension, and (4) the synthetic attempts a grand unification of them. Arguing from the theologian's perspective, this essay is intended to demonstrate that different models/methods for relating science and religion are really reflections of deeper religious attitudes and argues that the task for which a method is employed ultimately determines its adequacy within that attitude's constraints.

Rapid magnetic heating treatment by highly charged maghemite nanoparticles on Wistar rats exocranial glioma tumors at microliter volume

One of the most significant challenges implementing colloidal magnetic nanoparticles in medicine is the efficient heating of microliter quantities by applying a low frequency alternating magnetic field. The ultimate goal is to accomplish nonsurgically the treatment of millimeter size tumors. Here, we demonstrate the synthesis, characterization, and the in vitro as well as in vivo efficiency of a dextran coated maghemite (gamma-Fe(2)O(3)) ferrofluid with an exceptional response to magnetic heating. The difference to previous synthetic attempts is the high charge of the dextran coating, which according to our study maintains the colloidal stability and good dispersion of the ferrofluid during the magnetic heating stage. Specifically, in vitro 2 mul of the ferrofluid gives an outstanding temperature rise of 33 degrees C within 10 min, while in vivo treatment, by infusing 150 mul of the ferrofluid in animal model (rat) glioma tumors, causes an impressive cancer tissue dissolution.

Mössbauer spectra of two extended series of basic iron(III) carboxylates [Fe3O(O2CR)6(H2O)6]A (A− = ClO4 −, NO3 −)

Two series of basic iron(III) carboxylates [Fe3O(O2CR)6(H2O)3]A were prepared, with R = CCl3, CHBr2, CH2F, CH2Cl, C(OH)Ph2, H, Ph, (CH2)3Cl, Me, CHMe2, Et, CMe3. For the former series (1–12) A − = ClO $_{4}^{\,\,-}$ and for the latter (13–24) A − = NO $_{3}^{\,\,-}$ . Complexes with R = CF3 were inaccessible for either counteranion, with all synthetic attempts leading to the butterfly complex [Fe4O2(O2CCF3)8 (H2O)6]. Crystal structures of 1, 2, 5, 7, 9–12, 14, 16, 21 and 23 revealed the close structural similarity of the complexes. Mossbauer studies revealed very similar isomer shifts for all complexes in the region of 0.51–0.54 mm s − 1, and variable quadrupole splittings, ranging from 0.36 to 0.76 mm s − 1. Mossbauer studies of the complexes were carried out in frozen MeCN solutions in order to assess their stability in solution. All complexes proved to be stable in MeCN solutions, except complex 13 (R = CCl3, A − = NO $_{3}^{\,\,-})$ , which dissociated to a butterfly-type complex.

Synthesis and Characterization of Polymerized Ionic Liquids

Polymerized ionic liquids are prepared using a dibromoalkane reacted with 2 methyl imidazole. Two different dibromoalkanes are used, 1,5-dibromopentane and 1,6-dibromohexane. In order to increase the molecular weight of these two polymers, two different synthetic attempts were used to create poly-(2-methyl-1-pentyl imidazolium bromide and poly-(2-methyl-1-hexyl imidazolium bromide) with molecular weights of 7400 and 8900. Anion exchanges are performed to replace the bromide with hexafluorophosphate. These polymers are then doped with LiPF6 in a solution of acetonitrile which was subsequently drop cast. Ionic conductivity measurements indicate ionic conductivity above 0.01 mS/cm, with no liquid electrolyte present.

4-Hydroxy-2-pyridone alkaloids: Structures and synthetic approaches

Covering: 1982 to 2009 4-Hydroxy-2-pyridone alkaloids exert diverse biological effects, ranging from antifungal, antibacterial, insecticidal and cytotoxic activity to the induction of neurite outgrowth in different cell assays. For this reason, this class of compounds has attracted much attention in the scientific community, resulting in the elucidation of the biosynthesis of some members which are formed by fungal polyketide synthases via tetramic acids by fungal polyketide synthases as well as different total synthesis approaches. This article will give a summary of the so far known structures, overview the different activities of the compounds and disclose the synthetic attempts since 1982.

A unique approach to the synthesis of a dengue vaccine and the novel tetrasaccharide that results

An approach to the development of a dengue vaccine by synthesizing the hexasaccharide epitope on the viral surface is examined. The stereochemical and structural challenges include the synthesis of a β-mannoside bond. Synthesis of this bond is approached via a trisaccharide analogue portion of the epitope. A novel tetrasaccharide with a mannose–mannose anomeric linkage results in the course of the synthetic attempts.

Perfect planar tetracoordinate carbon in neutral unsaturated hydrocarbon cages: A new strategy utilizing three‐dimensional electron delocalization

A new series of unsaturated pure and boron-substituted hydrocarbons containing a perfect planar tetracoordinate carbon (ptC) have been proposed by performing density functional computations. The ptC is effectively stabilized through three-dimensional delocalization of ptC's lone pair into pi-conjugated systems, by utilizing a new strategy opening a brand new way of designing ptC structures. Compared to previously proposed ptC-containing hydrocarbon cage compound, a neutral hydrocarbon designed here might be a more viable target for synthetic attempts.

Pyrrolo[1,2-b]pyridazines. A revisit

Although a relatively simple system, pyrrolo[1,2-b]pyridazines have been subject to numerous studies and synthetic attempts. The present review represents an update to the 1976 review of Kuhla and Lombardino.

Bruce Merrifield's contribution to antimicrobial peptide research

Although within the scientific community at large Bruce Merrifield is and will remain celebrated for the pivotal discovery and dedicated crafting of solid phase peptide synthesis methodology, there are also other areas where his unique scientific acumen was applied to with distinctive success. Among them, those of glucagon antagonists and antimicrobial peptides are arguably the better known. Over my 25 year-long relationship with Bruce, I had occasion to work with him in both areas, but it is to the latter I will devote these brief reminiscences, as our collaboration in this fast expanding research field reached from its very dawn till relatively recently. 2006, the year of Bruce’s passing, marked the silver jubilee of antimicrobial peptide research, officially initiated with the publication of the seminal paper on the cecropins by Boman (see Figure 1) and coworkers. 1 Hans had befriended Bruce during his postdoc (1958–60) in Fritz Lipmann’s group at Rockefeller, and his logical enthusiasm over the finding of a family of eukaryotic, geneencoded peptides with remarkably potent antimicrobial activities must have been contagious for Bruce, who started to collaborate with Hans on the cecropins in late 1981. On joining Bruce’s lab in January 1982, the very first project given to me was to synthesize the putative 37-residue sequence of cecropin A, to confirm some structural assignations tentatively proposed for the C-terminal region. A previous synthetic attempt 2 had turned out an active compound, albeit nonidentical with the natural peptide. Building on that result and benefiting from several improvements emanating at the time from Bruce and Jimmy Tam’s joint research—not least the very useful high-low HF cleavage method 3 —I completed my assignment in two-and-a-half months, which at the time was regarded a reasonable time for a relative novice charged with the fully manual synthesis of a 37-residue, tritiumlabeled peptide. Our synthetic product was completely identical with the native peptide by microbiological as well as biochemical (enzyme digest + HPLC) criteria, and we were able to confirm the hitherto uncertain structure of the C-terminal end by means of plasma desorption MS, a forerunner of modern MALDI-TOF MS. In addition, our report 4 discussed the relevance of the Trp-2 residue for antimicrobial activity and thus set the basis for further analogue work. 5 In retrospect, that initial 2-year stint in the cecropin project appears as a decisive period, where Bruce’s gracious support and encouragement became the beacon blazing away the often usual angst of a nascent scientific career. A thorough and constructive draft reviewer if ever I saw one, Bruce returned each one of my versions generously endowed with pencil scribbles which, readily deciphered, brought gradual improvement to my struggling manuscripts. To Bruce I owe a great deal of any abilities I may have achieved as a (non-native) writer of English scientific texts. Those early 1980s cecropin manuscripts, first examples of the substantial contri