Volume 64, Issue 6

Alkyl-substituted acetylenes and diacetylenes with terminal ferrocenyl groups were synthesised starting from ferrocene. The reactivity of the triple bonds in the resulting compounds was used to prepare cobalt-alkyne complexes. Cyclotrimerisation of the monoacetylene resulted in a hexa-substituted benzene derivative with six pending ferrocenyl groups. Graphical Abstract Synthesis and Reactions of Ferrocenyl-capped Long-chain Alkynes

The structures of the equiatomic germanides REPdGe with the heavy rare earth elements have been reinvestigated with respect to palladium-germanium ordering. The samples were prepared by arc-melting of the elements followed by annealing procedures in sealed silica ampoules at different temperatures. The structures of YPdGe, HT-TbPdGe, LT-DyPdGe, HT-DyPdGe, LT-HoPdGe, HT-HoPdGe, ErPdGe, and TmPdGe, and of the new germanide LuPdGe, were refined from single crystal diffractometer data. LT-DyPdGe and LT-HoPdGe crystallize with the YPdSi-type structure, space group Pmmn. The other germanides crystallize with the non-centrosymmetric YbAuSn structure, space group Imm2. All structures are orthorhombically-distorted superstructure variants of AlB2, and they show strong intralayer Pd-Ge bonding within the ordered Pd 3 Ge 3 hexagons. There is weak Pd-Ge and Pd-Pd interlayer bonding. The crystal chemical relationship between the different superstructures is discussed. Graphical Abstract Polymorphism in the Germanides REPdGe with the Heavy Rare Earth Elements

Quaternary salts were prepared by reaction of 4-amino-1,2,4-triazole and 4-amino-3,5-dialkyl- 1,2,4-triazoles (alkyl = Me, Et) with dimethyl and diethyl sulfate at ambient temperature. Subsequent ion metathesis gave hexafluorophosphates and bis(trifluoromethylsulfonyl)imides as crystalline derivatives or ionic liquids.Methylation at 100 ◦ C gave the 4-(dimethylamino)-1-methyl-1,2,4- triazolium salt, a precursor for a new carbene ligand which was incorporated into Ag and Rh complexes. The synthesis of 5-bromo-4-(dimethylamino)-1-methyl-1,2,4-triazolium hexafluorophosphate is also reported. Crystal structures of fourteen compounds have been determined by X-ray diffraction Graphical Abstract Quaternary 4-Amino-1,2,4-triazolium Salts: Crystal Structures of Ionic Liquids and N-Heterocyclic Carbene (NHC) Complexes

Aiming at the structural diversification of phakellin- and isophakellin-type pyrrole-imidazole alkaloids on the skeleton level, the reaction of dipyrrolopyrazinones and pyrroloindolizines with dichlorocarbene was investigated. Conversions resulted in ring expansion affording novel chlorinated and brominated dipyrroloazepinones, pyridopyrroloazepinones, and dipyrrolopyrazinones. Structures of the tetracyclic products with hitherto unknown architectures have been secured by X-ray analyses. Graphical Abstract Skeleton Diversity by Cyclopropanation of Tricyclic Acylenamines

Cyanobenzoic acids proved to be suitable starting materials for the transformation into multifunctional products of the 4H-imidazole type. Employing two different pathways, the new derivatives 1b-d which possess carboxy/cyano groups were synthesized. In addition, derivative 1d formed the basis for the construction of novel bis-4H-imidazoles with two different complexation spheres. The structures of all new derivatives were confirmed by NMR spectroscopy, mass spectrometry, elemental analysis, UV/Vis-/fluorescence spectroscopy, and electrochemical measurements. Graphical Abstract The Synthesis of Carboxy- and Cyano-substituted 4H-Imidazoles: Redoxactive Ligands as Starting Materials for Metal-Metal Multiply Bonded Compounds and Heterobimetallic Complexes

Using ab initio calculations (B3LYP 6-31G*) the geometries of diethyl, dimethoxy and dimethylamino imidazolium salts were studied as representative models of imidazolium salts bearing heteroatoms directly attached to the ring nitrogen atoms of the imidazolium core units. In all cases the syn and anti arrangement of the substituents could be identified. In addition to the theoretical studies, eleven dialkoxy imidazolium salts were prepared by alkylation of six 1-hydroxy-imidazole-3-oxides using dimethyl or diethyl sulfate as strong alkylating reagents. The kinetic acidities of these compounds were studied by measuring the pseudo-first order reaction rates of the H/D exchange process of the C 2 -H proton of compounds 3 - 9. The observed kinetic acidities are much higher than reaction rates observed for simple imidazolium salts; half-lifes of the H/D exchange are usually in the range of minutes. Similar to dialkyl/aryl imidazolium salts, all prepared dialkoxy imidazolium salts could be used as precatalysts in standard aqueous Suzuki coupling reactions. In addition, two representative dialkoxy imidazolium salts could be used in supramolecular anion recognition, as demonstrated by binding studies towards iodide as guest. Graphical Abstract Hydroxy-1H-imidazole-3-oxides – Synthesis, Kinetic Acidity, and Application in Catalysis and Supramolecular Anion Recognition

Unnatural (+)-capensifuranone (+)-2 and its epimer (-)-5-epi-capensifuranone 6 were prepared from enantiopure methyl-branched aldehyde 4, employing cyclisation with 3-bromomethacrylic acid to 4-bromofuranones 5a,b followed by Negishi cross coupling. Compound 4 was obtained from the preen-gland wax-derived ester 3 after ozonolysis and reductive work-up. The configuration of 6 was determined via the X-ray crystal structure analysis of a derivative 10. Compounds (+)-2, 5a,b and 6 showed cytotoxic activity against L-929 mouse fibroblasts, and KB-3-1 HeLa and U-937 lymphoma cells. Graphical Abstract Ex Chiral Pool Synthesis from a Highly Methyl-branched Wax Ester and Biological Properties of (+)-Capensifuranone

Activation of imines of aromatic aldehydes by N-glycosylation with O-pivaloyl-galactopyranosyl bromide (pivalobromogalactose) and subsequent addition of organotin, organolithium, Grignard, or organozinc reagents afforded α-arylalkylamines with moderate to high diastereoselectivity. Graphical Abstract Stereoselective Synthesis of α-Arylalkylamines by Glycosylation-induced Asymmetric Addition of Organometallic Compounds to Imines

“Asymmetric Electrophilic α-Amidoalkylation” reactions with a chiral alkylaminocarbonyl unit as chiral auxiliary are used for the stereoselective synthesis of 2-substituted piperidine derivatives. Intramolecular condensation of the nitrogen of the aminocarbonyl group with the keto function present in the newly introduced side chain of the amidoalkylation products results in the formation of hexahydropyrido[1,2-c]pyrimidinones. After reduction and removal of the N-alkyl moiety of the chiral auxiliary the target compounds, enantiopure octahydro-1H-pyrido[1,2-c]pyrimidin-1-ones, are obtained. Graphical Abstract Asymmetric Synthesis of Pyrido[1,2-c]pyrimidinones

A synthetic access to novel cinnamoamides 6 was discovered by chance and explored following a two-step route. Compounds 3 were available from 6-amino-1,3-dimethyluracil (1) by acylation using benzoyl chlorides 2 and subsequently converted to 2-cyano-3-(N-methylamino)cinnamic acid methyl amides 6. This sodium methoxide-catalyzed reaction involves ring opening of the pyrimidine ring followed by elimination of CO to form dimethyl carbonate and rearrangement. The application of 6 as potential catecholamine-O-methyl transferase (COMT) inhibitors for the treatment of Parkinson’s disease is discussed. Graphical Abstract Unexpected Sodium Methoxide-catalyzed Rearrangement of 6-Amino-5-aroyl-1,3-dimethyluracils to Form Novel Cinnamoamides

Stable 3-oxosultams were synthesized by oxidation of the 2-hetaryl-substituted isothiazolium salts. X-Ray crystal structure analyses of the sultams reveal the existence of strong and weak hydrogen bonds, which lead to different interaction combinations and solid state structures. While the bond lengths and angles in the isothiazol rings of the sultams are similar, the dihedral angles between the isothiazol rings and the hetaryl substituents are influenced by the position of the nitrogen atom in the pyridine ring and its substituents. The sultams form chain structures, dimeric head-to-tail structures or two-dimensional networks. Graphical Abstract Sultam and Sultim Structures, Part 5 [1]. Weak Hydrogen Bonds in Molecular Networks of 2-Hetaryl-3-oxosultams in Comparison with 2-Aryl-3-oxosultams

Reaction of (E)-3-aminomethylene-α-D-erythro-hexopyranosid-2-ulose 5 with substituted 5- aminopyrazoles afforded the pyrano-anellated pyrazolo[1,5-a]pyrimidines 8. The treatment of the corresponding (E)-2-aminomethylene-α-D-erythro-hexopyranosid-3-ulose 6 with 5-aminopyrazoles and (benzimidazol-2-yl)acetonitrile yielded in a ring transformation process the D-erythronoyl-pyrazolo[ 1,5-a]pyrimidine-3-carbonic acid derivatives 10 and D-erythronoyl-pyrido[1,2-a]benzimidazole- 4-carbonitrile (12), respectively Graphical Abstract Anellation and Ring Transformations of Push-pull-functionalized Deoxypyranosiduloses

A series of 1-substituted diethyl 1H-pyrrole-3,4-dicarboxylates 4a - o were prepared in 14 - 93% yield by acid-catalysed treatment of diethyl 2,3-bis[(E,E)-(dimethylamino)-methylidene]succinate (2) with various aliphatic and (hetero)aromatic primary amines 3a - o. The configuration of the C=C double bonds in the bis-enaminone 2 was determined by 1H NMR and HMBC spectroscopy. Graphical Abstract A Simple Synthesis of 1-Substituted Diethyl Pyrrole-3,4-dicarboxylates

The synthesis of a 24-membered cyclic depsipeptide with an alternating sequence of phenyllactic acid and α-aminoisobutyric acid (Aib) is described. The linear precursor was prepared via the ‘azirine/oxazolone method’ using 2,2-dimethyl-3-amino-2H-azirines as building blocks for the α,α-disubstituted α-amino acid Aib. The macrolactonization leading to the cyclodepsipeptide was achieved by the ‘direct amide cyclization’, i. e., by treatment of a solution of the linear precursor in toluene with HCl gas. Graphical Abstract Synthesis of a Regular 24-membered Cyclodepsipeptide by Direct Amide Cyclization

Bicyclic salicylates were prepared by [3+3] cyclization of 1,3-bis(silyl enol ethers) with cyclic 3-(silyloxy)alk-2-en-1-ones. Graphical Abstract Synthesis of Bicyclic Salicylates by [3+3] Cyclization of 1,3-Bis(Silyl Enol Ethers) with Cyclic 3-(Silyloxy)alk-2-en-1-ones

Ethynyl phenothiazines are oxidatively coupled to symmetrical dumbbell-shaped butadiynylbridged diphenothiazines in good yields. These molecules show intense absorption bands, intense blue-green luminescence with large Stokes shifts, and reversible oxidation potentials in the anodic region. Thermally, these butadiynes do not undergo topochemical polymerization, but oligomerizations to oligomeric polycyclic heterocycles with complex structures in the melt. STM images of two representatives on HOPG (highly oriented pyrolytic graphite) show the formation of monolayers adsorbed by attractive π-π interactions. Graphical Abstract Butadiynyl-bridged Diphenothiazines – Redox-active Fluorophores and Self-assembly on HOPG

Treatment of the 1,3,4-oxadiazoles 3a and 3b with 3-chloropentane-2,4-dione gave the thiazoles 4a and 4b, respectively, which were methylated to furnish compounds 5a and 5b. The formation of 1,3,4-oxadiazoles using the 1,3-dithietane 1 as starting material, and the consecutive reactions mentioned above were transferred into sugar chemistry to provide the corresponding derivatives 6 - 9 in good yields. The reaction of 5a with benzyl amine, ethylene diamine and o-phenylene diamine afforded compounds 10, 11, and 12, respectively, which possess better stabilized push-pull systems than 5a. The structures of 3a, 4a, 5a, 10, 11, and 12 were compared with the previously proposed structures I - VI, respectively. The structures of compounds 1, 3b, and 11 were confirmed by X-ray diffraction studies. Graphical Abstract Reinvestigation of the Thiazole Synthesis with Ethyl 3-Amino-2- [5-aryl-1,3,4-oxadiazol-2(3H)-ylidene]-3-thioxopropanoates and Related Reactions

Anthranicine, a cyclic hexapeptide containing anthranilic acid and pipecolic acid, was isolated from a mycophilic Acremonium species. The structure and stereochemistry of the compound featuring two D-configurated amino acids are discussed. Graphical Abstract Anthranicine, an Unusual Cyclic Hexapeptide from Acremonium sp. A29-2004

The etherification of the hydroxyl group of citric acid with saturated and unsaturated long-chain alkyl groups is described. This is a new approach to polydentate acids which may serve as ligands for metal or metal oxide nanoparticles. For this purpose we developed a synthetic route to long-chain ω-unsaturated alcohols and their triflate derivatives. Graphical Abstract Amphiphilic Long-chain Citric Acid Ethers

Numerous core-fluorinated perylene bisimide (PBI) dyes with various substituents at the imide positions have been synthesized by different methods. Core-difluorinated PBIs 4a-f are obtained by imidization of difluoro-substituted perylene bisanhydride 1 with appropriate primary amines or, alternatively, by nucleophilic halogen exchange reactions (Halex process) of the corresponding dibromosubstituted PBIs 2a-d,f with potassium fluoride. Core-tetrafluorinated PBIs 5a-c could also be synthesized by halogen exchange reactions of the respective tetrachlorinated PBIs 3a-c. In particular, core-fluorinated perylene bisimide pigments 4h, 5h containing hydrogen atoms in the imide positions could be obtained for the first time by deprotection of α-methylbenzyl-substituted precursors. Compared with core-unsubstituted perylene bisimides, these fluorinated dyes display hypsochromically shifted absorption and fluorescence spectra, and they exhibit fluorescence quantum yields up to unity, enabling bright yellow emission. The electrochemical properties of these electron-poor perylene bisimides have been studied. Furthermore, the packing features of a tetrafluorinated PBI derivative in the solid state have been discussed. Graphical Abstract Synthetic Routes to Core-fluorinated Perylene Bisimide Dyes and their Properties

The reaction of aniline (AH 2 ) with an oxidizing agent in acidic solution gives rise to the formation of a mixture of products containing, besides a variety of oligoanilines named as Aniline Black or Polyaniline, Mauvein as a deeply purple phenazine derivative. Although this Mauvein synthesis was developed by W.H. Perkin more than 150 years ago and has opened the era of industrial dyestuff chemistry, the detailed mechanism of this reaction has remained rather unclear until today. The elucidation of the mechanism of the Mauvein formation as an oxidative coupling process of AH 2 is hindered by the fact that several different types of coupling reactions occur simultaneously. Among them the C,N-coupling reaction is the most important one and responsible for the formation of Polyaniline and Mauvein. It gives rise to the formation of, e. g. 2 different aniline dimers, 7 trimers and more than 20 tetramers including Mauvein as one representative of these tetramers. In the present study, the oxidative coupling of a mixture of AH 2 and 4-amino-4`-(N-anilino)-diphenylamine (TaH2) as one of the aniline trimers was studied in more detail. The reaction leads to the formation of Mauvein in satisfactory yields and, after some manipulations, widely free of byproducts. By using simple aniline derivatives as co-reagents in the oxidative coupling with TaH 2 , the reaction can be extended to the synthesis of different Mauvein derivatives most of which have been unknown to date. Graphical Abstract On the Formation of Mauvein: Mechanistic Considerations and Preparative Results

The Residual Volume Approach (RVA), a recently developed method for the prediction of fundamental physical properties of ionic liquids (ILs) is extended and now allows the estimation of ionic conductivity of unknown ILs, using a simple linear correlation between the ionic conductivity and previously defined substituent parameters - β x . The proposed method is applied to the conductivity correlations of 61 n-alkyl substituted imidazolium, tetraalkylammonium, pyrrolidinium, piperidinium, sulfonium and phosphonium homologous ILs, containing [BF 4 ]−, [Tf 2 N]−, [C 2 F 5 PF]−, [CF 3 BF 3 ]−, [C 2 H 5 BF 3 ]−, [F(HF) 2.3 ]−, [Br]−, [I]−, and [formate]− as anions. The influence of the ion type - both anion and cation - on the property changes is discussed. Moreover, it is shown that relatively rigid cations with C 2 symmetry decrease the expected conductivity in the same manner as they increase the viscosity of the ILs. Graphical Abstract The Residual Volume Approach II: Simple Prediction of Ionic Conductivity of Ionic Liquids

The guanidinium salt-based ionic liquid N,N,N`,N`,N``-pentabutyl-N``-benzyl-guanidinium bromide was synthesized and characterized by 1H and 13C NMR spectroscopy in solution and by single crystal X-ray structure analysis. The MO computational hybrid method of Morokuma and coworkers (ONIOM method) is applied to compare experimental and quantum chemical results. Four calculation models for two layer ONIOM calculations are defined based on differences of the area for the high-level layer region. Optimized geometries, interaction energies between the cation and the anion, and atomic charges are compared to data of full-QM calculations for the optimized geometry as well as of an experimental X-ray structure determination. The results indicate that it is mandatory for obtaining reasonable results that the parts of the substituent groups which are directly bound to the amino nitrogen atoms are included into the high-level layer. This least required ONIOM model for guanidinium-type ionic liquids can save computational cost of 90% compared to the full-QM SCF calculation. Graphical Abstract An ONIOM Study of a Guanidinium Salt Ionic Liquid. Experimental and Computational Characterization of N,N,N`,N`,N``-Pentabutyl-N``-benzylguanidinium Bromide

The establishment of quantitative relationships between numerous molecular properties and chemical structures is now of great importance to society in understanding and improving environmental, medicinal and technological aspects of life. Quantitative structure-activity (property) relationships (QSA(P)R) relate physical, chemical, physico-chemical, technological and biological properties of compounds to their structure. A major factor driving the widespread use of QSP(A)R models is the rational estimation of properties of new compounds, without first synthesizing and testing them. Some of our recent findings in the field are briefly discussed below. Graphical Abstract Computational Chemistry Approaches for Understanding how Structure Determines Properties