Reaction rates as a function of scale within ionic liquids: microscale in droplet microreactors versus macroscale reactions in the case of the Grieco three-component condensation reaction

Task-specific ionic liquids (TSILs) and more specifically binary task-specific ionic liquids (BTSILs), a unique subclass, have been shown to be excellent supports for solution-phase chemistry. The negligible volatility of ionic liquids enables their use as stable droplet microreactors in atmospheric environments without oil protection or confinement. These droplets can be moved, merged and mixed by electrowetting on a chip. Solution-phase synthesis can be performed on these open digital microfluidic labs-on-a-chip as illustrated by a study of the Grieco three-component reaction in [tmba][NTf(2)]-droplet (tmba=N-trimethyl-N-butylammonium NTf(2)=bis(trifluoromethylsulfonyl)imide) microreactors. A detailed study of matrices and scale effects on conversion and kinetic rates of this three-component condensation is presented in this paper. Reactions have been shown to be slower in droplets than in batches in the absence of additional mixing. Also, a significant influence of the ionic-liquid matrix has been observed. Finally, an increase of droplet's temperature resulted in a kinetics enhancement so as to reach macroscale reaction rates, probably because of a much better mixing of reaction's components involving a Marangoni's effect.     

Carboxylic acid functional group analysis using constant neutral loss scanning-mass spectrometry

The present study describes the development of a new analytical technique for the functional group determination of the carboxylic moiety using atmospheric pressure chemical ionization-mass spectrometry (APCI-MS/MS) operated in the constant neutral loss scanning (CNLS) mode. Carboxylic groups were first derivatized into their corresponding methyl esters by reacting with BF₃/methanol mix and the reaction mixture was then directly injected into the APCI chamber. The loss of methanol (m/z = 32 amu) resulting from the fragmentation of the protonated methyl esters was then monitored. Applying this method together with a statistical approach to reference mixtures containing 31 different carboxylic acids at randomly calculated concentrations demonstrated its suitability for quantitative functional group measurements with relative standard deviations below 15% and a detection limit of 0.005 mmol L⁻¹. Its applicability to environmental matrices was also shown through the determination of carboxylic acid concentrations inside atmospheric aerosol samples. To the best of our knowledge, it is the first time that the tandem mass spectrometry was successfully applied to functional group analysis, offering great perspectives in the characterization of complex mixtures which are prevailing in the field of environmental analysis as well as in the understanding of the chemical processes occurring in these matrices.     

Synthesis of a novel cage-functionalized chiral binaphthol host: a potential new agent for enantioselective recognition of chiral ammonium salts

Optically active, cage-functionalized crown ether (R)-3 which contains a 1,1′-bi-2-naphthol moiety has been prepared. Subsequently, the ability of (R)-3 to selectively recognize the enantiomers of guest ammonium salts, i.e., 4 and 5 in transport experiments was studied. Host (R)-3 displays significantly enhanced enantiomeric selectivity toward complex formation with 4 vis-à-vis complex formation with 5. The relative energetics of various relevant host–guest complexes have been investigated computationally.     

The 0-1 Knapsack problem with a single continuous variable

Specifically we investigate the polyhedral structure of the knapsack problem with a single continuous variable, called the mixed 0-1 knapsack problem. First different classes of facet-defining inequalities are derived based on restriction and lifting. The order of lifting, particularly of the continuous variable, plays an important role. Secondly we show that the flow cover inequalities derived for the single node flow set, consisting of arc flows into and out of a single node with binary variable lower and upper bounds on each arc, can be obtained from valid inequalities for the mixed 0-1 knapsack problem. Thus the separation heuristic we derive for mixed knapsack sets can also be used to derive cuts for more general mixed 0-1 constraints. Initial computational results on a variety of problems are presented. Received May 22, 1997 / Revised version received December 22, 1997 Published online November 24, 1998     

Renormalization Group for Strongly Coupled Maps

Systems of strongly coupled chaotic maps generically exhibit collective behavior emerging out of extensive chaos. We show how the well-known renormalization group (RG) of unimodal maps can be extended to the coupled systems, and in particular to coupled map lattices (CMLs) with local diffusive coupling. The RG relation derived for CMLs is nonperturbative, i.e., not restricted to a particular class of configurations nor to some vanishingly small region of parameter space. After defining the strong-coupling limit in which the RG applies to almost all asymptotic solutions, we first present the simple case of coupled tent maps. We then turn to the general case of unimodal maps coupled by diffusive coupling operators satisfying basic properties, extending the formal approach developed by Collet and Eckmann for single maps. We finally discuss and illustrate the general consequences of the RG: CMLs are shown to share universal properties in the space-continuous limit which emerges naturally as the group is iterated. We prove that the scaling properly ties of the local map carry to the coupled systems, with an additional scaling factor of length scales implied by the synchronous updating of these dynamical systems. This explains various scaling laws and self-similar features previously observed numerically.     

Dibenzofuran Derivatives Inspired from Cercosporamide as Dual Inhibitors of Pim and CLK1 Kinases

Pim kinases (proviral integration site for Moloney murine leukemia virus kinases) are overexpressed in various types of hematological malignancies and solid carcinomas, and promote cell proliferation and survival. Thus, Pim kinases are validated as targets for antitumor therapy. In this context, our combined efforts in natural product-inspired library generation and screening furnished very promising dibenzo[b,d]furan derivatives derived from cercosporamide. Among them, lead compound 44 was highlighted as a potent Pim-1/2 kinases inhibitor with an additional nanomolar IC₅₀ value against CLK1 (cdc2-like kinases 1) and displayed a low micromolar anticancer potency towards the MV4-11 (AML) cell line, expressing high endogenous levels of Pim-1/2 kinases. The design, synthesis, structure–activity relationship, and docking studies are reported herein and supported by enzyme, cellular assays, and Galleria mellonella larvae testing for acute toxicity.     

Diisothiocyanates as heterodienophiles or dipolarophiles in the presence of α‐thioxothioamides or mesoionic thiazoles

Reactions of α‐thioxothioamides ( 1 ) with diisothiocyanates were carried out in the hope of generating the N,N′‐bis(1,3‐thiazoline‐2‐thiones) ( A ). Although that purpose could not be achieved, we succeeded in preparing the monocycloadducts 7 from the phenylene‐1,2‐diisothiocyanate ( 4 ). The benzimidazole derivatives 8 and 9 were also characterized and a mechanism was assumed to account for this intramolecular process. On the other hand, the regioselective synthesis of the N,N′‐biimidazole ( 13 ) containing the phenylene bridge was performed by the treatment of the 5‐aminothiazolium chloride ( 2 ) with the diisothiocyanate ( 4 ) in a basic medium. The mesoionic derivative 13 probably arises from the monoimidazolium‐4‐thiolate ( 12 ) which was shown to react with the salt 2 under similar conditions to give the primary cycloadduct 14 as an intermediate towards the bis(imidazolium) ( 13 ). © 2001 John Wiley & Sons, Inc. Heteroatom Chem 12:617–624, 2001     

Addition of isocyanides to α‐(methylthio)‐benzylidenamidinium iodides: A surprising access to 2‐(dialkylamino)imidazoles and 3,5‐diamino‐2H‐pyrrolium salts

A number of 2‐(dialkylamino)‐5‐(methylthio)imidazoles 2 are obtained by treating the formamidinium iodides 1a,b with isocyanides R³ NC under mild conditions. Reduction of these species can occur in the reaction medium to furnish the corresponding imidazoles 3 . In some cases, double cycloaddition across the imine bond of starting salts 1 also provides the (azetidin‐1‐yl‐methylene)ammonium iodides 4 . Reactions with tert‐butyl and isopropyl isocyanides in refluxing acetonitrile convert the acetamidinium iodide 1c into the 3,5‐diamino‐2H‐pyrrolium salts 7 . Mechanisms are suggested to account for these ring‐closure processes. © 2000 John Wiley & Sons, Inc. Heteroatom Chem 11:370–376, 2000     

Ferrocene and Porphyrin Monolayers on Si(100) Surfaces: Preparation and Effect of Linker Length on Electron Transfer

The missing link : Ferrocene and porphyrin monolayers are tethered on silicon surfaces with short (see picture, left) or long (right) linkers. Electron transfer to the silicon substrate is faster for monolayers with a short linker.

     

5-Aminooxazole as an internal traceless activator of C-terminal carboxylic acid: rapid access to diversely functionalized cyclodepsipeptides

A conceptually novel macrolactonization protocol has been developed. It is a domino process involving a sequence of: 1) protonation of 5-aminooxazole leading to the electrophilic iminium salt; 2) trapping of the iminium species by the neighboring C-terminal carboxylic acid leading to a putative spirolactone; and 3) intramolecular nucleophilic addition of the tethered alcohol to the spirolactone followed by fragmentation. The strategically incorporated 5-aminooxazole serves as an internal traceless activator of the neighboring C-terminal carboxylic acid, since it became an integral part of the peptide backbone after cyclization. No coupling reagent is required and the entire sequence is triggered by just a few equivalents of trifluoroacetic acid under very mild conditions (MeCN as the solvent at room temperature). The spirolactone as an activated form of the carboxylic acid has been evidenced by a sulfur-migration experiment. By combining with a three-component synthesis of 5-aminooxazole, a two-step synthesis of structurally complex cyclodepsipeptides from readily accessible starting materials was developed.