Association of liquid-assisted grinding with aging accelerates the inherently slow slipping-on of a dibenzo-24-crown-8 over the N -hydroxysuccinimide ester of an ammonium-containing thread

International audienceSolvent-free and solvent-less slipping-on of the dibenzo-24-crown-8 (DB24C8) over the N-hydroxysuccinimide end of an ammonium-containing thread has been studied and compared to the same reaction operated in solution. Slippage proved to be possible in solvent-free conditions, but the fastest slippage was obtained under heating when preliminary Liquid-Assisted Grinding (LAG) conditions were applied to the reactants followed by aging under an atmosphere of acetonitrile. The recently awarded 2016 Nobel Prize in chemistry 1 has put a light on molecular machines. 2 Some of these machines benet from their interlocked molecular architecture 3 so that the relative displacement of one interlaced element among others becomes possible and controllable. Hence, the straightforward synthesis of interlocked molecules is appealing in order to access novel molecular machines. Using the slippage strategy, 4 we recently reported the preparation of an insulated and stor-able, albeit activated, N-hydroxysuccinimide (NHS) ester-containing [2]rotaxane building block (Scheme 1 and entry 1 of Table 1). 5 This compound is a valuable activated building block for post-interlocking elongation of the encircled axle using bulky amino compounds. 6 As the mechanism of such aminolysis reactions preserves the mechanical bond, it allowed the efficient and straightforward preparation of more sophisticated interlocked compounds such as [2] and [3]rotaxane molecular shuttles. 5,6 Improving the access to the NHS ester-containing [2]rotaxane building block 2 is therefore of real interest. This is particularly justied since in acetonitrile solution , the slipping-on of the DB24C8 (3 equiv.) over the NHS extremity of an ammonium-containing thread (at a concentration of 3 Â 10 À2 M) is very slow and necessitates heating (13 days and 333 K, respectively). In this paper, we wondered if this slipping-on process could be possible, nay improved, by drastically reducing the amount of solvent. Since solvent-free/ solvent-less conditions are highly prone to induce mass transfer limitations, utilisation of ball-milling was envisaged. Indeed it was previously shown that ball-milling could improve the speed of inherently slow reactions. 7 A few examples of solvent-free/solvent-less synthesis of rotaxanes have been reported to date, 8 and to the best of our knowledge, only three of these examples are related to slippage process through a co-melting process 9 or an immediate solvent evaporation method. 10 Herein, different experimental procedures were considered to yield the activated [2]rotaxane 2: solvent-free grinding, 11 Liquid-Assisted Grinding (LAG), 12 and aging by heating with or without an acetonitrile atmosphere. 13 LAG is dened as the use of small amounts of a non-reactive liquid during grinding. 14 It has been shown by us and by other research groups to have a considerable effect on the course of reactions run under mechanical forces. 15 Besides, aging is the action of letting the reaction take place in the absence of any mechanical agitation. This reactivity Scheme 1 Slippage process of the NHS ester-containing molecular axle 1 by the DB24C8

Poly(ethylene) glycols and mechanochemistry for the preparation of bioactive 3,5-disubstituted hydantoins

International audienceMechanochemistry was effective for the preparation of 3,5-disubstituted hydantoins from a-amino methyl esters, using either 1,1 0-carbonyldiimidazole (CDI) or alkyl isocyanates. The preparation of the antimicrobial additives, 3-allyl-5,5 0-dimethyl hydantoin (ADMH) and 1-chloro-3-ethyl-5,5 0-dimethyl hydantoin (CEDMH) were performed by grinding. A chlorination reaction, never described before by mechanochemistry was achieved by Ca(ClO) 2 , while the preparation of the bioactive anticonvulsant marketed drug ethotoin was achieved by a novel approach based on poly(ethylene) glycol (PEGs) assisted grinding

Cu(0), O2 and mechanical forces: a saving combination for efficient production of Cu-NHC complexes

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A more sustainable and efficient access to IMes·HCl and IPr·HCl by ball-milling

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Faster and cleaner dynamic kinetic resolution via mechanochemistry

International audienceApplication of the ball-milling techniques to dynamic kinetic resolution accelerates reactions while avoiding the use of toxic organic solvents and reactants commonly required in these processes. In this way, dynamic kinetic resolutions can be both faster and “cleaner” in the sense that mechanochemistry enables the reduction of their environmental impact

Peptide synthesis: ball-milling, in solution, or on solid support, what is the best strategy?

International audienceWhile presenting particularly interesting advantages, peptide synthesis by ball-milling was never compared to the two traditional strategies, namely peptide syntheses in solution and on solid support (solid-phase peptide synthesis, SPPS). In this study, the challenging VVIA tetrapeptide was synthesized by ball-milling, in solution, and on solid support. The three strategies were then compared in terms of yield, purity, reaction time and environmental impact. The results obtained enabled to draw some strengths and weaknesses of each strategy, and to foresee what will have to be implemented to build more efficient and sustainable peptide syntheses in the near future

High Catalytic Activity of Heterometallic (Fe6Na7 and Fe6Na6) Cage Silsesquioxanes in Oxidations with Peroxides

International audienceTwo types of heterometallic (Fe(III),Na) silsesquioxanes—[Ph5Si5O10]2[Ph10Si10O21]Fe6(O2‒)2Na7(H3O+)(MeOH)2(MeCN)4.5.1.25(MeCN), I, and [Ph5Si5O10]2[Ph4Si4O8]2Fe6Na6(O2‒)3(MeCN)8.5(H2O)8.44, II—were obtained and characterized. X-ray studies established distinctive structures of both products, with pair of Fe(III)-O-based triangles surrounded by siloxanolate ligands, giving fascinating cage architectures. Complex II proved to be catalytically active in the formation of amides from alcohols and amines, and thus becoming a rare example of metallasilsesquioxanes performing homogeneous catalysis. Benzene, cyclohexane, and other alkanes, as well as alcohols, can be oxidized in acetonitrile solution to phenol—the corresponding alkyl hydroperoxides and ketones, respectively—by hydrogen peroxide in air in the presence of catalytic amounts of complex II and trifluoroacetic acid. Thus, the cyclohexane oxidation at 20 °C gave oxygenates in very high yield of alkanes (48% based on alkane). The kinetic behaviour of the system indicates that the mechanism includes the formation of hydroxyl radicals generated from hydrogen peroxide in its interaction with di-iron species. The latter are formed via monomerization of starting hexairon complex with further dimerization of the monomer

Nouvelles approches en synthèse organique : de l'activation micro-onde à la chimie sans solvant. Applications en chimie hétérocyclique

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Nouvelles approches en synthèse organique : de l'activation micro-onde à la chimie sans solvant. Applications en chimie hétérocyclique

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Le poly(éthylène glycol) en synthèse organique : du support au solvant

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