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

Benjamin Riss-Yaw (1) , Thomas-Xavier Métro (1) , Frédéric Lamaty (1) , Frédéric Coutrot (1)

1 IBMM - Institut des Biomolécules Max Mousseron [Pôle Chimie Balard]

Solvent-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.

Domaines: Chimie organique

Benjamin Riss-Yaw, Thomas-Xavier Métro, Frédéric Lamaty, Frédéric Coutrot. 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. RSC Advances, 2019, 9 (37), pp.21587-21590. ⟨10.1039/C9RA05045K⟩. ⟨hal-02322306⟩