Synthesis of borasiloxane-based macrocycles by multicomponent condensation reactions in solution or in a ball mill

Abstract

Large macrocycles containing imine and borasiloxane links are obtained in polycondensation reactions of 4-formylbenzeneboronic acid, t-Bu₂Si(OH)₂, and diamines. The multicomponent reactions can be performed in solution or – advantageously – by mechanochemical syntheses in a ball mill.

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Condensation reaction of polyamines with polyaldehydes can be used to construct molecularly defined nanostructures¹ and covalent organic frameworks.² Imine links are highly successful in this context because they are dynamic covalent bonds,³ which allow error correction processes to occur during the synthesis. We and others have shown that imines can be used in combination with boronic acid–diol condensations.^4,5 The parallel utilization of imines and boronate esters permits the construction of complex nanostructures such as macrocycles or cages in multicomponent reactions from simple building blocks. In extension of this work, we have explored whether imines could be combined with other types of condensation reactions. The condensation of silane diols with boronic acids appeared to be a potentially suited coupling reaction. This reaction is known to give cyclic borasiloxanes of the general formula (R₂SiO)₂(R′BO)₂.⁶ Diboratetrasiloxanes have been employed in polymer chemistry,⁷ but their utilization in structural supramolecular chemistry is mostly unexplored.⁸ Below we show that large organic macrocycles with borasiloxane and imine linkages are indeed accessible in simple polycondensation reactions. We also demonstrate that the macrocycles are best made by mechanochemical syntheses in a ball mill.

To test the compatibility of diboratetrasiloxanes with imine condensations, we have synthesized dialdehyde 1 in 65% yield by reacting t-Bu₂Si(OH)₂ with 4-formylbenzeneboronic acid in toluene (Scheme 1). Borasiloxane 1 was characterized spectroscopically as well as by single crystal X-ray diffraction (see ESI‡). The eight-membered (SiOBO)₄ ring of crystalline 1 is nearly flat with the coplanar 4-formylbenzene rings pointing in opposite directions. The bond lengths and angles of 1 are similar to what has been observed for (t-Bu₂SiO)₂(p-BrC₆H₄BO)₂⁹ and (t-Bu₂SiO)₂(PhBO)₂.¹⁰

Scheme 1 Step-wise and one-pot synthesis of macrocycles 2 and 3.

Subsequently, the dialdehyde 1 was combined with the diamines 4,4′-bis(aminomethyl)biphenyl and (1R,2R)-1,2-diaminocyclohexane. The latter diamine was chosen because it has been used previously with good success for the synthesis of imine macrocycles (‘trianglimines’).^1,11 The diamine with the biphenyl spacer, on the other hand, was expected to result in an expanded structure. Condensation of 1 with the diamines in organic solvents gave macrocycles 2 and 3 in moderate yields (2:33%; 3:50%). The products were characterized by NMR spectroscopy (¹H, ¹³C, ²⁹Si), elemental analysis, and mass spectrometry (see ESI‡). Attempts to obtain single crystals for crystallographic analysis were unfortunately not successful. In order to estimate the size of 2 and 3, we have performed molecular modeling using the crystallographic data of 1 for calibration (see ESI‡). The 81-membered macrocycle 2 displays a diameter (max. C⋯C distance) of approximately 2.4 nm, and the 57-membered macrocycle 3 of around 1.5 nm (Fig. 1).

Fig. 1 The structures of macrocycles 2 (left) and 3 (right) as determined by molecular modeling. Color coding: C: grey; N: blue, O: red; B: green; Si: cyan. Hydrogen atoms are not shown.

Next, we have examined whether it is possible to obtain macrocycle 2 in a one-pot reaction from t-Bu₂Si(OH)₂, 4-formylbenzeneboronic acid and 4,4′-bis(aminomethyl) biphenyl. This three-component reaction indeed gave the desired product, albeit in low isolated yield (20%). The ¹H NMR spectrum of the crude product showed that macrocycle 2 had formed as the major product, but the recrystallization procedure employed for purification resulted in significant loss of material.

The mechanochemical synthesis of compounds by grinding solids in a mortar or – advantageously – in a ball mill is rapidly gaining popularity.¹² We have recently shown that nanometer-sized cages with imine and boronate ester linkages can be obtained by polycondensation reactions in a ball mill.^5b,13 These results prompted us to explore whether macrocycle 2 could also be obtained by ball-milling. The reaction was performed using a MM200 Retsch mill operating at 30 Hz. Ball milling of the boronic acid, the silane diol and the diamine for 2 × 45 min gave a white powder. ¹H NMR spectroscopic analysis of this powder revealed that macrocycle 2 had formed in high yield (>90%; see ESI‡). Washing with dry diethyl ether gave pure 2 in an isolated yield of 85% (Scheme 2). Macrocycle 3 could be prepared in a similar fashion. The crude product was less pure (see ESI‡), but a simple recrystallization gave 3 in 65% yield. These results are evidence that borasiloxanes are accessible by ball-milling. Furthermore, they show that the mechanochemical syntheses of borasiloxane macrocycles can be achieved with high yields, outperforming more classical solution-based methods.

Scheme 2 Synthesis of macrocycles 2 and 3 by mechanochemistry.

In summary, we have described the synthesis of large macrocycles with imine and borasiloxane linkages. The macrocycles are obtained in simple multicomponent condensation reactions of t-Bu₂Si(OH)₂, 4-formylbenzeneboronic acid, and diamines. It is conceivable that related reactions with polyfunctional building blocks (e.g. triamines) can be used to generate borasiloxane-based cages or networks. Our work is also further evidence for the utility of mechanochemistry in structural supramolecular chemistry.¹⁴

This work was supported by a Marie-Curie fellowship (M.P. IEF-2009-252716), by the Swiss National Science Foundation and by the EPFL.

Notes and references

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Footnotes

† This article is part of the ChemComm ‘Mechanochemistry: fundamentals and applications in synthesis’ web themed issue.

‡ Electronic supplementary information (ESI) available. CCDC 905956. For ESI and crystallographic data in CIF or other electronic format see DOI: 10.1039/c2cc37538a

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