Octa(3-aminopropyl)silsesquioxane (OAS-POSS) Synthesis Routes

Wacker-Chemie Patent Origins and the Absence of Early Characterization Data

Octa(3-aminopropyl)silsesquioxane hydrochloride (OAS) was first described in a patent filed by Wacker-Chemie GmbH.¹ That document, however, reports neither a method for its preparation nor the spectroscopic data required for its full identification.²

Feher's Hydrolytic Condensation Route to OAS-POSS Hydrochloride

Seven years later, Feher³ investigated the hydrolytic condensation of (3-aminopropyl)triethoxysilane in methanolic solution, using hydrochloric acid as the catalyst, in order to obtain the octakis(3-aminopropyl)octasilsesquioxane chloride salt. Under these conditions the yield was 30% and the reaction required four weeks. Modifications of this procedure reported in the literature involve replacing the hydrolyzable group with a methoxy group or adding PtCl₄ as a cocatalyst, although such changes do not significantly increase the yield.^4–6

Kaneko and co-workers subsequently developed another valuable approach.⁷ They examined the hydrolytic condensation of APTMS in the presence of a range of acid catalysts and found trifluoromethanesulfonic acid to be the most effective. Under these conditions OAS-POSS-CF₃SO₃ was obtained after 5 to 6 hours in approximately 90% overall yield, although the authors observed deca-substituted polyhedral silsesquioxane as a minor by-product.⁸

A modified method based on commercially available (3-aminopropyl)triethoxysilane (APTES) was reported later. Compounds 1-3 (see the scheme below) are accessible in a one-step hydrolytic condensation of APTES with an appropriate amount, relative to APTES, of either hydrochloric acid (3.6 eq) or trifluoromethanesulfonic acid, which affords a high yield while avoiding the formation of deca-substituted and other polyhedral silsesquioxanes that are difficult to separate.⁹

Scheme 1. Synthesis of [OAS-POSS-NH₃]X (Chemistry - A European Journal 2014, 20, 15966-15974)

Alternative Synthetic Routes and Purification Considerations

The outcome of these preparations is governed not only by the choice of silane precursor but by the entire reaction environment, because the yield and the constitution of the resulting silsesquioxane depend simultaneously on the acidity of the catalyst, the polarity and proticity of the solvent, the concentration of the precursor, the amount of water available for hydrolysis and the temperature at which the condensation is allowed to proceed. The formation of a closed cage is therefore a compromise between two consecutive processes that respond differently to these variables. Hydrolysis of the trifunctional silane generates the silanol pool from which the cage is assembled, whereas condensation determines whether that pool closes into a discrete polyhedral oligomeric silsesquioxane (POSS) scaffold of T₈ polyhedron type or drifts toward larger cages, incompletely condensed silanols and, ultimately, cross-linked polymeric material. Optimizing the preparation of octa(3-aminopropyl)silsesquioxane salts amounts to accelerating the first step relative to the second.^9,10

The influence of the catalyst is the most pronounced of these effects and follows the acid strength in a systematic manner. Hydrochloric acid, applied in methanol at room temperature, delivers the chloride salt slowly, since hydrolysis of the ethoxy groups is only moderately accelerated and several weeks are required before crystallization of the product is complete. Trifluoroacetic acid, a considerably stronger acid with a pK_a of 0.52, shortens the hydrolysis of APTES to a few hours at 50 °C and raises the yield of the trifluoroacetate salt to approximately 90%. Trifluoromethanesulfonic acid, whose Hammett acidity function H₀ reaches −14.1 and whose pK_a is close to −12, is more effective still and furnishes the triflate salt in 95% yield under the same thermal regime.¹¹ The rationalization is straightforward, in that the stronger the acid, the faster the initial hydrolytic step, the shorter the total reaction time and the narrower the window during which uncontrolled condensation can generate by-products. Attempts to reproduce this behavior with sulfuric acid, phosphoric acid or acetic acid were unsuccessful, since these systems either left the reaction essentially unchanged or promoted the formation of by-products.⁹

The nature of the hydrolyzable group at silicon acts in concert with the catalyst and cannot be treated as a trivial substitution. Trifluoroacetic acid applied to (3-aminopropyl)trimethoxysilane, where the methoxy groups hydrolyze very rapidly, was reported to give hexagonally twisted silsesquioxane oligomers or mixtures of silanol-containing silsesquioxanes rather than a discrete cage. Replacing the methoxy group by the more slowly hydrolyzing ethoxy group under otherwise comparable conditions restores control over the assembly and delivers the closed cage architecture. The same balance underlies the appearance of T₁₀ cages as competing products in related systems, where cage size and the possibility of cage rearrangement are determined by the relative rates of hydrolysis and condensation rather than by the stoichiometry alone.¹⁰

The solvent exerts a comparable influence, primarily through its ability to dissolve both the silane and the ammonium salt formed and through the amount of water it can carry. Methanol remains the medium in the hydrochloric acid protocol, in which the moderate polarity of the alcohol and its miscibility with the aqueous acid keep both the silane and the emerging ammonium salt in solution throughout the condensation, whereas water is the medium of choice when trifluoroacetic or trifluoromethanesulfonic acid is used, because the ammonium salts are highly soluble and the hydrolysis is no longer water limited. A survey of propan-1-ol, propan-2-ol, tetrahydrofuran, dimethylformamide and acetonitrile produced no improvement, since these solvents either failed to support the condensation or promoted side reactions. The product itself imposes a further constraint, in that the chloride salt is markedly hygroscopic and the trifluoroacetate salt more so, which makes the removal of solvent and the storage of the isolated material as important as the condensation step itself. The triflate salt is the most convenient in this respect, being non-hygroscopic and readily soluble in dimethyl sulfoxide, dimethylformamide, methanol and water.⁹

Concentration and reaction time are closely coupled to the preceding variables. Raising the concentration of APTES from 0.178 to 0.534 mol dm⁻³ in the hydrochloric acid protocol increases the yield of the chloride salt from 30% to 45% and shortens the reaction from six weeks to two, because a more concentrated silanol pool favors intramolecular closure over slow oligomerization. Literature variants that pursue the same objective by seeding the mixture with a small quantity of the product or by concentrating the filtrate are considerably less practical, since seeding is impossible when the reaction is performed for the first time and the evaporation of several liters of solvent is time consuming on a laboratory scale. Concentration also raises the local water content and precipitates unwanted by-products, which either redissolve the hygroscopic product or promote its decomposition. The routes based on the fluorinated acids avoid this difficulty entirely, in that the trifluoroacetate salt is obtained within a few hours at 50 °C, with drying at 100 °C and washing with acetone completing the isolation.⁹

The spectroscopic response to this optimization is unambiguous and provides the criterion by which the conditions were selected. All three salts display a single symmetric resonance in the ²⁹Si NMR spectrum between −66.5 and −66.6 ppm, a value characteristic of octameric silsesquioxanes, and the absence of any further signal demonstrates that formation of the T₈ cage is strongly preferred under the conditions employed. The ¹H and ¹³C NMR spectra show a single set of resonances consistent with the high symmetry of the cage. High resolution mass spectrometry confirms the octameric constitution through the ions at 881.29, 441.15 and 294.44 corresponding to the successive loss of the acid and to the singly, doubly and triply protonated cage, with no evidence for cages other than T₈, for silanol-terminated species or for polymeric material. In the infrared spectra the Si-O-Si stretching vibration of the cage appears at 1132 to 1138 cm⁻¹ and the N-H vibrations of the ammonium group between 2944 and 3041 cm⁻¹, while spectra recorded for nujol mulls show no band attributable to silanol groups, which confirms that the cage is fully closed. Powder X-ray diffraction establishes the crystallinity of the salts and provides the reference patterns against which the phase purity of subsequently functionalized derivatives is assessed.^9,10

Applications of OAS-POSS as an Amine-Functionalized T8 Scaffold

These considerations explain why the free amine is rarely used directly. Octakis(3-aminopropyl)octasilsesquioxane can be liberated from the chloride salt on an ion exchange resin, but it is stable in methanol only at concentrations below 30 mg per liter and at −35 °C, since the basicity of the 3-aminopropyl group generates hydroxide ions in the presence of water and these cleave the Si-O-Si bonds of the cage. The resulting ring opening affords a tetrasilanol which subsequently condenses to polymeric material. Conversion of the amine into the chloride, trifluoroacetate or triflate salt suppresses this pathway and renders the compound storable, which is the reason why the ammonium salts, rather than the free amine, serve as the practical entry point to the wide family of POSS derivatives bearing nitrogen in the organic arms, including porous silsesquioxane-imine frameworks and amide-POSS derivatives.^3,9

References

(1) Weidner, R.; Zeller, N.; Deubzer, B.; Frey, V. Organooligosilsesquioxanes. 5047492, 1991.

(2) Hill, A. F.; Fink, M. J. Advances in Organometallic Chemistry; Academic Press, 2011.

(3) Feher, F. J.; Wyndham, K. D. Amine and Ester-Substituted Silsesquioxanes: Synthesis, Characterization and Use as a Core for Starburst Dendrimers. Chem. Commun. 1998, No. 3, 323–324.

(4) Gravel, M.-C.; Zhang, C.; Dinderman, M.; Laine, R. M. Octa(3-Chloroammoniumpropyl) Octasilsesquioxane. Appl. Organomet. Chem. 1999, 13, 329–336.

(5) Feher, F. J.; Wyndham, K. D.; Soulivong, D.; Nguyen, F. Syntheses of Highly Functionalized Cube-Octameric Polyhedral Oligosilsesquioxanes (R8Si8O12). J. Chem. Soc. Dalton Trans. 1999, 1491–1498.

(6) Gültek, A.; Seçkın, T.; Adigüzel, H. İ. Design and Characterization of Amino and Chloro Functionalized Rhombohedral Silsesquioxanes. Turk. J. Chem. 2005, 29, 391–399.

(7) Kaneko, Y.; Shoiriki, M.; Mizumo, T. Preparation of Cage-like Octa(3-Aminopropyl)Silsesquioxane Trifluoromethanesulfonate in Higher Yield with a Shorter Reaction Time. J. Mater. Chem. 2012, 22, 14475–14478.

(8) Tokunaga, T.; Shoiriki, M.; Mizumo, T.; Kaneko, Y. Preparation of Low-Crystalline POSS Containing Two Types of Alkylammonium Groups and Its Optically Transparent Film. J. Mater. Chem. C 2014, 2, 2496–2501.

(9) Janeta, M.; John, Ł.; Ejfler, J.; Szafert, S. High-Yield Synthesis of Amido-Functionalized Polyoctahedral Oligomeric Silsesquioxanes by Using Acyl Chlorides. Chem. – Eur. J. 2014, 20, 15966–15974. https://doi.org/10.1002/chem.201404153

(10) Janeta, M.; John, Ł.; Ejfler, J.; Szafert, S. Novel Organic–Inorganic Hybrids Based on T8 and T10 Silsesquioxanes: Synthesis, Cage-Rearrangement and Properties. RSC Adv. 2015, 5, 72340–72351. https://doi.org/10.1039/C5RA10136K

(11) Raamat, E.; Kaupmees, K.; Ovsjannikov, G.; Trummal, A.; Kütt, A.; Saame, J.; Koppel, I.; Kaljurand, I.; Lipping, L.; Rodima, T.; Pihl, V.; Koppel, I. A.; Leito, I. Acidities of Strong Neutral Brønsted Acids in Different Media. J. Phys. Org. Chem. 2013, 26, 162–170.