Acetic Acid Mediated Synthesis of Phosphonate-Substituted Titanium Oxo Clusters

New phosphonate/acetate-substituted titanium oxo/alkoxo clusters were prepared from Ti(OiPr)4 and bis(trimethylsilyl) phosphonates in the presence of acetic acid, which served to generate water in situ through ester formation. The process led to clusters with a higher degree of condensation than in previously known phosphonate-substituted titanium oxo clusters. The clusters [Ti6O4(OiPr)10(OAc)2(O3PR)2] (OAc = acetate) were obtained for a large variety of functional and non-functional groups R under a range of reaction conditions. This cluster type, which is also retained in solution, therefore appears to be very robust. Two other clusters, [Ti5O(OiPr)11(OAc)(O3PCH2CH2CH2Br)3] and [Ti5O3(OiPr)6(OAc)4(O3P-xylyl)2], were only isolated in special cases.


Introduction
Metal alkoxides are often substituted by less easily hydrolyzable organic groups to moderate their reactivity in sol-gel processes and to introduce functional or non-functional organic groups for inorganic-organic hybrid materials. [1] Such substituted metal alkoxide derivatives are obtained by reacting metal alkoxides with a protic compound, such as β-diketonates, amino alcohols, or oximes. Reaction with carboxylic acids is a special case because this normally does not result in carboxylate-substituted metal alkoxides but, instead, in carboxylate-substituted metal oxo clusters. This is due to the fact that carboxylic acids not only provide carboxylate ligands but also act as an in situ water source through esterification with the eliminated alcohol. Such oxo clusters have been used as nanosized building blocks for the construction of inorganic-organic hybrid polymers or as linker units in metal-organic frameworks (MOF). [2] Whereas carboxylate-substituted oxo/alkoxo clusters of titanium have been particularly well investigated, [3] only a few phosphonate-substituted derivatives are known. [4,5] The latter are interesting for hybrid materials because of the strong Ti-O-P bonds, especially when phosphonate ligands with functional organic groups are employed. [6] We have recently shown that titanium oxo clusters can be easily prepared by using bis(trimethylsilyl) esters. [5] Com-pared with the corresponding phosphonic acids, the esters have the advantage that they are soluble in organic solvents. Their reaction with alcohol liberates phosphonic acid, which substitutes part of the OR groups of Ti(OR) 4 in a relatively fast reaction. Oxo groups are generated in situ by esterification of either coordinated or non-coordinated phosphonic acid, as in the case of carboxylic acids. However, because esterification of phosphonic acids appears to be slow, oxo clusters with a low degree of condensation (defined O/Ti ratio of the Ti/O core [7] ) (0.25 or 0.29) were obtained, although higher degrees of condensation can be achieved under solvothermal conditions. [8] In this article we report the results of experiments in which Ti(OiPr) 4 was treated with mixtures of various bis-(trimethylsilyl) esters of phosphonic acids and acetic acid. The fundamental idea was to increase the proportion of in situ generated water by taking advantage of the easier ester formation of acetic acid. We will show that this approach leads to the formation of titanium oxo clusters substituted by both phosphonate and acetate ligands with an increased degree of condensation.

Results and Discussion
Reaction of one molar equivalent of bis(trimethylsilyl) ethylphosphonate with two equivalents of acetic acid and four equivalents of Ti(OiPr) 4 led to the centrosymmetric cluster [Ti 6 (μ 3 -O) 2 (μ 2 -O) 2 (μ 2 -OiPr) 4 (OiPr) 6 (OAc) 2 (O 3 PEt) 2 ] (1; Figure 1, OAc = acetate), with a high degree of condensation (0.67). The cluster was, to the best of our knowledge, also the first mixed carboxylate-phosphonate titanium oxo cluster to be characterized. This new cluster type consists of a Ti 6 O 4 cluster core with two parallel Ti 3 O triangles connected by μ 2 -oxo and phosphonate bridges. The nearly cu-bic Ti 6 P 2 O 10 core resembles that of polyhedral oligomeric silsesquioxanes (POSS) with a Si 8 O 12 core. The titanium and phosphorus atoms form a distorted parallelepiped ( Figure 2).  In contrast to the previously obtained clusters with symmetrical, phosphonate-substituted Ti 3 (μ 3 -O)(μ 2 -OiPr) 3 -(OiPr) 3 units as the basic structural motif, [4,5] the structure of 1 is based on unsymmetrically substituted Ti 3 (μ 3 -O)(μ 2 -OiPr) 2 (OiPr) 3 (μ 2 -OAc) units. Two Ti atoms (Ti1 and Ti2) of this unit are bridged by both an OiPr and an acetate ligand, whereas Ti1 and Ti3 are singly bridged by a μ 2 -OiPr group. A terminal OiPr ligand is coordinated to each Ti atom. The two Ti 3 O triangles are connected through a μ 2 -O unit between Ti2 and Ti3* (* denotes the symmetry-related atom in the second Ti 3 O unit) as well as two phosphonate ligands connecting Ti2, Ti3 and Ti1* (and Ti2*, Ti3*, Ti1, respectively). The acetate-bridged atoms Ti1 and Ti2 are thus octahedrally coordinated, whereas Ti3 has a distorted trigonal bipyramidal coordination sphere. Because of the asymmetric substitution of the Ti 3 O triangle, the μ 3 -oxygen (O1) is not in the center of the triangle but has instead a significantly shorter distance to Ti3 [190.61(6) pm] than to the octahedrally coordinated atoms Ti1 and Ti2 [198.04(6) and 199.58 (5) pm]. Otherwise, the Ti-O bond lengths at the five-coordinate Ti3 are longer than the corresponding distances of Ti1 and Ti2.
(1) Clusters 1-5 crystallized from the reaction mixture at room temperature within several weeks. To obtain the cluster faster and in higher yield, the synthesis of 1, as an example, was repeated by heating the reaction mixture (1:2:3) to reflux overnight. The NMR spectra of the resulting powder were the same as those of the sample prepared at room temperature. With this faster preparation process, the isostructural clusters 6 (R = CH 2 Ph) and 7 (R = CH 2 CH 2 CH 2 Br) 2 were additionally obtained. It can be assumed that clusters 2-5 can also be more rapidly obtained by this modification of the synthesis. Cluster 7 was only obtained for RPO 3 H/HOAc/Ti(OiPr) 4 ratios of 1:2:4 or 1:2:3; surprisingly, for a 1:1:2 ratio another cluster was obtained (see below for cluster 8).
Clusters 1-7 were well-soluble in organic solvents. Their NMR spectra were very similar, and were consistent with the solid-state structures (see the Supporting Information), which shows that the clusters are stable in solution and are not in equilibrium with other structures. The 1 H NMR spectroscopic data of 1-7 show five doublets for the CH 3 of the OiPr ligands, although the signals of two bridging OiPr ligands overlap at about 1.7 ppm; the other three doublets partly overlap at 1.3-1.5 ppm. For the CH group of the OiPr ligands, three different multiplets were found, in a few cases two of them partly overlap. The singlet for the CH 3 group of the acetate ligands was observed at about 2.0 ppm. Only one signal between 10 and 30 ppm was observed in the 31 P NMR spectra, indicating that the clusters are centrosymmetric in solution. 13 C NMR spectra were in good agreement with the 1 H NMR spectroscopic data, with six signals for the CH 3 groups at 23-26 ppm, three signals for the CH groups at 76-79 ppm, and one signal at around 180 ppm for the carboxylate ligand.
Upon reaction of the aforementioned bis(trimethylsilyl) phosphonates with acetic acid and Ti(OiPr) 4 in a 1:1:2 ratio, in one case another cluster type was obtained. Reaction of bis(trimethylsilyl) 3-bromopropylphosphonate at room temperature reproducibly resulted in the cluster [Ti 5 (μ 3 -O)(μ 2 -OiPr) 4 (OiPr) 7 (OAc)(O 3 PCH 2 CH 2 CH 2 Br) 3 ] (8), the structure of which ( Figure 3) is related to those of previously observed clusters [Ti 4 (μ 3 -O)(μ 2 -OiPr) 3 (OiPr) 5 (O 3 PR) 3 L] (L = neutral ligand). [4,5] The latter consist of a symmetrical Ti 3 (μ 3 -O)(μ 2 -OiPr) 3  group is replaced by a Ti 2 (μ 2 -OiPr)(OiPr) 4 (μ 2 -OAc) moiety. Two of the phosphonate ligands are coordinated to only one Ti atom of the Ti 2 unit, whereas the third bridges both of them. This phosphonate ligand has a binding mode of 4.211 (w.xyz refers to the number of metal atoms to which the phosphonate ligand is coordinated [w], and the number of metal atoms to which each oxygen is coordinated [x,y,z] [10] ), whereas the other two phosphonate ligands, as well as those in the cluster 1-7, have a 3.111 binding mode. The Ti 2 (μ 2 -OiPr)(OiPr) 4 (μ 2 -OAc) moiety in 8 is structurally related to Ti 2 (OR) 6 (μ 2 -OOCRЈ) 2 . [11] The solution 1 H NMR spectrum showed several overlapping signals in the region of 1.2-2.0 ppm that can be assigned to the CH 3 groups of OiPr as well as to the PCH 2 group. The CH signals of OiPr appear at 4.6-5.4 ppm as five multiplets. The two well-separated triplets for the CH 2 Br group at δ = 3.52 and 3.71 ppm have an intensity ratio of 1:2. The same is true for the two resonances at δ = 27.44 and 30.34 ppm in the 31 P NMR spectrum. This is in good agreement with the structure in the crystalline state. Solution 13 C NMR spectroscopic data confirm the 1 H NMR spectroscopic data, with corresponding signals at 23-25 ppm for CH 3 and 77-80 ppm for CH groups. Two doublets were found for each CH 2 group of the bromopropyl moiety; the signals of the P-CH 2 groups could not be unequivocally assigned.
Another Ti 5 cluster was obtained from the reaction of bis(trimethylsilyl) 3,5-dimethylphenylphosphonate with Ti(OiPr) 4 2 and can be derived from the basic structural motif Ti 3 (μ 3 -O)(μ 2 -OiPr) 3 (OiPr) 3 in the previously obtained acetate-free clusters [4,5] and in 8, and the monosubstituted unit Ti 3 (μ 3 -O)(μ 2 -OiPr) 2 (OiPr) 3 (μ 2 -OAc) in 1. The Ti 3 O triangles are connected with each other by one μ 2 -O and two phosphonate ligands in a 3.111 binding mode. The central Ti3 atom is coordinated by an oxygen atom of both phosphonate ligands and the other four Ti atoms are coordinated by the oxygen atoms of just one phosphonate ligand.
Cluster 9 has another degree of condensation (0.6) and a higher proportion of acetate ligands than the Ti 5 cluster 8 or the Ti 6 clusters 1-7. This is attributed to the higher amount of acetic acid used for the preparation, which apparently led to the higher proportion of acetate ligands in the product. The steric hindrance and the increased acidity of xylylphosphonic acid (aromatic phosphonic acids are slightly more acidic) possibly play an additional role. In previous experiments, when only phosphonates were treated with Ti(OiPr) 4 , the steric bulk of the phosphonate substituents had a significant influence on the cluster structure. [5] The approximate C 2 symmetry is retained in solution because only one signal was observed in the 31 P NMR spectrum. The solution 1 H NMR spectrum show three singlets for the xylyl CH groups at δ = 6.91, 8.03 and 8.08 ppm and three multiplets for the isopropoxo CH groups at δ = 5.07, 5.22 and 5.66 ppm. One singlet at δ = 2.18 ppm was assigned to the CH 3 groups of the xylyl moieties and two singlets at δ = 1.95 and 1.98 ppm to the two acetate ligands. These signals are consistent with respect to shift, number and intensity with the solid-state structure.
Five doublets were found for the CH 3 groups of the OiPr ligands. Their total intensity corresponded to the calculated value, but only three were expected because of the C 2 symmetry. Two doublets at δ = 1.90 and 1.91 ppm overlap with a shift difference of only 0.01 ppm and can be assigned to the two bridging OiPr ligands, which should be symmetryequivalent. It is therefore assumed that rotation around the O-CH bond is hindered, resulting in different chemical shifts for the two CH 3 groups. The same can be assumed for one of the terminal CH 3 groups (possibly interacting with each other) leading to two doublets at δ = 1.46 and 1.51 ppm. The other two terminal OiPr ligands show a doublet at δ = 1.54 ppm. The same observations were made in the 13 C NMR spectrum. The increased number of signals in the CH 3 region is also attributed to sterically hindered rotation of the OiPr groups.

Conclusions
We have shown that addition of acetic acid to an appropriate mixture of reactants does indeed result in a higher degree of condensation of the obtained oxo clusters compared with the clusters prepared from only bis(trimethylsilyl)phosphonates. This is attributed to the easier esterifica-tion of acetic acid compared with phosphonic acids. The higher condensation ratio goes hand in hand with incorporation of acetate ligands in the coordination sphere of the clusters; the new titanium oxo clusters are the first examples of a mixed ligand sphere containing carboxylate, phosphonate and alkoxo ligands.
Whereas reactions of Ti(OR) 4 with carboxylic acids lead to a great variety of cluster types, depending on the OR group, the acid, and the Ti(OR) 4 /acid ratio, [3] the reaction with various phosphonates and acetic acid led to the same cluster type [Ti 6 O 4 (OiPr) 10 (OAc) 2 (O 3 PR) 2 ] (1-7), which therefore appears to be a rather robust structural entity. The cluster core has an inversion center, and therefore the phosphonate ligands are opposite to each other. Because phosphonate ligands with functional organic groups are easily introduced, reactions of these groups should be possible, e.g., polymerization, thiol-en or addition reactions, by which chains of clusters and hybrid materials with anisotropic structures could be generated.
The bis(trimethylsilyl) esters were prepared by adding bromotrimethylsilane (3 equiv.) to a solution of the corresponding diethyl phosphonate (1 equiv.) in CH 2 Cl 2 followed by removing all volatiles in vacuo and characterization of the compounds by 31 P and 1 H NMR spectroscopy.
Isopropyl alcohol was dried by heating to reflux over sodium and distillation. Samples for NMR measurements were obtained by washing the crystalline compounds with isopropyl alcohol and drying. Acetic acid was purified by distillation from P 4 O 10 .
The given yields refer to crystallized compounds. No attempts were made to increase the crystal crop; i.e., the actual yields were higher.

[Ti 6 O 4 (OiPr) 10 (OAc) 2 (O 3 PCH 2 CH 2 CH 2 Br) 2 ] (7):
Ti(OiPr) 4 (29 mL, 100 mmol) and acetic acid (3.83 mL, 67 mmol) were added to a solution of bis(trimethylsilyl) (3-bromopropyl)phosphonate (11.63 g, 33.4 mmol) in iPrOH (50 mL). After heating to reflux overnight and cooling to room temperature, a cloudy mixture was obtained. The suspension was concentrated under vacuum and filtered. After washing two times with n-hexane and drying, a white powder of 7 was obtained. For single-crystal measurements, part of the powder was crystallized from CH 2 Cl 2 , yield 8 g (33 %). 1     X-ray Structure Analyses: All measurements were performed at 100 K using Mo-K α (λ = 71.073 pm) radiation. Data were collected with a Bruker AXS SMART APEX II four-circle diffractometer with κ-geometry. Crystals of 5 cracked when cooled to 100 K; apparently a phase transition took place at about 180 K. The measurements of 5 were therefore carried out at 213 K. Data were collected with φ and ω-scans and different frame widths. The data were corrected for polarization and Lorentz effects, and an empirical absorption correction (SADABS) was employed. The cell dimensions were refined with all unique reflections. SAINT PLUS software (Bruker Analytical X-ray Instruments, 2007) was used to integrate the frames. Details of the X-ray investigations are given in Table 1 (for 1-3), Table 2 (for 4-6), and Table 3 ( for 7-9). The structures were solved by the Patterson method (SHELXS97 [13] ). Refinement was performed by the full-matrix least-squares method based on F 2 (SHELXL97) with anisotropic thermal parameters for all non-hydrogen atoms. Hydrogen atoms were inserted in calcu-