Naturally Occurring Oxazole Structural Units as Ligands of Vanadium Catalysts for Ethylene-Norbornene (Co)polymerization

: 1,3-Oxazole and 4,5-dihydro-1,3-oxazole are common structural motifs in naturally occurring peptides. A series of vanadium complexes were synthesized using VCl 3 (THF) 3 and methyl substituted (4,5-dihydro-1,3-oxazol-2-yl)-1,3-oxazoles as ligands and analyzed using NMR and MS methods. The complexes were found to be active catalysts both in ethylene polymerization and ethylene-norbornene copolymerization. The position of methyl substituent in the ligand has considerable impact on the performance of (co)polymerization reaction, as well as on the microstructure, and thus physical properties of the obtained copolymers.


Introduction
Catalysts reactions play an irreplaceable role in the synthesis of organic compounds, which are useful as crucial chemicals, pharmaceuticals, and advanced polymers [1]. Transition metal catalysis is one of the foremost processes in production of polymer materials, mostly in olefin polymerization [2]. Polyolefins constitute more than half of global synthetic polymers, which results in a continuous search for new catalysts, composed of various transition metals and ligands. Amongst the transition metal tested, vanadium attracts considerable interest as vanadium-based catalysts display advantageous features. They enable to produce high molecular weight polyethylene, as well as copolymers with higher comonomer incorporation of alpha-olefins [3][4][5]. In particular, cyclic olefin copolymers (COCs) are a promising group of materials with specific, projectable properties, which can be also produced using vanadium catalysts [6,7]. In addition to the transition metal, ligands are also important because they influence both activity of catalysts and properties of copolymers. In particular, N-donor ligands are crucial in many recent developments [2].
Encouraged by the previous results, we focused on new oxazole structural motifs. The oxazole rings, especially 1,3-oxazole and 4,5-dihydro-1,3-oxazole, are common structural motifs in naturally occurring peptides, because they can be easily obtained from the serine or threonine residues, when the hydroxyl group of side chain reacts with the preceding peptide group in the main chain by cyclodehydration, and further, by dehydrogenation processes [19]. The oxazole rings joined to each other can be found for example, in muscoride A [20], hennoxazole A [21], and diazonamides [22]. Moreover, the method of biosynthesis enables to obtain larger structures consisting of more than two oxazole rings, as in the cases of plantazolicins [23], ulapualide A [24], azolemycin [25], or telomestatin [26].
In order to check the potential usefulness of these structures, we have decided to study a relatively small structural motif, (4,5-dihydro-1,3-oxazol-2-yl)-1,3-oxazole ( Figure 1). These heterocyclic rings, commonly described as oxazoline and oxazole, contain nitrogen atom in sp2 hybridization and electron pair in the plane of the ring, which can act as nucleophiles, and, thus, N-donors. The route of synthesis is also promising as it requires rather simple and commonly accessible substrates. The presence of methyl group can test possible differences in performance of catalysts. It also mimics the synthesis from threonine/serine side chains.
The vanadium complexes, denoted as L1-V, L2-V, and L3-V, were synthesized using VCl 3 (THF) 3 precursor and the proper ligand L1-3 in methylene dichloride solution using Schlenk system. The complexation reaction were confirmed by both the NMR and MS spectra of complexes (Figures S14-S19). There is a considerable shift in position of the signals, in particular for 4,5-dihydro-1,3-oxazole (oxazoline) ring. In 13 C NMR spectra ∆δ of C2 carbon is shifted 4 ppm downfield whereas C5 (C-O) and C4 (C-N) methylene carbons are shifted about 23 and 13 ppm up-field, respectively. In the 1 H NMR spectra of complexes the shift of signals of methylene group of about ∆δ 0.5 ppm downfield is observed. Additionally, the multiplicity of these signals are diffused due to partial presence of paramagnetic oxidation state of vanadium element. The MS spectra of complexes show the ligand fragment at m/z = 152 (L1), 166 (L2), and 152 (L3) (Figures S6, S11, S13, S15, S17, and S19). There are also characteristic groups of ions at m/z = 323, 325, and 327, regardless of the complex determined, which correspond to the formula C 7 H 8 Cl 3 N 2 O 3 V (LVCl 3 O).
In the case of complex with the ligand L2 this can be explained by the loss of additional methyl group. This indicates the presence of ligand and chlorine atoms, and suggests that the structure of complexes resembles that determined for metal-organic framework stabilized vanadium catalyst for olefin polymerization [28]. Efforts to obtain crystal form of the complexes suitable for X-ray analysis were not successful.

Polymerization and Copolymerization
The obtained vanadium complexes, in the presence of activator AlEt 2 Cl and ethyl trichloroacetate re-activator, were found to be active as catalysts both in ethylene homopolymerization and ethylene-norbornene co-polymerization (Table 1). In the ethylene polymerization, the most effective turned out to be the catalyst L3-V resulting up to 4800 kgPE/molV·h. Interestingly, in the L3 ligand, the methyl group is at the position 5 of the 1,3-oxazole ring, which imposes a steric hindrance between the heterocyclic rings and prevents their co-planarity. In contrast, the lowest activity reveals the catalyst L2-V with substituted oxazoline ring (3150 kgPE/molV·h). Table 1. Selected parameters of (co)polymerization performed using studied vanadium catalysts.
The same catalyst systems, at similar reaction conditions, were applied in copolymerization of ethylene with norbornene (NB). The activity of copolymerization reaction considerably decreases as compared to the ethylene polymerization. The concentration of norbornene was relatively low in the reaction medium (0.5-1.5 mol/dm 3 ). Nevertheless, the NB incorporation in the range from 11 to 32 mol% was obtained, and increases with the increase in norbornene concentration. Again, differences amongst the catalysts activity are observed. The catalyst L2-V produces the copolymer with the highest NB content (32.4 mol%), even at the lowest NB concentration in the reaction medium. The catalysts L1-V and L3-V reveal similar level of NB incorporation, with the lowest incorporation 11.4 mol% at the NB concentration 0.5 mol/dm 3 for the catalyst L3-V.

Polymer Properties
The polyethylene samples obtained using the studied vanadium complexes were subjected to thermal analysis DSC, to determined melting point (T m ) and crystallinity degree (X). After the second heating cycle, the T m of polyethylene was similar (136.2 • C, 138.3 • C, and 135.3 • C), as was their crystallinity (52.3%, 54.6%, 63.5%) ( Figures S21, S25 and S29). Based on the results of average molecular weight (M w ) and the molecular weight distribution (M w /M n ) determined by the GPC method, it was found that polyethylene samples are characterized by high homogeneity (M w /M n~2 .0) and the M w does not exceed 900 × 10 3 g/mol. It is worth noting that the PE obtained using the catalyst L2-V was characterized by slightly higher values of all the parameters determined ( Table 1).
The obtained copolymers have lower molecular weight than polyethylene (M w , 180-410 × 10 3 g/mol). The molecular weight distribution is typical for vanadium catalysts (M w /M n , 2.2-2.8). The copolymers M w decreases with increase in incorporation of norbornene units in copolymer chain (Table 1). DSC analysis (Figures S22-S24, S26-S28, S30-S32) shows that copolymers are amorphous materials with a glass transition temperature (T g ) that increases with increasing NB content. Differences amongst the copolymers produced using the studied catalysts are observed ( Figure 2). Interestingly, the DSC curves of the copolymers prepared by the complex L1-V show both the glass transition temperature (T g ) and the melting point (T m ). Low melting peaks observed indicates relatively long ethylene sequences. The melting points (128 • C) of these copolymers are lower than those of polyethylene. This can be attributed to the long PE sequences in the copolymer containing small amounts of isolated NB units [29]. In contrast, the copolymers obtained using the catalysts L2-V and L3-V do not reveal melting points (T m ). This is evidence of the considerable homogeneity of copolymer, its amorphous nature. The microstructure of the copolymers was further determined by analyzing the 13 C NMR spectra (Figure 3, Figures S33-S41) according to literature [30,31]. Generally, the spectra show the signals assigned to the isolated NB units (45.02 ppm C2/C3, 39.50 ppm C1/C4, 30.89 ppm C7, and 28.33 ppm C5/C6). The signals 45.20 (C2/C3 racemo) and 45.72 ppm (C2/C3 meso), 39.54 ppm (C4 meso), 39.89 ppm (C1 meso), 31.04 ppm (C7 meso), 30.99 ppm (C7 racemo) are assigned to NB in the syndiotactic and alternating isotactic sequences, respectively. This shows that the copolymers have a random tacticity. The signals at 27.76-28.78 ppm are assigned to the methylene sequences. Increasing the comonomer incorporation reduces the number of isolated NB units.
In summary, differences amongst the copolymers produced using the studied catalysts are observed. The catalyst L2-V gives the higher incorporation of NB units than the catalysts L1-V and L3-V, which results in higher amount of alternated units. The copolymers obtained using the catalysts L1-V and L3-V, reveal similar NB incorporation and rather similar microstructure. However, the ethylene sequences of the copolymer obtained using the catalyst L1-V are longer and more organized, which is shown by DSC method.
The presented data show the influence of catalyst structure on the performance of polyreaction and the properties of polymer product. Substituent (methyl group) at the position 4 of oxazoline ligand reduces the catalyst activity (L2-V), what was observed previously [15]. The substituent at the position 5 of oxazole ring (L3-V), which imposes a steric hindrance and prevents co-planarity of both heterocyclic rings, increases the catalyst activity, but it does not influence the norbornene incorporation.  (Table 1, items 3, 7, 11, Figures S34, S37 and S40).

Materials and Ligand Synthesis
The substrates for syntheses and the methods of purification of solvents, as well as the detailed method of ligands synthesis are given in Supplementary Materials.

Polymerization Procedure
The (co)polymerizations were performed in a glass reactor (500 mL) in nitrogen atmosphere. Hexane (total 150 mL), norbornene (0.5, 1.0 and 1.50 mol/dm 3 ) or not (as hexane solution), AlEt 2 Cl, (6.0 × 10 -3 mol Al), ethyl trichloroacetate (ETA) (3.5 × 10 -4 mol), vanadium catalysts (L-V, 7.1 × 10 -6 mol Mt) as toluene solution (2 mL), and ethylene were successively added. The reactions were performed at 60 min, ethylene pressure 0.5 MPa, and temperature 30 • C. To terminate the reactions, the ethylene feeding was closed, pressure reduced to 0.1 MPa, and acidified methanol was added. The polymer product was separated by filtration, washed first by hexane and then by methanol, and dried to constant mass at 50 • C. The reactions were repeated to ensure reproducibility of the results.
EI + MS spectra were obtained using mass spectrometer Finnigan Polaris Qequipped with a Direct Insertion Probe. Xcalibur data system was directly coupled to the spectrometer. The range of heating in an ion source, 50 • C to 500 • C. The mass monitoring interval, 50 to 1000 amu. Cyclical scans used to collect the spectra, 1.0 s. The electron energy, 70 eV.
Melting temperatures (T m ), crystallinity degree (X), and glass transition temperatures (T g ) of the polymers samples were recorded by differential scanning calorimetry (DSC) The calorimeter (2010 TA) with an automated sampler was used. The cycle heat-coolheat, heating rate of 10 • C/min, and nitrogen atmosphere were applied to collect data. The crystallinity degree of polyethylene was calculated using the following equation: X = (DH f /DH t,c ) × 100% (DH f is enthalpy of fusion of the polyethylene sample and DH t,c is enthalpy of fusion of standard, 290 J/g).
Molecular weight (M w ) and molecular weight distribution (M w /M n ) of polymer samples were measured using gel permeation chromatography system (PL-GPC 220) equipped with refractive index and viscosity detector. Run conditions: temperature 160 • C, solvent 1,2,4-trichlorobenzene (TCB), flow rate 1 mL/min. The polymers were analyzed on a set of gel columns (Olexis). polyethylene and polystyrene standards with narrow M w /M n were applied for calibration.

Conclusions
The vanadium catalyst with oxazole-oxazoline ligands revealed activity both in ethylene polymerization and ethylene-norbornene copolymerization. The work shows that the search of structural units in natural compounds and their further adaptation as ligands for transition metal catalysts can be promising procedure. The presented relatively simple bidentate oxazole-oxazoline ligands can be further developed both to bidentate oxazoleoxazole ligands, but also tridentate oxazole ligands. Both these structure are present in natural compounds. It would be also worth to check these ligands using various transition metals. Furthermore, the route of synthesis from simple serine/threonine peptide substrates is potentially possible, which should fulfill requirements of green chemistry.  Figure S6: MS for L1, Figures S7-S10: NMR for L2 synthesis, Figure S11: MS for L2, Figures S12 and S13: NMR and MS spectra for L3, Figures S14-S19: NMR and MS spectra for vanadium complexes, Figure S20: synthesis of complexes, Figures S21-S32: DSC thermograms of polymer samples, Figures S33-S41: 13C NMR spectra of (co)polymer samples.