Zinc Complexes Containing Coumarin-Derived Anilido-Aldimine Ligands as Catalysts for Ring Opening Polymerization of l-Lactide

The coumarin-derived ligand precursors L1H–L6H have been prepared. Treatment of these ligand precursors with 1.2 equiv. of ZnEt2 in toluene affords zinc ethyl complexes (LZnEt) 1–6 (where L = coumarin-derived ligands bearing different functional groups). Reaction of ligand precursor L3H with 1.5 equiv. of Zn[N(SiMe3)2]2 in toluene affords the zinc amide complex, L3ZnN(SiMe3)2, 7. All these compounds were characterized by NMR spectroscopy and elemental analysis. The molecular structures are reported for 1 and 7. The catalytic activities of complexes 1–7 towards the ring opening polymerization of l-lactide in the presence of 9-AnOH have been investigated.


Introduction
Due to the biodegradability, biocompatibility, and permeability properties demonstrated by polylactide, development of well-defined metal complexes involved in ring opening polymerization as catalysts/initiators has recently become attractive [1][2][3][4]. Among these studies, metal complexes bearing nitrogen-based ligands are extensively applied, and their structures and chemistry have been reviewed [5][6][7][8][9][10][11]. The promising activities and controlled behavior demonstrated by those complexes OPEN ACCESS have encouraged diverse research groups to synthesize similar chelating ligand precursors and examine the bonding and electronic features related to these ligands. Recently some metal complexes containing anilido-aldimine ligands have been reported and demonstrated catalytic activities in ring opening polymerization of cyclic esters [12][13][14][15][16][17][18][19]. New ligand precursors working with similar chelating systems should be the attractive candidates. Therefore we introduce similar bonding mode as found in the anilido-aldimine ligand into coumarin molecules whose derivatives demonstrate biological activity [20][21][22][23], or are sensitive fluorescent probes [24] or organic dyes [25], to prepare several coumarin-derived anilido-aldimine ligand precursors. We expect those precursors to have the potential to work as mono anionic dentate ligands upon reacting with zinc reagents. The catalytic activities of these zinc complexes towards the ring opening polymerization of L-lactide in the presence of alcohols have also been investigated.

Syntheses and Characterization of Ligand Precursors and Zinc Complexes
Ligand precursors L 1 H-L 6 H were prepared in a straightforward fashion by the condensation between 4-(mesitylamino)-2-oxo-2H-chromene-3-carbaldehyde and substituted anilines or aliphatic amines to afford the target compounds in fair to high yield. Due to the promising catalytic activities exhibited by zinc anilido-aldimine complexes in ring opening polymerization reactions [12,[15][16][17]19], preparations of zinc ethyl complexes were examined by the reactions of L 1 H-L 6 H with ZnEt2 in a ratio of 1:1 in toluene solution resulting in the isolation of zinc ethyl complexes 1-6. The zinc amide complex 7, L 3 ZnN(SiMe3)2, was prepared by the reaction of L 3 H with Zn[N(SiMe3)2]2. The spectroscopic and elemental analysis data of 1-7 are consistent with the structures proposed in Scheme 1. Attempts to synthesize zinc benzyl oxide complexes have so far been proved unsuccessful.

Scheme 1. Preparation of ligand precursors and zinc complexes.
Suitable crystals for structural determination of 1 or 7 were obtained from toluene/hexane solution (compound 1) or concentrated hexane solution (compound 7). The molecular structure of 1 exists as a coordination polymer and the diagrams of its molecular structure are depicted in Figures 1 and 2. Selected bond lengths and bond angles are summarized in Table 1.      (6)  Each of the zinc atoms is four-coordinate, and is bonded to one nitrogen atom from the imino group with a Zn-N(1) bond distance of 2.0650(17)Å, one nitrogen atom from the anilido group with a Zn-N(2) bond distance of 2.0256(17)Å, one carbon atom from the ethyl group with a Zn-C(29) bond distance of 1.987(2)Å, and one oxygen atom from the carbonyl group of another molecule with a Zn-O(2) bond distance of 2.1062(16)Å. The coordination of another molecule via the carbonyl oxygen atom could be another evidence for the coordination-insertion mechanism of ring opening polymerization [26][27][28]. The geometry around the zinc centre of 1 can be described as a distorted tetrahedral geometry with N(2)-Zn-N(1) and C(29)-Zn-O(2) angles of 90.95(7)° and 106.29(8)°. These data are within the range of the known distances and angles for zinc anilido-aldimine complexes [12,[15][16][17]19] and structurally-related zinc complexes [29,30]. Basically, compound 7 is quite similar to compound 1 albeit with a 2-methylthio substituent instead of 2,4,6-trimethyl substituents on the phenyl group of the imino part for 1 and the amide group instead of an ethyl group, as shown in Figure 3. Like 1, the zinc atom is four-coordinate with one nitrogen atom from the imino group with a Zn-N(2) bond distance of 2.0314(19)Å, one nitrogen atom from the anilido group with a Zn-N(1) bond distance of 1.9932(19)Å, one nitrogen atom from the amide group with a Zn-N(3) bond distance of 1.916(2)Å, and one sulphur atom from the pendant functionality with a Zn-S bond distance of 2.6488(6)Å. The geometry around the zinc centre of 7 can be described as a distorted tetrahedral geometry with a smaller N(2)-Zn-S angle [76.57(6)°]. Bond lengths and bond angles are similar to those discussed above for 1. The bond distance of the zinc amide is close to those found in the literature [31,32]. The Zn-S bond distance is a bit longer than that reported in the literature [33].

Polymerization Studies
Since several zinc anilido-aldimine complexes are known as efficient catalysts/initiators for the ring opening polymerization (ROP) of cyclic esters [12,[15][16][17]19], the catalytic activities of structurally-related zinc ethyl complexes 1-6 towards the ROP of L-lactide were examined in the presence of 9-AnOH in toluene at 50 °C for 30 min. under a dry nitrogen atmosphere (entries 1-6). Among these catalysts compound 3 demonstrates better activity. Poor conversion was observed by running the polymerization in tetrahydrofuran (entry 7). We also introduced isopropyl alcohol or benzyl alcohol as initiators, 9-anthracenemethanol was identified as the best choice for this system after several polymerization trials in toluene at 50 °C (entries 3 and 8-11). To save reaction time, the reaction temperature was raised to 80 °C for examination of the effects on both living and immortal characteristics. Typical polymerization reactions were carried out at 80 °C in 5 mL toluene solution in the presence of 9-AnOH for L-lactide (LLA) using prescribed equivalent ratios of the monomers, catalysts (0.025 mmol) and 9-AnOH for the prescribed time. Representative results are collected in Table 1.
The linear relationship between the number-average molecular weight (Mn) and the monomer-to-initiator ratio (   Table 2). The immortal character could be demonstrated with polymers formed in the presence of an excess of alcohol, which molecular weights could be predicted from the monomer-to-alcohol ratio. The 'immortal' character in this system was examined using different equiv. ratios  Figure 5. Peaks are similar to those found on the 1 H-NMR spectra of polymers produced by aluminium benzotriazole phenoxide complexes [34], and are assignable to the corresponding protons in the proposed structure. The ESI-MS analysis of a low molecular weight PLLA (Mn(obsd) = 1600, Table 1, entry 22) clearly revealed a major population of PLLAs unequivocally confirmed as Na + 9-AnO-PLA-H ( Figure 6). The degree of polymerization indicated by this spectrum is in good agreement with the experimental value and the mass spectrum shows a cluster of homologous peaks separated by a molecular mass of ~144 Da corresponding to one lactide repeating unit. Based on those results, the metal alkoxide might form first, followed by the coordination-insertion mechanism [15,19].  Figure 7 (entries [23][24][25][26][27][28][29]. Compound 7 also demonstrated catalytic activity in the absence of alcohol. According to the molecular structure demonstrated by compound 1, the polymerization catalyzed by 7 in the absence of alcohol might involve a coordination-insertion mechanism using amide group as initiator.  Table 2).

General Information
All manipulations were carried out under an atmosphere of dinitrogen using standard Schlenk-line or drybox techniques. Solvents were refluxed over the appropriate drying agent and distilled prior to use. Deuterated solvents were dried over molecular sieves. 1 H and 13 C{ 1 H} NMR spectra were recorded either on Varian Mercury-400 (400 MHz) or Varian Inova-600 (600 MHz) spectrometers in chloroform-d at ambient temperature unless stated otherwise and referenced internally to the residual solvent peak and reported as parts per million relative to tetramethylsilane. Elemental analyses were performed by Elementar Vario ELIV instrument. The GPC measurements were performed in THF at 35 °C with a Waters 1515 isocratic HPLC pump, a Waters 2414 refractive index detector, and a Waters Styragel column (HR4E). Molecular weights and molecular weight distributions were calculated using polystyrene as standard. The electrospray ionization mass spectrometry (ESI-MS) analyses were carried out with a Thermo Finnigan TSQ Quantum Triple Quadrupole Mass Spectrometer.
ZnEt2 ( [36] were prepared by the literature method. Benzyl alcohol and 2-propanol were dried over calcium hydride and distilled before use. L-Lactide was recrystallized from toluene prior to use.

Preparations
To a flask containing 4-chloro-3coumarincarbaldehyde (2.80 g, 10.0 mmol) in ethanol (40 mL) was added NEt3 (1.54 mL, 11.0 mmol) followed by the addition of 2,4,6-trimethylaniline (1.54 mL, 11.0 mmol) at room temperature. After 12 hours of stirring, all the volatiles were pumped off and the residue was extracted with toluene to afford a brown oil that was rinsed with hexane (5 mL) to afford a yellow solid. Yield, 2.24 g, 72.8%.      L 3 ZnN(SiMe3)2 (7). A solution of Zn[N(SiMe3)2]2 (0.23 g, 0.6 mmol) in toluene (10 mL) was added dropwise at 0 °C to a flask containing L 3 H (0.22 g, 0.50 mmol) in toluene (10 mL). The reaction mixture was allowed to warm to room temperature and reacted overnight. All the volatiles were pumped off, and the residue was washed with hexane (15 mL) to afford a yellow solid. Yield, 0.18 g, 58%. 1  Procedure for Polymerization of L-Lactide. Typically, to a flask containing a prescribed amount of L-lactide, 9-AnOH and catalyst toluene (5 mL) was added. The reaction mixture was stirred at 50 °C or 80 °C for the prescribed time. After the reaction was quenched by the addition of acetic acid solution (10 mL, 0.35 M), the resulting mixture was poured into n-hexane (25 mL) to precipitate polymers. Crude products were recrystallized from THF/hexane and dried in vacuo to a constant weight.

Crystal Structure Data
Crystals were grown from toluene/hexane (compound 1) or concentrated hexane solution (compound 7), and isolated by filtration. Suitable crystals of 1 or 7 were mounted onto Mounted CryoLoop (Hampton Research, Aliso Viejo, CA, USA; size: 0.5-0.7 mm) using perfluoropolyether oil (FOMBLIN ® Y, Aldrich) and cooled rapidly in a stream of cold nitrogen gas using an Oxford Cryosystems Cryostream unit. Diffraction data were collected at 100 K using an Oxford Gemini S diffractometer. Empirical absorption correction was based on spherical harmonics, implemented in the SCALE3 ABSPACK scaling algorithm from CrysAlis RED (Oxford Diffraction Ltd., Abingdon, UK). The space group determination was based on a check of the Laue symmetry and systematic absences and was confirmed using the structure solution. The structure was solved by direct methods using a SHELXTL package [37]. All non-H atoms were located from successive Fourier maps, and hydrogen atoms were refined using a riding model. Anisotropic thermal parameters were used for all non-H atoms, and fixed isotropic parameters were used for H atoms. Some details of the data collection and refinement are given in Table 3. CCDC reference numbers 1045465-1045466 (for 1 and 7, respectively) contain the supplementary crystallographic data for this paper. These data can be obtained free of charge from The Cambridge Crystallographic Data Centre via www.ccdc.cam.ac.uk/data_request/cif.

Conclusions
A series of zinc complexes containing coumarin-based anilido-aldimine ligands has been prepared and fully characterized. Based on the molecular structures demonstrated by 1 and 7, the metal center adopts a distorted tetrahedral geometry with the coumarin-based anilido-aldimine ligands. Coordination of the carbonyl group from another molecule happens in the case of ligands without pendant functionalities, resulting in the formation of a coordination polymer. This phenomenon also supports the expected coordination to the metal center from the carbonyl group of monomers. Under optimized condition, compound 3 and 7 demonstrate efficient activities for the controlled polymerization of LLA with both living and immortal characteristics. Preliminary studies on fine-tuning of ligand precursors and further application of metal complexes to the catalytic reactions are currently underway.