Synthesis and Characterisation of Palladium (II

Australian Journal of Basic and Applied Sciences, 7(9): 149-155, 2013 ISSN 1991-8178

Synthesis and Characterisation of Palladium (II) Complex of (N-Pentanoylthioreido)N’-Propanoic Acid and Its Application as Catalyst in Heck Cross Coupling Reaction 1

Saidatul Radhiah Ghazali, 1Wan M. Khairul, 2Mustaffa Shamsuddin

1

Advanced Materials Research Group, Department of Chemical Sciences, Faculty of Science and Technology, Universiti Malaysia Terengganu, 21030 Kuala Terengganu, Terengganu, Malaysia 2 Department of Chemistry, Faculty of Science, Universiti Teknologi Malaysia, 81310 Skudai, Johor, Malaysia. Abstract: (N-pentanoylthioreido)-N’-propanoic acid (L1) has been successfully synthesised and characterised via typical spectroscopic and analytical techniques and was undergone complexation with palladium (II) chloride, to obtain palladium(II) thiourea complex which has been applied as homogenous catalyst. A homogenous palladium (II) thiourea complex was successfully developed to catalyse Heck cross-coupling reaction of 4-bromoacetophenone, iodobenzene and methyl acrylate to produce methyl cinnamate as final product. This ligand (L1) and palladium (II) thiourea complex (M1) were characterized by several spectroscopic and analytical techniques such as FTIR, 13C and 1H NMR spectroscopy. The result showed that with 1.0 mmol% catalyst loading, this new homogenous palladium complex had given 100% conversion of the starting materials for the formation of the designated final product at 24 hours reaction period. As comparison, this palladium (II) thiourea gives an excellent and higher conversion of starting material into final product compared to palladium Schiff-base. Thus, this new molecular system can act as an ideal catalyst in Heck cross-coupling reaction. Key words: Palladium II)-thiourea complex, Heck cross-coupling reaction, homogenous catalyst. INTRODUCTION The Heck reaction is referred to the palladium-catalyzed arylation or vinylation of olefins has gained prominence over past decade, as it is a selective method for C-C bonds formation in a single operational step and has proven to be an extremely powerful and useful tool for the construction of carbon-carbon bonds (Hermann et al., 1995; Polshettiwar and Molnar, 2007; Mohanty et al., 2008; Md. Nazmul Alam, 2001). Many palladium complexes have been investigated as homogeneous catalysts because palladium is arguably the most versatile and the most widely applied catalytic metal in Heck reaction (Blaser et al., 2001; Mohammed Al-Hashimi et al., 2007). Traditionally, soluble phosphine palladium complex employed as catalysts for Heck reaction (Beletskaya and Cheprakov, 2000; Aydemir et al., 2008). Thus, it is no doubt the vitality to develop and construct new array of metal-phosphine ligands to be used in those catalytic cycles should be taken with serious consideration (Hong et al., 2005; Delaude, 2009). However, phosphine is very sensitive to air and moisture (Buckley and Neary, 2010). Thus, inert atmosphere conditions are required for efficient catalyst. Moreover, the oxidation of the phosphine to phosphine oxide as well as cleavage of the of the P-C bond, causing degradation of the ligand, hence the reduction of the metal and termination of the catalytic cycle could take place. Besides, the world is in constant demand for an efficient, safe and recyclable catalyst in order to sustain the world’s ecosystem. Thus, researchers are eager to design the best catalyst that can be applied widely in industrial which can give an excellent productivity but less toxicity. Due to these problems, a long-standing unique and versatility role of thiourea derivatives as ligands have attracted great interest in catalysis where as thiourea derivatives are suggested to be used in the study to replace the functionality of phosphine as ligand in catalysis system. In this study, a new thiourea compound (L1) was successfully synthesised. Then, the complexation of thiourea with palladium (II) chloride (PdCl2) has given a new designated metal complex (M1). In turn, M1 was tested as homogenous catalyst in Heck cross-coupling reaction and the progress of the reaction was constantly monitored by 1H and 13C NMR and GC-FID. The ligand (L1) and metal complex (M1) were fully characterised via several typical spectroscopic and analytical techniques.

Corresponding Author: Wan M. Khairul, Advanced Materials Research Group, Department of Chemical Sciences, Faculty of Science and Technology, Universiti Malaysia Terengganu, 21030 Kuala Terengganu, Terengganu, Malaysia. E-mail: [email protected]

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Aust. J. Basic & Appl. Sci., 7(9): 149-155, 2013

MATERIALS AND METHODS Materials: All chemicals used in this study were purchased from standard suppliers and used as received without further purification. The infra-red (IR) spectra were recorded on a Fourier Transform-Infrared Spectrometer, Perkin Elmer Spectrum 100 in the range of 4000-400cm-1 as potassium bromide (KBr) disc. The proton (1H) and carbon (13C) NMR spectra were recorded in deuterated Dimethyl Sulfoxide (DMSO) solvent on Bruker Avance III 400 Spectrometer. The chemical shifts are reported in part per million (ppm) with solvent resonance as internal standard. The CHNS Analyzer Flash Elemental Analyzer 1112 series was used to determine the experimental percentage of C, H, N and S elements of the compounds. Besides that, thin-layer chromathography (TLC) also was carried out on precoated plate of TLC Silica Gel 60 F254 (Merck), and spots were visualised with UV-Vis Spectrophotometer Shimadzu UV-1601PC. Preparation of Thiourea Derivative as Ligand (L1): A solution of pentanoyl chloride (5.01 g, 41.74 mmol) in 50 ml acetone was added dropwise into a solution of ammonium thiocyanate (3.17 g, 41.71 mmol) in 50 ml acetone. The reaction mixture was stirred for 8 hours at room temperature. Then, the mixture was filtered and the filtrate was added with β-alanine (3.71 g, 41.66 mmol) in 25ml acetone. The reaction mixture was stirred for 10 hours at room temperature prior heated at reflux for ca. 7 hour in a two-necked 250 ml round-bottomed flask. After adjudged completion by TLC (ethyl acetate: hexane; 2:3), the reaction mixture was cooled to room temperature and filtered. Then, three ice cubes were added into the filtrate to obtain yellow precipitate. The yellow precipitate was then recrystallised from hot methanol to afford the title compound as yellow solid (yield: 6.20g, 64%). Scheme 1 below shows the preparation of (N-pentanoylthioreido)-N’-propanoic acid (L1).

Scheme 1: The preparation of (N-pentanoylthioreido)-N’-propanoic acid (L1). Preparation of Palladium Thiourea Complex as Catalyst (M1): Complexation of L1 with palladium (II) salt of PdCl2 was prepared by dissolving L1 (0.23 g, 1.00 mmol) and PdCl2 (0.18 g, 1.00 mmol) in 10 ml of dry acetonitrile respectively under an atmosphere of purifies nitrogen gas. The metallic solution was added drop wise into a 250 ml three-necked round bottom flask which contains the L1 solution. The solution mixture was put at reflux for ca. 2 hours. The colour of the mixture solution changed from dark brown to reddish brown with black precipitate formed. When adjudged completion by TLC (dichloromethane: hexane; 3:2), the reaction was cooled down to room temperature before it was filtered to give black solid compound (yield: 0.36g, 88%). The general experimental procedure of the catalyst (M1) is shown in Scheme 2 below.

Scheme 2: The preparation of palladium thiourea complex (M1). Homogenous Catalytic Test on Heck Cross-Coupling Reaction: Iodobenzene (1 mmol, 0.20g), methyl acrylate (3 mmol: 0.3 ml), triethylamine (2.4 molar equiv.), palladium catalyst (M1) (1 mol %) and solvent N,N-dimethylacetamide (15 ml) were mixed together in Radley’s 12-placed reaction carousel whilst purged with nitrogen and heated to 120°C for 24 hours. The reaction was repeated by using different arylhalide (i.e: 4-bromoacetophenone). The progress of the reaction was monitored regularly by NMR and GC FID. Scheme 3 below shows the general experimental procedure of Heck crosscoupling reaction.

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Scheme 3: Catalytic studies on Heck cross-coupling reaction. RESULT AND DISCUSSION Fourier Transform Infra Red (FTIR) Analysis: The infrared spectra of synthesised ligand (L1) and metal complex (M1) were analysed in range 4000-400 cm-1 using KBr pellet. The IR spectrum for ligand (L1) shows seven absorption bands of interest namely υ(OH), υ(N-H), υ(C=O)COOH, υ(C=O)amide, υ(C-N), υ(C-S) and υ(C-O). Based on the spectrum, the absorption band for secondary amide N-H stretching is observed at 3054 cm-1. Meanwhile, the absorption band for C=O (amide) are observed at 1694 cm-1, which almost identical in the previous report on the similar systems (Akiyama et al., 2008; Mureseanu, 2010). The frequency for C=O(amide) of the ligand is decreased compared with ordinary carbonyl absorption which are at 1700 cm-1 plausible due to the interaction hydrogen bonding between the N-H and C=O groups (Rode et al., 2002; Saeed et al., 2010; Ke and Cao, 2010; Weiqun et al., 2004; Rahamathullah et al., 2012; Khairul et al., 2013) . Somehow, the infrared spectrum for metal complex (M1) shows five absorption bands of υ(O-H), υ(N-H), (C=O)amide, υ(C-N), υ(C-S) and υ(C-O). Apparently, there is elimination of C=O amide functional group in metal complex (M1). The IR spectrum of metal complex (M1) exhibits the vibration signal of C=O has disappeared, which was suggesting the strong participation of bonding to the metalcentre (Wan Ibrahim and Yamin, 2007). This is because, during complexation, palladium withdraws an electron of oxygen atom (C=O) towards itself which cause the intermolecular bonding between carbon and oxygen atom become weak and tend to form a bonding with palladium metal. On the other hand, a strong band appeared at 736.96 cm-1 in IR spectrum of free ligand (L1) is believed to be C=S stretching vibration (Yusof et al., 2010; Azam et al., 1998). This band was shifted to 771.38 cm-1 in IR spectrum of metal complex (M1) due to the reduced double bond character of C=S bond (El-Bahy et al., 2003). Besides, during complexation, the electron density of double bond (C=S) from ligand has been donated to the metal centre making the (C=S) bonding becomes weak (Budacoti et al., 2007). The empty π* orbital of the metal had been occupied and the interaction between (Pd-C-S) become stronger. Thus, the FTIR result shows the possible coordination of PdCl2 with L1 via oxygen atom in (C=O) and sulphur atom in (C=S). The results were supported by NMR analysis to determine the most favourable configuration of (M1). Table 1: IR data for ligand (L1) and palladium complex (M1). Compounds υ(O-H) υ(N-H) υ(C=O) COOH (L1) 3185.02 3054.04 1703.07 Intensity (m) (w) (m) (M1) 3117.97 3025.63 1719.49 Intensity (w) (w) (s)

υ(C=O) amide 1694.50 (m) -

υ(C-N) 1228.31 (m) 1176.83 (m)

υ(C-S) -

υ(C-O) -

771.38 (m)

1053.29 (w)

Nuclear Magnetic Resonance (NMR) Spectroscopy: 1 H NMR spectra for compound L1 and M1 show the methyl resonance in the range of δH 0.83 – 0.88 ppm. Protons for hydroxyl group are observed at δH 11.12 ppm for L1 and δH 11.15 ppm for M1 as single signal. Protons for N-H are observed as singlet resonances for compound L1 which can be observed at δH 3.40 for 8 and δH 10.82 ppm for 6 (Rode et al., 2002; Saeed et al., 2010; Tian et al., 2009). The broad resonance at ~3.00 ppm could be NH which as it is usually broadened due to quadpolar effect. Instead, N-H protons for compound M1 are appeared at δH 3.53 and 9.71 ppm respectively. The displacement shift of N-H in the M1 could be indicated to substantial reduction in the electron density around the nitrogen atom due to the coordination with Pd (II) (Moro et al., 2009; Weiqun et al., 2004). The chemical structure and numbering scheme for a metal complex (M1) is presented in Figure 1. From the 13C NMR spectra data in Table 2, resonance of methyl group for compounds L1 and M1 are observed at δC 14.04 and 14.05 ppm whilst, carbon resonance for carboxylic acid groups in both compounds (L1 and M1) can been seen at δC 175.42 and 184.97 ppm respectively. The resonance for C=O in L1 is observed at δC 173.31 ppm due to the deshielding effect in the presence of oxygen atom that withdraws crtain amount of electrons from the alkyl chain (Tadjarodi et. al., 2007). However, the resonance for C=O in M1 has shifted to downfield at δC 175.42. This displacement has shown that there is the coordination between oxygen of carbonyl group with the palladium metal (Ferrari et al., 2007; Dominguez et al., 2002; Al-Allaf et al., 2005; Sawant et al., 2010) . Furthermore, there is also a large displacement resonance of thione carbon where as C=S for L1 has 151


shifted from δC 180.54 ppm to the down field δC 173.31 ppm in M1. It is because of the coordination of sulphur atom with the palladium metal. These findings are supported with FTIR spectrum in which the ligand is coordinated to the palladium atom through the sulphur atom of C=S and the oxygen atom of the carbonyl group.

Fig. 1: Numbering Scheme for 1H and 13C NMR spectral assignment of complex (M1). Table 2: Significant 1H and 13C spectral data of ligand (L1) and complex (M1). Chemical shift, δ ppm Assignments Ligand (L1) Pd complex (M1) 1 13 1 H C H CH3 (1) 0.84-0.88 14.05 0.83-0.87 (t, JHH= 7 Hz, 4H, CH3) (t, JHH= 7 Hz, 4H, CH3) CH2 (2) 1.22-1.31 22.04 1.26-1.29 (m, 5H, CH2) (m, 5H, CH2) CH2 (3) 1.45-1.53 26.87 1.46-1.50 (m, 5H, CH2) (m, 5H, CH2) CH2 (4) 2.34-2.38 35.75 2.07 (t, JHH= 7 Hz, 7H, CH2) (t, JHH= 7 Hz, 7H, CH2) C=O (5) NH (6) C=S (7) NH (8) CH2 (9) CH2 (10) COOH (11) OH (12)

10.82 (s) 3.40 (s) 3.71-3.76 (d, JHH= 6, CH2) 2.57-2.60 (t, JHH= 6 Hz, NH) 11.12 (s)

173.31 180.54 40.71 32.81 175.42 -

9.71 (s) 3.53 (s) 2.50 (d, JHH= 6, CH2) 2.07 (t, JHH= 6 Hz, NH) 11.15 (s)

13 C 14.04

21.98 27.38 35.81

175.42 207.03 37.94 32.77 184.97 -

Catalytic Studies: The palladium complex (M1) prepared in this study was tested as homogenous catalyst in Heck crosscoupling reaction between iodobenzene and methyl acrylate in the presence of triethylamine as base in N,Ndimethylacetamide at reflux temperature (120°C). Triethylamine was chosen as base due to the capability of this base to give highest conversion compared to other bases (Mohanty et al., 2008; Weiqun et al., 2004). In Heck cross-coupling reaction, the high temperature usually more than 100°C is needed to asist the activation of substrate such as iodobenzene (Sawant et al., 2010; Wan Ibrahim, 2008). The reaction then has been repeated between bromo acetophenone and methyl acrylate in the same time and condition. According to Beletskaya and Cheprakov, 2009, the efficiency reaction of metal-catalysed Heck cross-coupling reaction is strongly depending on the condition of the reaction such as substrate, base and solvent choice are important to obtain the best yield of product (Guerrero et al., 2010; Yu et al., 2010; Chapman et al., 2010; Roshin and Polunin, 2008). Catalytic loading was kept to 1.0 mol%, so as to give an expected turnover number of 100 if 100% conversion was achieved. The reaction was monitored by percentange (%) conversion of the aryl iodide and aryl bromide as starting materials by Gas Chromatography Flame Ionization Detector (GC-FID). All these data indicate that M1 may be utilised as homogenous catalyst in the Heck cross-coupling reaction where as it gave 100% conversion of starting materials into the desired Heck product of methyl cinnamate for iodobenzene and acid methyl ester for bromo acetophenone as shown in Scheme 2. The catalytic activity of this newly developed system is summarized in Table 3 below. Table 3: The catalytic activity and performance of the palladium-thiourea complex M1. Complex Without catalyst Synthesised Pd-thiourea complex Catalyst loading 0.00 mmol 1.00 mmol Retention time 24 hours 24hours Conversion of iodobenzene 44.11% 100% Conversion of bromo acetophenone 16.95% 100%

Pd-Schiff Base complex 1.00 mmol 24 hours 83% -

Characterization of Heck Final Product: The final product of the reaction was characterised by several selected spectroscopic techniques to determine the assignment of the expected compound. The methyl cinnamate as a product was obtained from 152


Heck reaction with iodobenzene and assisted by synthesised catalyst (MI). The final product can be afforded as off white precipitate with the yield 38.93%. IR (KBr): ν(COOCH3) 1716.85 cm-1, ν(C=C) 1637.50 cm-1, ν(C-O) 1173.45 cm-1; 1H NMR (400 MHz,CDCl3) δH 3.85 (s, CH3), 6.50 (d, JHH= 23 Hz, CH), 7.42 (s, 3H, CH), 7.55 (s, 3H, CH), 7.70 (d, JHH= 15.2 Hz, 7H, CH); 13C NMR (100.6 MHz, CDCl3) δC 30.85 (s, CH3), 117.83 (s, CH), 128.04, 128.86, 130.25 (6 x s, C6H4), 144.84 (s, CH), 206.76 (s, C=O). Then, the reaction was repeated as above by changing the different aryl halide namely bromoacetophenone to afford methyl ester acid as final product.Yield of product 38.78%. IR (KBr): ν(COOCH3) 1711.28 cm-1, ν(C=OCH3) 1682.51 cm-1, ν(C=C) 1640.84 cm-1, ν(C-O) 1211.67 cm-1; 1H NMR (400 MHz, CDCl3) δH 2.64 (s, CH3), 3.85 (s, CH3), 6.57 (d, JHH= 16.0 Hz, CH), 7.64 (pseudo-d, JHH= 16 Hz, 2H, C6H4), 7.71 (d, JHH= 16 Hz, CH), 8.01 (pseudo-d, JHH= 10 Hz, 2H, C6H4); 13C NMR (100.6 MHz, CDCl3) δC 26.71, 51.93 (2 x s, CH3, CH3), 120.34 (s, CH) , 128.16, 128.87, 138.04, 138.71 (6 x s, C6H4), 143.32 (s, CH), 166.96, 197.34 (2 x s, C=O). Conclusion: In conclusion, an amino acid thiourea (L1) and its designated palladium complex (M1) were successfully synthesised and characterised via several typical spectroscopic and analytical techniques. The catalytic studies indicate that this type of palladium complex bearing this linear thiourea as ligand can act as ideal potential homogenous catalyst in the Heck cross-coupling reaction. This newly developed system described here appears to be highly competitive with other systems reported in the literature, and in some cases, better results are obtained for the reaction duration, work-up, product isolation and yields. In addition, preparation of the thiourea used in this method is easier than other methods reported by other researchers. ACKNOWLEDGMENT The authors would like to acknowledge Ministry of Higher Education (MOHE) for Fundamental Research Grant Schemes (FRGS), grant no. 59158, Department of Chemical Sciences, Universiti Malaysia Terengganu for Final Year Project Funding, Institute of Marine Biotechnology UMT for the NMR facility, Civil Service Department, for undergraduate scholarship and Department of Chemistry, UTM for research collaboration and facilities. REFERENCES Akiyama, Y., S. Fujita, H. Senboku, C.M. Rayner, S.A. Brough, M. Arai, 2008. An in situ high pressure FTIR study on molecular interactions of ketones, esters, and amides with dense phase carbon dioxode. J. Supercritical Fluids, 46: 197-205. Alonso, F., I.P. Beletskaya, M. Yus, 2005. Non-conventional methodologies for transition-metal catalysed carbon-carbon coupling: a critical overview. Part 1: The Heck reaction. Review article, Tetrahedron, 61: 1177111835. Al-Hashimi, M., A.C. Sullivan, J.R.H. Wilson, 2007. Palladium ethylthioglycolatemodified silica-a new heterogeneous catalyst for Suzuki and Heck cross-coupling reactions.Journal of Molecular Catalysis A: Chemical, 273: 298-302. Aydemir, M., A. Baysal, B. Gümgüm, 2008. Synthesis and characterization of tris{2-(N,N-bis (diphenylphosphino) aminoethyl} amine derivatives: Application of a palladium(II) complex as a pre-catalyst in the Heck and Suzuki cross-coupling reactions, Journal of Organometallic Chemistry, 693: 3810-3814. Bally, I., C. Simion, M.D. Mazus, C. Deleanu, N. Popa, D. Bally, 1998. The molecular structure of some urea and thiourea derivatives, Journal of Molecular Structure, 446: 63-68. Beletskaya, I.P., A.V. Cheprakov, 2000. The Heck Reaction as a Sharpening Stone of Palladium Catalysis. Chem.Reviews, 100: 3009-3066. Blaser, H.U., A. Indolese, A. Schnyder, H. Steiner, M. Studer, 2001. Supported palladium catalysts for fine chemicals synthesis. J Mol Catal A Chem., 173: 3-18. Buckley, B.R., S.P. Neary, 2010. Thiadiazolidine 1-oxide systems for phosphine-free palladium-mediated catalysis, Tetrahedron, 66: 7988-7994. Budakoti, A., M. Abid, A. Azam, 2007. Synthesis, characterization an in-vitro anti-amoebic activity of new Pd(II) complexes with 1-N-substituted thiocarbamoyl-3,5-biphenyl-2-pyrazoline derivatives. European Journal of Medicinal Chemistry, 42: 544-551. Chapman, L.M., B. Adams, L.T. Kliman, A. Makriyannis, C.L. Hamblett, 2010. Intramolecular Heck reactions of aryl chlorides with alkynes. Tetrahedron Letters, 51: 1517-1522. Delaude, Lionel. Chapter 18: University of Liege in Belgium. http://chemistry.lsu.edu/stanley/webpub/ 4571-Notes/chap18-Cross-Coupling.doc [17th December 2009]. Domínguez, M., E. Anticό, L. Beyer, A. Aguirre, S. García-Granda, V. Salvadό, 2002. Liquid-liquid extraction of palladium (II) and gold (III) with N-benzoyl-N’, N’-diethylthiourea and the synthesis of a palladium benzoylthiourea complex Polyhedron, 21: 1429-1437. 153


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