Synthesis Of Cryptands For Eu2+-Containing Complexes

Wayne State University Wayne State University Theses 1-1-2015 Synthesis Of Cryptands For Eu2+-Containing Complexes Chengcheng Wang Wayne State University, Follow this and additional works at: http://digitalcommons.wayne.edu/oa_theses Part of the Inorganic Chemistry Commons Recommended Citation Wang, Chengcheng, "Synthesis Of Cryptands For Eu2+-Containing Complexes" (2015) Wayne State University Theses Paper 395 This Open Access Thesis is brought to you for free and open access by DigitalCommons@WayneState It has been accepted for inclusion in Wayne State University Theses by an authorized administrator of DigitalCommons@WayneState SYNTHESIS OF CRYPTANDS FOR Eu2+-CONTAINING COMPLEXES by CHENGCHENG WANG THESIS Submitted to the Graduate School of Wayne State University, Detroit, Michigan in partial fulfillment of the requirements for the degree of MASTER OF SCIENCE 2015 MAJOR: CHEMISTRY Approved By: Advisor Date DEDICATION To my parents ii ACKNOWLEDGEMENTS It has been a wonderful journey! First and foremost, I would like to thank my advisor Professor Matthew J Allen from whom I have learned a lot I am deeply grateful for his support on my decisions Also, I would like to thank my committee members: Professor Stanislav Groysman and Professor Jennifer L Stockdill for their valuable suggestions on my thesis As an international student, I would like to thank Melissa Barton for her assistance with all kinds of paperwork, and Sara M Tipton for her help with my English A special thanks to Lauren, Akhila, Zhijin, Levi, Chamika, Lina, and Mike Working in the Allen lab has been a privilege I really enjoyed the time we spent together! Last but not least, I would like to thank all my friends You guys make my life more colorful I would like to share my smile with all of you iii TABLE OF CONTENTS Dedication ii Acknowledgements .iii List of Tables .vi List of Figures vii List of Schemes ix List of Abbreviations x Chapter 1: Introduction to the Developments in the Coordination Chemistry of Eu2+ 1.1 Introduction 1.2 Properties and applications of Eu2+-containing complexes 1.3 Methods to stabilize Eu2+ .3 1.4 Aims of my research .4 Chapter 2: Synthesis of Cryptand Ligands for Eu2+-Containing Complexes as Potential Contrast Agents 2.1 Introduction 2.2 Experimental Procedures 2.2.1 Materials 2.2.2 Characterization 2.2.3 Synthesis 2.3 1H- and 13C-NMR Spectra of 2.4 and 2.6–2.11 16 Chapter 3: Synthesis of Azacryptand Ligands for Luminescence Studies of Eu2+ 30 3.1 Introduction 30 iv 3.2 Experimental Procedures 33 3.2.1 Materials 33 3.2.2 Characterization 33 3.2.3 Synthesis 34 3.3 1H- and 13C-NMR Spectra of compounds 3.7, 3.9, and 3.10 .37 Chapter 4: Synthesis of Tetraoxolene-Bridged Cryptand Ligands for Magnetic Studies of Divalent Lanthanides .43 4.1 Introduction 43 4.2 Experimental Procedures 44 4.2.1 Materials 44 4.2.2 Characterization 45 4.2.3 Synthesis 45 4.3 1H- and 13C-NMR Spectra of compounds 4.2 and 4.3 47 Chapter 5: Summary and Future Outlook 51 5.1 Summary and Future Outlook 51 References 53 Abstract 57 Autobiographical Statement .58 v LIST OF TABLES Table 1.1 Calculated Ln3+/Ln2+ reduction potentials (versus normal hydrogen electrode) of lanthanides5 .1 vi LIST OF FIGURES Figure 1.1 Chemical Structure of complex 1.1 Figure 1.2 Structures of Eu2+-containing complexes 1.2–1.4 .3 Figure 1.3 Chemical structures of unfunctionalized Eu2+-containing cryptate 1.5 and functionalized Eu2+-containing cryptates 1.6–1.10 (coordinated water molecules and counter ions are not shown for clarity) Figure 1.4 Chemical structures of compounds 1.11–1.14 Figure 2.1 Examples of Eu2+-containing [2.2.2]cryptates (2.1–2.3) that are more effective contrast agents for magnetic resonance imaging at ultra-high field strengths compared to lower fields Figure 2.2 1H-NMR spectrum of 2.4 16 Figure 2.3 13C-NMR spectrum of 2.4 17 Figure 2.4 1H-NMR spectrum of 2.6 18 Figure 2.5 13C-NMR spectrum of 2.6 19 Figure 2.6 1H-NMR spectrum of 2.7 20 Figure 2.7 13C-NMR spectrum of 2.7 21 Figure 2.8 1H-NMR spectrum of 2.8 22 Figure 2.9 13C-NMR spectrum of 2.8 23 Figure 2.10 1H-NMR spectrum of 2.9 .24 Figure 2.11 13C-NMR spectrum of 2.9 25 Figure 2.12 1H-NMR spectrum of 2.10 .26 Figure 2.13 13C-NMR spectrum of 2.10 27 Figure 2.14 1H-NMR spectrum of 2.11 .28 Figure 2.15 13C-NMR spectrum of 2.11 29 Figure 3.1 Unfunctionalized cryptand 3.1 and modified cryptands 3.2–3.6 .31 vii Figure 3.2 Structures of ligands 3.7 and 3.8 31 Figure 3.3 1H-NMR spectrum of 3.7 37 Figure 3.4 13C-NMR spectrum of 3.7 38 Figure 3.5 1H-NMR spectrum of 3.9 39 Figure 3.6 13C-NMR spectrum of 3.9 40 Figure 3.7 1H-NMR spectrum of 3.10 .41 Figure 3.8 13C-NMR spectrum of 3.10 42 Figure 4.1 1H-NMR spectrum of 4.2 47 Figure 4.2 13C-NMR spectrum of 4.2 48 Figure 4.3 1H-NMR spectrum of 4.3 49 Figure 4.4 13C-NMR spectrum of 4.3 50 viii LIST OF SCHEMES Scheme 2.1 Metalation of 2.4 to form neutral Eu2+-containing complex 2.5 Scheme 2.2 Synthesis of cryptands 2.4 and 2.6 Scheme 3.1 Synthesis of azacryptand 3.7 32 Scheme 3.2 Proposed synthetic procedures for azacryptand 3.8 .32 Scheme 4.1 Proposed synthetic procedures for ligand 4.1 44 ix 44 divalent lanthanides such as Eu2+, Sm2+, and Yb2+, which are less studied compared to trivalent lanthanides The proposed synthetic procedures for ligand 4.1 are shown in Scheme 4.1 Dihydroxybenzoquinone was reduced using tin in concentrated hydrochloric acid,40 and reacted with methyl bromoacetate to give ester 4.2 It was hydrolyzed using DOWEX to give the corresponding acid 4.3 Reaction of this acid with oxalyl chloride afforded the acid chloride which was further reacted with aza-crown ether to give the corresponding amide In the mass spectrometry I observed the peak of the amide, but I was not able to purify it using silica gel chromatography Scheme 4.1 Proposed synthetic procedures for ligand 4.1 4.2 Experimental Procedures 4.2.1 Materials 45 Commercially available chemicals were of reagent-grade purity or better and were used as received unless otherwise noted Water was purified using a PURELAB Ultra Mk2 purification system 4.2.2 Characterization H- and 13 C-NMR spectra were recorded at ambient temperature on a Varian Unity 400 spectrometer (400 MHz for 1H and 101 MHz for 13C) Chemical shifts were referenced to solvent residual signals (CDCl3: 1H δ 7.26 ppm, 13C δ 77.16; DMSO-d6: H δ 2.50, 13C δ 39.52) 1H-NMR data are assumed to be first order, and the apparent multiplicities are reported as follows: „„s‟‟ = singlet and „„br‟‟ = broad Italicized elements are those that are responsible for the shifts High resolution electrospray ionization mass spectra (HRESIMS) were recorded on a Waters LCT Premiere Xe TOF mass spectrometer Low resolution mass spectra (MS) of known compounds were recorded on a Shimadzu LCMS-2010EV mass spectrometer 4.2.3 Synthesis Tetramethyl 2,2',2'',2'''-(benzene-1,2,4,5-tetrayltetrakis(oxy))tetraacetate (4.2): To a stirred mixture of 2,5-dihydroxy-1,4-benzoquinone (1.98 g, 14.1 mmol, equiv) in HCl (36%, aqueous, 50 mL) was slowly added granular tin metal (2.12 g, 17.8 mmol, 1.3 equiv).40 The reaction mixture was heated at reflux for h then filtered while hot The filtrate was cooled to °C to produce an off-white solid that was crystallized from tetrahydrofuran to yield 0.776 g of a white solid The solid was dissolved in acetone (20 mL), and added dropwise into a stirred mixture of K2CO3 (7.80 g, 56.4 mmol) and methyl bromoacetate (8.56 g, 56.0 mmol) in acetone (130 46 mL) The reaction mixture was stirred at reflux under Ar for 24 h After cooling to ambient temperature, solids were removed by filtration, and the solvent was removed under reduced pressure to produce an orange oil The oil was dissolved in ethyl acetate (50 mL), washed with water (3 × 50 mL) and dried over anhydrous Na2SO4 The solvent was removed under reduced pressure to produce a yellow solid that was recrystallized twice from ethanol to yield 0.508 g (8.4%) of 4.2 as white solid 1Hand 13 C-NMR spectra were assigned using DEPT, GCOSY, GHMQC, and GHMBC experiments 1H NMR (400 MHz, CDCl3) δ 6.66 (s, CH, 2H), 4.65 (s, CH2, 8H), 3.78 (s, CH3, 12H); 13C NMR (101 MHz, CDCl3) δ 169.5, 143.6, 107.8 (CH), 67.8 (CH2), 52.3 (CH3); HRESIMS (m/z): [M + Na]+ calcd for C18H22O12Na, 453.1009; found, 453.1009 2,2',2'',2'''-(Benzene-1,2,4,5-tetrayltetrakis(oxy))tetraacetic acid (4.3): Dowex 50WX8 (hydrogen form, 200–400 mesh, 0.22 g) was added to a mixture of 4.2 (1.05 g, 2.44 mmol) in H2O (100 mL) The reaction mixture was heated at reflux for 24 h then filtered while hot The filtrate was cooled to ambient temperature to yield 0.847 g (93%) of 4.3 as white solid 1H- and 13 C-NMR spectra were assigned by comparison with published assignments.41 1H NMR (400 MHz, DMSO-d6) δ 12.90 (brs, 4H), 6.70 (s, 2H), 4.62 (s, 8H); 13 C NMR (101 MHz, DMSO-d6) δ 170.4, 142.0, 105.3, 66.4; MS (m/z): [M + Na]+ calcd for C14H14O12Na, 397.0; found, 397.0 47 4.3 1H- and 13C-NMR Spectra of compounds 4.2 and 4.3 Figure 4.1 1H-NMR spectrum of 4.2 48 Figure 4.2 13C-NMR spectrum of 4.2 49 Figure 4.3 1H-NMR spectrum of 4.3 50 Figure 4.4 13C-NMR spectrum of 4.3 51 Chapter 5: Summary and Future Outlook 5.1 Summary and Future Outlook Coordination chemistry is one of the most important fields in modern inorganic chemistry Ligand synthesis using organic techniques plays an important role in coordination chemistry This thesis describes my efforts to synthesize different cryptands for Eu2+-containing complexes Subsequent metalation with Eu2+ will produce Eu2+-containing cryptates Cyclic voltammetry experiment can be performed to study the oxidative stability of these complexes As with the ligand for MRI application, 5,6-(4-(3-(3,5-dicarboxyphenyl)thioureido)benzo)-4,7,13,16,21,24-hexaoxa-1,10-diaz abicyclo[8.8.8]hexacosane, a series of molecules with two carboxylic groups can be attached to cryptand unit through thiourea linkage For example, the positions of two carboxylic groups can be changed in phenyl ring; amino acids such as aspartic acid and glutamic acid can also be used The Allen group has studied Eu2+ complexes of ligand 1,4,7,10,13,16,21,24-octaazabicyclo[8.8.8]hexacosane (aza222) It was found that this complex has bright yellow luminescence.42 Based on this result, I did a literature search to find ways to incorporate the aza222 ligand into polymers Jackson and coworkers recently reported methods to synthesize aza222-based polymers.43 Thus, future work based on this ligand could include synthesizing Eu2+-containing aza222-based polymers, and measuring their luminescence properties 52 In the process of synthesizing phenyl derivatives of aza222, the synthetic methods need to be modified to increase the yield to produce one of the intermediates 2,3,8,9,11,12,17,18,19,20,25,26-hexabenzo-1,4,7,10,13,16,21,24-octaazabicyclo[8.8.8 ]hexacosane-5,614,15,22,23-hexaone Also, the low solubility of the intermediate in common organic solvents prevents further characterizations except high resolution electrospray ionization mass spectra One possible solution is to grow single crystals by slow vaporization of its concentrated CH2Cl2 or THF solution Finally, efforts are needed to synthesize the tetraoxolene bridged dicryptand ligand Lower reaction yields are expected compared to the synthesis of ligand that has only one cryptand In addition, functionalized tetraoxolene such as hydrochloranilic acid can also be used as bridging ligand 53 REFERENCES (1) Meyer, G In The Rare Earth Elements: Fundamentals and Applications; 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Asada, H.; D‟Andreq, S V J Org Chem 1985, 50, 4276–4281 (41) Johnson, M R.; Seok, W K.; Ma, W.; Slebodnick, C.; Wilcoxen, K M.; Ibers, J A J Org Chem 1996, 61, 3298–3303 (42) Kuda-Wedagedara, A N W.; Wang, C.; Martin, P D.; Allen, M J J Am Chem Soc in press (43) Redko, M Y.; Manes, K M.; Taurozzi, J S.; Jackson, J E.; Tarabara, V V React Funct Polym 2014, 74, 90–100 57 ABSTRACT SYNTHESIS OF CRYPTANDS FOR Eu2+-CONTAING COMPLEXES by CHENGCHENG WANG May 2015 Advisor: Dr Matthew J Allen Major: Chemistry Degree: Master of Science Eu2+-containing complexes have considerable applications in synthetic chemistry, medical diagnosis, and materials science However, Eu2+ is easily oxidized in solution when exposed to air Allen and coworkers have demonstrated that Eu2+ can be stabilized by functionalized cryptands Based on this idea, I focused my research on synthesizing cryptands The progress towards synthesizing several modified cryptands is described in the thesis The Eu2+-containing complexes of these cryptates have potential applications as magnetic resonance imaging contrast agents, luminescent materials, and magnetic materials 58 AUTOBIOGRAPHICAL STATEMENT Education Wayne State University, Detroit, MI, USA August 2013–May 2015 Degree: M.S (Chemistry) Soochow University, Suzhou, Jiangsu, China September 2009–June 2013 Degree: B.S (Chemistry) Honors and Awards Chun-Tsung Scholar: 2011 National Scholarship: 2011 Zhu Jingwen Scholarship: 2011 Suzhou Industrial Park(SIP) Scholarship: 2012 People‟s Scholarship 1st grade: 2011, 2012 Teaching Service Citation: 2014-2015 Publications Kuda-Wedagedara, A N W.; Wang, C.; Martin, P D.; Allen, M J Aqueous Eu(II)-Containing Complex with Bright Yellow Luminescence J Am Chem Soc in press Teaching Experience Department of Chemistry, Wayne State University Graduate Teaching Assistant: September 2013–May 2014 Graduate Teaching Assistant: January 2015–May 2015 .. .SYNTHESIS OF CRYPTANDS FOR Eu2+-CONTAINING COMPLEXES by CHENGCHENG WANG THESIS Submitted to the Graduate School of Wayne State University, Detroit, Michigan in partial fulfillment of the... applications of Eu2+-containing complexes 1.3 Methods to stabilize Eu2+ .3 1.4 Aims of my research .4 Chapter 2: Synthesis of Cryptand Ligands for Eu2+-Containing Complexes. .. spectrum of 4.2 48 Figure 4.3 1H-NMR spectrum of 4.3 49 Figure 4.4 13C-NMR spectrum of 4.3 50 viii LIST OF SCHEMES Scheme 2.1 Metalation of 2.4 to form neutral Eu2+-containing