MATERIAL ASPECTS OF H-BONDED MACROCYCLIC AROMATIC PENTAMERS REN CHANGLIANG NATIONAL UNIVERSITY OF SINGAPORE 2011     MATERIAL ASPECTS OF H-BONDED MACROCYCLIC AROMATIC PENTAMERS REN CHANGLIANG (B.Sc.), SICHUAN UNIVERSITY, CHINA A THESIS SUMBITTED FOR THE DEGREE OF DOCTOR OF PHILOSOPHY DEPARTMENT OF CHEMISTRY NATIONAL UNIVERSITY OF SINGAPORE 2011     Acknowledgement First and foremost, I would like to take this opportunity to thank my supervisor, Professor Zeng Huaqiang, not only for his expert guidance and warm encouragement but also for his confidence and unlimited trust in me throughout my Ph.D study. I would like to express my deeply-felt gratitude to all the lab members of Prof. Zeng’s group, especially to Ong Wei Qiang, Dr. Qin Bo, Dr. Zhao Huaiqing, Dr. Li Zhao, Ye Ruijuan, Fang Xiao, Yan Yan, Shu Yingying, Sun Chang, Liu Ying, Shen Jie, Shen Sheng, Xu Shengyu, Ting Ying Chang, Liew Sisi, Liang Qian, Zhu Danping, Yap Wei Liang and Yip Yeow Kwan for their friendship, valuable advice and precious collaboration. It was a great pleasure to share my doctoral study and life with those wonderful people. I am grateful to our collaborators, Prof. Su Haibin, Dr. Chen Xiuying and Zhou Feng, from Nanyang Technological University for their kind help on the theoretical calculations of molecular modeling. I would like to thank Prof. Chen Hongyu, Xun Jun and Dr. Zhu Liangfang from Nanyang Technological University for their great support and assistant on the TEM measurement. I would like to thank faculty and staff members from deparment of chemistry, especially to Prof. Koh Lip Lin and Ms. Tan Geok Kheng for their assistance in resolving the crystal structures, Mr. Lee Ka Yau for his assistance in SEM and TEM analysis, Mdm Wong Lai Kwai, Mdm Lai Hui Ngee and Dr. Liu Qiping i    for their assistance in Mass analysis, Mdm Han Yanhui for her assistance in NMR analysis and Mdm Toh Soh Lian for her assistance in XRD analysis. I would like to express my special thanks to all of my local friends. Their kind hospitality, help and friendship made my life in Singapore a meanful and enjoyable experience. Lastly, I appreciate National University of Singapore for its generous financial support for my Ph.D study. This dissertation is dedicated to my parents, Ren Zequan and Xiong Hong, who raise me up with love. Without their understanding, encouragement, and value support, this work would never have been completed. Ren Changliang National University of Singapore July, 2011 ii    Thesis Declaration The work in this thesis is the original work of Ren Changliang, performed independently under the supervision of Dr. Zeng Huaqiang, (in the laboratory of chemical biology), Chemistry Department, National University of Singapore, between 06/08/2007 and 06/08/2011. The content of the thesis has been partly published in: 1) Changliang Ren, Victor Maurizot, Huaiqing Zhao, Jie Shen, Wei Qiang Ong, Feng Zhou, Zhiyun Du, Kun Zhang, Haibin Su, and Huaqiang Zeng*, Fivefold-Symmetric Aromatic Pentamers: High Affinity Cation Recognition, Ion-Pair Induced Columnar Stacking and Nanofibrillation, J. Am. Chem. Soc., 2011, 133, 13930. 2) Changliang Ren, Feng Zhou, Bo Qin, Ruijuan Ye, Sheng Shen, Haibin Su, and Huaqiang Zeng*, Crystallographic realization of the mathematically predicted densest “All Pentamer” packing lattice by C5-symmetric “sticky” fluoropentamers, Angew. Chem., Int. Ed., 2011, 50, 10612. 3) Changliang Ren, Shengyu Xu, Jun Xu, Hongyu Chen, and Huaqiang Zeng*, Planar Macrocyclic Fluoropentamers as Supramolecular Organogelators, Org. Lett., 2011, 13, 3840. Ren Changliang iii    Table of Contents Acknowledgement…………………………………………………….……i  Table of Contents……………………………………….… ……………. iv  Summary……………………………………………… .…… ………….  viii  List of Tables……………………………………………………… … …. xi  List of Figures………………………………………… .……… .….  xiii  Abbreviation and Symbols………………………………… .……. xxiii  Chapter Introduction 1.1 Background…………………………………………………………………1 1.2 H-bonded Aromatic Macrocycles……………… ………………… …….3 1.3 Aim of the Study………………………………… ………………… … 10 Chapter Two-dimensional Crystal with the Densest “All Pentamer” Packing Lattice 2.1 Introduction…………………………………………………………… 14 2.1.1 Background……………………………………………………….…14 2.1.2 Packing Arrangement Study of Equal Regular Pentagons…… .… 15 2.1.3 Mathematically Sketched Abstract 2D Packing Patterns of Equal Regular Pentagons…………………………………………… … 23 2.2 Result and Discussion…………………………………………………… 25 2.2.1 Ab initio Molecular Modeling at the B3LYP/6-31G* Level for Conformational Search……………………… .…………… .…….….27 2.2.2 Synthesis of Macrocyclic Pentamer 2………………… .……….…28 2.2.3 Conformation Study of Oligoamides……………………………… 29 iv    2.2.3.1 Solid State Stucture of Dimer 2c……………… .………… …29 2.2.3.2 1H NMR, 19F NMR for Selected Oligoamides…… .………….32 2.2.4 Characterization of Macrocyclic Pentamer 2………… .………… 33 2.2.5 Solid State Stucture of Macrocyclic Pentamer and its Twodimensional Molecular Packing Lattice……………….……… ….35 2.2.6 Two-dimensional Molecular Packing Lattice of Macryclic Pentamer 1……………………….…………………………………… …… 40 2.2.7 Determination of the Bonding Energy per Pentamer in Forming an Ordered 2D Pentagonal Lattice……………… .………………… 42 2.2.8 Deciphering/Quantifying the Driving Forces for Forming an Ordered 2D Pentagonal Lattice……………… .………………… 45 2.3 Conclusion and Future Work……………………… .………………… 51 2.4 Experimental Section…………………………………………………… 53 Chapter Planar Macrocyclic Fluoropentamers as Supramolecular Organogelators 3.1 Introduction……………………………… .………………………… …64 3.1.1 Background………………………………………………………….64 3.1.2 Strategies Used to Design Gelators……… .………………….……67 3.2 Result and Discussion……………………………………………….…….68 3.2.1 Synthesis of Macrocyclic Fluoropentamer and 3………… .…….70 3.2.2 Conformation Study of Oligoamide……………………… .………72 3.2.3 Photographs of Gels……………………………………… .………73 3.2.4 Gelating Ability of Pentamer and 3…………………… .……… 73 3.2.5 Stacking Study of Pentamer and in Solutions…………… .… .74 3.2.5.1 Concentration-dependent 1H NMR Experiment……………… 74 3.2.5.2 Temperature-dependent 1H NMR Experiment…………………75 3.2.5.3 UV/Vis Spectra of Pentamer and in Different Solvents .76 v    3.2.5.4 UV/Vis Spectra of Pentamer and at Variable Temperature ………………………………………… .…………………… 78 3.2.6 Thermal Behavior of Gels Formed by Pentamer and 3……… .80 3.2.7 Morphology Study of Gels by TEM and SEM…………………… .83 3.2.8 3D Arrangement Study of 1D H-aggregates by Powder XRD…… .86 3.3 Conclusion and Future Work……………………………… .…… .… .88 3.4 Experimental Section………………………………………………….….90 Chapter Pyridone-based Aromatic Pentamers: High Affinity Cation Recognition, Ion-Pair Induced Columnar Stacking and Nanofibrillation 4.1 Introduction……………………………………………………………109 4.1.1 Background…………………………………………………… ….109 4.1.2 Metal-containing 1D Materials Assembled from G-quartet and Its Derivatives………………………………………… .………….….110 4.1.3 Metal-containing 1D Materials Assembled from Schiff Base Macrocycles………………………………………………….…… 111 4.1.4 Metal-containing 1D Materials Assembled from Porphyrin and Its Analogs…………………………………………………………… 112 4.2 Result and Discussion……………………………………………………113 4.2.1 Ab initio Molecular Modeling at the B3LYP/6-31G* Level for Conformational Search……………………………………… …113 4.2.2 Ab initio Molecular Modeling at the B3LYP/6-31G* Level for Complexes formed between or and Li+, Na+, K+, Rb+ and Cs+…………………………………………………………….….114 4.2.3 Synthesis of Macrocyclic Pyridone Pentamers…………………….116 4.2.3.1 Stepwise Synthesis of Cyclic Pentamer and 2………………116 4.2.3.2 One-pot Synthesis of Cyclic Pentamers………………… .119 vi    4.2.4 Solid State Conformation Study of Oligoamides and Cyclic Pentamer……………………………………….……………… .128 4.2.4.1 Solid State Structure of Dimer 1q………… .……………… 128 4.2.4.2 Solid State Structure of Pentamer 1………………………… .130 4.2.5 Stacking Study of Cyclic Pentamers……………… .……… .… 130 4.2.6 Binding Study of Pentamers towards Akali Metal Ions… … .… 135 4.2.6.1 Preparation of Alkali metal Picrates……………… .… …….136 4.2.6.2 Picrate Extraction Experiment…………………………… .…136 4.2.6.3 TLC-mediated Separation of Metal-containing Complexes from Free Pentamer 2…………………………… .…….……137 4.2.7 Cation Induced Columnar Stacking Study by ESI MASS Spectroscopy……………………………………………………… 138 4.2.8 Morphology Study of Nanofibers Formed by Pentamers’ Alkali Metal Tetraphenylborate Complex…………… .………………….141 4.2.9 Morphology Study of Nanofibers Formed by Pentamers’ Alkali Metal Halide Complex…………………………………………… .147 4.2.10 TEM-EDX Study for the Confirmation of Ion/Ion Pair Induced Nanofiber Formation………………………………………… 155 4.2.11 Ab Initio Theoretical Investigations at the B3LYP/6-31G* Level under Periodic Boundary Conditions………………… .……… .166 4.2.12 Inter-columnar Association Study of Fibers Using Powder XRD……………………………………………………………….169 4.3 Conclusion and Future Work……………………… .……………… 176 4.4 Experimental Section……………………………………………………177 4.4.1 Stepwise Preparation of Pentamer and 2………… .………… 177 4.4.2 One-pot Preparation of Pentamer 1~6……………… .………… .200 Publications………………………………………………………….……214 Appendices……………………………………………… .…………….215 vii    Summary This study systematically investigated the structural features (backbone folding and planar conformation, self-assembly and 1D columnar stacking) of H-bonded fivefold-symmetric macrocyclic aromatic pentamers. Furthermore, the material property and application of those macrocyclic pentamers has been studied including 2D packing, organic solvent gelation, cation recognition and cation or ion-pair induced nanofiber formation. In chapter 2, a C5-symmetric fluoropentamer has been designed and synthesized based on intramolecular H-bond. The crescent backbones and intramolecular H-bonds of oligomers with repeating units were confirmed by X-ray diffraction analysis of single crystal and 1H NMR. The 2D packing of this fivefold pentamer was examined by X-ray diffraction analysis of its single cystal. The results 1) prove, for the very first time, that pentagons are experimentally compatible with the crystal lattice, and can pack highly densely and crystallographically; 2) confirm that the mathematically sketched densest 2D packing by pentagons indeed can have an experimentally verifiable 2D packing density of as high as 0.921. The driving forces responsible for the formation of the ordered 2D pentagon lattice was investigated by theoretical calculation at the B3LYP/6-31G(d,p) level, which reveals that 2D pentagonal lattice was stablized by intermolecular H-bonding interactions between “sticky” hydrogen and oxygen atoms with a bonding energy of -6.82 kcal/mol. viii    H NMR and 13C NMR Spectra of Major Compounds in Chapter Bn N EtOOC O O N H N Bn O NHBoc 1g Bn N EtOOC O O N H N Bn O NHBoc 1g 228    229    230    Bn N O Bn N N H O O O O N H N O H O 1k O Et Bn H O N O N N BocHN Bn O N Bn Bn N O Bn N N O O H O O N H N O H O 1k O Et Bn O BocHN H N O N N Bn O N Bn 231    Bn N O N H Bn N O H O O N O O H N O N N H O N Bn O O O N H Bn O Bn N Bn N O HN N Bn O Bn O N H N H N Bn O O N O HN H N O N Bn O 232    C8H17 N O C8H17 N N O O H N H O O N C8H17 O NHBoc 2g O Et 233    C8H17 N O C8H17 N N H O O O N H O N O H O 2h O Et C8H17 N C8H17 N N O O O Et N O N BocHN O H O 2h C8H17 N H C8H17 O N C8H17 O H O BocHN N O N C8H17 234    C8H17 N O C8H17 N N H O N H O O O N O N H O 2i O Et C8H17 H O O N N BocHN C8H17 O N C8H17 C8H17 N O C8H17 N N H O O O N H O Et O N O H O 2i O C8H17 H N N N BocHN O C8H17 O N C8H17 235    236    237    238    iBu N O iBu N O N H H O O N O O H N O N iBu O iBu N iBu N O HN N iBu O iBu O N H N N H O N iBu H O O N H O O H N N N iBu O O HN O N iBu O 239    240    O O N O O O N H N N H H O O N O O O O HN O H N N O N O N O O O O O O O O N O O O N N H N H O O N H O O O O O H N N N O O O HN O O N O O O 241    O O O O N O O N H O N N H H O O O O O O N O O O O N O N O O HN H N O O N O O O O O O O N O O O N N H N H O O O O O O N O H N O O O N O HN H N O O O N O O O O 242    243    [...]... restrict the rotation of Ar-CONHAr bond in foldamers 2    O O N N H R N O N H N + O - O O O H O N H N N N H O N F H H N H O O N H N R O N H O N O H N N O O N N H + O - O O O N N O O H H F N H N N H M O O H N   Figure 1.1 Typical intramolecular H- bonding patters for restricting the roration of the Ar-CONHAr bond 1.2 H- bonded Aromatic Macrocycles The noncovalent interactions responsible for the foldamer formation... arrangement of nearly perfect C5 symmetry in the solid state It is noteworthy that by omitting the methoxy group pentamer 1 possess a cavity of ~1.4Å, which is near the same size as K+ Thus, in further work, replacement of methoxy group with hydroxyl group opens up the cavity and the new pentamers demonstrated selective and tighting binding towards metal ions with a high binding constant higher than 105M-1... 2-( 1H- 7-Azabenzotriazol-1-yl)-1,1,3,3-tetramethyl uronium hexafluorophosphate Methanaminium HBTU O-Benzotriazole-N,N,N’,N’-tetramethyl-uronium-hexafluorophosphate Hobt N-Hydroxybenzotriazole Hz Hertz i e that is (Latin id est) m multiplet TLC Thin Layer Chromatography xxiii    Me methyl min minute(s) MeOH methanol NMR Nuclear Magnetic Resonance NMM N-methyl morpholine NOE Nuclear Overhauser Effect NOESY Nuclear Overhuser Effect Spectroscopy... considerable progress in the synthesis of H- bonded macrocycles with well-defined and highly preorganized structure Another essential development is the investigation of multifaceted functions of these structures The convenient one-pot synthesis and the self-assembling capabilities of macrocycles make them promising assembled scaffolds for the design of new functionalized architectures, materials and organic...In chapter 3, two planar macrocylic organogelators with high gelling abilities in organic solvents such as n-hexane, ethyl acetate, cyclohexane and 1,4-dioxane were developed based on the crystallographic observation of the H- bond enhanced intermolecular aggregation occurring in the 2D-shaped fluoropentamer described in chapter 2 The 1D aggregation of the pentamers in solution was... spectrum of pentamer 2 with the addition of 1 equivalent of CsBPh4 salt………………………………………………… ……………….141 Figure 4.24 TEM images of fibers from pentamers 1 in the presence of 1 equivalent of LiBPh4 salt…………………………………………………… 143 Figure 4.25 TEM images of amorphous solids from pentamers 2 in the presence of 1 equivalent of LiBPh4 salt………………………………………… … 144 xviii    Figure 4.26 TEM images of fibers from pentamers. .. for cyclization through intramolecular hydrogen bonding Furthermore, because of the low solubility of this product in the reaction solvent, there was a thermodynamic driving force for the formation of this macrocycle These giant marocycles possess 6 N2O2 coordination environment, which allows them to bind 6 metals at the same time And the complex demonstrated a boat conformation as the minimum energy... 1 in the presence of 1 equivalent of NaBPh4 salt…………………………………………………… 144 Figure 4.27 TEM images of amorphous solids from pentamers 2 in the presence of 1 equivalent of NaBPh4 salt…………………………… …… ………… 144 Figure 4.28 TEM images of amorphous solids from pentamers 1 in the presence of 1 equivalent of KBPh4 salt…………………………… ………….……….145 Figure 4.29 TEM images of amorphous solids from pentamer 2 in the presence... presence of 1 equivalent of KBPh4 salt……………………………………… ………145 Figure 4.30 TEM images of fibers from pentamers 1 in the presence of 1 equivalent of RbBPh4 salt…………………………………………….……….145 Figure 4.31 TEM images of fibers from pentamers 2 in the presence of 1 equivalent of RbBPh4 salt……………………………………………… ……146 Figure 4.32 TEM images of fibers from pentamers 1 in the presence of 1 equivalent of CsBPh4 salt………………………………………... planar macrocyclic trimer and a strained tetramer from 4    8-amino-2-quinolinecarboxylic acid which adopts unusual stable helical conformation (Figure 1.3) The macrocyles were synthesized by a one pot reaction with high yield (20% for each) using triphenyl phosphite as the coupling reagent in the presence of N-methyl pyrrolidone and pyridine Interesting, by modifying the exterior sidechain the cationic .     MATERIAL ASPECTS OF H-BONDED MACROCYCLIC AROMATIC PENTAMERS REN CHANGLIANG NATIONAL UNIVERSITY OF SINGAPORE 2011   MATERIAL ASPECTS OF H-BONDED MACROCYCLIC. self-assembly and 1D columnar stacking) of H-bonded fivefold-symmetric macrocyclic aromatic pentamers. Furthermore, the material property and application of those macrocyclic pentamers has been studied. spectrum of pentamer 2 with the addition of 1 equivalent of CsBPh 4 salt………………………………………………… ……………….141 Figure 4.24. TEM images of fibers from pentamers 1 in the presence of 1 equivalent of LiBPh 4