`Substitnent Effects on The BOAT Conformation of Six Membered Rings'
by
KAPIL SHARMA
DEPARTMENT OF CHEMISTRY
Submitted
in fulfillment of the requirements of the degree of
DOCTOR OF PHILOSOPHY
to the
;la
A 91
7f
Dedicated to My Beloved Grandfather
Late. Sh. Rattan Chand Biala
Certificate
This is to certify that the thesis entitled "Substituent Effects On The "BOAT"
Conformation Of Six Membered Rings" being submitted by Mr. Kapil Sharma to the Indian Institute of Technology, Delhi for the award of Doctor of Philosophy is a record of bonafide research work carried out by him. Mr. Kapil Sharma has worked under my guidance and supervision and has fulfilled the requirements for the submission of thesis which to my knowledge has reached the requisite standards.
The results embodied in this thesis have not been submitted in part or full to any other university or institute for the award of any degree / diploma.
o <47 i
alin Pant‘4‘
Thesis Supervisor Associate Professor, Department of Chemistry,
Indian Institute of Technology, Delhi, Hauz Khas, New Delhi 110016, India
Acknowledgement
This thesis has been kept on track and been seen through to completion with the support and encouragement of all faculty and of numerous . friends and colleagues.
It is therefore a pleasant task to express my thanks to all those who contributed in many ways to the success of this study.
I am heartily thankfitl to my supervisor, Dr. Nalin Pant, whose, guidance, invaluable suggestions and support from the initial to the final level enabled me to develop an understanding of the subject. Above all and the most needed, he provided me unflinching encouragement and support in various ways. His truly scientist intuition has made him as a constant oasis of ideas and passions in science, which exceptionally inspire and enrich my growth as a student, a researcher and a scientist.
I am indebted to him more than he knows.
I would like to express my gratitude to Prof B. Jayaram, Ex. Head of Chemistry
Department for providing the opportunity to work on this intriguing project and for taking
some of innovative decisions to raise the departmental research level. I would also like to
thank Prof A. K. Singh, Head of Chemistry Department and Prof A.K. Ganguly, Ex. Head
of Chemical Society, for taking up the task of upgrading the research and extracurricular
It is a honour for me to thank Dr. N.G. Ramesh for his constructive criticism during project evaluation, which helped one to make necessary improvements. My special thanks goes to Prof M. S. Hundal and Dr. Geeta Hundal for their all time support starling from my B. Sc. career.
This thesis completion would not have been possible without the support of both technical and non technical staff. I have also been fortunate that many members of technical staff were willingly to share their knowledge and skills. It is not possible to list all of these people here but at least I would like to acknowledge the support from all of them especially Mr. Agarwal, Mrs. Shanta, Mr. Sharma (Instrumental Lab), Mr. Manna Lal, Mr. Keshav (NMR Lab), Mr.
Virender (Glass Blowing Lab), Mr. Gulani, Mr. Kuldeep (Electronic Workshop). In this context. 1 am also grateful to Mr. Kuldeep for teaching me techniques and other crucial daily life useful skills.
1 owe my deepest gratitude to the whole team from crystallography lab especially Dr.
Shailesh, Dr. Monika, Jency Thomas, Monica and Dr. Senthil for their useful discussions and help in data collections. Also I am highly thankful to all my friends Neeraj, Naagraj, Yogesh, for doing Mass spectra. and Anurag for helping me in dealing with Fluorimeter.
I would like to convey my special thanks to Dr. Mukesh Gupta to familiarize myself with the research work in lab during early stages of iny PhD and also to all other lab mates Sandeep, Nilesh and Rumit for their timely help. I owe, Dr. Karun Gandotra, Mr.
Vaneet Sharma (GNDLT, Amritsar) Dr. Sunil Pratap Singh, Dr. Prosenjit Chattopadhyay (HTD), a lot, for being my role model
P is a pleasure to thank all those who made this thesis possible Dr. Sarabjot Singh, Dr. Praveen Kumar, Dr. Sumit, Dr. Vipin, Dr. Vijay Khatri, Dr. N. Behra, Dr. And, Dr.
Shalabh, Dr. Parmider, Dr. Vivek, Manoj T. P, Anjul, Rajesh, Yogesh, Neeraj, Ram Kumar, Anand, Ashok, Arvind, Chandan.
iii
I would also like to thank Ajay Saxena, Chandraveer Abhishek Narayan, Shivendu Pratap and Deepak for being a great companion. My thanks are due to my IIT-Delhi, Vindhyanchal hostel friends who have made each day a new experience for me.
I am also thankfid to CUR for providing me the financial support as a Junior and Senior Research Fellowship over a period of five years.
Last but not the least; I would like to thank my family whose constant inspiration and guidance kept me focused and motivated. I am grateful to my Mom-Dad for giving me the lip I ever dreamed, and also for giving me unconditional love. In the meantime it is may duty to pay homage to my grandmother late Smt. Trishna Wati whose constant blessings have certainly kept my, fighting spirits on, all the times. The constant love and support of my elder sister, Poonam is sincerely acknowledged. I also express my gratitude to Vikas Jija Ibr being an friend CUM a torch bearer in my life. I am also indebted to my Didi, who stood by me to favor me in all the conditions and she was the source of inspiration for me to choose chemistry as my research field.
Finally, my greatest regards goes to the Almighty for bestowing upon me the patience and courage to face the complexities of life and for the completion of this project successfully.
Abstract
The thesis titled "Substituents effects on the boat conformation of six membered ring systems" is a study of the less well understood phenomenon of boat to boat ring inversion in six membered rings, using experimental and computational methods. A molecular framework capable of displaying this phenomenon is designed. Subsequently, modifications to this skeleton allows the generation of conformational switches and fluorescent metal ion sensors.
Molecular design, chemical synthesis, and structural analysis constitute the three principle components of modern stereochemistry. The transmission of structural and stereochemical information is fundamental to selective chemical processes. The molecular recognition regulating biochemical interactions, all rely on the transfer of such information with great integrity. This makes the field of conformational analysis central to the pursuit of chemical science.
Scheme I: Design and Synthesis of series of molecules based on Tetrahydrobenzofluorene (scaffold analogous to tricyclic natural product `taiwaniaquinones') skeleton was accomplished. The closed/open boat conformation as suggested by the computational results was further revealed, after performing a systematic and deep conformational study using solid state (single crystal X-ray) and solution (ID, 2D NMR) data.
Figure I
Open Closed
X = CH2
X = CO ConforniatiOntil preferences for the ben,olhlfloorene lecular skeleton
!Where X= 0, (112, CH2011, C=CH-Ph, C=C11-PhNO2, C=CH-PhNH2, C=CH-PhNI13-", CH-CH2-PhNH2, CH-CH2-PhNH31.
LOWS
'OPEN'
_ .':`)Ztrcr:A7k
[Figure 2]
! 1 '
191
pH Sensitive Conformational Switch
CI nsF,
A distinct preference for one of the two boat conformations [open or closed] can be engineered by changing either the substituent, size of five membered ring or by modulating the polarization over benzene rings flanking the boat cyclohexene based skeleton [Figure I].
The designed cavity size as well as conformational flexibility was later exploited towards the analysis of hazardous metal ion such as lead. The lead ion triggered "switchable"
conformational change resulting in enhanced ratiometric fluorescence has also been delineated in current research work to yield us a fluorescent Pb2+ selective probe.
Scheme II: After getting encouraged by the previous results, we in second part of our research developed Molecular switches whose conformation can be varied by controlling the pH. For that purpose we designed and synthesized PR amine and a controlled target TR.
Furthermore, a selective complex isomerism was also seen for conjugated amine owing to its preorganised U shaped cavity.
In contrast, TR amine revealed a boat to boat ring Inversion in presence of pH fluctuations. Hence a novel pH-controlled molecular switch has been devised by exploiting ring inversion, on a very simple looking skeleton [Figure 2].
Table of Contents
Contents Paze no.
Certificate
Acknowledgements ii
Abstract
Table of Contents vii
List of Figures xix
List of Schemes xxvii
List of Tables xxviii
Chapter -1 Introduction and Literature Survey 1
1.1 Molecular Conformation 2
1.2 Conformational Preferences of Cyclohexane 2-7
1.2.1 Why are Boat Conformers Less Stable?
1.2.2 Cyclohexane preferring a stable boat Conformation
1.2.3 Recent examples showing dual Conformation for six membered
ring in fused system
1.3 Conformational Preferences of Cyclohexene 7
1.4 Tetrahydrobenzo[a]luorene THBF Analogues and their 8
vii
Utility
1.5 Recent work using Computational Modeling. Design of 10-13 Clamshell receptors
1.5.1 Role of rigid five membered rings. preliminary Computational
work from our Lab
1.5.2 Application of Conformational mobility in a system
1.6 Ring Inversion. Factors responsible for ring inversion 13-22
1.6.1 Inversion in Chair:
1.6.1.1 Chair-Chair ring inversion
1.6.1.2 Chair —Boat ring inversion
1.6.2 Inversion in Boat:
1.6.2.1 Boat — Boat ring inversion
1.6.3 BC to CB equilibrium
1.6.4 Ring Inversions in other systems
1.7 Molecular switches 22-28
1.7.2.2 Host-guest molecular switches
1.7.2.3 Mechanically-interlocked molecular switches
1.8 pH induced Conformational change. Applications of 28-32 pH switch
1.8.1 pH effect on six membered ring Chair to Chair ring inversion
1.9 Conclusions 32
2.0 References 33-39
Chapter- 2 Design, Synthesis & Crystal Packing of Boat 40 Conformers [Factors Influencing Conformational Preferences]
2.1 Introduction and Aim 41
2.2 Present Work: Design and Retrosynthetic approach 42
2.3 Computational Investigations and Design of Boat 43 Cyclohexene
2.4 Synthesis, Characterization and Crystallographic Studies 44-52 for I and II
2.4.1 An unsuccessful attempt 2.4.2 Synthesis of I and II
ix
2.4.3 Characterization and Conformational analysis for I, II 2.4.4 Crystal Structure and Packing of
2.4.4.1 X-ray Structure determination of I
2.4.4.2 Crystal Packing of I. Role of weak interactions 2.4.5 Crystal Structure and Packing of II
2.4.5.1 X-ray Structure determination of II
2.4.5.2 Crystal Packing of II. Role of weak interactions
2.5 Synthesis, Characterization and structure prediction for 52-57 hydroxyl substituted cyclohexenes III and IV
2.5.1 Characterization and Conformational analysis of III and IV 2.5.1.1 Computational analysis
2.5.2 Crystal Structure and Packing of III
2.5.2.1 X-ray Structure determination of III
2.5.2.2 Crystal Packing of III. Role of weak interactions
2.7 Necessity of having a fused five membered ring 59-62 2.7.1 Computational analysis of VII
2.7.2 Synthesis and Characterization of VII 2.7.3 Crystal Structure and Packing of VII
2.7.3.1 X-ray Structure determination of VII
2.7.3.2 Crystal Packing of VII. Role of weak interactions
2.8 Comparison of Crystal packing Motif and Consequences 61-65 among all the boat six membered ring containing compounds I-III.
2.8.1 Role of weak interactions in stabilizing Closed and Open Boat
2.9 Conclusions 65
2.10 References 65-66
Chapter -3 Boat to Boat Ring Inversion 67
[ Design and Synthesis of a Putative Molecular Switch I
3.1 Background and Objective 68
3.2 The Boat Conformation 69
3.3 Present work and Aim 70-73
3.3.1 Initial Investigation
3.3.2 Design rationale towards our target molecule
xi
3.3.3 Retrosynthetic approach
3.4 Synthesis and Characterization of Diels-Alder adduct IX, XIa 73-75 and XIb
3.4.1 Synthesis and Characterization of E-benzylidene indene VIII and E-nitrobenzylideneindene X
3.4.2 Single Crystal X-ray analysis of E-nitrobenzylideneindene X 3.4.3 X-ray Structure determination and Crystal Packing of X
3.5 Synthesis and Spectral comparison for various 76-80 Diels-Alder adduct IX, XIa and XIb
3.5.1 Single Crystal X-ray analysis of 11-(4-nitro-benzylidene) -5,10,10a,11-tetrahydro-4bH-benzo[b]fluorene (XI) 3.5.1.1 X-ray structure determination of XI
3.5.1.2 Crystal packing. Role of weak interaction
3.6 Synthesis and purification of XII and XIII. Charge Transfer 81-82 Complexation
systems
3.8.1 Effect of pH on both PR and TR amines.
3.8.2 Titration plot for PR and TR amines 3.8.3 pH results in different solvents
3.9 Conclusions 91
3.10 References 91-92
Chapter- 4 Boat to Boat Ring Inversion 93
[Conformational Analysis -NMR and Computational]
4.1 Introduction/ Background 94
4.2 Present Work and our Objective 95
4.3 Results and Discussion : Detailed Conformational study of 95-98 XIII. NMR analysis and Model Building
4.3.1 Solution state Conformation prediction for XIa
4.3.2 Solution state Conformation prediction for XIII and XIIa 4.3.2.1 General diagram demonstrating structural prediction
4.4 2-Dimentional Correlation Spectroscopy 99-111 4.4.1 T1 Plots for PR and TR amine and their picrates
4.4.2 1H NMR COSY Data
4.4.2.1 COSY analysis of I, II and XIII 4.4.3 NOESY Data
4.4.3.1 Comparison of NOESY data between I, II and XIa 4.4.4 NOESY results for PR (XIII) and its protonated species
4.4.4.1 Assigned Conformation for Protonated PR amine 4.4.5 NOESY data for TR and its protonated species
4.4.5.1 NOESY results for TR ()Ma) 4.4.5.2 Alternative Open Conformations
4.4.5.3 NOESY results for protonated TR species
4.5 Conclusions 111
4.6 References 111-112
Chapter- 5 Metal ion studies using Fluorescence Spectroscopy 113
5.0 Introduction and Background 114
5.1 Hazardous effects of Lead. Lead ion selective probes 114
5.2 Use of Fluorescence spectroscopy 114-116
5.4 Present work. Possibility of ring flip in II 118-120
5.5 Titration results 120-122
5.5.1 Preliminary investigation/Qualitative analysis of II with various metal ions
5.5.2 Quantitative analysis of II against Pb2+
5.6 Ratiometric fluorescence 123-124
5.6.1 Role of Spacer length on ratiometric fluorescence
5.6.2 Present work: Ratiometric analysis of II towards various metal ions
5.7 Rationalized approach behind the fluorescence response 124
5.8 Conclusions 125
5.9 References 126-128
Chapter-6 Computational, 2D NMR and 129
Experimental Protocols
6.1 Introduction 130
6.2 Computational Protocols 130
6.2.1 How to achieve complete structure solution?
6.3 Experimental Instrumentation 132-139
XV
6.3.1 Melting Point 6.3.2 Mass Measurement 6.3.3 Infrared Spectra
6.3.4 Nuclear Magnetic Resonance Spectroscopy 6.3.5 UV/vis spectroscopy
6.3.6 Fluorescence spectroscopy
6.3.6.1 General procedure for Fluorescence Titrations 6.3.7 Single Crystal X-ray Diffraction studies
6.3.8 Brief Description of various NMR Techniques used
6.3.8.1 Two Dimentional (2D) NMR Spectroscopic Techniques 6.3.8.1.1 2D COSY Spectroscopy
6.3.8.1.2 NOESY Spectroscopy 6.3.8.2 T1 'pseudo 2D NMR Spectroscopy'
6.4 Synthetic protocols and Characterization data for I-XIII 139-147
6.4.5 Synthesis of 5,10,10a,11-tetrahydro-4b11-benzo[b]fluoren-11-ol III
6.4.6 Synthesis of 11-methy1-10,10,10a,11-tetrahydro-4bH-
benzo[b]fluoren-11-ol IV
6.4.7 Synthesis of 1-( 2-acetyl-5,10,10a,11-tetrahydro-4bH-benzo
lbjfluoren-8-y1)-ethanone Va and 1-(5,10,10a,11-Tetrahydro
-413H-benzo{b}fluoren-8-y1)-ethanone Vb
6.4.8 Synthesis of 8-nitro-4b,5,10,10a-tetrahydro-benzofluoren-
11-one VI
6.4.9 Modified synthesis of 5a,6,11,11a-tetrahydrotetracene
-5,12-dione VII
6.5 Synthesis of 11-benzylidene-5,10,10a,11-tetrahydro- 147-151
4bH-benzo[b]fluorene IX and its nitro derivatives
XIa and XIb
6.5.1 Synthesis of E-1-benzylidene-1H-indene VIII
6.5.2 Synthesis of E-benzylidene-5,10,10a,11-tetrahydro-4bH- benzo[b]fluorene IX
6.5.3 Synthesis of E-1-(4-nitrobenzylidene)-1H-indene X
6.5.4 Synthesis of 11-(4-nitrobenzylidene)-5,10,10a,11-tetrahydro
xvii
-4bH-benzo[b]fluorene XI
6.6 Reduction 150-152
6.6.1 Synthesis of 4((5,10,10a,11-tetrahydro-4bH-benzo[b]fluoren-11- yl)methyl)aniline, TR (XII)
6.6.2 General procedure for synthesis of (Z)-4-((10,10a-dihydro-4bH- benzo[b]fluoren-11(5H)-ylidene)methyl)aniline, PR (XIII)
6.7 Separation and purification of XIH (PR) 153-156
6.7.1 Charge transfer with PA
6.7.2 Towards Trifluoroacetic acid (TFA)
6.7.3 Recovery of free amine from picrate
6.8 References 156-158
Brief Bio-data of the Author 159
List of Figures
Figure Description Page No
Chanter-1
Figure 1.1 Strain free structures for cyclohexane. 3 Figure 1.2 Conventional Covalent 1, 4-intra-ring restraint to 4 stabilize twist boat and boat conformation (up). Non-covalent 1,4-
intra-ring restraint stabilizing the boat cyclohexane (down).
Figure 1.3 Alchol 11 and its corresponding hemi-acetal. 5 Figure 1.4a Molecules showing the preference for the boat over chair. 6 Figure 1.4b Molecules showing the preference for the boat over 7 chair by six membered rings for 15, 16.
Figure 1.5 Different conformations of cyclohexene. 8 Figure 1.6 a) Interrelationship of various forms of cyclohexene:
half chair); B and B' (boat); AB, A'B, A'B', AB'(transition states).
b) Diagrammatic representation of energies of various forms of cyclohexene.
Figure 1.7 Tetrahydrobenzofluorene 17, 18 and Hexahydrochrysene 19. 9 Figure 1.8 a) Natural products based on THBF skeleton (left). 9 b) Lab synthesis using Meldrum's Acids (right).
Figure 1.9 Crystal structure of Taxol having both eight and six 10 membered ring.
Figure 1.10 Inversion Pathway of cyclohexane in 25, 26, 27 and 11 28 as computed by ab initio (STO-3G) method.
Figure 1.11 Inversion pathway for cis-1,2 fused cyclohexanes. 11 Figure 1.12 Ring closening upon Ag+ encapsulation by clamshell receptor. 12 Figure 1.13 Conformational map of cyclohexane on sphere. 13 Each tropic corresponds to a family of transition state between the
chair and twist boat.
Figure 1.14 Demonstration of chair-chair inversion for 32 and a 14
xix
twist boat conformation for 33.
Figure 1.15 Metal ion triggered conformational change 15 depicting hinge motion in sugars i.e. chair to chair ring flip.
Figure 1.16 Examples showing chair to chair ring flip for 16 symmetrical diester 36 and a mixed ester 37.
Figure 1.17 a) Smith's Calf- sensors. b) Koertz's Zn2+ sensors. 17 c) Solvent dependent conformation change of methyl 2,4-di-0-
pyrenecarb onyl -(3 -D-xyl opyranosi de. d) Na+ c ompl exati on dependent conformation change for cyclohexane-based cis-1,3-dipodand 41.
Figure 1.18 chair—boat ring inversion for 17
cis-4-hydroxycycl oh ex anecarb oxyl i c acid.
Figure 1.19 Solvent dependent conformation changes for protonated 18 Staurosporine.
Figure 1.20 chair to boat inter-conversion exhibited by 47. 19 Figure 1.21 Fullerene based systems showing Temperature dependent 20
boat—boat ring inversion.
Figure 1.22 Example showing BC to CB equilibrium. 20 Figure 1.23 Example showing ring flips in other systems. 21 Figure 1.24 Pi: Piperidine ring inversion, Ni:Nitrogen 22 inversion for cyclic cis vicinal tertiary diamines.
Figure 1.25 A classical example of photo molecular switches. 23
Figure 1.32 pH switchable polymeric capsule. 29 Figure 1.33 Schematic illustration of working cycle and 29
color change of gold nanoparticle-DNA assembly at different
pH solution and DNA sequence used herein, where NP1 indicate the gold nanoparticle modified with "i-motif' DNA. NP2 is nanoparticle
modified with DNA complementary to "i-motif'.
Figure 1.34 Examples showing pH switches providing a recognition 30 -mediated control.
Figure 1.35 Chair to chair ring inversion in cyclohexane 30 based molecular switch.
Figure 1.36 pH triggered conformational change of 31 trans-2-amino-cyclohexanol-derived lipids.
Figure 1.37 Comparison of ring inversion in chair and boat 32 conformations.
Figure 1.38 The tetrahydrobenzofluorenone skeleton. 33 Chapter-2
Figure 2.1 The only known system with most preferred boat 41 conformation OR IEP representation (with 50% probability).
Figure 2.2 Skeletal comparison between Clamshell receptor 42 and target molecule I.
Figure 2.3 Retrosynthetic approach for II and I. 43 Figure 2.4 Potential Energy Profile for the designed Targets I and 43
II using MM plus and CNDO calculations.
Figure 2.5 Generation of ortho-quinodimethane from sultine. 44
Figure 2.6 Attempted synthesis of H. 44
Figure 2.7 Comparison between the 1HNMR spectra of I and II. 46 Figure 2.8 a) COSY data in CDC13 for I. b) COSY, HETCOR and 47 DEPT-135 in CDC13 for II.
Figure 2.9 a) ORLEY diagram for II at 50% probability level. 48
xxi
b) Packing along a axis for I.
Figure 2.10 a) OR'I'EP diagram for II where ellipsoids
are drawn at the 50% probability level (H atoms are represented as small spheres of arbitrary radii). b) Existing weak interactions.
Figure 2.11 Crystal packing for II along b axis.
Figure 2.12 Spectral comparisons between III and IV for conformational prediction.
Figure 2.13 a) ORTEP diagram at 50% probability showing a
interactions involved between both the symmetry unrelated molecules for III (H atoms are represented as small spheres of arbitrary radii).
Figure 2.14 a) 1/4th of unit cell for III b) Spiral filling in the
lattice along b-axis, green and blue color shows different diastereomers.
Figure 2.15 Crystal packing along b axis.
Figure 2.16 a) ORTEP diagram for VII where ellipsoids are
drawn at the 50% probability level (H atoms are represented as small spheres of arbitrary radii). b) Interactions involved.
Figure 2.17 Ladder shaped crystal packing of VII along b axis.
Figure 2.18 Comparison of crystal packing for I, II, III.
Chapter-3
Figure 3.1 Molecular Switch based on bis Benzo[3,4,0] skeleton, showing boat to boat ring inversion (Inset picture shows a classical
Figure 3.6 a) ORTEP diagram. b) Unit cell demonstrating 74 the weak interactions for Nitrobenzylideneindene shown at 50%
probability level.
Figure 3.7 Crystal packing for E-Nitrobenzylideneindene along b-axis. 75 Figure 3.8 Spectral comparison between various D-A adducts. 76 Figure 3.9 CNDO optimised structure for IX, XIa, XIa. 78 Figure 3.10 a) ORTEP view and unit cell demonstration of 78 XIa Thermal ellipsoids are drawn at the 50% probability level (up).
Crystal packing along b axis (down).
Figure 3.11 Crystal Packing showing all possible weak interactions 80 along a axis.
Figure 3.12 Space fill model showing a dense packing along b axis. 80 Figure 3.13 Procedure for the Purification of PR amine: Charge 82
Transfer complex.
Figure 3.14a Partial 11-INMR showing spectral comparison between 83 XIa, XIIa and XIII for aliphatic region (2.2-3.9 ppm).
Figure 3.14b Partial 11-1NMR showing spectral comparison between 84 XIa, XIIa and XIII for aromatic region (6.6-8.4 ppm).
Figure 3.15 'H-'H COSY NMR for both PR (XIII) and TR (XIIa) 85 amines in CDC13.
Figure 3.16 Partial 'H NMR in CD3CN showing spectral comparison 87 between TR, PR and their picrate.
Figure 3.17 'H NMR Titrations showing changes in shift 88 value upon incremental addition of PA to (a) PR amine (aromatic region)
(b) TR amine (aromatic region) in CDCI3-CD3CN (1:1, v/v) at 25°C.
Figure 3.18 'H NMR Titrations showing changes in shift upon 89 incremental addition of PA to (a) PR amine (aliphatic region)
(h) TR amine (aliphatic region) in CDCI3-CD3CN (1:1, v/v) at 25°C.
Figure 3.19 Titration of PR and TR with Picric acid using a) 1H NMR. 89
Chapter-4
Figure 4.1 Diagrammatic presentation of temperature dependent 95 boat to boat ring inversion.
Figure 4.2 Molecular structures for I, II, XIa. 95 Figure 4.3 Molecular structure showing dihedral angles for XIa and 97 XIII.
Figure 4.4 Generalized view for Conformation prediction for our 98 designed systems based on intramolecular n--11 interaction between aromatic rings.
Figure 4.5 Relaxation profile of unshifted methine protons for various 99 amines and their picrates.
Figure 4.6 Relaxation profile of C ring protons for various amines and 100 their picrates.
Figure 4.7 Molecular structure and COSY Spectrum 101 (300MHz, CD3CN, 25 °C) for XIII.
Figure 4.8 a) NOESY Spectrum (300MHz, Tm = 500 msec, CD3CN, 102 25 °C) of I, XIa, H. b) Molecular structure of I, XIa, II. c) Proposed
structures showing bond distances, using NM plus calculations (aliphatic-aliphatic cross region).
Figure 4.9 a) NOESY Spectrum (300MHz, Tm = 500 msec, CD3CN, 25 °C) 103 of XIII, XIII-}1±. b) Molecular structure of XIII, XIII-H+. c) Proposed
structures showing bond distances using HYPERCHEM (aliphatic-aliphatic cross region).
Figure 4.10 a) NOESY Spectrum (300MHz, Tm = 500 msec, CD3CN, 104
(down)]. b) Geometrically optimised structures. c) Molecular structure for XIIa and
Figure 4.13 Other unfeasible conformations.
Figure 4.14 Overall Picture depicting effect of protonation on
conformational preferences of both conjugated (PR) and non conjugated amines (TR).
Figure 4.15 Summary of our studies: A computed model
presentation of Proposed optimized structure possible for all our molecules, showing J13 and J23 dihedrals.
Chapter-5
Figure 5.1 Other simple unsubstituted aromatic systems showing fluorescence.
Figure 5.2 Schematic representation of variable conformation
adopted by 111 against different metal ions and their comparison with non complexing 112 towards fluorescence changes.
Figure 5.3 Anthrylazamacrocycles 113 showing CHEF towards Cd21.
Figure 5.4 Molecular structures of polycyclic aromatic hydrocarbon solutes: alkyl substituted coronenes (114,115) and pyrenes (116-124).
Figure 5.5 Two possible stable conformations for II in solution state showing the change in cavity size upon ring closening.
Figure 5.6 Comparison of a) aliphatic. b) aromatic region: Partial
1HNMR for II in both CD3CN and CDC13.
Figure 5.7 Intensity vs wavelength curve after the addition of 1 equiv. of metal ions (100 pM) against II (10 laM) with I excitation at
265 nm, I emission at k=330-450 nm in CH3CN-CHC13 (1:9, v/v).
Figure 5.8 Intensity vs wavelength curve during the Titration of II
(101.1M) with increasing concentrations of Pb2+ (100 [iM) with I excitation at 265 nm, I emission at 330-450 nm in CH3CN-CHC13 (1:9, v/v). b) Variation
xxv
in intensities towards the addition of Pb2+ at two different wavelengths.
c) Job's Plot for peak 1342-
Figure 5.9 Role of length of spacer and presence of metal ion, on the 123 exciplex formation: Modulation of exciplex formation against a) 125, b) 126,
c) 127, d) 128 and e) Na+ addition on 127.
Figure 5.10 Ratiometric analysis showing the change in monomer 124 in CH3CN-CHC13 (1:9, v/v) after the addition of lequiv. of metal ions
for II. b) Residual fluorescence intensity at 1359 for II upon the addition of lequiv. metal ions at I excitation at 265 nm, I emission at 330-450 nm. c) Ratiometric
analysis of II against lead ions.
Figure 5.11 Possible mechanism for metal induced 125 fluorescence enhancement.
Chapter-6
Figure 6.1 Flow chart depicting the used computational protocol. 131 Figure 6.2 Flowchart depicting the steps followed for solving the crystal 136
data.
Figure 6.3 Pulse programme for COSY and NOESY. 137 Figure 6.4 Pulse programme for T1 experiment. 139
List of Schemes
Scheme la: Experimental details towards the preparation of I and H.
Scheme lb: Synthesis of some more boat cyclohexene Derivatives III and IV.
Scheme Ic: Synthesis of some more derivatives containing boat six membered ring as backbone VI and VII.
Scheme Id: Synthesis of control target VII.
Scheme Ha: Steps involved in the preparation of IX and Xl.
Scheme IIb: Schematic diagram for the preparation of XIIa, XIIb and XIII
List Of Tables
Table No. Description Page no.
Table No. 2.1 Comparison of computational and solid state X-ray data 58 for various molecules.
Table No. 2.2 Comparison of structural parameters for crystalline I-III 64 and VII systems.
Table No. 3.1 3J values of aliphatic protons for PR, TR and their protonated 90 species towards both PA and TFA in various solvents.
Table No. 4.1 Detailed study of conformational preferences for I, II, XIa 96 using computed, solid and solution state data.
Table No. 4.2 Depiction of perturbation in various parameters before 108 and after the protonation.
Table No. 4.3 Summary of studies: Resultant coupling constants for 110 amines and their protonated species.
Table No 5.1 Showing the 3J coupling constant value for the aliphatic protons. 119