Speciman Copy :

STUDIES IN THE CHEMISTRY OF METAL POLLUTANTS

A thesis submitted to the

JAWAHARLAL NEHRU TECHNOLOGICAL UNIVERSITY ANANTAPUR

For the award of

DOCTOR OF PHILOSOPHY

in

CHEMISTRY

BY

K.B.CHANDRASEKHAR

[ Reg.No]

Under the Guidance of

Dr. K.HUSSAIN REDDY & Dr. R. SREENIVASULU

RESEARCH AND DEVELOPMENT JAWAHARLAL NEHRU TECHNOLOGICAL UNIVERSITY ANANTAPUR

ANANTAPURAMU-515002(A.P) INDIA

JANUARY – 2013

i

DECLARATION

I declare that the thesis entitle “STUDIES IN THE CHEMISTRY OF METAL

POLLUTANTS” has been prepared by me under the guidance of Dr. K. HUSSAIN REDDY,

Professor of Chemistry, Sri Krishna Devaraya University, Anantapuramu, A.P. ( INDIA). No part

of this thesis has formed the basis for the award of any degree or fellowship previously.

K.B. Chandra Sekhar

Department of Chemistry,

Jawaharlal Nehru Technological University Anantapur,

Anantapuramu, 515 002 A.P. ( INDIA)

DATE: 20.11.2013

ii

CERTIFICATE

I certify that K.B. Chandra Sekhar has prepared his/her thesis entitled “STUDIES IN THE

CHEMISTRY OF METAL POLLUTANTS”, for the award of Ph.D. degree of the Jawaharlal Nehru

Technological University Anantapur, under my guidance. He/she has carried out the work at the

Department of Chemistry, Jawaharlal Nehru Technological University Anantapur, Anantapuramu.

SUPERVISOR CO-SUPERVISOR

Dr. K. Hussain Reddy Dr. R. Sreenivasulu

Department of Chemistry, Prof. of Chemistry

Sri Krishna Devaraya University, Sri Krishna Devaraya University

Anantapuramu. Anantapuramu.

DATE: 20.11.2013

iii

ACKNOWLEDGEMENTS

A major research project like this is never the work of anyone alone. The contributions of many

different people, in their different ways, have made this possible. I would like to extend my appreciation

especially to the following.

First and foremost, I owe deep debt of gratitude to my research guide Prof. K.N.Jayaveera, for

giving me an opportunity to work under his continuous guidance, for his support and encouragement

through this study and he has also guided my personal development and maturation as an independent,

confident and strong researcher, something I never could have learned from a book. I am extremely lucky

to work with such a high profiled persona. His guidance was the next best thing to knowledge, which I will

cherish throughout my life. He is truly a source of inspiration to pursue a research–oriented career.

I express my profound sincere gratitude to my beloved teacher Prof. L.K.Ravindranath,

Head, Department of chemistry, Sri Krishnadevaraya University Anantapur, for his kind cooperation and

friendly advices to carry out this investigation. He gave tireless efforts through discussions and valuable

suggestions ensured the success of this undertaking. I am in great debt to my teacher, who not only

instructed me in my work, but also opened the path for higher knowledge. His critical advice as a teacher

and friendly nature has greatly helped and inspired me to submit this thesis in the present form. I hereby

record my sincere and affectionate gratitude for what all he has done during my research work.

I thank to Prof. N. Devanna, Director OTRI, Jawaharlal Nehru Technological University

Anantapur, Anantapur (A.P.).

I thank all my teachers for their support and their interest on me to do this research work.

iv

ABSTRACT

[Type your Abstract here]

Amongst different heterocyclic systems, the chemistry of fused heterocycles with one

heteroatom has gained importance because many of them exhibit pronounced bioactive nature. Specifically,

those containing the quinoline nucleus have been shown to possess antituberculosis, antineoplastic,

antidiabetic, anti-fertility and antithyroid activity besides antimalarials, antibacterials, antifungals and some

of them possess anticancer activity.

Heterocycles like azetidine-2-one, thiazolidin-4 one and tetrazoles posses very good biological

activities like antimicrobial, pesticidal, antitumor, antitubercular, anticancer and cytotoxic activities.

Novel Mannich bases (Z)-2-(5-(3-chloro-2-oxo-4-p-tolylazetidin-1-yl)quinolin -8-yl oxy) -N’-(2-

oxo-1-(piperidin-1-ylmethyl)indolin-3-ylidine)acetohydrazides were synthesized by the condensation of 2-

(5-(3-chloro-2-oxo-4-p-tolylazetidin-1-yl)quinolin-8-yloxy) acetohydrazide with Isatin afford

corresponding (Z)-2-(5-(3-chloro-2-oxo-4-p-tolylazetidin-1-yl)quinolin-8-yloxy)-N’-(2-oxoindolin-3-

ylidene) acetohydrazide. This was subjected to mannich reaction with cyclic secondary amines such as

piperidine / morpholine / N-Methyl Piperazine in presence of formaldehyde in DMF to give corresponding

Mannich bases (Z)-2-(5-(3-chloro-2-oxo-4-p-tolylazetidin-1-yl)quinolin-8-yloxy)-N’-(2-oxo-1-(piperidin-

1-yl methyl)indolin-3-ylidine)acetohydrazide in excellent yields.

A series of total six novel Quinoline Schiff bases were prepared from 5-amino-8-hydroxy quinoline

and substituted aldehydes. All quinoline schiff bases were refluxed with thioacetic acid in presence of

anhydrous zinc chloride and solvent N,N-dimethyl formamide to afforded novel series of 4-thiazolidinone

[1a-f]. Novel Mannich bases (Z)-N'-(2-oxo-1-(piperidin-1-ylmethyl)indolin-3-ylidene)-2-((5-(4-oxo-2-(4-

substitutedphenyl)thiazolidin-3-yl)quinolin-8-yl)oxy)acetohydrazide were synthesized by the condensation

of 2-((5-(4-oxo-2-(4-substitutedphenyl)thiazolidin-3-yl)quinolin-8-yl)oxy)acetohydrazide with Isatin afford

corresponding (Z)-2-((5-(4-oxo-2-(4-substitutedphenyl)thiazolidin-3-yl)quinolin-8-yl)oxy)-N'-(2-

oxoindolin-3-ylidene) acetohydrazide. This was subjected to mannich reaction with cyclic secondary

amines such as piperidine / morpholine / N-Methyl Piperazine in presence of formaldehyde in DMF to give

corresponding Mannich bases bases (Z)-N'-(2-oxo-1-(piperidin-1-ylmethyl)indolin-3-ylidene)-2-((5-(4-oxo-

2-(4-substitutedphenyl) thiazolidin-3-yl)quinolin-8-yl)oxy) acetohydrazide.

v

PREFACE

[Type your Preface here]

A heterocyclic compound represents an important class of biologically active

molecules. This is reflected by the voluminous data available in the literature on heterocyclic

chemistry. Many useful drugs indeed have emerged from such investigations which strengthens

the trend. Spectacular advanced have been made in this field to furtherance the knowledge of

relationship between chemical structure and biological activity. Thus, the successful application

of this class of compounds in various fields ensures a limitless scope for the development of

structurally novel compounds with a wide range of psycho-chemical and biological properties.

Amongst different heterocyclic systems, the chemistry of fused bicyclic heterocyclics with one

heteroatom has gained importance as many of them exhibit pronounced bioactive behaviour. One such

type of compounds includes hydroxyquionolones. Quinoline, Isoquinoline, Quinoxaline and hydroxyl

quinoline belongs to quinolone family. Hence, any attempt to study their detailed chemistry would add

new dimensions to the existing knowledge. Quinolinnes, isoquinolines and related heterocycles possess

various types of biological activities. A good deal of importance is given to quinoline derivatives. It is due

to their wide use in medicinal chemistry.

Specifically, those containing the quinoline nucleus have been shown to possess

antituberculosis, antineoplastic, antidiabetic, anti-fertility and antithyroid activity besides

antimalarials, antibacterials, antifungals and some of them possess anticancer activity.

Heterocycles like azetidine-2-one, thiazolidin-4 one and tetrazoles posses very good

biological activities like antimicrobial, pesticidal, antitumor, antitubercular, anticancer and

cytotoxic activities, In this perspective, a study on “Synthesis, characterization and biological

evaluation of quinolines bearing azetidine-2-one, thiazolidin-4 one and tetrazoles”, have been

taken up and incorporated in the thesis.

The research work embodied in this thesis is planned to synthesize some new quinolinne

hetero cycles in order to assess their antimicrobial profile. The plan of work consists of synthesis,

characterization, antimicrobial activity, experimental details and docking studies, which are

incorporated in eight chapters. At the end of each chapter literature citations are given.

vi

TABLE OF CONTENTS

[Type your Table of Contents here]

Chapter No. Name of the Chapter Page No

1 Introduction

1-20

2 Literature Survey

21-50

3 Theoretical Analysis

51-65

4 Experimental Investigations

66-87

5 Experimental result

88-111

6 Discussion of results

112-150

7 Summary & Conclusion and Recommendations

151-166

References

167-173

Index

174-177

vii

LIST OF TABLES

[Type your List of Tables here]

TABLE NO DESCRIPTION Page

CHAPTER-1

1.1 Biologically potent quinoline derivatives 8

Chapter-2

2.1 Biologically potent azetidin-2-one derivatives 13

2.2 Biologically potent 4-thiazolidinone derivatives 17

2.3 Biologically potent Tetrazole derivatives 20

Chapter-3

3.0 Biologically potent Mannich base derivatives 23

3.1.1 1HNMR spectra of compounds 3a-f 31

3.1.2 13

CNMR spectra of compounds 3a-f 33

3.1.3 IR spectra of compounds 3a-f 35

3.1.4 1HNMR spectra of compounds 5a-f 37

3.1.5 13

CNMR spectra of compounds 5a-f 39

3.1.6 IR spectra of compounds 5a-f 41

3.1.7 Primary fragmented mass spectral data of 5a 42

3.1.8 1HNMR spectra of compounds 6a-h 45

3.1.9 13

CNMR spectra of compounds 6a-h 48

viii

LIST OF FIGURES

[Type your List of figures here]

FIG. No. DESCRIPTION Page

CHAPTER-1

1.1 Clinically used quinoline derivatives 7

Chapter-3

3.1.1 1HNMR spectra of compounds 3a 90

3.1.2 13

CNMR spectra of compounds 3a 91

3.1.3 IR spectra of compounds 3a 92

3.1.4 1HNMR spectra of compounds 5a 93

3.1.5 13

CNMR spectra of compounds 5a 94

3.1.6 IR spectra of compounds 5a 95

3.1.7 1HNMR spectra of compounds 6a 97

3.1.8 13

CNMR spectra of compounds 6a 98

3.1.9 IR spectra of compounds 6a 99

3.2.1 1HNMR spectra of compounds 3a 101

3.2.2 13

CNMR spectra of compounds 3a 102

3.2.3 IR spectra of compounds 3a 103

3.2.4 1HNMR spectra of compounds 5a 104

3.2.5 13

CNMR spectra of compounds 5a 105

xi

List of Abbreviations

Co2 Carbon-dioxide

oC Deree centigrade

oCA Degree crank angle

Q Heat release

K Kelvin

kW Kilojoule

x

LIST OF APPENDICES

APPENDIX A; [Type your Appendix A here]

APPENDIX B; [Type your Appendix B here]

APPENDIX C; [Type your Appendix C here]

APPENDIX D; [Type your Appendix D here]

Chapter-1

INTRODUCTION

1

CHAPTER 1

[Type your Table of Contents of First Chapter]

Chapter - 1. Introduction

S. No

Name of the Sub-Title Page No

1.1

General Introduction 2

1.2

Metal Pollutants 3-4

1.3

Water Pollutants 5-7

1.4

Air pollutants 8-9

1.5

Radioactive pollutants 10-12

1.6

Significance of study 13-20

2

CHAPTER 1

[Type your contents of first chapter here]

Introduction:

Metals like led Chromium, Arsenic and Cadmium are known metal pollutants.

Chapter-2

LITERATURE SURVEY

21

Chapter - 2

Chapter - 2. Literature Survey

S. No

Name of the Sub-Title Page No

2.1

21-24

2.2

25-28

2.3

29-34

2.4

35-40

2.5

41-44

2.6

45-50

Chapter-3

THEORITICAL ANALYSIS

51

Chapter - 3

Chapter - 3. Theoritical Analysis

S. No

Name of the Sub-Title Page No

3.1

51-52

3.2

53-55

3.3

56-58

3.4

59-60

3.5

61-62

3.6

63-65

Chapter-4

EXPERIMENTAL

INVESTIGATIONS

66

Chapter -4

Chapter - 4. Experimental Investigations

S. No

Name of the Sub-Title Page No

4.1

66-69

4.2

70-73

4.3

74-76

4.4

77-79

4.5

80-81

4.6

82-87

Chapter-5

EXPERIMENTAL RESULTS

88

Chapter - 5

Chapter - 5. Experimental Result

S. No

Name of the Sub-Title Page No

5.1

88-92

5.2

93-97

5.3

98-100

5.4

101-103

5.5

104-106

5.6

107-111

Chapter-6

DISCUSSION OF RESULTS

112

Chapter - 6

Chapter - 6. Discussion of Results

S. No

Name of the Sub-Title Page No

6.1

112-116

6.2

117-120

63

121-126

6.4

127-133

6.5

134-143

6.6

144-150

Chapter-7

SUMMARY,CONCLUSION &

RECOMMENDATIONS

151

Chapter - 7

Chapter - 7. Summary & Conclusion & Recommendations

Chapter-8

REFERENCE/BIBILIOGRAPHY

167

Bibilography/References

1.Chandrasekhar,K.B.;Hussain Reddy, K. ; and Devanna, N.; J.Chem.Rev.26(5),2006,117.

2.Chandrasekhar,K.B.Engineering Chemistry,5th

edition, S. Chand Publications, 2007, 116

INDEX

174

INDEX

Arsenic, 1

C

Cadmium , 1

Chromium,1

L

Led, 2

LIST OF PUBLICATIONS

LIST OF PUBLICATIONS

(List and enclose Hard Copies of Publications)