synthetic studies towards 1-deoxythionojirimycin, 1,4-anhydro-4-thio

377 Pages·2009·4.12 MB·English

SYNTHETIC STUDIES TOWARDS
1-DEOXYTHIONOJIRIMYCIN, 1,4-ANHYDRO-4-THIO-
D-ARABINITOL AND RELATED THIOSUGARS AND
DEVELOPMENT OF IONIC LIQUID MEDIATED ORGANIC
TRANSFORMATIONS

A THESIS
SUBMITTED TO THE
UNIVERSITY OF PUNE

FOR THE DEGREE OF
DOCTOR OF PHILOSOPHY
IN
CHEMISTRY

BY
MAHESH H. BHURE

DR. THOMAS DANIEL
(RESEARCH GUIDE)

DIVISION OF ORGANIC CHEMISTRY
NATIONAL CHEMICAL LABORATORY
PUNE 411008, INDIA
MARCH 2013

DECLARATION BY THE CANDIDATE

I hereby declare that the thesis entitled “Synthetic studies towards
1-Deoxythionojirimycin, 1,4-anhydro-4-thio-D-arabinitol and related
thiosugars and development of ionic liquid mediated organic
transformations” submitted for Ph. D. degree to the University of Pune
has been carried out at National Chemical Laboratory, under the
supervision of Dr. Thomas Daniel. This work is original and has not
been submitted in part or full by me for any degree or diploma to this or
any other university.

Date: Mahesh H. Bhure
Division of Organic Chemistry
National Chemical Laboratory
Pune 411 008.
Dedicated to…………...
my beloved Parents, brother,
sisters and my adorable wife
Acknowledgements

First of all I wish to express my deep sense gratitude and respect to my research
supervisor Dr. Thomas Daniel, for introducing me to the fascinating field of Organic
chemistry, his valuable guidance and helpful suggestions throughout my Ph.D.
programme.
I owe a very special word of gratitude to Dr. U. R. Kalkote, Dr. (Mrs) S. R.
Deshpande and Dr. (Mrs) S. S. Joshi, for their time to time discussion, suggestions,
help and encouragement.
It is my pleasant duty to express my grateful and sincere thanks to Dr. C. K. John, Dr.
H. Thulasiram and Dr. Vincent Paul for their valuable co-operation during this
work.
I am also thankful to Dr. Ganesh Pandey (Head, Division of Organic Chemistry) and
Dr. Sourav Paul (Director, NCL) for permitting me to work in NCL.
I extend my gratitude to Dr. S. P. Chavan, Dr. H. B. Borate, Dr. C. V. Ramana, Mr.
I. Shivakumar, Dr. Muthukrishnan, Dr. Bhattacharya, Dr. R. A. Joshi, Dr. (Mrs)
R. R. Joshi, Dr. M. Shashidhar, Dr. N. N. Joshi, Mr. P. B. Jadkar, Dr. P.
Rajmohan and all other scientists of NCL.
I would also like to acknowledge all the staff members of GC-MS, HPLC, IR, NMR,
Mass, Microanalysis, X-ray analysis, Library, Administration and technical divisions
of NCL for their assistance during the course of my work.
I take this opportunity to thank my seniors as well as labmates Sharad, Abhijeet,
Ganesh, Murali, Devavaram, Satyawan, Amol, Roshan, Machhindra, Satej,
Shrikant and Hanuman for their support. They made working in the lab enjoyable. I
wish to thank division office staff, Mrs. Catherine, Mrs. Kulkarni, Mr. Fernandis,
Mr. Ranawade, Mr. Kakade and others for their help whenever needed.
My thanks are due to my NCL friends Nilesh, Sharanappa, Lalit, Prakash, Kailash,
Raivannath, Sachin, Tanpreet, Swati and Trupti for their sincere co-operation.
My feeling go beyond the limit of my language in acknowledging my out of NCL
friends Rahul Lavekar, Sachin Tambat and Yogesh Jungle for their constant moral
support throughout the course of my work. I am also thankful to my beloved parents,
family members, relatives and teachers who have contributed a lot for me to reach
this stage. The love and support from my wife Mrs. Smita for the healthy and
inspiring environment without whom I would not been able to stand out as a person
and my deep sense of gratitude remains forever. The thesis is a form to pay respect to
their attributes.
Last but not least, I am thankful to NCL for this opportunity and CSIR, New Delhi
for financial support.

NCL, Pune Mahesh H. Bhure
CONTENTS

Page No.
General Remarks i
Abbreviations ii
Abstract v

Chapter 1. Introduction to aldol reaction and synthetic studies
towards 1-Deoxythionojirimycin

Section 1. Introduction to aldol reaction

1.1.1 Aldol reaction 01
1.1.2 Catalytic Asymmetric Aldol Reaction 06
1.1.3 Aim of the Thesis and survey of the contents 32

Section 2. Synthetic studies towards 1-Deoxythionojirimycin

1.2.1 Introduction 42
1.2.2 Literature review for 1-deoxythionojirimycin 43
1.2.3 Present work 45
1.2.4 Result and discussion 48
1.2.5 Conclusion 63
1.2.6 Experimental 64
1.2.7 Analytical data 79
1.2.8 References 109
Chapter 2. Synthetic studies towards 1,4-anhydro-4-thio-D-arabinitol
and formal synthesis of Salacinol, Salaprinol and Neosalaprinol

2.1 Introduction 112
2.2 Inhibitory activities of thiosugars isolated from Salacia species 114
2.3 Literature review for 1,4-anhydro-4-thio-D-arabinitol, 115
Salacinol, Salaprinol and Neosalaprinol
2.4 Present Work 121
2.5 Result and discussion 122
2.6 Conclusion 133
2.7 Experimental 134
2.8 Analytical data 143
2.9 References 162

Chapter 3. Synthetic studies towards seven membered thiosugar and
thio-mimic of Isofagomine

Section 1. Synthetic studies towards seven membered

thiosugar
3.1.1 Introduction 164
3.1.2 Intramolecular Aldolization reaction of 1,8-dicarbonyl 164
compounds
3.1.3 Present work 167
3.1.4 Result and disscussion 168
3.1.5 Conclusion 173
3.1.6 Experimental 174
3.1.7 Analytical data 178
3.1.8 References 184
Section 2. Synthetic studies towards thio-mimic of

Isofagomine
3.2.1 Introduction 186
3.2.2 Present work 186
3.2.3 Result and discussion 187
3.2.4 Conclusion 193
3.2.5 Experimental 194
3.2.6 Analytical data 200
3.2.7 References 208

Chapter 4. Introduction to ionic liquids, synthesis of crown ether and
imidazolium based novel ionic liquids and development of ionic
liquid mediated organic transformations

Section 1. Introduction to ionic liquids

4.1.1 Introduction 209
4.1.2 Solvent alternatives for chemical synthesis 209
4.1.3 Classification of ionic liquids 213
4.1.4 Recent developments in cations and anions 213
4.1.5 Features of ILs which make them as attractive potential 216
solvents
4.1.6 Applications of ionic liquids 216
4.1.7 References 220

Section 2. Synthesis of crown ether and imidazolium based

novel ionic liquids
4.2.1 Introduction 228
4.2.2 Present work 229
4.2.3 Result and discussion 230
4.2.4 Conclusion 234
4.2.5 Experimental 235
4.2.6 Analytical data 243
4.2.7 References 263

Section 3. [Bbim]Br mediated N-Boc protection of alkyl/aryl

amines
4.3.1 Introduction 265
4.3.2 Present Work 265
4.3.3 Result and discussion 266
4.3.4 Conclusion 271
4.3.5 Experimental 272
4.3.6 Analytical data 279
4.3.7 References 306

Section 4. [Bbim]Br mediated synthesis of 1,3,5-triphenyl-1H-

pyrazoles
4.4.1 Introduction 307
4.4.2 Present work 308
4.4.3 Result and discussion 309
4.4.4 Conclusion 312
4.4.5 Experimental 313
4.4.6 Analytical data 316
4.4.7 References 325

* List of publications, posters and patents 327