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Title of Thesis

Synthesis X-ray Studies And Biological Evaluation of Thiazine Related Heterocycles

Author(s)

Muhammad Nadeem Arshad

Institute/University/Department Details
Department Of Chemistry / Government College University, Lahore
Session
2011
Subject
Chemistry
Number of Pages
158
Keywords (Extracted from title, table of contents and abstract of thesis)
Palladium, Heterocycles, Synthesis, Compounds, Biologically, Novel, Related, Various, Studies, Thiazine, Derivatives, Evaluation

Abstract
Number of thiazine related heterocyclic compounds were synthesized using various approaches to utilize indigenously available raw materials.The syntheses of targeted molecules were afforded by the easy to handle and cost effective routes with the high possible purity and yield.Synthesis of various 1,2-benzothiazine 1,1-dioxides was accomplished via Heck reaction using ligand free palladium catalyst.It involved synthesis of halogen containing sulfonyl chloride, alkyl/aryl sulfonamide, N-alkylation with different alkenyl groups by conventional methodologies followed by improved Heck cyclization with Pd(OAc)2/DIPA in 1-methyl-pyrolidin-2-one or toluene.In this way, two isomeric benzothiazines (with endocyclic & exocyclic double bonds) along with seven membered thiazipene products were obtained.It was also found that endocyclic product dominates over the exocyclic isomer.In accordance with the yield, endocyclic product and thiazipines were isolated in almost equal amounts (38.3% & 37.2%).
Synthesis of [Cp*Ru(η6-((R)-8-(Hydroxy)-2-S-oxa-2-S-phenyl-2,1- benzothiazine))]Cl for their application as catalyst in chiral synthesis is was also accomplished. Chiral 2,1-benzothiazine derivative was employed to its complexation with cyclopentadiene-Ru salt under microwave radiations. One pot synthesis of a series of N-alkyl 1, 2-benzothiazine 1, 1-dioxide derivatives was carried out from commercially available saccharine with improved yield in less time avoiding extra work-ups. Number of carboxamide derivatives were also synthesized by reacting ester with different amines. Further, methyl 4-hydroxy-2H-1,2- benzothiazine-3-carboxylate-1,1-dioxide , N-alkylated derivatives methyl 4-hydroxy-2- methyl-2H-1,2-benzothiazine-3-carboxylate 1,1-dioxide, methyl 4-hydroxy-2-ethyl-2H- 1,2-benzothiazine-3-carboxylate 1,1-dioxide & methyl 4-hydroxy-2-propyl-2H-1,2- benzothiazine-3-carboxylate 1,1-dioxide , and carboxamide derivative N-(2-bromo-4- nitrophenyl)-4-hydroxy-2H-1,2-benzothiazine-3-carboxamide 1,1-dioxide were oxidized at C-3 carbon to get corresponding alcoholic products which were found dehydrated during crystallization process in methanol.
In another scheme, a novel series of potentially biologically active, 4-hydroxy-N'- (phenylsulfonyl)-2H-1,2-benzothiazine-3-carbohydrazide 1,1-dioxide were synthesized starting from N-alkylation of sodium saccharin with methyl chloroacetate.Ring expansion of methyl(1,1-dioxido-3-oxo-1,2-benzisothiazol-2(3H)-yl)acetate followed by its hydrazinolysis afforded, 4-hydroxy-2H-1,2-benzothiazine-3-carbohydrazide 1,1- dioxide, which was reacted in a straight forward manner with various substituted sulfonyl chlorides to get the title compounds.The newly synthesized compounds were characterized by spectroscopic techniques (FT-IR, NMR, MS) and Single Crystal X-ray diffraction analyses.Antibacterial and anti-oxidant activity of some of the series was also studied.Some of the compounds showed the better activities than the standards.The results are reported in respective units.

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S. No. Chapter Title of the Chapters Page Size (KB)
1 0 CONTENTS

 

ix
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2

1

INTRODUCTION

1.1 Benzothiazines dioxides
1.2 Biological Applications of thiazine related heterocycles
1.3 Chiral benzothiazines
1.4 Metal catalyzed synthesis of Benzothiazines
1.5 X-Ray Diffraction Crystal structure studies of Benzothiazines

1
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3 2 LITERATURE REVIEW

2.1 Aim And Schemes For Present Studies

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4 3 EXPERIMENTAL WORK

 

48
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5 4 RESULTS AND DISCUSSION

4.1 Chemistry
4.2 Single Crystal X-ray Crystallographic Studies
4.3 Biological Activities

113
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6

5

REFERENCES

 

147
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