ABSTRACT

The synthesis and characterization of five new linear diazaphenoxazine compounds is reported. The key intermediate, 3-chloro-1-9-diazaphenoxazine, was prepared via a base catalyzed reaction of 2-amino-3-hydroxypyridine with 2,3,5-trichloropyridine in aqueous 1, 4-dioxane.

Five 3-amino derivatives of the key intermediate were prepared via Buchwald – Hartwigamination coupling reaction between 3-chloro-1,9-diazaphenoxazine and various heterocyclic amines, under the catalytic influence of palladium acetate.

The assignment of structures to the synthesized compounds was done by the use of combined information from Uv-vis, IR, and NMR spectra.

 

TABLE OF CONTENTS

Title page…………………………………………………………………………………………………….i

Approval page………………………………………………………………………………………………………ii

Certification…………………………………………………………………………………………………………iii

Dedication……………………………………………………………………………………………………………iv

Acknowledgement………………………………………………………………………………………………..v

Abstract……………………………………………………………………………………………………………….vi

Table of contents………………………………………………………………………………………………..vii

CHPTER ONE…………………………………………………………………………………………………………1

1.0  Introduction…………………………………………………………………………………………….…….1

1.1 Background of study………………………………………………………………………………….……3

1.2 Statement of the problem………………………………………………………………………….…..5

1.3 Objectives of the study…………………………………………………………………………………..6

1.4 Justification of the study………………………………………………………………………………..6

CHAPTER TWO…………………………………………………………………………………………………….7

2.0  LiteratureReview………………………………………………………………………………………….7

2.1  TandemAmination and Amidation………………………………………………………………..7

2.2  LinearPhenoxazines……………………………………………………………………………….……19

2.2.1  Non-azaanalogues of phenoxazines…..……………………………………………….…..20

2.2.1.1Benzo[b]phenoxazine……………………………………………………………………………..20

2.2.1.2   2-Amino-4,4α-dihydro-4α,7-dimethyl-3H-Phenoxazine-3-one………………22

2.2.2       Aza analogues of phenoxazines……………………………………………………………23

2.2.2.1         1-Azaphenoxazine……………………………………………………………………………24

2.2.2.2         2-Azaphenoxazine……………………………………………………………………………27

2.2.2.3        3–Azaphenoxazine……………………………………………………………………………28

2.2.2.4        4–Azaphenoxazine……………………………………………………………………………33

2.2.2.5       3,4-Diazaphenoxazine……………………………………………………………………….34

2.2.2.6       1,4-Diazaphenoxazine…………..…………………………………………………………..35

2.2.2.7       1,9-Diazaphenoxazine ………………………………………………………………………37

2.2.3           Nitro, Amino, N-Acetyl and N-Alkyl Phenoxazines…………………………….38

CHAPTER THREE………………………………………………………………………………………………..42

3.0        Experimental……………………………………………………………………………….…………42

3.1       General Information……………………………………………………………………………….42

3.2        3-Chloro-1,9-diazphenoxazine………………………………………………………………..43

3.3         Preparations of Single Crystals of 3-Chloro-1,9-diazaphenoxazine ………..43

3. 4 1,4-Bis(2-hydroxy–3,5–ditert–butylbenzyl)piperazine…………………..………..44
4. 5 General Procedure for the Synthesis of 3-AminoDerivativesof 1,9-Diazaphenoxazine……………………………………………………………………………………..……….44
5. 5. 1 3-(2-Amino-3–nitropyridino)-1,9-diazaphenoxazine……………………………..45
6. 5. 2 3-(2–Aminopyrazino)–1,9–diazaphenoxazine……………………………………..45
7. 5. 3 3-(2-Aminopyridino)–1,9–diazaphenoxazine……………………………………….46
8. 5. 4 3–(2–Aminophenyl)–1,9–diazaphenoxazine………………………………………..46
9. 5. 5 3–Anilino-1,9–diazaphenoxazine………………………………………………………..46

CHAPTER FOUR …………………………………………………………………………………………………47

4.0       Results and Discussion ……………………………………………………………………………47

4.1        3–Chloro–1,9-diazaphenoxazine ……………………………………………………………47

4.2        1,4–Bis(2–hydroxy–3,5-ditert–butylbenzyl)piperazine …………………………..49

4.3       Catalyst Preactivation …………………………………………………………………………….49

4.4      3–(2–Amino-3–nitropyridino)-1,9-diazaphenoxazine ………………………………49

4.5      3–(2–Aminopyrazino)-1,9–diazaphenoxazine…………………………………………50

4.6      3–(2–Aminopyridino)-1,9–diazaphenoxazine………………………………….………..51

4.7       3–(2–Aminophenyl)–1,9–diazaphenoxazine………………………………….…………52

4.8         3–Anilino–1,9–diazaphenoxazine………………………………………………..…………52

CHAPTER FIVE ……………………………………………………………………………………………………54

5.0   Conclusion …………………………………………………………………………………………….……54

REFERENCES…………………………………………………………………………………….…..55

 

 

LIST OF FIGURES

Fig 1:Uv-visible spectrum for 3-(2-amino-3-nitropyridino)-1,9-diazaphenoxazine……………………………………………………………………………………………….66

Fig 2:Uv-visible spectrum for 3-(2-aminopyrazino)-1,9-diazaphenoxazine………….67

Fig 3:Uv-visible spectrum for 3-(2-aminopyridino)-1,9-diazaphenoxazine…………..68

Fig 4:Uv-visible spectrum for 3-(2-aminophenyl)-1, 9-diazaphenoxazine…………..69

Fig 5:Uv-visible spectrum for 3-chloro-1, 9-diazaphenoxazine …………………………..70

Fig 6:Uv-visible spectrum for 3-anilino-1,9-diazaphenoxazine…………………………….71

Fig 7:IR spectrum for 3-chloro-1,9-diazaphenoxazine………………………………..……….72

Fig 8:IR spectrum for 3-(2-amino-3-nitropyridino)-1,9-diazaphenoxazine…………..73

Fig 9:IR spectrum for 3-(2-aminopyrazino)-1,9-diazaphenoxazine………….…………..74

Fig 10:IR spectrum for 3-(2-aminopyridino)-1,9-diazaphenoxazine…………………….75

Fig 11:IR spectrum for 3-(2-aminophenyl)-1,9-diazaphenoxazine……………………….76

Fig 12:IR spectrum for anilino-1,9-diazaphenoxazine………………………………………….77

Fig 13:¹H-NMR Spectrum for 3-chloro-1,9-diazaphenoxazine……………………………..78

Fig 14:¹H-NMR Spectrum for 3-(2-amino-3-nitropyridino)-1,9-diazaphenoxazine……………………………………………………………………………………………….79Fig 15:¹H-NMR Spectrum for 3-(2-aminopyrazino)-1,9-diazaphenoxazine………….80

Fig 16:¹H-NMR Spectrum for 3-(2-aminopyridino)-1,9-diazaphenoxazine…………..81

Fig 17:¹H-NMR Spectrum for 3-(2-aminophenyl)-1,9-diazaphenoxazine……………..82

Fig 18:¹H-NMR Spectrum for 3-anilino-1,9-diazaphenoxazine…………………………….83

Fig 19:¹³C-NMR Spectrum for 3-chloro-1,9-diazaphenoxazine…………………………….84

Fig 20:¹³C-NMR Spectrum for 3-(2-aminopyrazino)-1,9-diazaphenoxazine…..…….85

CHAPTER ONE

1.0   INTRODUCTION

Phenoxazine(1) is a compound analogous in structure to phenothiazine(2) with oxygen in place of sulphur.Its other systematic names are 10H-phenoxazine and 2,2,5,6-dibenzo-1,4-oxazine¹.They are tricyclic nitrogen-oxygen heterocycles². Owing to the wide range of application of phenoxazine compounds, the synthesis of their derivatives and isolation of the natural phenoxazines have been a subject of great interest over the years³. Phenoxazine compounds have a wide range of applications, particularly as drugs and dyes.

 

The naturally occurring phenoxazine derivatives have been classified as Ommochromes, fungal metabolites, Questiomycins and Actinomycins⁴.

Phenoxazines are generally grouped into linear phenoxazines and angular phenoxazines. The linear phenoxazine, as the name implies, has a linear arrangement of rings like compounds 3 and 4 below.