synthesis and characterization of heterocyclic derivatives...

I

Synthesis and characterization of heterocyclic derivatives from 2-azo benzothiazole

A thesis Submitted to

the Department of Chemistry/ College of Science / University Of Baghdad, in partial fulfillment

of the Requirements for the Degree of Doctor of Philosophy in Chemistry

By

Maha Kasem mahmmod

B.SC. Babelon University (1998) M.Sc. Baghdad University (2006)

Supervised by

Prof. Dr. Entesar O. Al-Temimi

2012 AD 1434 AH

II

الرحمن ابسم الرحيم

وعنده مفاتح الغيب

هو ويعلم ما إال اليعلمها

في البر والبحر وما تسقط

يعلمها وال حبة إالمن ورقة

وال رطب وال األرضفي ظلمات

كتاب مبين في إاليابس

العلي العظيم اصدق

) ٥۹اآلية( األنعامسورة

III

Amendment Report

This is to certify that I have read the thesis entitled '' Synthesis and

characterization of heterocyclic derivatives from 2-azobenzothiazole ''

and corrected the linguistic mistakes I found . The thesis is, therefore,

qualified for debate.

Signature:

Name:

Data:

IV

Scientific Evolution Report

This is to certify that I have read the thesis entitled '' Synthesis and

characterization of heterocyclic derivatives from 2-azobenzothiazole ''

and corrected the mistakes I found . The thesis is, therefore, qualified for

debate.

Signature:

Name: Dr.

Title: Assist. Professor

Data:

V

Supervisor Certification

I certify that this thesis was carried out under supervision at the

Department of Chemistry, College of Science , University of Baghdad, as

partial fulfillment of the requirements for the degree of Doctor of

Philosophy in Organic Chemistry.

Signature:

Name: Dr. Entesar O. Al-Temimi

Title: Professor

Data:

In review of the available recommendations, I forward this thesis for

debate by the examining committee

Signature :

Name: Assist. Prof. Dr. Mohmmed R. Mohmad

Chairman Department of Chemistry

College of Science/ University of Baghdad

Data:

VI

Examination Committee

We have read this thesis entitled '' Synthesis and characterization of

heterocyclic derivatives from 2-azobenzothiazole have possible

biological activity ''and as examining committee, examined the student''

Maha K. Mahmmod'' in its contents and that in our opinion it meets the

standards of a thesis for the degree of Doctor of philosophy in Organic

Chemistry.

Chairman Signature: Name: Dr.

Title: Professor Data:

)Member( )Member( Signature: Signature:

Name: Dr. Name: Dr. Title: Professor Title: Assist. Professor

Data: Data:

)Member( )Member( Signature: Signature:

Name: Dr. Name: Dr. Title: Assist. Professor Title: Assist. Professor Data: Data:

Approved by the Council of the College of Science, University of Baghdad.

Signature: Name: Dr. Title: Professor Dean of the College of Science, University of Baghdad.

Data:

VII

اإلهداء

ا ذرى الحياة......هسلما الرتقي ب األيامسخيا وصاغو جهد السنين Çبذلو إلى اللذين

)اهللاأبي وأمي (حفظهما

تحيطنـي أسـوار المحبـة التـي Ç... وكـانو .......لي سندا في كل لحظة وثانية Çإلى من كانو ........ بالحب والوفـاء

أخي وأخواتي

.......إلى الينبوع الذي ينضح بالحب والحنان ، والشعاع الذي يضيء دربي ...

زوجي العزيز

الذي أرجو له التوفيق .........................إلى ثمرة قـلبي وروحي ومستقبلي

ولدي (محمد حسين)

روحي التي هي معي دائما .................. صديقتي العزيزة وتوءم إلى

زينب

Ãهدي ثمرة جهدي

مها

Acknowledgement

VIII

Initially, I am most grateful to Allah, who gave me the strength and

guidance throughout my life especially during this work.

I wish to express my deepest gratitude and sincere appreciation to the

main advisor, Dr. Entesar O. Al- Temimi, Professor of organic

chemistry, College of Science, Baghdad University, for the support

consistently received throughout this work. She thoroughly scrutinized

this thesis at every stage of development with keen interest and

enthusiasm.

I am deeply grateful to the Dean of the college of Science, the

Chairman of the Chemistry Department and Vice-Dean of the College of

Science, Baghdad University, for their kind support and for the

facilities they offered throughout this work.

My great thanks are extended to all the members of Department of

Chemistry, College of Science Baghdad University, for their helpful

support that made this work possible.

A word of thanks to non-teaching staff: members of college for

providing all the help when required.

Foremost indebt to my mother, father brother and sisters for all their

hard work to bring me up with a high quality education .

My warmest thanks go to my husband, Ali, who has always stood by

me. His encouragement and patience made it possible to realize my

wishes of pursuing search for knowledge.

I would be failing in my duties if I do not thank my beloved

friends for their constant support in every endeavor of mine and provided

me with necessary stimulus for keeping the driving force integrated for

successful completion of the project.

IX

Mere words and acknowledgement are not enough to express the

valuable help and encouragement rendered by all people. I finally

conclude with a saying that “thanking may just be a formality, but if done

inwardly, it surely reflects your noblest thoughts within”.

Date: Place : (Maha K. Mahmmod)

X

List of abbreviation used

0C

Degree centigrade OCH3 Methoxy

Mol Mole

ML Milli Liter KBr Potassium Bromide

g Gram

FT-IR Fourier Transform Infrared

DMF Dimethyl Formamide

CHCl3 Chloroform

CH3OH Methanol

C2H5OH Ethanol Ph- Benzene DMSO Dimethyl sulfoxide

1H-NMR Proton Nuclear Magnetic Resonance

TLC Thin layer Chromatography % Percentage Me Methyl M.p Melting point TMS Tetra methyl Silane Rf

Retention factor

CNBr cyanogen bromide IBD Hypervalent iodine TFA Tri fluoro acetic acid Abs Absorption MWI Micro wave irradiation S Second

XI

List of Contents

Subject Page

-List of abbreviations………………. …………………………………X

-List of figures ……………………………………………………..…XV

-List of tables…………………………………………………….....XXIII

-List of schemes ……………………………………………………XXVI

-Summary………………………………………………………..…XXVII

Chapter one: Introduction

1-1 Heterocyclic compounds……………………………………………..1

1-2 Thiazole compounds………………………………………………..1

1-2-1 2-aminobenzothiazole compounds…………………,….…….2

1-2-2 Some methods for preparation of 2-aminobenzothiazol and

derivatives……………………………………………………3

1-2-3 Some reaction of 2- aminobenzothiazole...……….…………10

1-2-4 Biological activity of 2-aminobenzothiazole

derivatives…….………………………………………….…16

1-3 Triazole……………………………………………...……………16

1-3-1 Biological activity of triazole derivatives…………....….…16

1-3-2 Synthesis of some biologically active compounds

containing triazole nucleus…………………...…….……17

1-3-3 Reaction of 1,2,4 triazole…………………………..………21

1-4 Oxadiazole………………………………………………………..23

1-4-1 The chemistry of oxadiazoles...…..………………………..23

1-4-2 Synthesis of 1,3,4-oxadiazoles………….……………….24

1-4-3 Reactions of 1, 3, 4-oxadiazole…………….…………..…29

1-4-4 Biological activity of 1,3,4 oxadiazole………..……..……30

XII

1-5 Thiadiazole……………………………………………..……….....31 1-5-1 Synthesis of 1,3,4-thiadiazoles nuclei……………...…......31

1-5-2 Some Reaction of 2-amino 1,3,4-thiadiazole……...….....37

1-5-3 Pharmacological properties of

1,3,4-thiadiazole derivative……....……………….……40

Chapter two: Experimental part

2-1 Identification and characterization…………………………………41 2-2 Supplied chemicals companies ..………………………………..… 43

2-3 preparation of 2-aminobenzothiazole derivatives( I )…..….……….45

2-4 Synthesis of azo compounds ( II )………………………….……....45

2-4-1 Synthesis of substituted benzothiazolyl-2-diazonium

chloride………………………………………………….…...45

2-4-2 Synthesis of r- (2-azo-substituted benzothiazolyl)

sodiophenoxides…………………………………………….46

2-4-3 Synthesis of r-(2-azo-substituted benzothiazolyl)

substituted phenols………………………….…………...…46

2-5 Synthesis of ethyl { r- (2-azo-substituted benzothiazolyl)

substituted phenoxy } 2-propionate( III )….………………..47

2-6 Synthesis of five member heterocyclic derivatives…………….....47

2-6-1 Synthesis of N-thiosemicarbazide and N-semicarbazide

derivative ( IV ), ( V )………………………..…………...…..…47

2-6-2 General procedure for preparation of 5-{substituted }

2-amino 1,3,4 oxadiazole(VI)…………………………...…....…48

2-6-3 General procedure for preparation of 5-{ substituted }

1,2,4 triazole 3-thione (VII) ….………......…….………….....49

XIII

2-6-4 General procedures preparation of 2-amino

5-( substituted )1-3-4 thiadiazole(VIII)……………..……...49

Chapter three: Results and Discussion

Part One 1-3

3-1-1-Synthesis of 2-aminobenzothiazole………………………...69

3-1-2- Spectroscopic identification of 2-aminobenzothiazole…….70

3-1-3-Subsituted 2-amino benzothiazole …………………………72

Part two 2 -3

3-2-1-Synthesis of azo compounds.…….………………………...83

3-2-2- Spectroscopic properties of r-(2-azo-substituted

benzothiazolyl) substituted phenols………………..………84

3-2-3-Subsituted azo compounds ……………………………..…85

3-3 Part three

3-3-1- Synthesis of ethyl {r- (2-azo- substituted benzothiazolyl)

……………….....…121 substituted phenoxy} 2-propionate

3-3-2- Spectroscopic properties of ethyl {r- (2-azo- substituted

benzothiazolyl) substituted phenoxy} 2-propionate.............122 3-3-3- Substituted ester compounds ………………………….….123

Part four4 -3

3-4-1- Synthesis of N-substituted thiosemicarbazade and

N-substituted semicarbazide…………………………....144

3-4-2- Spectroscopic properties of N-substituted

thiosemicarbazide and N-substituted semicarbazide….........145

XIV

3-4-3- N-Substituted thiosemicarbazide ………………….............145

3-4-4- N-Substituted semicarbazide………………………………157

Part five -5-3

3-5-1- Synthesis of heterocyclic compounds...……………………169

3-5-2- Spectroscopic properties of prepared compounds………171 3-5-3- Substituted 1,3,4-oxadiazoles…………………………....171

3-5-4- Substituted 1,2,4-triazoles……………………………….186

3-5-5- Substituted 1,3,4-thiadiazoles……...………..………….200

XV

List of Figures

Page

Title Fig. No.

7۷ FT-IR Spectrum of 4-nitro 6- chloro-2-aminobenzothiazole [1] ۱

7۷ FT-IR Spectrum of 4,6-dinitro-2-aminobenzothiazole [2] 2 78 FT-IR Spectrum of 6-methyl-2-aminobenzothiazole [3] ۳

7۸ FT-IR Spectrum of 6-nitro-2-aminobenzothiazole [5] ٤

79 UV Spectrum of 4-nitro-6- chloro-2-aminobenzothiazole [1] ٥

۷۹ UV Spectrum of 4,6-dinitro-2-aminobenzothiazole [2] ٦

۸۰ UV Spectrum of 6-methyl-2-aminobenzothiazole [3] ۷ ۸۰ UV Spectrum of 6-carboxylic acid-2-aminobenzothiazole [4] ۸

۸۱ 1H-NMR spectrum of compound [5] ۹

81 The expantion of H-NMR spectrum of compound [5] ۱۰

۸۲ 13C-NMR spectrum of compound [5] ۱۱

۱۰۲ FT-IR Spectrum of r-( 2-azo-6-carboxylic acid benzothazolyl) 3-amino phenol [8]

۱۲

۱۰۲ FT-IR Spectrum of r-(2-azo-6-nitro benzothazolyl ) 2,6-dimethyl phenol [14]

۱۳ 103 FT-IR Spectra of r-(2-azo-6-nitro benzothazolyl ) 3-bromo

phenol [15] 14

۱۰۳ FT-IR Spectrum of r- (2-azo-6-nitro benzothazolyl) 3-amino phenol [16]

۱٥ ۱۰٤ FT-IR Spectrum of r-(2-azo-6-nitro benzothazolyl) 3-ethyl

phenol [17] ۱٦

۱۰٤ FT-IR Spectrum of r-(2-azo-6-nitro benzothazolyl) 2-methoxy phenol [18]

۱۷

۱۰٥ FT-IR Spectrum of r-( 2-azo-6-nitro benzothazolyl) 3-methyl phenol [19]

۱۸

۱۰٥ FT-IR Spectrum of r-(2-azo-6-nitro benzothazoleyl) 2-nitro phenol [20]

۱۹

۱۰٦ FT-IR Spectrum of r-(2-azo-6-nitro benzothazolyl) phenol [21] ۲۰ ۱۰٦ FT-IR Spectrum of r-(2-azo-6-methyl benzothazolyl) 3-bromo

phenol [23] ۲۱

XVI

Page

Title

Fig. No.

۱۰۷ FT-IR spectrum of r-( 2-azo-6-chloro-4-nitro benzothazolyl)2-nitro phenol [36]

22

۱۰۷ FT-IR spectrum of r-(2-azo-6,4-dinitro benzothazolyl) 3-amino phenol [40]

۲۳

۱۰۸ FT-IR Spectrum of r-( 2-azo-6,4-dinitro benzothazolyl) phenol [45]

24

۱۰۸ UV Spectrum of r-(2-azo-6-carboxylic acid benzothazolyl) 2,6-dimethyl phenol [6]

۲٥

۱۰۹ UV Spectrum of of r-(2-azo-6-carboxylic acid benzothazolyl) 3-bromo phenol [7]

۲٦

۱۰۹ UV Spectrum of r-( 2-azo-6-carboxylic acid benzothazole ) 3-amino phenol [8]

۲۷

۱۱۰ UV Spectrum of r-( 2-azo-6-carboxylic acid benzothazolyl ) 2-methoxy phenol [10]

28

۱۱۰ UV Spectrum of r- 2-azo-6-nitro benzothazolyl )2,6-dimethyl phenol [14]

۲۹

۱۱۱ UV Spectrum of r-( 2-azo-6-nitro benzothazolyl )3-bromo phenol [15]

30

۱۱۱ UV Spectrum of r-(2-azo -6-nitro benzothazolyl) 3-amino phenol [16]

۳۱

۱۱۲ UV Spectrum of r-(2-azo-6-nitro benzothazolyl) 3-ethyl phenol [17]

32

۱۱۲ UV Spectrum of r-( 2-azo-6-nitro benzothazolyl ) 2-methoxy phenol [18]

۳۳

۱۳۳ UV Spectrum of r-( 2-azo-6-nitro benzothazolyl) 3-methyl phenol [19]

34

۱۳۳ UV Spectrum of 4 r-(2-azo-6-nitro benzothazolyl ) 2-nitro phenol [20]

۳٥

۱۱٤ UV Spectrum of r-( 2-azo-6-nitro benzothazolyl ) phenol [21] 36

۱۱٤ UV Spectrum of r-( 2-azo-6-methyl benzothazolyl) 3-bromo phenol [23]

۳۷

۱۱٥ UV Spectrum of r-( 2-azo-6-chloro 4-nitro benzothazolyl) 2,6-dimethyl phenol [30]

38

۱۱٥ UV Spectrum of r-( 2-azo-6-chloro 4-nitro benzothazolyl) 3-ethyl phenol [33]

۳۹

۱۱٦ UV Spectrum of r-( 2-azo-6-chloro 4-nitro benzothazolyl) 2-ethoxy phenol [34]

40

XVII

Page

Title

Fig. No.

۱۱٦ UV Spectrum of r-( 2-azo-6-chloro 4-nitro benzothazolyl) 2-nitro phenol [36]

41

۱۱۷ UV Spectrum of r-( 2-azo-6-chloro 4-nitro benzothazolyl) phenol [37]

42

۱۱۷ UV Spectrum of r-(2-azo-6-chloro 4-nitro benzothazolyl) 3- bromo phenol [31]

٤۳

۱۱۸ UV Spectrum of r-( 2-azo-6,4-dinitro benzothazolyl) 2,6-dimethyl phenol [38]

44

۱۱۸ UV Spectrum of r-( 2-azo-6,4-dinitro benzothazolyl) 3-amino phenol [40]

٤٥

۱۱۹ 1H-NMR Spectrum of r-( 2-azo-6-nitro benzothazolyl) 3-amino phenol [16]

46

119 The expantion of 1H-NMR spectrum of r-( 2-azo-6-nitro benzothazolyl) 3-amino phenol [16 ]

47

۱۲۰ 13C-NMR Spectra of r-( 2-azo-6-nitro benzothazolyl ) 3-amino phenol [16]

48

۱۳۲ FTIR Spectrum of ethyl {r- (2-azo-6-carboxylic acid benzothiazolyl ) 2,6- dimethyl phenoxy } 2- propionate [46]

٤۹

۱۳۲ FTIR Spectrum of ethyl {r- (2-azo 6- nitrobenzothiazolyl ) phenoxy } 2- propionate .[47]

50

۱۳۳ FTIR Spectrum of ethyl {r- (2-azo 6-nitrobenzothiazolyl )3-ethyl phenoxy } 2- propionate .[49]

٥۱

۱۳۳ FTIR Spectrum of ethyl {r- (2-iazo 6-nitrobenzothiazolyl )2-nitro phenoxy} 2- propionate.[50]

52

۱۳٤ FTIR Spectrum of ethyl {r- (2-azo 6-nitrobenzothiazolyl )3-amino phenoxy} 2- propionate.[51]

٥۳

۱۳٤ FTIR Spectrum of ethyl {r- (2-azo 6-chloro 4-nitro benzothiazolyl ) [54] propionate 3-amino phenoxy } 2-

54

۱۳٥ FTIR Spectrum of ethyl {r- (2-azo 6-chloro 4-nitro benzothiazolyl ) phenoxy } 2- propionate [53]

55

۱۳٥ FTIR Spectrum of ethyl {r- (2-azo 6-chloro-4-nitro benzothiazolyl ) 3-ethyl phenoxy } 2- propionate [58]

56

۱۳٦ FTIR Spectrum of ethyl {r- (2-azo 6,4-dinitro benzothiazolyl ) 2-nitro phenoxy } 2- propionate [59]

57

۱۳٦ UV Spectrum of ethyl {r- (2-azo 6- nitro benzothiazolyl ) phenoxy } 2- propionate [47]

58

XVIII

Page

Title

Fig. No.

۱۳۷ UV Spectrum of ethyl {r- (2-azo-6- methyl benzothiazolyl )3-bromo phenoxy } 2- propionate [48]

59

۱۳۷ UV Spectrum of ethyl {r- (2-azo-6-nitrobenzothiazolyl )3-ethyl phenoxy } 2- propionate [49]

60

۱۳۸ UV Spectrum of ethyl{ r-(2-azo-6-chloro-4-nitro benzothiazolyl) 2,6-dimethyl phenoxy } 2- propionate [52]

61

۱۳۸ UV Spectrum of ethyl {r- (2-azo-6-chloro-4-nitro benzothiazolyl ) phenoxy } 2- propionate [53]

62

۱۳۹ UV Spectrum of ethyl {r- (2-azo-6-chloro-4-nitro benzothiazolyl ) 3-amino phenoxy } 2- propionate [54]

63

۱۳۹ UV Spectrum of ethyl {r- (2-azo-6-chloro-4-nitro benzothiazolyl ) 2-nitro phenoxy } 2- propionate [55]

64

۱٤۰ UV Spectrum of ethyl {r- (2-azo-6-chloro-4-nitro benzothiazolyl ) 3-bromo phenoxy } 2- propionate [56]

65

۱٤۰ UV Spectrum of ethyl {r- (2-azo-4,6-dinitro benzothiazolyl ) phenoxy } 2- propionate [57]

66

۱٤۱ UV Spectrum of ethyl {r- (2-azo-4,6-dinitro benzothiazolyl )3-ethyl phenoxy } 2- propionate [58]

67

۱٤۱ UV Spectrum of ethyl {r- (2-azo-4,6-dinitro benzothiazolyl ) 2-nitro phenoxy } 2- propionate [59]

68

۱٤۲ 1H-NMR Spectrum of ethyl {r- (2-azo-6- nitrobenzothiazolyl ) phenoxy } 2- propionate [47]

69

۱٤۲ The expantion of 1H-NMR spectrum of ethyl {r- (2-azo-6- nitro benzothiazolyl ) phenoxy } 2- propionate (47 )

70

۱٤۳ 13C-NMR Spectrum of ethyl {r- (2-azo-6- nitrobenzothiazolyl ) phenoxy } 2- propionate [47]

71

۱٥۱ FTIR spectrum of 2-propanyl{r- (2-azo-6-nitrobeonzothiazolyl) phenoxy}-N-thiosemicarbazide [64]

72

۱٥۱ FTIR spectrum of 2- propanyl {r- (2-azo-6-chloro-4-nitro beonzothiazolyl)2,6-dimethyl phenoxy}N-thiosemicarbazide[66]

73

۱٥۲ FTIR spectrum of 2-propanyl{r-(2-azo-6-nitro beonzothiazolyl) 3-ethyl phenoxy} -N-thiosemicarbazide [65]

74

۱٥۲ FTIR spectrum of 2-propanyl-{r-(2-azo-6-chloro-4-nitrobeonzothiazolyl ) 3-bromo phenoxy}N-thiosemicarbazide [69]

75

۱٥۳ UV Spectrum of 2- propanyl {r- (2-azo-6-nitro-beonzothiazolyl) phenoxy} N-thiosemicarbazide [64]

76

XIX

Page Title

Fig. No.

۱٥۳ UV Spectrum of 2- propanyl {r- (2-azo-6-nitrobeonzothiazolyl) 3-ethyl phenoxy} N-thiosemicarbazide [65]

77

۱٥٤ UV Spectrum of 2- propanyl {r- (2-azo-6-methyl beonzothiazolyl) 3-bromo phenoxy} N-thiosemicarbazide [63]

78

۱٥٤ UV Spectrum of 2- propanyl {r- (2-azo-6-chloro-4-nitro beonzothiazolyl)2,6-dimethylphenoxy}N-thiosemicarbazide [66]

79

۱٥٥ UV Spectrum of 2- propanyl {r- (2-azo-6-chloro-4-nitro beonzothiazolyl) 3-amino phenoxy} N-thiosemicarbazide [67]

80

۱٥٥ UV Spectrum of 2- propanyl {r- (2-azo-6-nitro beonzothiazolyl) 2-nitro phenoxy} N-thiosemicarbazide [68]

81

۱٥٦ UV Spectrum of 2- propanyl {r- (2-azo-6-chloro-4-nitro beonzothiazolyl) 3-bromo phenoxy} N-thiosemicarbazide [69]

82

۱٥٦ UV pectrum of 2- propanyl{r-(2-azo-6,4-dinitro beonzothiazolyl) phenoxy} N-thiosemicarbazide [70]

83

۱٦۳ FT-IR Spectrum of 2- propanyl {r-(2-azo-6-nitro beonzothiazolyl) phenoxy} N-semicarbazide [72].

84

۱٦۳ FT-IR Spectrum of 2- propanyl {r- (2-azo-6-chloro-4-nitro beonzothiazolyl) 3-amino phenoxy} N-semicarbazide [75]

85

۱٦٤ FT-IR Spectrum of 2- propanyl {r-(2-azo-6-nitro beonzothiazolyl) 3-ethyl phenoxy} N-semicarbazade [73].

86

۱٦٤ FT-IR Spectrum of 2- propanyl {r-(2-azo-6-nitro beonzothiazolyl) 2-nitro phenoxy} N-semicarbazide [76].

87

۱٦٥ UV Spectrum of 2- propanyl {r-(2-azo-6-methyl beonzothiazolyl) 3-bromo phenoxy} N-emicarbazide [71]

88

۱٦٥ UV Spectrum of 2- propanyl {r-(2-azo-6-nitro beonzothiazolyl) phenoxy} N-semicarbazide [72]

89

۱٦٦ UV Spectrum of 2- propanyl {r-(2-azo-6-nitro beonzothiazolyl) 3-ethyl phenoxy} N-semicarbazide [73]

90

۱٦٦ UV Spectrum of 2- propanyl {r- (2-azo-6-chloro-4-nitro beonzothiazolyl) 2,6-dimethyl phenoxy} N-semicarbazide [74]

91

۱٦۷ UV Spectrum of 2- propanyl {r- (2-azo-6-chloro-4-nitro beonzothiazolyl) 3-amino phenoxy} N-semicarbazide [75]

۹۲

۱٦۷ UV Spectrum of 2- propanyl {r-(2-azo-6-nitro beonzothiazolyl) 2-nitro phenoxy} N-semicarbazade [76]

۹۳

۱٦۸ UV Spectrum of 2- propanyl {r- (2-azo-6-chloro-4-nitro beonzothiazolyl)3-bromo phenoxy} N-semicarbazide [77]

۹٤

۱٦۸ UV Spectrum of 2- propanyl {r-(2-azo-6,4-dinitro beonzothiazolyl) phenoxy} N-semicarbazide [78]

95

XX

Page

Title

Fig. No.

۱۷۸ FT-IR Spectrum of 5-{r-(2-azo -6-nitro benzothiazolyl) phenoxy 2-ethyl }2- amino 1,3,4-oxadiazole [80].

۹٦

۱۷۸ FT-IR Spectrum of 5-{r- (2-azo-6-nitro benzothiazolyl) 2-nitro phenoxy-2-ethyl }2- amino 1,3,4-oxadiazole [84].

۹۷

۱۷۹ FT-IR Spectrum of 5-{r-(2-azo-6-nitro benzothiazolyl )3-ethyl phenoxy 2-ethyl }2- amino 1,3,4-oxadiazole [81] .

۹۸

۱۷۹ FT-IR spectrum of 5-{r- (2-azo-6-chloro 4-nitro benzothiazolyl) 3-amino phenoxy 2-ethyl }2-amino1,3,4-oxadiazole [83].

۹۹

۱۸۰ UV Spectrum of 5-{r-(2-azo-6-methyl benzothiazolyl ) 3-bromo phenoxy 2-ethyl }2- amino 1,3,4-oxadiazole [79].

100

۱۸۰ UV Spectrum of 5-{r-(2-azo-6-nitro benzothiazolyl) phenoxy 2-ethyl } 2- amino 1,3,4-oxadiazole [80].

101

۱۸۱ UV Spectrum of 5-{r-(2-azo-6-nitro benzothiazolyl) 3-ethyl phenoxy 2-ethyl }2- amino 1,3,4-oxadiazole [81].

102

۱۸۱ UV Spectrum of 5-{r-(2-azo-6-chloro-4-nitro benzothiazolyl) 2,6-dinitro phenoxy 2-ethyl }2- amino 1,3,4-oxadiazole [82].

103

۱۸۲ UV Spectrum of 5-{r-(2-azo-6-chloro-4-nitro benzothiazolyl) 3-amino phenoxy 2-ethyl }2- amino 1,3,4-oxadiazole [83].

104

۱۸۲ UV Spectrum of 5-{r-(2-azo-6-nitro benzothiazolyl) 2-nitro phenoxy 2-ethyl }2- amino 1,3,4-oxadiazole [84].

105

۱۸۳ UV Spectrum of 5-{r-(2-azo-6-chloro-4-nitro benzothiazolyl) 3-bromo phenoxy 2-ethyl }2-amino 1,3,4-oxadiazole [85].

106

۱۸۳ UV Spectrum of 5-{r- (2-azo-4,6-dinitro benzothiazolyl) phenoxy 2-ethyl }2- amino 1,3,4-oxadiazole [86].

107

۱۸٤ 1H-NMR Spectrum of 5-{r-(2-azo-6-nitro benzothiazolyl) phenoxy 2-ethyl }2- amino 1,3,4-oxadiazole [80].

108

۱۸٤ The expantion of 1H-NMR spectra of 5-{r-(2-azo-6-nitro benzothiazolyl) phenoxy2-ethyl }2-amino 1,3,4-oxadiazole [80].

109

۱۸٥ 13C-NMR Spectrum of 5- {r-(2-azo-6-nitro benzothiazolyl) phenoxy 2-ethyl }2- amino 1,3,4-oxadiazole [80].

110

۱۹۲ FT-IR Spectrum of 5-{r- (2-azo-6-nitro benzothiazolyl) phenoxy 2-ethyl }3- thione 1,2,4 triazole [88].

۱۱۱

۱۹۲ FT-IR Spectrum of 5-{r-(2-azo-6-nitro benzothiazolyl) 3-ethyl phenoxy 2-ethyl }3- thione 1,2,4 triazole [89] .

۱۱۲

۱۹۳ FT-IR Spectrum of 5-{r- (2-azo-6-chloro-4-nitro benzothiazolyl) 3-amino phenoxy 2-ethyl }3- thione 1,2,4 triazole [90].

۱۱۳

XXI

Page

Title

Fig. No.

۱۹۳ FT-IR Spectrum of 5-{r-(2-azo-4,6-dinitro benzothiazolyl) phenoxy 2-ethyl }3- thione 1,2,4 triazole [92].

۱۱٤

۱۹٤

UV Spectrum of 5-{r- (2-azo-6-nitro benzothiazolyl) phenoxy 2-ethyl}3- thione 1,2,4 triazole [88] .

۱۱٥

۱۹٤ UV Spectrum of 5-{r-(2-azo-6-nitro benzothiazolyl) 3-ethyl phenoxy 2-ethyl }3- thione 1,2,4 triazole [89].

۱۱٦

۱۹٥ UV Spectrum of 5-{r- (2-azo-6-chloro-4-nitro benzothiazolyl) 3-amino phenoxy 2-ethyl }3- thione 1,2,4 triazole [90].

۱۱۷

۱۹٥ UV Spectrum of 5-{r- (2-azo-6-chloro-4-nitro benzothiazolyl) 3-bromo phenoxy 2-ethyl }3- thione 1,2,4 triazole [91] .

۱۱۸

۱۹٦ UV Spectrum of 5-{r- (2-azo-6,4-dinitro benzothiazolyl) phenoxy 2-ethyl }3- thione 1,2,4 triazole [92]

۱۱۹

۱۹٦ UV Spectrum of 5-{r-(2-azo-6-nitro benzothiazolyl) 2-nitro phenoxy 2-ethyl }3- thione 1,2,4 triazole [93].

۱۲۰

۱۹۷ UV Spectrum of 5-{r- (2-azo-6-chloro-4-nitro benzothiazolyl) 2,6-dimethyl phenoxy 2-ethyl }3-thione 1,2,4-triazole [94].

۱۲۱

۱۹۸ 1H-NMR Spectrum of 5-{r-(2-azo-6-nitro benzothiazolyl) phenoxy 2-ethyl }3- thione 1,2,4 triazole [88].

۱۲۲

۱۹۸ The expantion of 1H-NMR Spectrum of 5-{r-(2-azo-6-nitro benzothiazolyl) phenoxy 2-ethyl }3- thione 1,2,4 triazole [88].

۱۲۳

۱۹۹ 13C-NMR Spectrum of 5-{r- (2-azo-6-nitro benzothiazolyl) phenoxy 2-ethyl}3- thione 1,2,4 triazole [88].

124

۲۰۸ FT-IR Spectrum of 5-{r- (2-azo-6-nitro benzothiazolyl) phenoxy 2-ethyl}2-amino 1,3,4- thiadiazole [95].

125

۲۰۸ FT-IR Spectrum of 5-{r- (2-azo-6-nitro benzothiazolyl) 3-ethyl phenoxy 2-ethyl }2-amino 1,3,4- thiadiazole [96].

126

۲۰۹ FT-IR Spectrum of 5-{r- (2-azo-6-nitro benzothiazolyl) 2-nitro phenoxy 2-ethyl }2-amino 1,3,4- thiadiazole [98].

127

۲۰۹ FT-IR Spectrum of 5-{4-(2-azo-6,4-dinitro benzothiazolyl) phenoxy 2-ethyl }2-amino 1,3,4- thiadiazole [99].

128

۲۱۰ UV Spectrum of 5-{r- (2-azo-6-nitro benzothiazolyl) phenoxy 2-ethyl }2-amino 1,3,4- thiadiazole [95].

129

۲۱۰ UV Spectrum of 5-{r- (2-azo-6-nitro benzothiazolyl) ۳-ethyl phenoxy 3-ethyl}2-amino 1,3,4- thiadiazole [96].

130

۲۱۱ UV Spectrum of 5-{r- (2-azo-6-chloro-4-nitro benzothiazolyl) 2,6-dimethyl phenoxy 2-ethyl }2-amino 1,3,4-thiadiazole [97].

131

XXII

Page

Title

Fig. No.

۲۱۱ UV Spectrum of 5-{r- (2-azo-6-nitro benzothiazolyl) 2-nitro phenoxy 2-ethyl }2-amino 1,3,4- thiadiazole [98].

132

۲۱۲ UV Spectrum of 5-{r- (2-azo-6,4-dinitro benzothiazolyl) phenoxy 2-ethyl }2-amino 1,3,4- thiadiazole [99].

133

۲۱۲ UV Spectrum of 5-{r- (2-azo-6-methyl benzothiazolyl) 3-bromo phenoxy 2-ethyl }2-amino 1,3,4- thiadiazole [100].

134

۲۱۳ UV Spectrum of 5-{r- (2-azo-6-chloro-4-nitro benzothiazolyl) 3-amino phenoxy 2-ethyl }2-amino 1,3,4- thiadiazole [101].

135

۲۱۳ UV Spectrum of 5-{r- (2-azo-6-chloro-4-nitro benzothiazolyl) 3-bromo phenoxy 2-ethyl }2-amino 1,3,4- thiadiazole [102].

136

۲۱٤ 1H-NMR Spectrum of 5-{r- (2-azo-6-nitro benzothiazolyl) phenoxy 2-ethyl }2-amino 1,3,4- thiadiazole [95].

137

۲۱٤ The expantion of 1H-NMR Spectrum of 5-{r- (2-azo-6-nitro benzothiazolyl) phenoxy 2-ethyl} 2-amino 1,3,4-thiadiazole [95].

138

۲۱٥ 13C-NMR Spectrum of 5-{r- (2-azo-6-nitro benzothiazolyl) phenoxy 2-ethyl }2-amino 1,3,4- thiadiazole [95].

۱۳۹

XXIII

List of Tables

Page

Title

Table No.

43 Employed chemicals and their supplier companies 1

50 Starting material and conditions for prepared of 2-amino-

benzothiazole derivatives [1-5].

2

51 Conditions for the prepared derivatives of r-(2-azo- [6-45]. benzothiazolyl) substituted phenol

3

56

Conditions for the prepared derivatives of ethyl { r- (2-azo- substituted benzothiazolyl) substituted phenoxy} 2-propionate [46-62].

4

٥۹

Conditions for the prepared derivatives of 2-propanyl {r- (2- azo-substituted benzothiazolyl) substituted phenoxy }

N-thiosemicarbazide [63-70].

٥

٦۱ Conditions for the prepared derivatives of 2-propanyl {r- (2- azo-substituted benzothiazolyl) substituted phenoxy }

N-semicarbazide [71-78].

٦

٦۳

Conditions for the prepared derivatives of 5 -substituted 2- amino 1,3,4-oxadiazole [79-86].

۷

٦٥ Condition for the prepared derivatives of 5-subsituted 1,2,4 triazole 3-thione [87-94].

8

67 Conditions for the prepared derivatives of 2-amino 5-

substituted -1, 3,4-thiadiazole [95-102].

9

74

Physical properties of the prepared 2-aminobenzothiazoles

10

75

FT-IR absorption bands of the prepared 2-aminobenzothiazole derivatives [ 1 -5].

11

۷٦

Ultra violet spectra of the prepared 2-aminobenzothiazoles

12

۹۹

Physical properties of the prepared r-(2-azo-substituted benzothiazolyl) substituted phenols [6-45].

۱۳

XXIV

Page

Title

Table No.

۹٥ FT-IR absorption bands of prepared r-(2-azo-substituted benzothiazolyl) substituted phenols [6-45]

14

۹۹ Ultra violet spectra of the prepared r-(2-azo-substituted benzothiazolyl) substituted phenols .

15

۱۲٦ Physical properties of ethyl{r- (2-azo-substituted benzothiazolyl ) substituted phenoxy } 2-propionate [46-62].

۱٦

۱۲۸ FT-IR absorption of the prepared ethyl{r- (2-azo- substituted benzothiazolyl) substituted phenoxy} 2-propionate [46-62]

17

۱۳۰ Ultra violet spectra of the prepared ethyl{r-(2-azo-substituted benzothiazolyl ) substituted phenoxy } 2-propionate

۱۸

۱٤۷ Physical properties of the prepared 2- propanyl {r-(2-azo- substituted benzothiazolyl ) substituted phenoxy } N-thiosemicarbazide [63-70] .

۱۹

۱٤۸ FT-IR absorption bands of the prepared 2-propanyl {r -(2- azo- substituted benzothiazolyl) substituted phenoxy} N-

thiosemicarbazide [63-70].

20

۱٤۹

Ultra violet spectra of the prepared 2-propanyl {r-(2-azo-substituted benzothiazolyl) substituted phenoxy} N-

thiosemicarbazide .

۲۱

۱٥۹

Physical properties of the prepared 2- propanyl {r -(2-azo- substituted benzothiazolyl ) substituted phenoxy }

N-semicarbazide [71-78].

۲۲

۱٦۰

FT-IR absorption bands of the prepared 2-propanyl {r (2- azo-substituted benzothiazolyl ) substituted phenoxy }

[71-78]. N-semicarbazide

۲۳

۱٦۱

Ultra violet spectra of the prepared 2-propanyl {r -(2-azo- substituted benzothiazolyl ) substituted phenoxy } N-semicarbazide [71-78].

۲٤

۱٦٤

Physical properties of the prepared 5-substituted 2- amino 1,3,4-oxadiazole [79-86].

۲٥

XXV

Page

Title

Table No.

۱۷٥ FT-IR absorption bands of the prepared 5- substituted 2- amino 1,3,4-oxadiazole [79-86].

26

۱۷٦ Ultra violet spectra of the prepared 5-subsituted 2-amino 1,3,4-oxadiazole.

27

۱۸۸ Physical properties of the prepared 5-subsituted-1,2,4

triazole- 3-thione [87-94].

۲۸

۱۸۹ FT-IR absorption bands of the prepared 5-subsituted-1,2,4

triazole 3-thione [87-94].

۲۹

۱۹۰

Ultra violet spectra of the prepared 5-subsituted -1,2,4-triazole 3-thione .

۳۰

۲۰۱ Physical properties of prepared 2-amino 5-substituted

[95-102]. 1-3-4 thiadiazole-

31

۲۰۳ FT-IR absorption bands of the prepared 2-amino 5-substituted 1-3-4 thiadiazole [95-102].

32

۲۰٤ Ultra violet spectra of the prepared 2-amino 5-substituted

1-3-4 thiadiazole.

۳۳

۲۰٦

The 1H- NMR chemical shifts of some prepared compounds.

۳٤

XXVI

List of Scheme

Page

Title

Scheme No.

XXIX

synthesis of r-(2-azo-substituted benzothiazolyl) substituted phenols (6-45).

۱

XXX

synthesis of 2-amino 5-subsituted (1,3,4) thiadiazole and 5-subsituted (1,3,4) triazole 2-thione derivatives.

۲

XXXI

synthesis of 2-amino-5-subsituted (1,3,4) oxadiazole derivatives .

۳

۷۰

Mechanism for the preparation of 2-amino benzothiazole

4

۸٤

Mechanism for the preparation azo compound.

5

۱۲۱

Mechanism for Williamson ether synthesis

6

۱٤٤ Mechanism for the preparation N-substituted

thiosemicarbazide ( semicarbazide) .

7

۱٦۹

inter molecular cyclyzation of thiosemicarbazide (semicarbazide).

8

۱۷۰

Mechanism for the preparation of thiazole and oxadiazole derevatives.

9

۱۷۰

Mechanism for the preparation of triazole

8

XXVII

Summary

Several benzothiazole derivatives have long been known for their

diverse biological properties, mainly as antiviral, antibacterial, antifungal

and anti-inflammatory agents. Azo compounds also have biological

activity. In addition, 1,2,4-triazole,1,3,4-thiadiazole and 1,3,4-oxadiazole,

were reported to constitute the pharmacologically active moiety of

several compounds. On these bases, new series of 2-azobenzothiazole

derivatives, in which the adamantly moiety was attached to 1,2,4-triazole,

1,3,4- thiadiazole and 1,3,4-oxadiazole nucleus, have been synthesized as

possible potential bioactive agents. In order to obtain the target

compounds, the following routes were adopted :-

1- Preparation of 2-amino benzothiazole and their derivatives (1-5),

from reaction of r- substituted aniline with ammonium thiocyanate

in the present of bromine as catalyst.

2- Involved diazotation and coupling reaction to form azo compounds

by converted amino group to dizonum salt by react with NaNO2 /

H2SO4 in low temperatures then coupling with substituted phenols

to yield compounds (6-45).

3- Reaction of coupled products with ethyl 2-bromo propionate and

anhydrous K2CO3 in dry acetone to yield the new ester derivatives

(46 -62 ).

4- The ester group was converted to N-substituted thiosemicarbazide

by reaction with thiosemicarbazide in absolute ethanol to form

compounds ( 63 -70).

5- Also the ester group was converted to N-substituted semicarbazide

by reaction with semicarbazide in absolute ethanol to form

compounds (71-78).

6- The N-substituted semicarbazide react with acid to yield 5-

{substituted}2-amino-1,3,4-oxadiazole (79-86).

XXVIII

7- The N-substituted thiosemicarbazide react with base to yield

5-{substituted} 2-amino 1,2,4-triazole (87-94), also react with

acid to form 5-{substituted}2-amino 1,3,4- thiadiazole ( 95-

102).

XXIX

Scheme (1) : synthesis of r-(2-azo-substituted benzothiazolyl) substituted phenols (6-45).

XXX

Scheme ( 2) : synthesis of 2-amino 5-subsituted (1,3,4) thiadiazole and 5-subsituted (1,2,4) triazole 3-thione derivatives .

XXXI

Scheme (3 ) : synthesis of 2-amino 5-subsituted (1,3,4) oxadiazole derivatives .

XXXII

AIMS AND OBJECTIVES 1. To establish the method of synthesis for the proposed compounds

2. To synthesize the title compounds by appropriate methods.

3. To carry out the preliminary tests such as physical constant

determination and TLC.

4. To confirm the structures of the synthesized compounds by FT-IR, UV,

1H-NMR and 13C-NMR.

XXXIII

غير جديدة شتقاتتحضير وتشخيص م وبنزوثايازولاز-۲للمركبمتجانسة

األطروحة مقدمة إلى

جامعة بغداد -كلية العلوم

فلسفة في الكيمياء الدكتوراهكجزء من متطلبات نيل درجة

من قبل

مها قاسم محمود )۱۹۹۸جامعة بابل (– بكلوريوس علوم كيمياء

)۲۰۰٦جامعة بغداد ( -ماجستير علوم كيمياء

إشراف

د. انتصار عبيد التميمي أ. ۱٤۳٤ م ۲۰۱۱

الخالصة

XXXIV

كمض��ادات وتس��تعمل بنزوثاي��ازول فعالي��ة بايولوجي��ة مهم��ةال تمتل��ك مش��تقات

، وك��ذلك مماثل��ةال��دايازول فعالي��ة بايولوجي��ة للبكتري��ا وااللتهاب��ات ، و تمتل��ك مش��تقات

التراي��ازول ، الثاياداي��ازول و االوكس��ادايازول ص��فات دوائي��ة ت��ؤديتمتل��ك مركب��ات

حامل�ة و بنزوثاي�ازول زا-۲نفس الغرض . لهذا السبب تم تحضير مشتقات مختلفة من

تمتل��ك فعالي��ة محتم��ل أنلمش��تقات التراي��ازول ، الثاياداي��ازول و االوكس��ادايازول

: ذل��ك تطل��ب العم��ل الخط��وات التالي��ة وإلتم��امبايولوجي��ة.

نلين المعوض�ة ألاات امينوبنزوثايازول من خالل تفاعل مركب -۲تحضير مشتقات -۱

ب��الموقع ب��ارا م��ع ثايوس��يانات االموني��وم بوج��ود الب��روم كعام��ل مس��اعد.

-۲م��ين ف��ي مش��تقات ت االزو م��ن خ��الل إدخ��ال مجموع��ة األتحض��ير مركب��ا -۲

. عوضةمع فينوالت م زوتة وازدواجأ تفاعلول امينوبنزوثاياز

بروم�و بروبيوني�ت - ۲-اث�لم�ع تفاعل ت في مركبات األزو كسيلمجموعة الهيدرو -۳

. جديدة يةسترأبوجود كاربونات البوتاسيوم الجاف للحصول على مشتقات

N– سيميكاربازايد بتفاعلها م�ع المجم�وع - ٤ مش�تقات إل�ىي�تم تحويله�ا االس�ترية

)۱,۳,٤( امين��و -۲مش��تقات تك��ون الح��امض بوج��ود ت��ي ال لس��يميكاربازايد وا

وكزادايازول.أ

مشتقات إلىالمجموعة االسترية يتم تحويلها أيضا -٥ N -ثايوسيميكاربازايد وذلك

-۲الح��امض يك��ون مش��تقات ال��ذي بوج��ود يكاربازايدالثايوس��يم عن��د تفاعله��ا م��ع

(-مركبت��و -۳تقات ) ثايوداي��ازول وبوج��ود القاع��دة يك��ون مش��٤,۳,۱(-مين��وأ

) تراي��ازول .٤,۱,۲

الف��وق األش��عةالمركب��ات الت��ي ت��م تحض��يرها شخص��ت باس��تخدام مطيافي��ة

ي تح��ت الحم��راء ومطيافي��ة ال��رنين الن��ووي المغناطيس�� األش��عةالبنفس��جية ومطيافي��ة

وكان��ت جمي��ع النت��ائج مطابق��ة لم��ا ه��و متوق��ع .

Chapter one Introduction

- ۱ -

REVIEW OF LITERATURE 1-1 Heterocyclic Compounds

A cyclic organic compound containing all carbon atoms in ring

formation is referred to as a carbocyclic compound. If at least one atom

other than carbon, forms a part of the ring system designated as a

heterocyclic compound. Nitrogen, oxygen and sulfur are the most

common hetero atoms.

Heterocyclic compounds occur widely in nature and in a variety of

non-naturally compounds, large number of heterocyclic compounds are

essential to life such as alkaloids, antibiotics, essential amino acids, the

vitamins, hemoglobin, the hormones , a large number of synthetic drugs

and dyes (1).

ompounds c eThiazol 2 -1

It is a five-member aromatic ring in which two of the ring atoms are

nitrogen and sulfur and the other three are carbon atoms.

Thiazole compound is classified into two main types a simple one which

contains a single thiazole ring and the other, two thiazole rings associated

together (Bithiazole).


- ۲ -

Simple thiazole nucleus was first reported by Hantzsch and Weber in

1887; they proved the existence of both thiazole and isothiazole.

Benzothiazole derivatives represent an extensive group of

heterocyclic compounds, several of which have already found application

in the medical sphere as medicines. The compounds encompassing

benzothiazole moiety are of great interest and have been extensively used

in pharmaceutical chemistry and agriculture division. Heterocyclic

bearing a benzothiazole ring residue are reported to show anticancer, anti-

inflammatory, analgesic, muscle-relaxant, sedative, antitubercular,

diuretic, antimicrobial, anticonvulsant, antiallergic, antimalerial,

antiviral, antioxidant, CNS depressant, and plant growth regulatory

activity etc. (2) In addition, recently benzothiazole possess derivatives an

extended conjugated system. and longer fluorescence lifetime forms .(3)

ompoundsbenzothiazole c minoa-21 -2-1

2-amino benzothiazole compounds are considered one of an important

type of fused thiazoles which have a wide application. The chemistry of

2-amino benzothiazole has gained increasing interest in both synthetic

organic chemistry and biological fields (4).


- ۳ -

minoa-Some methods for preparation of 2 2 -2-1 erivatives.d and ebenzothiazol

A number of 2-amino benzothiazole derivatives were prepared by

two methods. The first is Hugersch's method which concerns the

reaction of thiourea derivative with bromine in acetic acid. The second,

method concerns the direct reaction of amine derivatives with potassium

thiocyanate and bromine in glacial acetic acid.

In 1887 Hoffmann (5) who first reported the cyclizations of 2-amino

thiophenol to 2-amino benzothiazole. Hofmann noted only the formation

of 2-anilineobenzothiazole from the reaction of 2-amino thiophenol and

phenyl isothiocyanate.

Investigations into the preparation of 2-amino benzothiazoles can

also be traced to the early 1900 with work of Hugerschoff, who found

that an r-methyl arylthiourea can be cyclized with liquid bromine in

chloroform to form a 5-methyl 2-aminobezothiazoles (6).

Johanson and Hamillton prepared 2-amino-5-methylmercaptoben-

zothiazole by the oxidation of 4-methyl-mecaptophenylthiourea with

bromine as a catalyst (7) .


- ٤ -

Stuckwish (8) used potassium thiocyanate to cyclizting r-methoxy

aniline into 2-amino-5-methoxy benzothiazole and sulfuric acid as

catalyst.

Allen and Van Allan (9) used sodium thiocyante to cyclizing r-methyl

aniline into 2-amino-6-methyl benzothiazole and sulfuric acid as catalyst.

Caldwell et. al (10) synthesized 2-anilinobenzothiazole with the help

of phenyl isothiocyanate in pyridine and aqueous sodium carbonate.


- ٥ -

Tweit (11) using alkyl isothiocyanates to cyclization of o-mercapto

aniline to 2-aminoalkyl benzothiazole in the presence of benzene.

Alamino (12) prepared 2-amino-5,6-dichloro and 2-amino-4,5-

dichlorobenzothiazole by cyclizing the suitable substituted anilines with

thiocyanogen.

Jeng Lin and Kasina(13) prepared 6-subsitited-2-aminobenzothiazole

by cyclizations of r-substituted anilines with ammonium thiocyanate and

bromine.

Naim et. al.(14) synthesized 2-amino benzothiazole-6-carboxalic acid

and 2-amino-6-substituted-carbonyl benzothiazoles by reaction of the


- ٦ -

corresponding r-substituted aniline with potassium thiocyanate followed

by oxidative cyclizations of the resultant thioureas with bromine.

Castro and Martinez (15) synthesized 2-amino ethyl benzothiazole by

intra molecular cyclizing of N-ethyl N-phenyl thiourea in the presence of

sulphuryl chloride and toluene.

Hendery (16) , Jayachandran et. al.(17) and Pattan et. al.(18) prepared

the 2-amino-6-fluro-7-chlorobenzothiazole by cyclizing 3-cloro-4-fluoro

aniline by potassium thiocyanate in the presence of catalytic bromine.

Morlacchi et. al.(19) also synthesized 6-fluoro-4 (5 or 7)-chloro-2-

aminobenzothiazoles by using a similar method and materials already

using by Pattan et. al.


- ۷ -

Patel and Agravat (20) synthesized various 4 (5 or 6)- substituted-2-

aminobenzothiazoles with the help of 4 (5 or 6)- substituted anilines

which was reacted with ammonium thiocyanate and bromine.

Jimonet et. al.(21) synthesized various substituted-2-amino benzothiazoles

derivatives by different methods.

Method A: One-Pot reaction of appropriate anilines with

thiocyanogens generated from bromine and alkaline thiocyanate in acetic

acid medium led to the formation of the desired product in good to

moderated yields.

Method B: In this method cyclization of phenylthiourea with

bromine in chloroform.

Matsui et. al.(22) prepared 6-subsituted-2-aminobenzothiazoles by the

reaction of 4-subsituted anilines with potassium thiocyanate in the

presence of bromine.


- ۸ -

Jordan et.al.(23) using benzyltrimethyl ammonium tribromide for

synthesized of 2-aminosubsituted benzothiazole from either aryl

isothiocyanate or tetra butyl ammonium thiocyanate with r- substituted

anilines.

Yong-Qian Wu et. al.(24) used di(imidazole-3-yl) methanimine for

synthesized of 2-aminobenzothiazole that already synthesized by treating

cyanogens bromide with imdazole,

Batey et. al.(25) reported the synthesis of 2-aminobenzothiazoles

from ortho-bromo and iodo-aryl thioureas.


- ۹ -

They prepared many of benzothiazole derivatives by the reaction of

thiourea derivatives with thionyl chloride.

Then, Rudolf synthesized 5,7-disubstituted 2-aminobenzothiazole

derivatives by reaction N-(2 , 4)-disubstituted phenyl thiourea with sulfur

halide which help in ring closure (26).

Also the reaction of acids chloride or acids anhydride or acids ester

with 2-aminothiophenol formed intermediate (2-acyl aminothiophenol)

which then undergoes with ring closing and produced 2-subsituted

benzothiazole (27).

In 2006 Al-Nuaimi (28) synthesized 2-amino 6-sulfonamide

benzothiazole derivatives using 4-aminobenzsulfonamide derivatives

with ammonium thiocyanate in a suitable solvent by the first step. The

second step included treatment of the product with bromine solution in

glacial acid.


- ۱۰ -

Then, another work prepared 2-( substituted imidazolylamino)

benzothiazoles from treatment of phenyl thioureide-3H-imidazole -4-

carboxylic acid derivatives with bromine in chloroform (29) .

benzothiazole amino -2 Some reaction of 3-2-1 Drapkina (30) synthesized azo compounds by reacting diazonium salt

for 2-aminobenzothiazole with b-naphthol or catechol in the presence of

sodium carbonate.

Also, Saleh (31) synthesized azo compounds by using 2-hydroxy

naphthaoic acid .


- ۱۱ -

Schely et,al. (32) synthesized schiff base by reacting 2-

aminobenzothiazole derivatives with salicyladehyde derivatives for

preparation of disubstituted salcylidine-N-(2-subsituted benzothiazole

amine).

Livshits (33) synthesized other schiff base by reaction 2-

aminobenzothiazole with N,N-disubstituted formamido substituted in the

presence of phosphorus oxychloride to form N,N-disubstituted

formamido-N-(2-benzothiazole amine).

Also Al-Jallo and Muniem (34) synthesized 6-phenyl-2-pyrimido [2,1-

b] substituted benzothiazo-2-one by the reaction of substituted 2-

aminobenzothiazole with ethyl phenyl propiolate.


- ۱۲ -

Also the reaction of substituted 2-aminobenzothiazole with acid

chloride produced N-(2-benzothiazolyl) substituted amide (35).

And the reaction of 2-aminobenzothiazole with isothiocyante carbonyl

ethoxy form N-ethoxy carbonyl-N-(2-benzothiazolyl) thiourea and ethyl-

N-(2-benzothiazolyl) carbamate (36).

N-( 2-substituted benzothiazolyl )-2-chloro-3-nicotinamid can be

prepared by the reaction of substituted 2-aminobenzothiazole with 2-

chloro 3-nicotinic acid chloride using benzene as a solvent. The product

reacted with potassium hydroxide in the presence of DMSO as a

solvent (37) to gave compound (1).


- ۱۳ -

but by using of DMF as solvent gave compound (2).

The reaction of substituted 2-aminobenzothiazole with hydrazine

formed substituted 2-hydrazino benzothiazole (38) .

It was found that the reaction of formic acid with hydrazino-4-methyl

benzothiazole produces 4-methyl-(3,4)1,2,4-triazole (2,3)benzothiazole

and when thionyl chloride is added at 550 C, 2-chloro-4-methyl

benzothiazole is yield (39).


- ۱٤ -

The reaction of 2-alkyl amino benzothiazole with Epoxid chlorohydrin

lead to the formation of different structures (40) .

The reaction of 2-aminobenzothiazole derivatives with adipoyl

chloride leads to the formation of compound (I) (41).


- ۱٥ -

The reaction of 6-fluoro -7-chloro 2-aminobenzothiazol with benzoic

acid in presence of pyridine form 2- ( amino phenyl amido) 6-fluoro -7-

chloro benzothiazole (42).

Substituted 2-aminobenzothiazoles were oxidatively ring-opened to

the corresponding bis (2-aminophenyl) disulfides in aqueous KOH then

cyclization to benzothiazole by condensation with benzaldehydes in

refluxing toluene containing triphenylphosphine and catalytic p-

toluenesulfonic acid (43) .

Several 2-aminobenzothiazoles carrying a benzenesulfonamide moiety

at position 2 of the heterocyclic nucleus were synthesized and tested as

antimicrobial agents by heating of substituted 2-aminobenzothiazole with

benzensulfonylchlorides in pyridine for several hours.(44)


- ۱٦ -

erivativesaminobenzothiazole d-tivity of 2cBiological a 4-2-1

The compounds encompassing benzothiazole or 2-aminobenzothiazole

moiety are of great interest and have been extensively used in

pharmaceutical chemistry and agriculture division as antimicrobial (45-47),

antifungal activity (48,49), antibacterial activity (50-55),antitumor activity (56-

63), anti-inflammatory (64,65), antitubercular (66), antiallergic activity (67).

Triazole 3 -1

Triazoles are five member heterocyclic compounds having three

nitrogen atoms. They are on two types:

1,2,4-Triazole and their derivatives constitute an important class of

organic compounds with diverse agricultural, industrial and biological

activities (68-70) . Also 1,2,4-triazole act as legend for complex synthesis

reaction that has considerable attention in recent years.(71)

erivativestriazole dof ctivity Biological a1 -3-1 Various triazoles are found to be linked with diverse pharmacological

activities as, antimicrobial (72-77) , antibacterial (78-80) , antitubercular (81,82),

Anticonvulsant (83,84) , antitumor (85) and plant growth regulating(89) .


- ۱۷ -

Synthesis of some biologically active compounds 2 -3-1

.azole nucleuscontaining tri

Shishoo et a l (87) in 1981 synthesized 1,2,4-triazolo- [3,2-e] thieno

[4,3-c]pyrimidines by refluxing 4-hydrazino-[2,3-d] thieno

pyrimidines with triethyl orthoformate.

Kangani et.al. (88) in 1996 synthesized 3-aryl-4-oxo 5-methyl- 1,2,4-

triazolo- [4,3-a] pyrimido [1,2] anthraquinones by treating 3-aryl-2-

hydrazino 4-oxo-pyrimido [5,6-] anthraquinones with acetic anhydride.

Deshmukh (89) in 1998 synthesized 7-methyl [1,2,4] triazolo-

[1,2-] benzothiazole by condensing 2-hydrazino-7-

methylbenzothiazole with formic acid.


- ۱۸ -

Bentiss et al (90) in 2000 reported the reaction of aromatic

nitriles with hydrazine dihydrochloride in the presence of hydrazine

hydrate in ethylene glycol under microwave irradiation, give 3,5-

disubstituted 4-amino-1,2,4-triazoles.

Ciesielski et al (91) in 2005 described a novel copper-

oxidative heterocyclization of hydrazones yielding the

corresponding 1,2,4-triazoles.


- ۱۹ -

Kapratwar et al (92) in 2005 synthesized 3’-hydroxy and 3’-mercapto-

1,2,4-triazolo [4’,5’:1,5] -1,2,4-triazolo [3,4-b] benzothiazole by

heating 5-hydrazino-1,2,4-triazolo [3,4-b] benzothiazole

independently with urea and carbon disulphide in the presence of

alkali.

Toliwal (93) reported synthesis (5-alkyl-[1,2,4]-triazole-

3-mercapto)-4-Phenyl from Phenyl thiosemicarbazide in the

presence of KOH/C2H5OH.


- ۲۰ -

Randhavane, et. al (94) reported the synthesis of triazole

derivative from aryl thiosemicarbazide and using ultra sound irradiation

method.

Metwally, et. al (95) in 2006 synthesized 3-subsituted arylamino 5-

alkyl-1,2,4- triazoles by refluxing the acidhydrazides and substituted

aryl-S-methylisothiouronium iodides in pyridine.

Mali, et. al (96) in 2009 synthesized 3-(3'-pyridyl)-1, 2, 4-

triazole-5-thiol in moderate to higher yields by refluxed of

potassium 3-pyridyldithiocarbazate salt with ammonia for 4-6 hrs.


- ۲۱ -

Reaction of 1,2,4 triazole3 -3-1

K. Zamani et.al (97) in 2003 prepared 3-mercaptomethyl-4-(4-

methylphenyl)-5- ( isomeric pyridyl )-1,2,4-triazoles from reaction

suitable substitute- triazole-3-thiol with corresponding alkyl halide

in ethanolic alkali.

D. Sunil et. al (98) in 2009 Synthesis of 3-substituted-5-(3-substituted-

1H-pyrazol-4-yl) [1,2,4] triazole [3,4-b] [1,3,4] thiadiazole from

reaction 3-substituted-4-amino-5-mercapto-1,2,4-triazoles and 3-

substituted-4-carboxypyrazoles.

Jian-yu Jin (99) in 2007 synthesized 6-aryl-5-(D-galactopentitol-1-yl)-

7H-1,2,4-triazolo [3,4-b] [1,3,4] thiadiazine (1) and 4-

(arylmethylidene) amino - 5 - ( D-galactopentitol-1-yl ) - 3 -mercapto-

1H-1,2,4-triazoles (2) from 4-amino-3-(D-galactopentitol-1-yl)-5-


- ۲۲ -

mercapto-1,2,4-triazole.

Mohamed A. Al-Omar (100) in 2010 using microwave irradiation to

synthesized 2-arylamino-5-(2-thiophenyl)-1,2,4-triazolo[3,4-b] [1,3,4]

thiadiazoles from the appropriate N,N'-disubstituted thiourea .


- ۲۳ -

iazoleadOx 4 -1

Oxadiazole is considered to be derived from furan by replacement of

two methane (-CH=) group by two pyridine type nitrogen (-N=). There

are four possible isomers of oxadiazole (1, 2, 3, 4) depending on the

position of nitrogen atom in the ring (101).

xadiazolesoThe chemistry of 1 -4-1

Oxadiazole is a very weak base due to the inductive effect of the extra

heteroatom (102). The replacement of two -CH= groups in furan by two

pyridine type nitrogen (-N=) reduces aromaticity of resulting oxadiazole

ring to such an extent that the oxadiazole ring exhibit character of

conjugated diene. The electrophillic substitutions in oxadiazole ring are

extremely difficult at the carbon atom because of the relatively low

electron density on the carbon atom which can be attributed to electron

withdrawal effect of the pyridine type nitrogen atom. However the

attack of electrophiles occurs at nitrogen, if oxadiazole ring is substituted

with electron-releasing groups.

Oxadiazole ring is generally resistant to nucleophilic attack. Halogen-

substituted oxadiazole, however, undergo nucleophilic substitution with

replacement of halogen atom by nucleophiles (103).


- ۲٤ -

xadiazoleso-Synthesis of 1,3,42 -4-1

1,3,4-oxadiazoles show various biological activities and have been

synthesized from different compounds. Many reaction were followed for

the synthesis of the ring some of them :-

M.C Hosur (104) reported synthesis of 2-mercapto-5-aryl-1, 3, 4-

oxadiazole from the properly substituted acid hydrazide in presence

of CS2/KOH. This method is very popular since ease in workup and

high yields are consistently observed. However, long reaction time is

a limiting factor. Number of examples are cited in literature

employing this methodology for synthesis of 1, 3, 4-oxadiazole

thione / thiol derivatives (105-108).

M.A. Elborai et al (109) reported synthesis of 2-amino-5-(2’-thienyl)-

1, 3, 4-oxadiazole by the condensation of 2-thienyl hydrazide with

cyanogen bromide CNBr. It is a convenient method of synthesis of

2-amino-1, 3, 4-oxadiazole because of shorter reaction time. More

reports are cited in literature, which employed this method to obtain the

1, 3, 4- amines.(110,111)

.


- ۲٥ -

H. Singh and coworkers (112) reported synthesis of 2-alkyl - 1, 3, 4-

oxadiazoline-5- ones from acylurea using bromine in NaOH .

D. H. Boschelli et al (113) synthesized 2-substituted aryl 1, 3, 4-

oxadizoline 2-one from substituted aryl acid hydrazide using

1, 1’- carbonyldiimidazole (CDI) in triethylamine (TEA) in presence of

tetrahydrofuran (THF) as solvent.

Condensation of various alkyl hydrazides with substituted aromatic

carboxylic acids in presence of POCl3 yielded respective 2-alkyl-5-

aryl -1, 3, 4- oxadiazoles has been accounted in various

literatures (114-117).


- ۲٦ -

N. Sikder et al (118) synthesized long chain bis-1,3,4-oxadiazoles

from the cyclization of bis-3,5-dinitrobezoyl malonic or adipic

dihydrazide in presence of POCl3 as dehydrating agent.

S. P. Singh and his group (119) reported the synthesis of 1, 3, 4-

oxadiazole through a one pot procedure involving the reaction of

acylhydrazide with aldehydes followed by cyclization using

chloramine T(r-CH3-C6H4SO2N-CINa+.3H2O) as an oxidizing agent.

The 5-(1-r-chorophenyl- 5-methyl-1, 2, 3 - triazol-4-yl)-2-

phenylamino-(1, 3, 4)- oxadiazole was synthesized from

corresponding thiosemacarbazide in presence of mercuric acetate as

an oxidizing agent (120) .


- ۲۷ -

The schiff’s bases of 2-phenyl 5- alkyl-3-benzyl semicarbazidoindole

on oxidative cyclodehydrogenation with ferric chloride in acetic acid

gave 2 [substituted-3- aminoindole -(5’-phenyl)]-1,3,4-oxadiazolyl (121)

The schiff’s bases can accrue for substituted

thiosemicarbazide by iodine at room temperature in presence of alkali to

yield cyclized product (122).

O. Parekh and Colleagues (123) employed hypervalent

iodine (IBD) for oxidation of schiff’s base to obtain 2, 5-

disubstituted 1, 3, 4-oxadiazole .

M Kidwai and coworkers (124) reported synthesis of disubstituted

1,3, 4-oxadiazole derivatives using mixture of hydrazide, substituted

aromatic acids and thionyl chloride under microwave irradiation

(MWI) within 6-7 min.


- ۲۸ -

Similarly, Khalid M. Khan and his group (125) reported the

microwave assisted synthesis of such dialkyl-1, 3, 4-oxadiazoles

from acid hydrazide using different carboxylic acids in the presence

of phosphorus oxychloride to afford the desired products .

Sherman (126) reported synthesis of 5-aryl-1,3,4-oxadiazole-2(3H)-

thione, by the reaction of thiophosgene and aryl hydrazides.


- ۲۹ -

xadiazoleo-Reactions of 1, 3, 4 3-4-1

The substituted and unsubstituted 1, 3, 4-oxadiazole undergoes

varieties of organic reactions. Due to very low p-electron density on the

carbon atom, the attack of electrophile preferentially occurs at the

position 3 with the formation of 1, 3, 4 -oxadiazolium salts.

However, the alkylation of 2-phenyl 5-methoxy-1, 3, 4- oxadiazole

with alkyl halides produces oxadiazolium salt which undergo

O-dealkylation to provide 2-phenyl-4-alkyl–oxadiazolin-5-ones.

The reaction of alkyl or aryl- 1, 3, 4-oxadiazoles with nucleophile

involve the cleavage of 1, 3, 4-oxadiazole ring to formation of hydrazine

derivative which may recyclize to form 1, 2, 4-triazoles . (127)


- ۳۰ -

2-thiol and 2-thione [ 1,3,4 oxadiazole ] be in toutomeric form , M.

Kopar et. al. (128) study the electronic structures and thiol-thione

tautomeric equilibrium of heterocyclic thione derivatives from the

reaction below.

Compound ( 1 ) prove the thiol form and the compound ( 2 ) prove the

thione form.

of 1,3,4 oxadiazole Biological activity 4-4-1

The capacity of 1, 3, 4-oxadiazole nucleus to undergo variety of

chemical reaction have made it medicinal backbone on which number of

potential molecules can be constructed (129-133). Literature survey reveals

that particularly 1, 3, 4-oxadiazole derivatives exhibit wide range of

biological activities including anticancer (134), anti-inflammatory (135),

fungicidal (136), herbicidal (137), pesticidal, analgesic (138) ,

anticonvulsant (139,140), anti-HIV (141), antibacterial and plant growth

regulator activities (142). A few therapeutic agents were synthesized

possessing of 1, 3, 4-oxadiazole nucleus are mentioned below:-.


- ۳۱ -

diazoleahiT5 -1 Thiadiazole contains the five membered diunsaturated ring structure

composed of two nitrogen atoms and one sulfur atom. There are four

isomeric types: 1,2,3-thiadiazole (1); 1,3,4-thiadiazole (2); 1,2,4-

thiadiazole (3) and 1,2,5-thiadiazole (4) (143) .

A references show that more studies have been carried out on the

1,3,4-thiadiazoles. Members of this ring system have found their way into

such diverse applications as pharmaceuticals, oxidation Inhibitors, dyes ,

metal complexing agents, and corrosion inhibitors (144-147). It was reported

that 1,3,4-thiadiazoles exhibit various biological activities possibly due to

the presence of the –N=C-S moiety that acts as two-electron donor

system. (148)

nuclei adiazoleshit-1,3,4of Synthesis 1-5-1

Frund and Meinecke (149) have shown that thiosemicarbazide cyclizes

directly to 2-amino-5-methyl-1, 3, 4-thiadiazole with acetyl chloride.

This simple route for 2-amino 5-substituted-1, 3, 4-thiadiazole seems

to be quite general.


- ۳۲ -

Hoggarth (150) has prepared a number of 2-benzoylamino-5-aryl-1,3,4-

thiadiazole from 1,4- dibenzoylthiosemicarbazide using phosphoric

acid as the dehydrating agents, in an example of smooth cyclization

and high yield by phosphoric acid.

A useful preparative method for 2-amino-5-mercapto-1, 3, 4-

thiadiazole was developed by Guha(151). When thiosemicarbazide

potassium salt of thiosemicarbazide-4-dithiocarboxylic acid is

formed, then heating to 140°causes cyclization to the salt of 2-amino-

5-mercapto-1, 3, 4-thiadiazole.

Young and Eyre (152) reported that benzalthiosemicarbazones could be

oxidatively cyclize to form 2-amino-5-phenyl-1, 3, 4-thiadiazole by

ferric chloride.

Guha and R.Choudhary using formic acid with heating to converted

1- phenylthiocarbazide to 2-phenylhydrazino-1, 3, 4-thiadiazole (153).


- ۳۳ -

The formation of 2,5-dimercapto- 1, 3, 4-thiadiazole also form by

the action of carbon disulphide on hydrazine in basic medium(154-155).

When 3-acyldithiocarbazic esters are treated with acids, they cyclize to

form substituted 1,3,4-thiadiazoles (156, 157). This is a quite general

reaction. Both benzyl and methyl 3-acyldithiocarbazates have been

employed.

Thioacylhydrazines may often serves as starting materials for the

preparation of 1, 3, 4-thiadiazole, if it was heated with ethyl

orthoformate, the 2-phenyl-1, 3, 4-thiadiazole was formed.(158-159)


- ۳٤ -

Thiobenzhydrazide is smoothly converted to 2-phenyl-1, 3, 4-

thiadiazole by the reaction with formic acid.(160) Thiobenzhydrazide is

reported by Holmberg (161) to form 2, 5-diphenyl-1,3,4-thiadiazole in

small amount when warmed in benzene.

Stolle found that benzoylhydrazine (162) or N,N’-dibenzoylhydraz-

ines (163) react with phosphorus pentasulfide to form 2, 5-diphenyl-1, 3,

4- thiadiazole.

Fromm et.al (164) found that treated of bithiourea with 3% hydrogen

peroxide was cyclized to 2, 5-diamino-1, 3, 4-Thiadiazole.


- ۳٥ -

Wright, W. B. et. al. (165) reported synthesis of 5-(3-chlorobenzo

thiophen-2-yl) - 1, 3, 4-thiadiazol-2-yl amine by the condensation

of 3-chlorobenzo[b]thiophene-2-carboxylic acid with thiosemicarba-

zide using phosphorous oxychloride as condensing agent (166).

M. S. Yar et. al.(167) synthesized compounds, 2-( substituted

phenyl) amino-5- (4-pyridyl)-1,3,4-thiadiazole by reaction between

isoniazid and various substituted isothiocyanates.

A. Hussain et. al.(168) prepared 3-chloro-2-chlorocarbonylbenzo

thiophene (II) from cinnamic acid(I) which converted into the acid

hydrazide by react with hydrazine hydrate then reacted with

formic acid to give the N-formyl acid hydrazide(III) which upon

refluxing with phosphorous pentasulphide in xylene gave (3-

chloro benzothiophene 2-yl) 1,3,4-thiadiazol(IV).


- ۳٦ -

M. Kidwai prepared 5-substituted-2-amino-1,3,4-thiadiazoles within

40–80 s with improved yield using acidic alumina, in microwave

irradiation.(169)

K. Sancak et. al (170) prepared 5-substituted 2-amino-1,3,4-thiadiazoles

compound from nitrile compounds.

W.Dehaen et. al.(171) prepared 1,3,4-thiadiazoles analogous by 1,3-

dipolar cycloaddition reaction of diazo compounds onto the C=S

double bond.


- ۳۷ -

V. Polshettiwar. et. al.(172) prepared 1,3,4-thiadiazoles by

condensation of acid hydrazide and triethoxy phnyl methan in

solvent free reaction under MW irradiation using P4S10 as catalyst,

this method find useful application in drug discovery.

hiadiazole t-1,3,4amino -2 Some Reaction of 2-5-1

The substituted and unsubstituted 2-amino 1, 3, 4-thiadiazole

undergoes varieties of organic reactions:-

The 1, 3, 4-thiadiazole ring is rather susceptible to attack by strong

neucleophile. Thus this compound is stable to acids but is readily cleaved

by bases (173) . Goerdeler and Galinke(174) showed that 2-amino- and 2-

methylamino -1, 3, 4- thiadiazole can be rearranged to 1, 2, 4-triazoline-

3(2H)-thiones.


- ۳۸ -

2-methyl-5-chloro-1,3,4-thiadiazole reacted with a large excess of

hydrazine hydrate on heating to give 5- methyl- 4-amino-1,2,4-triazolin-

3-thiones (175) .

Similar rearrangements can be affected by acids. When 1-benzyl-1-(1,

3, 4-thiadiazole-2-yl) hydrazine was refluxed with dilute hydrochloric

acid, the 4-amino-2-benzyl-(1,2,4-triazoline)-3-thione was formed in

quantitative yield .

Ban and co-workers (176) synthesized a number of compounds by

reaction of 5-subsituted-2-amino thiadiazole with a-bromo ketone .

Y. Song et. al.(177) synthesized 2- benzyl amine (1,3,4-thiadiazole ) in

good yields by treatment appropriate functionalized aromatic aldehyde


- ۳۹ -

with 2-amino thiadiazole in acidic conditions followed by sodium

borohydride.

A. A. Aly (178) et. al. synthesized N-di(methylthio) methylene-5-phnyl-

1,3,4-thiadiazol-2-yl-amine by the reaction of 5-phnyl -2-aminothiadiazol

derivative with methyl halide in the presence of CS2 .

M. Nath et. al. (179) report schiff bases derived from 2-amino-5-aryl-

l,3,4-thiadiazoles by reaction of amino group in 2-aminothiadiazole

derivatives with aldehyde or ketone.

H. Maradiya (180) reported the diazotization and coupling reaction for

2-amino-5-mercapto-1,3,4-thiadiazole to form azo dye.


- ٤۰ -

N. A. Salih (181) reported the synthesis of 2-amino-5-hydrazino-1,3,4-

thiadiazole. The thiol group of 2-amino-5-mercapto-1,3,4-thiadiazole

converted into hydrazino derivative by heating under reflux with an

ethanolic solution of hydrazine hydrate.

hiadiazole t-Pharmacological properties of 1,3,4 3-5-1erivativesd

The resistance towards available drugs is rapidly becoming a major

worldwide problem. The need to design new compounds to deal with this

resistance has become one of the most important areas of research today.

Thiadiazole is a versatile moiety that exhibits a wide variety of biological

activities. The literature review showed that the thiadiazole nuclei have

antimicrobial (196-201), anti-inflammatory (188-190), anticancer (191-194),

analgesic (195), anticonvulsant (202,203), antidepressant, antioxidant (204,205),

and anti-leishmanial activities(206,207) , antitubereular (208-209). Some 1,3,4-

thiadiazole derivatives possess central nervous system (CNS) depressant

activity (182-187).

Chapter two Experimental part

٤۱

Identification and characterization 1-2 The synthesized compounds were identified and characterized by

following methods:

* Melting point determination .

* Thin layer chromatography(TLC).

* Fourier Transform Infrared (FT-IR).

* Nuclear magnetic resonance spectroscopy (NMR).

* Ultra- violet spectroscopy (U.V).

Melting point determination: The melting point of an organic

compound was determined by melting point tube (capillary tube method).

The determination of melting point is the most important and easy way of

differentiating this physical constant of one compound from other.

Thin layer chromatography (TLC) : TLC is an important method for

synthetic chemistry to infer the formation of compound based on the Rf

value since different compound will have different Rf values. It also helps

in confirming the progress of the reaction.

Fourier Transform Infrared (FT-IR) : is the most important tools for

determining the various functional group and the possible chemical

structure. The important advantage of FT-IR over other technique is that

it gives fingerprints (3300-650 cm-1 ) information about the structure

(functional group, bonding with each other) of molecules easily, no two

compounds have identical fingerprint region. This technique is based

upon the molecular vibration of the compound such that each and every

bond will vibrate at the different frequency. FTIR spectra were recorded


٤۲

in KBr powder on a Jasco V410 FTIR spectrometer by diffuse

reflectance technique.

Nuclear magnetic resonance spectroscopy: The introduction between

matter and electromagnetic forces can be observed by subjecting a

substance simultaneously to two magnetic forces, one stationary and

other varying at some radio frequency. At a particular combination of

fields, energy is observed by the sample and absorption can be observed

as a change in single developed by a radio frequency detector and

amplifier. This energy of absorption can be related to a magnetic dipolar

nature of a spinning nucleus. This technique is known as Nuclear

Magnetic Resonance. This technique is useful in assuming the structure

of the molecule. 1H- NMR spectra were measured in CDCl3 and DMSO

on a Bruker Ultraspec 500MHz/ AMX400MHz spectrometer.

Ultra violet spectra were recorded using Shimadzu ( UV-Vis)-160

recording spectrophotometer using ethanol as a solvent in Baghdad

university college of science.


٤۳

es paniomSupplied chemicals c 2-2

All chemical used were of the highest purity available, the employed

chemicals and there supplier companies were listed in Table (1).

Table (1 ) : Employed chemicals and their supplier companies

Company Chemicals

Fluka Absolute ethanol

Fluka Acetone

BDH Ammonium thiocyante

BDH r-aminobenzoic acid

BDH 3- amino phenol

BDH Bromine (Br2)

Fluka 3-bromo phenol

BDH Benzene

BDH Chloroform

Fluka 4-Chloro 2- nitro aniline

BDH Carbon tetrachloride

Riedel-dehean m- cresol

Fluka 2,6-dimethyl phenol

Riedel-Dehaen 2,4- dinitro aniline

BDH Diethyl ether

BDH Dimethyl formamide (DMF)

BDH Dioxane


٤٤

Company Chemicals

Fluka 3- Ethyl phenol

BDH Ethyl acetate

Fluka Ethyl 2- bromo propionate

BDH Glacial acetic acid

Riedel-dehean Cyclohexane

BDH Hydrochloric acid

BDH 2-Methoxy phenol

BDH Methanol

BDH r-Nitro aniline

BDH Phenol

Fluka Potassium carbonate anhydrous

Fluka Petroleum ether (60-80)

Fluka Semicarbazide

BDH Sodium nitrate

BDH Sodium hydroxide

BDH sulfuric acid

BDH Thiosemicarbazide

BDH r-Toluidine


٤٥

212-210 (I) erivativesbenzothiazole d amino-ration of 2Prepa 3-2

In a 250 ml round bottomed flask equipped with a magnetic bar stirrer

and dropping funnel, a solution of bromine (1.2 ml) in glacial acetic acid

(75 ml) was allowed to run through the dropping funnel drop wise during

30 min. to a mixture of r-substituted aromatic amine (0.03 mole) and

ammonium thiocyanate (0.1 mole) in 150 ml glacial acetic acid with

stirring. The mixture was stirred for 1 hr., then diluted with water and

neutralized with solid sodium hydroxide. The precipitated substance was

collected and recrystallized from a suitable solvent to obtain 2-amino

benzothiazole derivatives (1-5) . The physical properties and starting

material of the synthesized compounds are given in Table ( 2 ).

2-4- Synthesis of azo compounds ( II ) 213

2-4-1 Synthesis of substituted benzothiazolyl-2-diazonium chloride

A solution of 2-aminobenzothiazole derivatives (0.054 mole) in

H2SO4 (12ml) was cooled to 00 C. To this solution was added a cold

solution of sodium nitrite (0.۰54 mole ) drop wise with constant stirring.

When the addition was complete, the resultant reaction mixture was left

in ice-chest for 1hr. It was used as such for further reaction.


٤٦

substituted benzothiazolyl) -azo-(2-rSynthesis of 2-4-2 sodiophenoxides

The ice cold solution of diazonium chloride (prepared in 2-4-1) was

added to the cold solution of substituted phenol (0.054mole) in dilute

NaOH drop wise with constant shaking. A dark dye resulted which

darkened on adding more alkaline solution of phenol. When the addition

was complete, the resultant reaction mixture was vigorously stirred and

filtered off. It was kept for further used.

2-4-3 Synthesis of r-(2-azo-substituted benzothiazolyl) substituted phenols

A saturated solution of the last compound in water was neutralized

with concentrate HCl. A solid separated out which was allowed to stand

at room temperature for 30 min. It was filtered off and washed with

water. The precipitated substance was collected and recrystallized from

redistilled ethanol to give compounds ( 6-45 ). The physical properties of

all synthesized compounds are given in Table ( 3 ).


٤۷

۲-5 Synthesis of ethyl-{r-(2-azo-substituted benzothiazolyl)substituted phenoxy }2-propionate 214(III ).

To a solution of r-(2-azo-substituted benzothiazolyl) substituted

phenols (0.5 mole) in dry acetone (150 mL), ethyl 2-bromo propionate

(0.60 mole) were added followed by addition of anhydrous K2CO3 (1.0

mole). After reflux for 20-24 hrs. the reaction mixture was filtered and the

solvent was removed under reduce pressure then poured into ice water,

the mixture was standing for 3 days then the precipitate was filtered

washed with water to give ester ( 46-62 ) that don’t need any farther

purification. The physical properties of all synthesized compounds are

given in Table (4).

2-6- Synthesis of five member heterocyclic derivatives.

and (IV)thiosemicarbazidesubstituted -N is of Synthes 1-6-2 ( V ) semicarbazide substituted-N

Ethyl{r-(2-azo-substituted benzothiazolyl ) substituted phenoxy}

2-propionate (0.01 mol), thiosemicarbazide (0.01 mol) or (0.01 mol)

semicarbazide and absolute alcohol (50 mL) were put in round bottom


٤۸

flask. A condenser with calcium guard tube was attached to the flask and

the mixture was refluxed for 4-5 hrs. on water bath the reaction

progression was monitored by thin layer chromatography (TLC). The

mixture was concentrated, cooled and poured in crushed ice. It was kept

for 3-4 hrs. at room temperature and the solid was filtered, dried and

recrystallized from methanol. The physical properties of the synthesized

compounds are given in table (5) and table (6).

2-6-2 General procedure for preparation of 5-{substituted } 2-amino (1,3,4) oxadiazole ( VI ) 215.

Mixture of 2-propanyl {r-(2-azo-substituted benzothiazolyl)

substituted phenoxy} N-semicarbazide ( 0.01 M) and concentrated

sulphuric acid (10 ml) was refluxed for half and hour then kept at room

temperature for 24 hrs., the content was poured into cold water and

neutralized with diluted sodium carbonate solution. The product was

isolated as syrup . The physical properties of the synthesized compounds

are given in table (7).


٤۹

2-6-3 General procedure for preparation of 5-{substituted} 1,2,4 triazole 3-thione (VII)216.

The 2- propanyl {r-(2-azo-substituted benzothiazolyl) substituted

phenoxy} N-thiosemicarbazide (3 mmol) were added portion wise to 25

mL of 2N sodium hydroxide solution. The reaction mixture was refluxed

for 3 hrs., the completion of the reaction was checked by TLC. The

mixture was allowed to cool to room temperature, and it was acidified

with 2N hydrochloric acid. The precipitated was filtered, washed

thoroughly with water, dried and recrystallized from ethanol/water

(80/20). The physical properties of the synthesized compounds are given

in table (8).

2-6-4 General procedures for preparation of 2-amino 5- ( substituted ) 1-3-4 thiadiazole ( VIII )217

The 2- propanyl {r-(2-azo-substituted benzothiazolyl) substituted

phenoxy } N-thiosemicarbazide (0.6 mmol) were added portion wise to

25mL of conc. sulfuric acid at 0 0 C with continuous stirring. The reaction

mixture was stirred further for 3 hrs. at room temperature. Poured into an

ice-water mixture to precipitate a crude solid. The physical properties of

the synthesized compounds are given in table (9).


٥۰

Table ( 2 ) : Starting material and conditions for prepared

of 2-amino benzothiazole derivatives (1-5).

Pro. No.

Recrystalization

Colour product

Structure of

product

Yield

%

Structure of

Starting material

1

Ethyl acetate

Dark

yellow

90

2

Ethyl acetate

Yellow

85

3

Benzene

White

90

4

Benzene

Yellow

84

5

Benzene

Yellow

90


٥۱

Table:(3) Conditions for the prepared derivatives of r-(2-azo- substituted benzothiazolyl) substituted phenols (6-45).

Recrystalization

Colour Product

Structure of product

Yield %

Com. No.

Ethanol

Orange

60

6

Ethanol

Yellow

65

7

Ethanol

Red

40

8

Ethanol

Red

45

۹

Ethanol

Red

50

۱۰

Ethanol

Dark

yellow

65

11

Ethanol

yellow

50

12

Ethanol

Brown

50

13


٥۲

Recrystalization

Colour Product


Yield %

Com. No.

Ethanol

Orange

70

14

Ethanol

Orange

30

15

Ethanol

Orange

30

۱٦

Ethanol

Red

70

17

Ethanol

Brown

60

18

Ethanol

Orange

70

19

Ethanol

Yellow Orange

40

20

Ethanol

Orange

90

21


٥۳

Recrystalization

Colour Product


Yield %

Com. No.

-

Browne

60

22

-

Browne

30

23

-

Yellow

45

۲٤

-

Orange

50

25

-

Orange

73

۲٦

-

Yellow orange

50

27

-

Browne red

30

28

-

Browne

65

29


٥٤

Recrystalization

Colour Product


Yield %

Com. No.

-

Orange

۷۰

30

-

Red

40

31

Ethanol

Red

۳۰

32

-

Brown

56

33

Ethanol

Dark red

70

34

-

Brown

85

35

Ethanol

Red

70

36

Ethanol

Brown

45

37


٥٥

Recrystalization

Colour product


Yield %

Com. No.

Ethanol

yellow

٥۰

38

-

Brown

۷۳

39

Ethanol

yellow

٥٥

40

-

Brown

٦۹

41

-

Brown

٥٤

42

-

Brown

80

43

-

Brown

۸۷

44

-

Brown

٦٥

45


٥٦

Table:(4) Conditions for the prepared derivatives of ethyl {r- (2- azo-substituted benzothiazolyl) substituted phenoxy } 2- propionate (46-62).

Recrystali

zation

Colour product

Structure of

product

Yield

%

Com. No.

-

Brown

60

٤٦

-

Orange

۸۰

47

-

Dark

orange

50

48

-

Dark green

66

49

-

Brown

٦٥

50

-

Yellow

٦۰

51


٥۷

Recrystalization

Colour product

Structure of

product

Yield

%

Com.

No.

-

Yellow orange

۸۰

52

-

Orange

۷٥

53

-

Dark brown

۸۳

54

-

Orange

٦۰

55

-

Brown

۹۰

56

-

Yellow

۷۰

57


٥۸

Recrystali

zation

Colour product

Structure of

product

Yield

%

Com. No.

-

Yellow

۸٥

58

-

Brown

۹٤

59

-

Dark red

۷٥

60

-

Orange

٥۰

61

-

Orange

٦٥

62


٥۹

Table: (5)Conditions for prepared derivatives of 2-propanyl {r-(2-azo-substituted benzothiazolyl) substituted phenoxy }

N-thiosemicarbazide (63-70).

Recrystalization

Colour product


Yield %

Com. No.

Methanol

Yellow

65

63

Methanol

Brown

55

64

Methanol

Brown

۷۸

65

Methanol

Yellow

٦۰

66

Methanol

Red

٦٥

67

Methanol

Orange

80

68


٦۰

Recrystalization

Colour product


Yield %

Com. No.

Methanol

Browne

70

٦۹

Methanol

Browne

۷٥

۷۰


٦۱

Table:(6) Conditions for prepared derivatives of 2 -propanyl {r-(2- azo-substituted benzothiazolyl) substituted phenoxy}

N-semicarbazide (71-78).

Recrystalization

Colour product


Yield %

Com. No.

-

Yellow orange

65

71

-

Dark red

50

72

-

Brown

۷٥

73

-

Orange

٦۰

74

-

Browne

٦٥

75

-

Yellow

80

76


٦۲

Recrystalization

Colour product


Yield %

Com. No.

-

Browne

75

۷۷

-

Browne

۸٥

۷۸


٦۳

Table: (7)Conditions for prepared derivatives of ٥ -substituted 2- amino 1,3,4-oxadiazole (79-86).

Recrystalization

Colour product


Yield %

Com. No.

-

Browne

٦٥

۷۹

-

Yellow

۷۰

۸۰

-

Browne

۸٥

۸۱

-

Orange

٥٥

۸۲

-

Browne

٦٥

۸۳

-

Browne

۸۰

۸٤


٦٤

Recrystalization

Colour product


Yield %

Com. No.

-

Browne

۷۳

۸٥

-

Browne

۸۸

۸٦


٦٥

Table:(8)Conditions for prepared derivatives of 5-subsituted 1,2,4 triazole 3-thione (87-94).

Recrystalization

Colour product


Yield %

Com. No.

-

Brown

۷۰

۸۷

Ethanol /water

Orange

٦٦

۸۸

-

Orange

۷٥

۸۹

-

Brown

۸۰

۹۰

-

Brown

۸٥

۹۱

-

Brown

60

۹۲


٦٦

Recrystalization

Colour product


Yield %

Com. No.

-

Brown

65

۹۳

-

Brown

٦۳

۹٤


٦۷

Table: (9)Conditions for the prepared derivatives of 2-amino 5- substituted 1,3,4-thiadiazole (95-102).

Recrystalization

Colour product


Yield %

Com. No.

-

Yellow

٥۰

۹٥

-

Dark violate

۷۰

۹٦

-

Yellow

63

۹۷

-

Brown

۷٥

۹۸

-

Brown

60

۹۹

-

Brown

77

۱۰۰


٦۸

Recrystalization

Colour product


Yield %

Com. No.

-

Brown

٥۰

۱۰۱

-

Brown

۷۷

۱۰۲

Chapter three Results and Discussion

٦۹

During the last decades, chemistry, synthesis and transformation of

five member heterocyclic compound has received considerable attention

and importance due to their remarkable and wide variety of application.

The work presented in the current thesis is concerned with the synthesis

and characterization of some novel 2-aminobenzothiazole bearing 5-

subsituted-(1,3,4-oxadiazole, 1, 3,4 thiadiazole and 1,2,4-triazole) moiety.

The moiety represented by the structure ( 1 ).

3-1 Part One /

aminobenzothiazole-2 ynthesis of S1 -1-3

Includes preparation of benzothiazole derivatives ( 1-5 ) by reaction of

r-substituted aniline with ammonium thiocyanate (NH4SCN) in the

presence of bromine (Br2) as catalyst . As shown below :


۷۰

The mechanism of the reaction involves a nuclephilic addition as shown

below :-

Scheme (4): Mechanism of preparation 2-amino benzothiazole

The compounds (1-5) which synthesized, recrystalyzed from ethyl

acetate or benzene, the precipitate was filtered and dried.

Structures confirmation of the prepared 2-aminobenzothiazole derivatives

in this part were proved by FT-IR, 1H-NMR and UV spectroscopy.

Physical properties including l max and Rf of the compounds were also

measured. The physical properties are summarized in Table (9) and Table

(10).

aminobenzothiazoles -Spectroscopic identification of 22 -1-3 Ultra Violet Spectra ( UV) A-2-1-3

The 2-aminobenzothiazole derivatives contain aromatic ring and N=C

group conjugated with amino group by nitrogen atom in thiazole ring


۷۱

Therefore, the UV spectra of such compounds showes an absorption band

at the range (226-264) nm due to (p - p*) transition. The second absorption

at the rang (281-414) nm, due to (n-p* ) transitions.

UV data of the prepared 2-aminobenzothiazoles are summarized in

Table (12). UV absorption of the prepared 2-aminobenzothiazoles are

shown in Figs. (5) to (8).

IR) -Fourier Transform Infrared Spectra ( FT -B-2-1-3

Infrared spectrum of all prepared 2-aminobenzothiazoles using KBr

disk showed many absorption bands of stretching and bending vibration of

different groups.

In general the FT-IR spectra of this compounds showed a band at

(3380-3420) cm-1 due to (NH) stretching vibration and the absorption

bands of the (N=C) stretching at ( 1617-1640) cm-1 which revealed a good

indication for formation of 2-aminobenzothiazoles.The FTIR data of the

prepared 2-aminobenzothiazoles are summarized in Table (11) and shown

in Figs. (1) to (4).

NMR) -H1Proton Nuclear Magnetic Resonance ( -C-2-1-3

1H-NMR spectra of 6-nitro 2-amino benzothiazole [5] was obtained in

DMSO-d6 as solvents and with TMS as internal standard. The chemical

shifts for the prepared compound showed four type of signal as shown in

Figs. (9 and 10) .


۷۲

Spectra NMR-C31 -D-2-1-3

The 13 C-NMR spectrum obtained from a 13 C-NMR spectrometer

operating in the normal mode consists of series sharp signals. Each signal

represents a different 13 C-NMR. In addition, the calibration signals TMS

as an internal standard.

13 C-NMR spectra of the prepared compound showed signal due to (C=C

arom.). This chemical shift and others are shown in Fig. (11).

eamino benzothiazol-2 Substituted3 -1-3

Compounds [1-5] were prepared as shown in chapter two by stirring of

r-substituted aniline with ammonium thiocyanate (NH4SCN) in the

presence of bromine (Br2) as catalyst for 1 hr., then diluted with water and

neutralized with solid sodium hydroxide after standing for several hours

the precipitate was collected . Compound [1,2] recrastilyzed with ethyl

acetate and compounds [3-5] recrastilyzed with benzene .

The FT-IR Spectrum of compound [1 ]using KBr disk shows the same

bands appearance in Sec. (3-2-B) following characteristic features:

Stretching band at (3100) cm-1, (1550) cm-1 , (1640) cm-1, (735) cm-1,

(3305) cm-1, (630) cm-1, 1353-1560 cm-1, was attributed to v (C-H)

aromatic, v(C-N), v(C=N), v(C-S), v(NH), v(C-Cl) and v(NO2) as shown in

Table (11) Fig. (1).

UV spectrum of shows an absorption l max at 233 nm and 263 nm

which attributed to (p-p*) and (n- p*) . The absorption is listed in Table

(12), Fig. (5).

The FT-IR Spectrum of compounds [2,5 ] using KBr disk shows the

same bands appearance in compound [1], as shown in Fig. (2) and (4)

The weaker (C-H) stretching band showed at (2731-2977) cm-1 due to


۷۳

(CH3) groups in FT-IR spectrum of compound [3] as shown in Fig. ( 3) .

UV spectrum of compound [2] showed an absorption l max at 257 nm

and 335 nm which attributed to (p-p*) and (n- p*) . The absorption is listed

in Table (12), Fig. (6).







1H-NMR spectrum of compound [5], showed a signal at d5.201 ppm

(2H, singlet) was attributed to (-NH) proton while a signal between d

(7.400- 8.122) ppm for three aromatic hydrogen (1H2, 1H3, 1H4) as shown

in Table ( 34 ), Fig. (9) .

The 13C-NMR spectrum of [5] showed the signal at 158.103 ppm for

carbon atom in thiazole ring, while the signal at 110.21-140.01ppm for

aromatic carbons, as shown in Fig. (11).


۷٤

Table (۱۰): Physical properties of prepared 2-amino benzothiazoles

Rf

Solvent used in

the reaction

M.P C0

Molecular formula

(Molecular weigh)

Substituted

Com. No.

R2

R1

0.6

glacial

acetic acid

112-114

C7H4N3O2SCl

(229)

NO2

Cl

1

0.72

glacial

acetic acid

90-92

C7H4N4O4S

(240)

NO2

NO2

2

0.83

glacial

acetic acid

130-133

C8H8N2S

(164)

H

CH3

3

0.54

glacial

acetic acid

160-164

C8H6N2O2S

(194)

H

COOH

4

0.37

glacial

acetic acid

120-122

C7H5N3O2S

(195)

H

NO2

5


۷٥

Table(11): FT-IR absorption bands of the prepared 2- aminobenzothiazole derivatives (1 -5).

other Bands

n N-H

n C-S

n C=N

n C-N C=C

n C-H

arom.

Structure

(C-NO2) 1349-1560 (C-Cl) 630

3305

735

1640

1550

3100

(C-NO2) 1340-1575

3301

724

1623

1520

3101

( C-H ) aliph 2920

3303

733

1620

1530

3102

(OH) of carboxylic acid

3300-3250 1720 due to

(C=O) of (COOH)

3390

724

1629

1509

3101

(C-NO2) 1356-1590

3401

735

1617

1600

3103


۷٦

Table(12):- Ultra violet spectra of the prepared 2-aminobenzothiazoles

Peak

Structure

Fig. No.

Com. No.

ABS l max /

nm Ethanol

1.39 1.20

۲۳۳ ۲٦۳

٥

1

1.5 2.28

۲٥۷ ۳۳٥

٦

2

1.31 0.318

235 414

۷

3

1.145 0.594

226 264

۸

4

1.629 1.305

۲۳۱ ۲۸۱

-

5


۷۷

Figure (1) FTIR spectrum of compound (1)



۷۸




۷۹

Figure (5): UV spectrum of compound (1)



۸۰




۸۱

Figure ( 9 ): 1H-NMR spectrum of compound (5)

Figure ( 10 ): The expantion of 1H-NMR spectrum of compound (5)


۸۲

Figure ( 11 ): 13 C-NMR spectrum of compound (5)


۸۳

3-2 Part two

szo compoundSynthesis of a 1-2-3 Synthesis of an azo compound requires two organic compounds a

diazonium salt and a coupling component. The general synthesis is shown

below:

When sodium nitrite is mixed with sulfuric acid, it produces nitrous

acid. The nitrous acid can be protonated under acidic conditions to cause

the loss of water and produce the nitrosonium ion. An aromatic amine can

attack the electrophilic nitrosonium ion to form a nitrosoamine, that

undergo a proton transfer (tautomerism), and under acidic conditions, the

OH group can be protonated to cause loss of water and yield diazonium

salt. To complete the synthesis of the azo compound, the diazonium salt

reacts as an electrophile with an electron-rich coupling component, like a

phenol or an aniline, through an electrophilic aromatic substitution

mechanism. The -OH or -NH2 group direct the aryl diazonium ion to the

para site unless that position is occupied, in which case the ion attaches

ortho. The mechanism of all these reaction are shown in scheme (5)

Compounds (6-45) were synthesized recrystalyzation from ethanol, and

the precipitate was filtered and dried.

Structures confirmation for all prepared azo derivatives in this part

were proved using FT-IR and UV spectroscopy. Physical properties


۸٤

including melting point and Rf of the compounds were also measured and

summarized in Table (13).

Scheme (5): Mechanism of preparation azo compound.

3-2-2- Spectroscopic properties of r-(2-azo-substituted

benzothiazolyl) substituted phenols.

Ultra Violet Spectra ( UV) -A-2-2-3

Absorption maxima of r-(2-azo-substituted benzothiazolyl) substituted

phenols ( 6-45 ) were recorded in ethanol .

As far as absorption maxima are concerned, λ max values are directly

proportional to the electronic power of the substituents in the coupled ring

system. The introduction of electron donating or electron attracting groups

at suitable positions in the coupled ring affect the absorption characteristics

of azo derivatives . As can be seen from the data in Table (15).


۸٥

IR)-Spectra ( FT Fourier Transform -B-2-2-3

The infrared spectra of compound (6- 45) are shown in Figure (12) to

Figure (24) showed the same bands revealed in part one with some

difference. The difference is indicated in Table (14) . The characteristic

band at 3350-3450 cm-1 indicates the O-H, stretching and 1520-1600 cm-1

for (N=N str.) This results give a good proof of the success of converting

2-aminobenzothiazole to azo compound.

NMR)-H1Proton Nuclear Magnetic Resonance ( -C-2-2-3

1H-NMR spectra of prepared compound was obtained in DMSO-d6 as

solvents and with TMS as internal standard. The chemical shifts showed

signal at d 6.781 for proton of phenol, this and other bands shown in

Table (34) and Figs . (46 ) .

Spectra NMR–C 31 -D-2-2-3

The 13 C-NMR spectrum obtained from a 13C-NMR spectrometer


represents a different 13C-NMR. In addition, the calibration signals TMS

as an internal standard as shown in Fig . ( 48 ) .

3-2-3- Substituted azo compounds

The new r-(2-azo-substituted benzothiazolyl) substituted phenols was

synthesized by reaction of substituted 2-amino benzothiazole with sodium

nitrate in 00C, the resultant reaction mixture was left in ice for 1hr.

Solution of r-substituted phenol in dilute NaOH was addedwith

vigorously stirred, the solution was neutralized with diluted acid and kept

standing for several hours. The precipitate was collect, dried then

recrystallized with ethanol.


۸٦

The FT-IR spectrum of compound [8] showed characteristic absorption

bands at 3419 cm-1, 1585 cm-1, 1600 cm-1, 3301-3249 cm-1 1721 cm-1 and

3390 cm-1due to v(OH) phenol, v(N=N) azo group, v(C=N) thiazole ring,

v(OH) of carboxylic acid v(C=O) of carboxylic acid and v(NH2)

respectively as shown in Table (14) and Fig.(12).

UV spectrum showed an absorption lmax at 209 nm and 257 nm which

was attributed to (p- p*) and (n -p*). The absorption is listed in Table (15),

Fig.(27).

The FT-IR spectrum of compound [14] showed characteristic absorption

bands at 3450 cm-1, 1595 cm-1, 1620 cm-1, 1366 cm-1, and 2990 cm-1 due to

v(OH) phenol, v(N=N) azo group, v(C=N) thiazole ring, v(NO2) and (C-H)

aliphatic respectively as shown in Table (14) and Fig.(13).

UV spectrum showed an absorption l max at 226 nm and 354 nm which

attributed to (p-p*) and (n -p*) . The absorption is listed in Table (15),

Fig. (29).

The FT-IR Spectrum of compound [15] showed characteristic absorption

bands at 3460 cm-1, 1590 cm-1, 1625 cm-1, 1360 cm-1, and 846 cm-1 due to

v(OH) phenol, v(N=N) azo group, v(C=N) thiazole ring, v(NO2) and (C-

Br) respectively as shown in Table (14) and Fig.(14).

UV spectrum showed an absorption l max at 353 which attributed to

(p-p*) . The absorption is listed in Table (15), Fig. (30).

The FT-IR Spectrum of compound [16] showed characteristic

absorption bands at 3468 cm-1, 1588 cm-1, 1620 cm-1, 3314 cm-1, 1365 cm-1

due to v(OH) phenol, v(N=N) azo group, v(C=N) thiazole ring, v(NH)

amine and v(NO2) respectively as shown in Table (14) and Fig.(15).


۸۷


was attributed to (p-p*) (n - p*). The absorption is listed in Table (15),

Fig.(31).

The 1H-NMR spectrum of compound [16] showed a signals between

d 7.251-8.750 ppm for six aromatic hydrogen (1H2, 1H3, 1H4, 1H6, 1H7,

,1H8) while the signal at d 6.781 ppm (1H, singlet ) was attributed to

(-OH) proton, also showed a signal at d3.45 ppm (2H, singlet) was

attributed to (-NH) proton as shown in Table ( 34 ), Fig. ( 46 ).

The 13C-NMR of compound [16] showed the signals at 118-139 ppm

for aromatic carbons, while the signal at 140 ppm for carbon in thiazole

ring as shown in Fig. (48).

The FT-IR Spectrum of compound [17,19] showed the same

characteristic absorption bands in compound [14] as shown in Table (14)

and Fig.(16) and (18).

UV spectrum of compound [17] showed an absorption lmax at 218 and

265 nm which was attributed to (p -p*) (n -p*). The absorption is listed in

Table (15), Fig.(32).

UV spectrum of compound [19] showed an absorption lmax at 355 nm

which was attributed to (p-p*) . The absorption is listed in Table (15), Fig.

(34).

The FT-IR spectrum of compound [18] showed characteristic

absorption bands at 3410 cm-1, 1593 cm-1, 1622 cm-1, 1355 cm-1 and 1230

cm-1due to v(OH) phenol, v(N=N) azo group, v(C=N) thiazole ring,

v (NO2) and v(OCH3) respectively as shown in Table (14) and Fig. (17).


was attributed to (p -p*) and (n-p*). The absorption is listed in Table (15),

Fig.(33).


۸۸

The FT-IR Spectrum of compound [20] showed the characteristic

absorption bands at 3395 cm-1, 1600 cm-1, 1625 cm-1 and 1366 cm-1 due to

v(OH) phenol, v(N=N) azo group, v(C=N) thiazole ring and v(NO2)

respectively as shown in Table (14) and Fig.(19) .


was attributed to (p -p*) (n -p*). The absorption is listed in Table (15),

Fig.(35).

The FT-IR Spectrum of compound [21] showed the characteristic

absorption bands at 3410 cm-1, 1585 cm-1, 1615 cm-1 and 1366 cm-1 due

to v(OH) phenol, v(N=N) azo group, v(C=N) thiazole ring and v(NO2)



was attributed to (p -p*) (n -p*). The absorption is listed in Table (15),

Fig.(36).

The FT-IR Spectrum of compound [23] showed the same characteristic

absorption bands in compound [15] as shown in Table (14) and Fig.(21).


was attributed to (p-p*) (n-p*). The absorption is listed in Table (15),

Fig.(37).


absorption bands at 3479 cm-1, 1552 cm-1, 1600 cm-1, 1365 cm-1 and 649

cm-1due to v(OH) phenol, v(N=N) azo group, v(C=N) thiazole ring, ,

v(NO2) and v(C-Cl) respectively as shown in Table (14) and Fig.(22).

UV spectrum showed an absorption lmax at 342 nm which was

attributed to (p-p*) . The absorption is listed in Table (15), Fig.(41).


absorption bands in compound [16] as shown in Table (14) and Fig.(23) .


۸۹


was attributed to (p -p*) and (n -p*) . The absorption is listed in Table

(15), Fig.(45).


absorption bands at 3390 cm-1, 1589 cm-1, 1620 cm-1 and 1365 cm-1due to

v(OH) phenol, v(N=N) azo group, v(C=N) thiazole ring and v(NO2)



۹۰

Table (13): Physical properties of prepared r-(2-azo-substituted benzothiazolyl) substituted phenols

Rf

Solvent used in

the reaction

M.P C0

Molecular formula

Molecular weigh

Substituted

Com. No.

R4

R3

R2

R1

0.55

Water

150

C16H13O3N3S

(327)

CH3

CH3

H

HO2C

6

0.54

Water

Syrup

C14H8O3N3SBr

(377)

H

Br

H

HO2C

۷

0.63

Water

240 Dec.

C14H10O3N4S

(314)

H

NH2

H

HO2C

۸

0.51

Water

Syrup

C16H13O3N3S

(327)

H

C2H5

H

HO2C

9

0.43

Water

Syrup

C15H11O4N3S

(329)

OCH3

H

H

HO2C

10

0.77

Water

Syrup

C15H11O3N3S

(313)

H

CH3

H

HO2C

11

0.53

water

Syrup

C14H8O5N4S

(344)

H

NO2

H

HO2C

12


۹۱

Rf

Solvent used in

the reaction

M.P C0

Molecular formula

Molecular weigh

Substituted

Com. No.

R4

R3

R2

R1

0.75

Water

Syrup

C14H9O3N3S

(299)

H

H

H

HO2C

13

0.47

Water

200 Dec.

C15H12O3N4S

(328)

CH3

CH3

H

NO2

14

0.84

Water

210

C13H7O3N4SBr

(378)

H

Br

H

NO2

15

0.63

Water

230 Dec.

C13H9O3N5S

(315)

H

NH2

H

NO2

16

0.85

Water

Syrup

C15H12O3N4S

(328)

H

C2H5

H

NO2

17

0.74

water

160 Dec.

C14H10O4N4S

(330)

OCH3

H

H

NO2

18

0.58

Water

215 Dec.

C14H10O3N4S

(314)

H

CH3

H

NO2

19

0.85

Water

Syrop

C13H7O5N5S

(345)

H

NO2

H

NO2

20

0.44

Water

۱٤٥

C13H8O3N4S

(300)

H

H

H

NO2

21


۹۲

Rf

Solvent used in

the reaction

M.P C0

Molecular formula

Molecular weigh

Substituted

Com. No.

R4

R3

R2

R1

0.49

Water

Syrup

C16H15ON3S

(297)

CH3

CH3

H

CH3

22

0.73

Water

Syrup

C14H10ON3SBr

(347)

H

Br

H

CH3

23

0.64

Water

Syrup

C14H12ON4S

(284)

H

NH2

H

CH3

24

0.73

Water

Syrup

C16H15ON3S

(297)

H

C2H5

H

CH3

25

0.83

Water

Syrup

C15H13O2N3S

(299)

OCH3

H

H

CH3

26

0.56

water

Syrup

C15H13ON3S

(283)

H

CH3

H

CH3

27

0.43

Water

Syrup

C14H10O3N4S

(314)

H

NO2

H

CH3

28

0.55

Water

Syrup

C14H11ON3S

(269)

H

H

H

CH3

29

0.73

Water

Syrup

C15H11O3N4SCl

(362)

CH3

CH3

NO2

Cl

30


۹۳

Rf

Solvent used in

the reaction

M.P C0

Molecular formula

Molecular weigh

Substituted Com. No.

R4

R3

R2

R1

0.67

Water

Syrup

C13H6O3N4SBrCl

(413)

H

Br

NO2

Cl

31

0.33

Water

250

C13H8O3N5SCl

(349)

H

NH2

NO2

Cl

۳۲

0.52

Water

Syrup

C15H11O3N4SCl

(362)

H

C2H5

NO2

Cl

۳۳

0.87

Water

220

C14H9O4N4SCl

(364)

OCH3

H

NO2

Cl

34

0.71

Water

Syrup

C14H9O3N4SCl

(348)

H

CH3

NO2

Cl

35

0.44

water

۱٦۰

C13H6O5N5SCl

(379)

H

NO2

NO2

Cl

۳٦

0.7

Water

۲٤۳

C13H8O3N4SCl

(335)

H

H

NO2

Cl

۳۷

0.82

Water

۱۹۰

C15H11O5N5S

(373)

CH3

CH3

NO2

NO2

38

0.39

Water

Syrup

C13H6O5N5SBr

(423)

H

Br

NO2

NO2

39


۹٤

Rf

Solvent used in

the reaction

M.P C0

Molecular formula

Molecular weigh

Substituted

Com. No.

R4

R3

R2

R1

0.89

Water

220

C13H8O5N6S

(360)

H

NH2

NO2

NO2

40

0.31

Water

Syrup

C15H11O5N5S

(373)

H

C2H5

NO2

NO2

41

0.92

Water

Syrup

C14H9O6N5S

(375)

OCH3

H

NO2

NO2

42

0.52

Water

Syrup

C14H9O5N5S

(359)

H

CH3

NO2

NO2

43

0.85

Water

Syrup

C13H7O7N6S

(345)

H

NO2

NO2

NO2

44

0.92

Water

Syrup

C13H8O5N5S

(345)

H

H

NO2

NO2

٤٥


۹٥

Table(۱٤) :- FT-IR spectra of the prepared r-(2-azo-substituted benzothiazolyl ) substituted phenols.

other Band

n C=N

n N=N

n O-H

Substituted

Com. No.

R4

R3

R2

R1 (OH) of carboxylic acid

3303-3255 (C=O) of (COOH)

1722 Alip.(C-H) 2995

1602

1581

3402

CH3

CH3

H

HO2C

6

( C-Br) 878

1601

1588

3411

H

Br

H

HO2C

۷

(OH) of carboxylic acid 3301-3249

(C=O) of (COOH) 1721

(NH2) 3390

1600

1585

3419

H

NH2

H

HO2C

۸



Alip.(C-H) 2925

1595

1568

3408

H

C2H5

H

HO2C

9



1364 (OCH3)

1598

1520

3350

OCH3

H

H

HO2C

10



aliph.(C-H) 2926

1606

1525

3355

H

CH3

H

HO2C

11


۹٦

other band

n C=N

n N=N

n O-H

Substituted

Com. No.

R4

R3

R2

R1


3308-3259 (C=O) of (COOH)

1725 (NO2)1360

1604

1593

3360

H

NO2

H

HO2C

12


3305-3256 (C=O) of (COOH)

1735

1611

1599

3410

H

H

H

HO2C

13

(NO2) 1366 aliph.(C-H) 2990

1620

1595

3450

CH3

CH3

H

NO2

14

(C-Br) 846 (NO2) 1360

1625

1590

3460

H

Br

H

NO2

15

(NO2) 1365 (NH2) 3314

1620

1588

3468

H

NH2

H

NO2

16

(NO2) 1350 aliph.(C-H) 2997

1600

1558

3390

H

C2H5

H

NO2

17

(NO2) 1355 (OCH3) 1230

1622

1593

3410

OCH3

H

H

NO2

18

(NO2) 1366 Aliph.(C-H) 2980

1630

1599

3452

H

CH3

H

NO2

19

(NO2) 1366

1625

1600

3395

H

NO2

H

NO2

20

(NO2) 1366

1615

1585

3410

H

H

H

NO2

21


۹۷

other band

n C=N

n N=N

n O-H

Substituted

Com. No.

R4

R3

R2

R1

aliph.(C-H) 2983

1620

1590

3360

CH3

CH3

H

CH3

22

(C-Br) 840 aliph.(C-H) 2970

1629

1582

3450

H

Br

H

CH3

23

(NH2) 3331 aliph.(C-H) 2998

1623

1604

3435

H

NH2

H

CH3

24

aliph.(C-H) 2989

1629

1608

3419

H

C2H5

H

CH3

25

(OCH3) 1360 aliph.(C-H) 2984

1622

1600

3407

OCH3

H

H

CH3

26

aliph.(C-H) 2991

1615

1590

3349

H

CH3

H

CH3

27

(NO2) 1359-1550 aliph.(C-H) 3001

1610

1592

3354

H

NO2

H

CH3

28

aliph.(C-H) 2988

1622

1513

3410

H

H

H

CH3

29

(NO2) 1366-1555 (C-Cl) 648

aliph.(C-H) 2995

1615

1597

3417

CH3

CH3

NO2

Cl

30

(NO2) 1353-1553 (C-Cl) 857 (C-Br) 877

1613

1601

3405

H

Br

NO2

Cl

31

(NO2)1350-1545 (C-Cl) 655 (NH2) 3331

1616

1585

3٤44

H

NH2

NO2

Cl

۳۲


۹۸

other band

n C=N

n N=N

n O-H

Substituted

Com. No.

R4

R3

R2

R1

(NO2) 1363 (C-Cl) 650

aliph.(C-H) 2980

1566

1591

3353

H

C2H5

NO2

Cl

۳۳

(OCH3) 1355

۱٥۸۹

۱٦۰۰

۳۳٥۰

OCH3

H

NO2

Cl

۳٤

(NO2) 1351 (C-Cl) 657

aliph.(C-H) 2992

1629

1590

3416

H

CH3

NO2

Cl

35

(NO2) 1365 (C-Cl) 649

1600

1552

3479

H

NO2

NO2

Cl

36

(NO2) 1344 (C-Cl) 657

1610

1588

3356

H

H

NO2

Cl

37

(NO2) 1341 aliph.(C-H) 2987

1623

1600

3351

CH3

CH3

NO2

NO2

38

(C-Br) 867 (NO2) 1342

1619

1599

3419

H

Br

NO2

NO2

39

(NO2) 1351 (NH2) 3310

1615

1587

3453

H

NH2

NO2

NO2

40

(NO2) 1349 aliph.(C-H) 2991

1620

1601

3401

H

C2H5

NO2

NO2

٤۱

(NO2) 1362 (OCH3) 1366

1609

1585

3359

OCH3

H

NO2

NO2

٤۲

(NO2) 1353 aliph.(C-H) 2987

1617

1605

3354

H

CH3

NO2

NO2

43

(NO2) 1382

1630

1606

3412

H

NO2

NO2

NO2

44

(NO2) 1383

1620

1589

3390

H

H

NO2

NO2

٤٥


۹۹

Table(15):- Ultra violet spectra of the prepared r-(2-azo-substituted benzothiazolyl) substituted phenols

Peak

Structure

Fig. No.

Com. No.

ABS

l max / nm

Ethanol

1.37 1.09

229 ۲۹۷

25

٦

2.43 1.49

231 271

26

۷

3.1 0.94

209 257

۲۷

8

1.57 0.25

۲۷۹ ۳٥۸

۲۸

۱۰

1.04 0.72

۲۲٦ ۳٥٤

۲۹

۱٤

1.39

۳٥۳

30

۱٥

1.18 0.8

۲۲۹ ۳۳٥

۳۱

۱٦


۱۰۰

Peak

Structure

Fig. No.

Com. No.

ABS l max /

nm Ethanol

1.55 1.01

۲۱۸ ۲٦٥

۳۲

۱۷

0.76 0.54

۲۲٦ ۳٥٤

۳۳

۱۸

1.88

۳٥٥

۳٤

۱۹

1.73 1.08

۲۷۳ ۳٤٦

۳٥

۲۰

0.83 0.64

۲۲٦ ۳٥٥

۳٦

۲۱

۳

1.29

۲۳۱ ۲۸٤

۳۷

۲۳

1.95 1.33

۲۳٤ ۲۸٥

۳۸

۳۰


۱۰۱

Peak

Structure

Fig. No.

Com. No.

ABS l max /

nm Ethanol

0.76 0.26

۲۰۹ ۲۷۳

۳۹

۳۳

1.66 1.09

۲۲۹ ۲۷۹

٤۰

۳٤

0.57

۳٤۲

٤۱

۳٦

3.64 1.06

۲۱۳ ۳٦۸

٤۲

۳۷

1.56 0.87

۲۳۳ ۳۹۰

٤۳

۳۱

2.29 1.48

۲۰٤ ۲٥۷

٤٤

۳۸

0.93 1.4

۲٥۷ ۳۳٦

٤٥

٤۰


۱۰۲




۱۰۳




۱۰٤




۱۰٥




۱۰٦




۱۰۷




۱۰۸


Figure (25) UV spectrum of compound (6)


۱۰۹




۱۱۰




۱۱۱




۱۱۲




۱۱۳




۱۱٤




۱۱٥




۱۱٦




۱۱۷




۱۱۸




۱۱۹

Figure ( 46 ): 1H-NMR spectrum of compound (16 )

Figure ( 47 ): The expantion of 1H-NMR spectrum of compound (16 )


۱۲۰

Figure ( 48 ): 13 C-NMR spectrum of compound (16)


۱۲۱

3-3 Part three

3-3-1 Synthesis of ethyl {r-(2-azo-substituted benzothiazolyl) substituted phenoxy} 2-propionate

Williamson ether synthesis is an example of an SN2 reaction that

requires three qualities: a strong nucleophile, a good leaving group, and a

polar a protic solvent. For our reaction, we have all three bases covered.

The nucleophile is a phenoxide, the leaving group is bromine in ethyl 2-

bromo propionate and reaction solvent is acetone, a classic solvent for SN2

reactions . The mechanism of this reaction is shown in scheme (6).

Scheme (6): Mechanism for Williamson ether synthesis

Compounds (III ) were prepared by refluxing compound (II) with ethyl

2-bromo propionate in the presence of anhydrous potassium carbonate as a

catalyst in dry acetone for 24 hrs., then poured in ice water , the precipitate

was collected washed with water, the precipitate was filtered and dried.

The formation of ester derivative [46-62] are not yet described in the

literature. Structures confirmation of all prepared derivatives in this part

were proved using FT-IR and UV spectroscopy and some of them with 1H-NMR and 13C-NMR. Physical properties including melting point and

Rf of the compounds were also measured and summarized in Table (16).


۱۲۲

subsituted -azo-(2 -r thyl {eSpectroscopic properties of 2-3-3 atepropion-d phenoxy}2substitutebenzothiazolyl)

Infrared spectra of all the prepared esters showed many absorption

bands of stretching and bending vibration of different groups.

In general, the FT-IR spectra in part three showed a new bands appears in

all the spectra, at (2823-2993) cm-1 due to the weaker C-H stretching for

(CH2, CH3) groups, the characteristic band at (1200-1270) cm-1 for the

( C-O-C ) stretching indicate the presence of ether group also band at

(1745-1755) cm-1 for (C=O) of ester stretching as shown in figure (49) to

(57) and this is good indication of complete the reaction. These and other

FT-IR absorption bands are listed in Table (17) and as shown in figures

(49) to (57) .

Absorption maxima of ethyl { r- ( 2-azo-substituted benzothiazolyl )

substituted phenols} 2-propionate (46-62) were recorded in ethanol and are

listed in Table (18) and as shown in figures (58) to (68) .

1H-NMR spectra of ethyl{r-(2-azo-6-nitro benzothiazolyl) phenoxy}

2-propionate [47] was obtained in DMSO-d6 as solvents and with TMS as

internal standard. The chemical shifts of the prepared compound showed in

Fig. ( 69 ) .

The 13C-NMR spectrum obtained from a 13C-NMR spectrometer


represents a different 13C-NMR. In addition, the calibration signals TMS as

an internal standard. The chemical shifts of the prepared compound shown

in Figs. ( 71 ) .


۱۲۳

3-3-3 Substituted ester compounds

The new ethyl-{r-(2-azo-subsituted benzothiazolyl) substituted

phenoxy}2-propionate was prepared by refluxing of r-(2-azo-subsituted

benzothiazolyl ) substituted phenols with ethyl 2-bromo propionate in dry

acetone as solvent and anhydrous K2CO3 as catalyst for 20-24 hrs., the

reaction mixture was filtered and the solvent was removed under reduce

pressure then poured into ice water, the mixture was standing for 3 days

then the precipitate was filtered washed with water, as mention in chapter

two.

FT-IR spectrum of compound [46], showed the following characteristic

features: significant bands at 1202 cm-1, 1745cm-1 , 1595 cm-1 , 3309-3249

cm-1 and 1799 cm-1 was attributed to stretching vibration of v(C-O-C)

ether, v(C=O) ester, v(N=N) azo group, v(OH) of (COOH) and v (C=O) of

(COOH) respectively as shown in Table (17), Fig.(49).


features: significant bands at 1253 cm-1, 1765 cm-1 , 1590 cm-1 , and 1338

cm-1 , was attributed to stretching vibration of v(C-O-C) ether, v(C=O)

ester, v(N=N) azo group and v(NO2) respectively as shown in Table (17),

Fig. (50).


was attributed to (p- p*) (n- p*). The absorption is listed in Table (18),

Fig.(58).


features: significant bands at 1233 cm-1, ۱۷٦۰ cm-1, 1593 cm-1 , 1361 cm-1

and 2943cm -1 was attributed to stretching vibration of v(C-O-C) ether,

v(C=O) ester, v(N=N) azo group, v(NO2) and v(C-H) aliphatic respectively

as shown in Table (17), Fig. ( 51).


۱۲٤


attributed to (p - p*). The absorption is listed in Table (18), Fig.(60).




features: significant bands at 1235 cm-1, ۱۷٥۹ cm-1 , 1599 cm-1 , 1367 cm-1

and 3382 cm -1 was attributed to stretching vibration of v(C-O-C) ether,

v(C=O) ester, v(N=N) azo group, v(NO2) and v(NH2) amine respectively as

shown in Table (17), Fig. (53).


features: significant bands at 1230 cm-1, ۱۷٥۰ cm-1, 1593 cm-1,1363 cm-1

and 640 cm -1 was attributed to stretching vibration of v(C-O-C) ether,

v(C=O) ester, v(N=N) azo group, v(NO2) and v(C-Cl) respectively as

shown in Table (17), Fig. (55).


was attributed to (p - p*) (n- p*). The absorption is listed in Table (18),

Fig.(62).

The FT-IR spectrum of compound [54] showed the same characteristic



was attributed to (p - p*) and (n -p*). The absorption is listed in Table

(18), Fig.( 63).

The FT-IR spectrum of compound [58,59] showed the same

characteristic absorption bands in compound [53] as shown in Table (17)

and Fig.(56 and 57) .

The 1H-NMR spectrum of compound [ 47] showed a signal between

d7.15-8.45 ppm for five aromatic hydrogen and the signal at d 5.19 ppm

( 1H, m ) which was attributed to (O-C-H) proton, while the signal at d


۱۲٥

4.25 ppm (2H, m ) was attributed to (-CH2) proton, also signal at

d1.123 ppm (3H, triplet ) was attributed to (-CH3), and signal at d1.63 ppm

(3H, d ) was attributed to (-CH3), as shown in Table ( 34 ), Fig. (69).


for aromatic carbons, while the signal at 160.25 ppm for carbon of

carbonyl ester, and signal at 42.02 ppm for carbon in thiazole ring, also

signals at 16-19 ppm for aliphatic carbons as shown in Fig. ( 71 ).


۱۲٦

Table (۱6): Physical properties of ethyl-{r-(2-azo-substituted benzothiazolyl) substituted phenoxy } 2-propionate

Rf

Solvent used in

the reaction

M.P C0

Molecular formula

Molecular weigh

Substituted

Com. No.

R4

R3

R2

R1

0.43

Dry acetone

۱۸۰ Dec.

C21H21O5N3S

(428)

CH3

CH3

H

HCOO

46

0.74

Dry

acetone

140

C18H16O5N4S

(400)

H

H

H

NO2

٤۷

0.46

Dry

acetone

Syrup

C19H18O3N3SBr

(448)

H

Br

H

CH3

٤۸

0.69

Dry

acetone

Syrup

C20H20O5N4S

(428)

H

C2H5

H

NO2

٤۹

0.66

Dry

acetone

۱٦٥ Dec.

C18H15 O7N5S

(445)

H

NO2

H

NO2

٥۰

0.61

Dry

acetone

Syrup

C18H17O5N5S

(415)

H

NH2

H

NO2

٥۱

0.78

Dry

acetone

Syrup

C20H19O5N4SCl

(462)

CH3

CH3

NO2

Cl

٥۲


۱۲۷

Rf

Solvent used in

the reaction

M.P C0

Molecular formula

Molecular weigh

Substituted

Com. No.

R4

R3

R2

R1

0.56

Dry

acetone

Syrup

C18H15O5N4SCl

(434)

H

H

NO2

Cl

٥۳

0.79

Dry

acetone

Syrup

C18H16O5N4SCl

(435)

H

NH2

NO2

Cl

٥٤

0.86

Dry

acetone

Syrup

C18H14O7N5SCl

(479)

H

NO2

NO2

Cl

٥٥

0.88

Dry acetone

syrup

C18H14O5N4SBrCl

(513)

H

Br

NO2

Cl

٥٦

0.66

Dry acetone

Syrup

C18H15O7N5S

(445)

H

H

NO2

NO2

٥۷

0.53

Dry

acetone

syrup

C20H19O7N5S

(473)

H

C2H5

NO2

NO2

٥۸

0.85

Dry

acetone

syrup

C18H14O9N6S

(490)

H

NO2

NO2

NO2

٥۹

0.77

Dry

acetone

syrup

C18H14O7N5SBr

(533)

H

Br

NO2

NO2

٦۰

0.36

Dry acetone

syrup

C18H16O7N6S

(460)

H

NH2

NO2

NO2

٦۱

0.51

Dry acetone

syrup

C20H19O7N5S

(473)

CH3

CH3

NO2

NO2

٦۲


۱۲۸

Table(17): FT-IR absorption bands of the prepared ethyl-{ r - (2-azo- substituted benzothiazolyl ) substituted phenoxy }2-propionate

Other band

n N=N C=C

n C=O Ester

n C-O-C

Substituted

Com. no.

R4

R3

R2

R1


3309-3249 C=O of (COOH)

1799

1595

۱۷٤٥

1202

CH3

CH3

H

HCOO

46

(NO2) 1338-1554

1590

۱۷٦٥

1253

H

H

H

NO2

٤۷

840 (C-Br)

1615

۱۷٤٤

1253

Br

H

H

CH3

٤۸

(NO2) 1361-1540 aliph.(C-H) 2943

۱٥۹۳

۱۷٥۰

1233

H

C2H5

H

NO2

٤۹

(NO2) 1367-1543

1601

۱۷٥۳

1255

H

NO2

H

NO2

٥۰

(NO2) 1367-1551

(N-H) 3382

1599

۱۷٤۹

۱۲۳٥

H

NH2

H

NO2

٥۱

(NO2) 1368-1551

(C-Cl) 845

1513

۱۷٤۰

۱۲٤٤

CH3

CH3

NO2

Cl

٥۲


۱۲۹

Other band

n N=N C=C

n C=O Ester

n C-O-C

Substituted

Com. No.

R4

R3

R2

R1

(NO2) 1363-1544 (C-Cl) 640

1593

۱۷٥۰

۱۲۳۰

H

H

NO2

Cl

٥۳

(NO2) 1365-1559

1570

۱۷٤٥

۱۲۲۰ H

NH2

NO2

Cl

٥٤

(NO2) 1375-1551

1605

۱۷۳٥

1270

H

NO2

NO2

Cl

٥٥

(NO2) 1353-1545 (C-Cl) 657 (C-Br) 877

1593

۱۷٤۰

1264

H

Br

NO2

Cl

٥٦

(NO2) 1355-1534

1605

۱۷٤٤

1253

H

H

NO2

NO2

٥۷

(NO2) 1344-1521

(C-Cl) 659

1585

۱۷٥۱

1230

H

C2H5

NO2

NO2

٥۸

(NO2) 1340-1544

1579

۱۷٥۷

1255

H

NO2

NO2

NO2

٥۹

(NO2) 1364-1550

1600

۱۷٤٥

1251

H

Br

NO2

NO2

٦۰

(NO2) 1324-1552

(NH2)1332

1601

۱۷٤٥

1245

H

NH2

NO2

NO2

٦۱

(NO2) 1334-1542

(C-Cl) 640 (NH2)1333

1605

۱۷٤۹

1253

CH3

CH3

NO2

NO2

٦۲


۱۳۰

Table(18): Ultra violet spectra of the prepared ethyl-{r -(2-azo- substituted benzothiazolyl ) substituted phenoxy} 2- propionate.

Peak

Structure

Fig. No.

Com. No.

ABC l max / nm

Ethanol

3.92

۲۱۲

-

٤٦

0.46 0.63

۲٥۸ ۳۷۷

58

٤۷

0.72 0.09

۲۲۷ ۳۲۸

59

٤۸

1.56

۳۸۲

60

٤۹

1.15 0.42

۲۱۱ ۳٥۲

٦۱

52

1.97 0.80

۲۳۲ ۲۷٤

62

٥۳


۱۳۱

Peak

Structure

Fig. No.

Com. No.

ABC l max / nm

Ethanol

0.78 0.45

۲۰۷ ۲٦۸

63

٥٤

2.95 2.05

۲۳٤ ۲٦۱

٦٤

٥٥

1.62 0.3

۲٦۳ ۳٤۲

65

٥٦

1.06 0.94

۲۲٥ ۲٥۷

٦٦

٥۷

2.17 1.71

۲٥٤ ۳۲٥

٦۷

٥۸

1.54 0.82

۲۲۱ ۳٤٥

٦۸

٥۹


۱۳۲

Figure (49): FTIR spectrum of compound (46)



۱۳۳




۱۳٤




۱۳٥




۱۳٦




۱۳۷




۱۳۸




۱۳۹




۱٤۰




۱٤۱




۱٤۲


Figure ( 70 ): The expantion of 1H-NMR spectrum of compound (47 )


۱٤۳

Figure ( 71 ): 1C-NMR spectrum of compound (47)


۱٤٤

3-4-Part four

substituted thiosemicarbazade( IV) and -Synthesis of N 1-4-3 . substituted semicarbazade(V) -N

A variety of procedures have been developed to prepare N-substituted

thiosemicarbazade and N-substituted semicarbazade . Acyl anhydride ,

ester, carboxylic acid and acid chloride all react with thiosemicarbazide

and semecarbazide to give N-substituted thiosemicarbazade (IV) and N-

substituted semicarbazade (V) respectively.

The most widely method is by refluxing compound (III) with

thiosemicarbazide or semicarbazide in absolute ethanol for 5 hrs. then the

mixture poured in ice water, the precipitate was collected and

recrystalyzide from ethanol, the precipitate was filtered and dried. The

formation of compounds (IV) and (V) are not yet described in the

literature. Mechanism of the reaction involves a nuclephilic addition as is

shown below :-

Scheme (7): Mechanism of preparation N-substituted thiosemicarbazide ( semicarbazide) .

Structures conformation of all prepared N-substituted thiosemicarbazone

(semicarbazone) in this part were proved using FT-IR, and UV,

spectroscopy. Physical properties including melting point, l max and Rf of

the compounds were also measured. These and other physical properties

are summarized in Tables (19) and (22).


۱٤٥

hydrazine hydrate cause redaction of azo group to amine 218, since in

this work hydrazine hydrate can not be used to prepare acidhydrazide .

substituted -pectroscopic properties of NS 2-4-3 substituted semicarbazide.-thiosemicarbazide and N

The structure of N-substituted thiosemicarbazide ( semicarbazide) was

established through by spectroscopic (IR, UV) Figures ( 72 ) to ( 83 ) IR

spectra showed characteristic bands for NH groups at 3210- 3330 cm-1,

and the absorption band for C=O amide group appeared at 1660- 1683 cm-1

and absorption band for C=S group appeared at 1110-1150 cm-1 ,the

absorption band of C=O ester group was disappear and this good indication

for complete the reaction as shown in Table (20).

3-4-3- N-Substituted thiosemicarbazide

It was prepared by refluxing of ethyl-{r-(2-azo-substituted

benzothiazolyl) substituted phenoxy } 2-propionate with thiosemicarbazide

in absolute ethanol for 4-5 hours. The mixture was concentrated, cooled

and poured in crushed ice. Kept for 3-4 hrs. at room temperature and solid

mass separated out was filtered and dried, recrystallized from methanol.


features: significant bands at 1663 cm-1,۱٥۸۱ cm-1 ,1115 cm-1 ,3200 cm-1

and 1338 cm-1 , was attributed to stretching vibration of v(C=O)amide ,


۱٤٦

v(N=N) azo group, v(C=S) thione group, v(NH2) and v(NO2) respectively

as shown in Table ( 20 ), Fig. ( 72 ).


was attributed to (p - p*) and (n - p*). The absorption is listed in Table

( 21), Fig.( 76 ).


features: significant bands at 1667 cm-1, ۱٥۸٥ cm-1 ,1153 cm-1 ,3237 cm-1

and 643 cm-1, was attributed to stretching vibration of v(C=O)amide ,

v(N=N) azo group, v(C=S) thione group, v(NH2) and v(C-Cl) respectively




( 21), Fig.( 79 ).


absorption bands in compound [64] as shown in Table ( 20 ) and Fig.(74) .



( 21 ), Fig.( 77 ).


features: significant bands at 1680 cm-1,۱٥۸۹ cm-1 ,1152 cm-1, 3307 cm-1


v(N=N) azo group, v(C=S) thione group, v(NH2) and v(C-Br) respectively




(21), Fig.( 82 ).


۱٤۷

Table (19): Physical properties of prepared {r- (2-azo-substituted benzothiazolyl) substituted phenoxy } 2- propanyl N-

thiosemicarbazaide.

Rf

Solvent used in

the reaction

M.P C0

Molecular formula

Molecular weigh

Substituted

Com. No.

R4

R3

R2

R1

0.72

Absolute ethanol

۱۷۰

C18H17O2N6S2Br

(492)

H

Br

H

CH3

٦۳

0.74

Absolute ethanol

۱٥۰

C17H15O4N7S2

(445)

H

H

H

NO2

٦٤

0.52

Absolute ethanol

Syrup

C19H19O4N7S2

(473 )

H

C2H5

H

NO2

٦٥

0.73

Absolute ethanol

Syrup

C19H18O4N7S2Cl

(507)

CH3

CH3

NO2

Cl

٦٦

0.54

Absolute ethanol

Syrup

C17H15O4N8S2Cl

(480)

H

NH2

NO2

Cl

٦۷

0.65

Absolute ethanol

Syrup

C17H14O6N8S2

(490)

H

NO2

H

NO2

٦۸

0.55

Absolute ethanol

Syrup

C17H13O4N7S2Br

(522)

H

Br

NO2

Cl

٦۹

0.61

Absolute ethanol

Syrup

C17H14O6N8S2

(490)

H

H

NO2

NO2

۷۰


۱٤۸

Table(۲۰): FT-IR absorption bands of the prepared { r-(2 -azo- substituted benzothiazolyl ) substituted phenoxy } 2- propanyl N-thiosemicarbazaide .

Other band

n N-H

n C=S

n N=N C=C

n C=O

Substituted

com. No.

R4

R3

R2

R1

(C-Br) 832 Alip. (C-H) 2932

3210

1105

1589

1669

H

Br

H

CH3

٦۳

(NO2) 1375-1553

3200

1115

1581

1663

H

H

H

NO2

٦٤

(NO2) 1371-1550 Alip. (C-H) 2944

3320

1118

1600

1683

H

C2H5

H

NO2

٦٥

(NO2) 1365-1554

(C-Cl) 642 Alip. (C-H) 2935

3237

1153

1585

1667

CH3

CH3

NO2

Cl

٦٦

(NO2) 1356-1551 (C-Cl) 645 (NH2) 3356

3230

1113

1585

1669

H

NH2

NO2

Cl

٦۷

(NO2) 1363-1550

3329

1110

1589

1672

H

NO2

H

NO2

٦۸

(C-Br) 863 (NO2) 1375-1552

3307

1152

1589

1680

H

Br

NO2

Cl

٦۹

(NO2) 1353-1550

3307

1139

1600

1668

H

H

NO2

NO2

۷۰


۱٤۹

Table(21): Ultra violet spectra of the prepared {r-(2-azo-substituted benzothiazolyl ) substituted phenoxy } 2- propanyl N-thiosemicarbazaide.

Peak

Structure

Fig. No.

Com. No.

ABS l max / nm

Ethanol

1.18 2.15

252 372

۷٦

٦٤

2.84 2.41

۲٦۷ ۳۸۰

۷۷

٦٥

0.84 0.17

۲٦۸ ۳۲۸

۷۸

٦۳

1.2 0.23

۲۳۱ ۳۹۳

۷۹

٦٦

0.78 0.45

۲۰۷ ۲٦۸

80

٦۷


۱٥۰

Peak

Structure

Fig. No.

Com. No.

ABS l max / nm

Ethanol

3.05 2.05

۲۳٥ ۲٥٥

۸۱

٦۸

2.43 0.32

۲۳۳ ٤۰۳

۸۲

٦۹

2.46 1.47

۲۳۷ ۳۳۷

۸۳

۷۰


۱٥۱


Figure (73): FT-IR spectrum of compound (66)


۱٥۲




۱٥۳

Figure(76): UV spectrum of compound (64)



۱٥٤




۱٥٥




۱٥٦




۱٥۷

3-4-4- N-Substituted semicarbazide

It was prepared by refluxing of ethyl {r-(2-azo-substituted

benzothiazolyl ) substituted phenoxy } 2-propionate with semicarbazide in

absolute ethanol for 4-5 hours. The mixture was concentrated, cooled and

poured in crushed ice. Kept for 3-4 hours at room temperature filtered ,

dried and recrystallized in methanol.


features: significant bands at 1653 cm-1,۱٥۸۸ cm-1 ,1600 cm-1 ,3320 cm-1


v(N=N) azo group, v(C=N) thiazole ring, v(NH2) and v(NO2) respectively




( 24 ), Fig.( 89 ). FT-IR spectrum of compound [73], showed the following characteristic

features: significant bands at 1668 cm-1,۱٥۸٥ cm-1 ,1600 cm-1 ,3411 cm-1 ,

2989 cm-1 and 1338 cm-1 , was attributed to stretching vibration of

v(C=O)amide , v(N=N) azo group, v(C=N) thiazole ring, v(NH2), v(C-H)

aliphatic and v(NO2) respectively as shown in Table (23), Fig. ( 86 ).



( 24 ), Fig.( 90 ). FT-IR spectrum of compound [75], showed the following characteristic

features: significant bands at 1665 cm-1,۱٥۳۰ cm-1 ,1605 cm-1 ,3325 cm-1 ,

650 cm-1 and 1327 cm-1, was attributed to stretching vibration of

v(C=O)amide , v(N=N) azo group, v(C=N) thiazole ring, v(NH2), v(C-Cl)

and v(NO2) respectively as shown in Table ( 23 ), Fig. ( 85 ).


۱٥۸



( 24 ), Fig.( 92 ).


features: significant bands at 1681 cm-1,۱٦۰۰ cm-1 ,1620 cm-1 ,3370 cm-1 ,

650 cm-1 and 1333 cm-1, was attributed to stretching vibration of

v(C=O)amide , v(N=N) azo group, v(C=N) thiazole ring, v(NH2), v(C-Cl)

and v(NO2) respectively as shown in Table ( 23 ), Fig. ( 87 ).

UV spectrum showed an absorption lmax at 217.5 nm and 258.5 nm

which was attributed to (p - p*) and (n - p*). The absorption is listed in

Table ( 24 ), Fig.( 93).


۱٥۹

Table (22): Physical properties of prepared {r-(2-azo- substituted benzothiazol ) substituted phenoxy }2- propanyl N-semicarbazaide.

Rf

Solvent used in

the reaction

M.P C0

Molecular formula

Molecular weigh

Substituted

com. No.

R4

R3

R2

R1

0.73

Absolute ethanol

Syrup

C18H17O3N6SBr

(476)

H

Br

H

CH3

۷۱

0.57

Absolute ethanol

Syrup

C17H15O5N7S

(429)

H

H

H

NO2

۷۲

0.69

Absolute ethanol

Syrup

C19H19O5N7S

(457)

H

C2H5

H

NO2

۷۳

0.43

Absolute ethanol

Syrup

C19H18O5N7SCl

(491)

CH3

CH3

NO2

Cl

۷٤

0.83

Absolute ethanol

Syrup

C17H15O5N7SCl

(464)

H

NH2

NO2

Cl

۷٥

0.92

Absolute ethanol

Syrup

C17H14O7N8S

(474)

H

NO2

H

NO2

۷٦

0.81

Absolute ethanol

Syrup

C17H13O5N7SBrCl

(541)

H

Br

NO2

Cl

۷۷

0.78

Absolute ethanol

Syrup

C17H14O7N8S

(474)

H

H

NO2

NO2

۷۸


۱٦۰

Table(۲۳):FT-IR absorption bands of prepared 2-propanyl{ r-(2- azo- substituted benzothiazolyl ) substituted phenoxy } N- semicarbazaide.

Other band

n N-H

n C=N

n N=N C=C

n C=O

Substituted

com. no.

R4

R3

R2

R1

aliph. (C-H) 2992

۳۳۲٥

۱٦۰۱

۱٥۸۳

۱٦٥۰

H

Br

H

CH3

۷۱

(NO2) 1338-1551

۳۳۲۰

۱٦۰۰

۱٥۸۸

۱٦٥۳

H

H

H

NO2

۷۲

aliph. (C-H) 2989

(NO2) 1335-1550

۳٤۱۱

۱٦۰۰

۱٥۸٥

۱٦٦۸

H

C2H5

H

NO2

۷۳

aliph. (C-H) 2995

(C-Cl) 655

۳۳٤۲

۱٦۰۳

۱٥٦٦

۱٦٥۱

CH3

CH3

NO2

Cl

۷٤

(C-Cl) 650 (NO2) 1327-1550

۳۳۲٥

۱٦۰٥

۱٥۳۰

۱٦٦٥

H

NH2

NO2

Cl

۷٥

(NO2) 1333-1550

۳۳۷۰

۱٦۲۰

۱٦۰۰

۱٦۸۱

H

NO2

H

NO2

۷٦

(C-Cl) 649 (C-Br)827

۳۳۸۱

۱٦۱۰

۱٥٦۳

۱٦٥۰

H

Br

NO2

Cl

۷۷

(NO2) 1344-1550

۳۳٥٥

۱٦۰۰

۱٥٤۹

۱٦۳۸

H

H

NO2

NO2

۷۸


۱٦۱

Table(24):Ultra violet spectra of the prepared 2-propanyl {r-( 2-azo- substituted benzothiazolyl ) substituted phenoxy }

N-semicarbazide .

Peak

Structure

Fig. No.

Com. No.

ABS l max / nm

Ethanol

0.52 0.04

۲۲۹ ۳۲۱

۸۸

۷۱

1.17 2.16

۲٥۱ ۳۷۱

۸۹

۷۲

2.48 2.31

۲۲۷ ۳۸۰

۹۰

۷۳

1.2 0.23

۲۳۲ ۳۹۱

۹۱

۷٤

0.98 0.85

217.5 258.5

۹۲

۷٥


۱٦۲

Peak

Structure

Fig. No.

Com. No.

ABS l max /

nm Ethan

ol

2.15 0.25

۲۹۱ ۳٥۲

۹۳

۷٦

2.33 0.22

۲۳۱ ٤۱۳

۹٤

۷۷

2.64 1.37

۲۲۷ ۳٤۷

۹٥

۷۸


۱٦۳

Figure( 84 ):FTIR spectrum of compound (72 )

Figure( 85):FTIR spectrum of compound (75 )


۱٦٤

Figure( 86):FTIR spectrum of compound (73)

Figure( 87 ):FTIR spectrum of compound (76)


۱٦٥

Figure( 88 ): UV spectrum of compound (71)



۱٦٦




۱٦۷




۱٦۸




۱٦۹

3-5-Part five / 3-5-1 Synthesis of heterocyclic compounds

In the 1-acylated semicarbazides and 1-acylated thiosemicarbazides,

the nucleophilic interaction inside semicarbazide and thiosemicarbazide

chain respectively, may originate others five-membered heterocycles. In

the most general way, the following scheme sums up these possibilities.

Scheme (8):- inter molecular cyclyzation of thiosemicarbazide

(semicarbazide)

The preparation of 5-subsituted-2-amino-1,3,4-thiadiazole and 5-

subsituted-2-amino-1,3,4-oxadiazole, was described in many reactions. As

the initial substance, N-substituted thiosemicarbazide and N-substituted

semicarbazide, respectively, is used. Their cyclization happens in the

presence of various substances, e.g. conc. sulphuric acid, phosphoric acid

and acetylchloride . The mechanism of the reaction is shown below :-


۱۷۰

Scheme (9): Mechanism of preparation thiazole and oxadiazole

The preparation of 5-subsituted-1,2,4-triazol-3-thione was also

described in various reactions. The cyclization of N-substituted

semicarbazide happens best in the presence of hydroxides. The

mechanism of the reaction involves a nuclephilic addition as is shown

below:-

Scheme (10): Mechanism for the preparation of triazole


۱۷۱

Structures confirmation of the prepared derivatives in this part were

proved using FT-IR, UV, 1H-NMR, and 13C-NMR spectroscopy. Physical

properties including melting point, Rf and l max of the compounds were

also measured and summarized in Table ( 25 ).

3-5-2 Spectroscopic properties of prepared compounds.

The absorption bands of N-substituted thiosemicarbazides (IV) in the

region between 1630 and 1680 cm−1, due to carbonyl, which was

eliminated by the formation of 1,2,4-triazoles (VIII) or 1,3,4-thiadiazoles

(VII), the substituted-triazole-3-thioles (VIII) showed a peak in the region

1210-1230 cm−1 attributed to (C=S). None of that triazoles showed

absorption in the region 2578-2650 cm−1 SH. The absence of S-H and

presence of absorptions C=S and N-H established that all the isolated

triazoles are in their thione rather than the thiole form.

The absorption bands of N-substituted semicarbazides (V) in the region

between 1635 and 1689 cm−1, due to carbonyl, which was eliminated by

the formation of 1,3,4-oxadiazoles ( VI ).

3-5-3 Substituted 1,3,4-oxadiazoles

It was prepared by refluxing of 2-propanyl {r-(2-azo-substituted

benzothiazolyl) substituted phenoxy} N-semicarbazide with concentrated

sulphuric acid then kept at room temperature for 24 hrs. The content was

poured into cold water and neutralized with diluted sodium carbonate

solution, as mention in chapter two.

FT-IR spectrum of compound [80], showed the following

characteristic features: significant bands at ۳۳۰۱ cm-1, ۱٥۷۲ cm-1 , ۱٦۰۰

cm-1 , ۱۲٥۰ cm-1 and 1345 cm-1 was attributed to stretching vibrations of


۱۷۲

v( NH ) amine, v( N=N ) azo group, v( C=N ) thiazole ring, v(C-O-C)

ether and v( NO2) respectively as shown in Table (26), Fig. ( 96).


was attributed to (p - p*) (n - p*). The absorption is listed in Table ( 27 ),

Fig. ( 101 ).

FT-IR spectrum of compound [81], showed characteristic significant

bands at ۳۳۰٥ cm-1, ۱٥۸٥ cm-1 , ۱٦۰۰ cm-1, ۱۲۲٥ cm-1 and 2988 cm-1

was attributed to stretching vibrations of v( NH2 ) amine, v( N=N ) azo

group, v(C=N ) thiazole ring, v( C-O-C) ether and v( CH ) aliphatic

respectively as shown in Table (26 ), Fig. ( 98 ).


was attributed to (p - p*) (n-p*). The absorption is listed in Table

( 27 ), Fig.( 102 ).

FT-IR spectrum of compound [83], showed characteristic significant

bands at ۳۳۱۰ cm-1, ۱٥۹۰ cm-1 , ۱٦۱٥ cm-1 and ۱۲٥٥ cm-1 was attributed

to stretching vibrations of v( NH2 ) amine, v( N=N ) azo group, v(C=N )

thiazole ring, v( C-O-C) ether respectively as shown in Table ( 26 ),

Fig. ( 99 ).


and 278 nm which was attributed to (p - p*) (n - p*). The absorption is

listed in Table ( 27 ), Fig.( 104 ).

FT-IR spectrum of compound [84], showed the same bands in

compound [81] and as shown in Table ( 26 ) Fig. ( 97 ).


and 262 nm which was attributed to (p - p*) (n - p*). The absorption is

listed in Table ( 27 ), Fig.( 105 ).

The 1H-NMR spectrum of compound [80] showed a signal between

d7.19- 7.93 ppm for five aromatic hydrogen , signals at d1.19 and at 2.48


۱۷۳

ppm for aliphatic hydrogen (3H, d ), (1H, m ) was attributed to (-CH3)

proton and (-CH) proton respectively, also the signal at d4.23 ppm

(2H, s ) was attributed to (-NH2) proton, as shown in Table (34 ), Fig.

( 108 ).

The 13C-NMR of compound [80] showed a signals at 120-125 ppm for

aromatic carbons, while the signal at 54 ppm for carbon in thiazole ring,

these and other are shown in Fig. ( 110 ).


۱۷٤

Table (25): Physical properties of prepared ٥ -substituted 2- amino 1,3,4-oxadiazole.

Rf

Solvent used in

the reaction

M.P C0

Molecular formula

Molecular weigh

Substituted

Com. No.

R4

R3

R2

R1

0.62

Absolute ethanol

Syrup

C18H15O2N6SBr

(458)

H

Br

H

CH3

۷۹

0.74

Absolute ethanol

Syrup

C17H13O4N7S

(411)

H

H

H

NO2

۸۰

0.59

Absolute ethanol

Syrup

C19H17O4N7S

(439)

H

C2H5

H

NO2

۸۱

0.77

Absolute ethanol

Syrup

C19H16O4N7SCl

(473)

CH3

CH3

NO2

Cl

۸۲

0.81

Absolute ethanol

Syrup

C17H13O4N8SCl

(460)

H

NH2

NO2

Cl

۸۳

0.66

Absolute ethanol

Syrup

C17H12O6N8S

(456)

H

NO2

H

NO2

۸٤

0.38

Absolute ethanol

Syrup

C17H11O4N7SBrCl

(524)

H

Br

NO2

Cl

۸٥

0.65

Absolute ethanol

Syrup

C17H12O6N8S

(456)

H

H

NO2

NO2

۸٦


۱۷٥

Table(26):- FT-IR absorption bands of prepared ٥ -substituted 2- amino 1,3,4-oxadiazole.

other band

n

C-O-C

n

C=N

n

N=N C=C

n

N-H

Substituted

Com. No.

R4

R3

R2

R1

aliph.(C-H) 2997

(C-Br) 843

۱۲٥٥

۱٦۰۱

۱٥۸۳

۳۳۳۱

H

Br

H

CH3

۷۹

(NO2) 1345-1550

۱۲٥۰

۱٦۰۰

۱٥۷۲

۳۳۰۱

H

H

H

NO2

۸۰

aliph.(C-H) 2988

۱۲۲٥

۱٦۰۰

۱٥۸٥

۳٤۰٥

H

C2H5

H

NO2

۸۱

aliph.(C-H) 2998

(C-Cl) 655

۱۲۳٤

۱٦۰٤

۱٥٦٦

۳۳۷۳

CH3

CH3

NO2

Cl

۸۲

(NO2) 1356-1551 (C-Cl) 651

۱۲٥٥

۱٦۱٥

۱٥۹۰

۳۳۱۰

H

NH2

NO2

Cl

۸۳

(NO2)

1341-1552

۱۲٥٥

۱٦۲۱

۱٦۰۰

۳۳۲۰

H

NO2

H

NO2

۸٤

(C-Cl) 665 (C-Br) 844

۱۲٥۸

۱٦۱٥

۱٥۸۹

۳۳۳٥

H

Br

NO2

Cl

۸٥

(NO2)

1345-1553

۱۲٥۰

۱٦۱۱

۱٦۰۰

۳۳۲٦

H

H

NO2

NO2

۸٦


۱۷٦

Table(27): Ultra violet spectra of the prepared ٥ -substituted 2- amino 1,3,4-oxadiazole.

Peak

Structure

Fig. No.

Com. No.

ABS l max / nm Ethanol

0.84 0.17

۲٤۳ ۲۷۸

۱۰۰

۷۹

0.69 0.14

۲٤۳ ۳۷۱

۱۰۱

۸۰

2.84 1.56

۲٥۷ ۳۸۱

۱۰۲

۸۱

1.20 0.23

۲۱۷ ۳۰۳

۱۰۳

۸۲

0.97 0.53

۲۱۰ ۲۷۸

۱۰٤

۸۳


۱۷۷

Peak

Structure

Fig. No.

Com. No.

ABS l max / nm Ethanol

2.95 2.15

۲۳٥ ۲٦۲

۱۰٥

۸٤

2.26 1.77

۲۳٥ ۳۳٤

۱۰٦

۸٥

0.95 1.37

۲۳۸ ۳۳۷

۱۰۷

۸٦


۱۷۸

Figure ( 96): FTIR spectrum of compound (80)

Figure ( 97 ): FTIR spectrum of compound (84)


۱۷۹

Figure ( 98) FTIR spectrum of compound (81)

Figure ( 99) FTIR spectrum of compound (83)


۱۸۰

Figure ( 100 ) UV spectrum of compound (79)



۱۸۱




۱۸۲




۱۸۳




۱۸٤

Figure ( 108 ): 1HNMR spectrum of compound (80)

Figure (109 ): The expantion of 1HNMR spectrum of compound (80)


۱۸٥

Figure (110 ) 13C-NMR spectrum of compound (80)


۱۸٦

3-5-4 substituted 1,2,4-triazoles


benzothiazolyl) substituted phenoxy} N-thiosemicarbazide with sodium

hydroxide solution, the mixture was filtered and the filtrate was acidified

with 2N hydrochloric acid. The precipitated solid was filtered, dried and

recrystallized from ethanol, as mention in chapter two.


features: significant bands at ۳۳۹۰ cm-1, ۱٥٥۱ cm-1 , ۱٦۲۰ cm-1 , ۱۲۲۰ cm-

1 and 1345 cm-1 was attributed to stretching vibrations of v( NH ) amine,

v( N=N ) azo group, v( C=N ) thiazole ring , v(C=S) thione and v( NO2 )

respectively as shown in Table (29), Fig. (111 ).


was attributed to (p- p*) (n- p*). The absorption is listed in Table (30),

Fig.( 115 ).


features: significant bands at ۱۲۱۰ cm-1, ۱٥۸۳ cm-1, ۱٦۲٥ cm-1, ۳۳۹٤ cm-1,

2910 cm-1, and 1339 cm-1 was attributed to stretching vibrations of v(C=S)

thion , v( N=N ) azo group, v( C=N ) thiazole ring, v (NH2) , v (C-H) alip.

and v( NO2 ) respectively as shown in Table (29), Fig. ( 112 ).



Fig.( 116).


features: significant bands at ۳۳۲٥ cm-1, ۱٥۸۹ cm-1 , ۱٦۲۰ cm-1 , ۱۲۲۲ cm-

1, 635 cm-1 , and 1328 cm-1 was attributed to stretching vibrations of v( NH

) amine, v( N=N ) azo group, v( C=N ), v( C=S )thion , v( C-Cl ) and v(

NO2 ) respectively as shown in Table ( 29 ), Fig. ( 113 ).


۱۸۷



Fig.( 117 ).

FT-IR spectrum of compound [92], showed the same bands in compound

[88] as shown in Table ( 29 ) Fig. ( 114 ).



Fig.(119).


d7.62-8.31 ppm for five aromatic hydrogen , signal at d1.25 and 4.02 ppm

for aliphatic hydrogen (3H, d ), (1H, m ) was attributed to (-CH3) proton

and (-CH) proton respectively, the signal at d6.23 ppm (H, singlet )was

attributed to (-NH 1) proton, signal at d9.15 ppm (H, singlet ) was

attributed to (-NH 2) proton, as shown in Table (34), Fig. ( 122 ).

The 13C-NMR of compound [88] showed the signal at 115-135 ppm

for aromatic carbons, while the signal at 60 ppm for carbon in thiazole ring

also signal at 165.25 for carbon of (C=S), these signals and other are

shown in Fig. (124).


۱۸۸

Table (28): Physical properties of the prepared 5-subsituted 1,2,4 triazole 3-thione

Rf

Solvent used in

the reaction

M.P C0

Molecular formula

Molecular weigh

Substituted

Com. No. R4 R3 R2 R1

0.71

Absolute ethanol

syrup

C18H15N6S2OBr

(484)

H

Br

H

CH3

۸۷

0.61

Absolute ethanol

۲۱۰ Dec.

C17H16N7 S2O3

(430)

H

H

H

NO2

۸۸

0.95

Absolute ethanol

syrup

C19H17N7 S2O3

(455)

H

C2H5

H

NO2

۸۹

0.49

Absolute ethanol

syrup

C17H13N8 S2O3Cl

(476)

H

NH2

NO2

Cl

۹۰

0.84

Absolute ethanol

syrup

C17H11N7 S2O3Cl Br

(549)

H

Br

NO2

Cl

۹۱

0.61

Absolute ethanol

syrup

C17H12N8S2O5

(472)

H

H

NO2

NO2

۹۲

0.95

Absolute ethanol

syrup

C17H12N8S2O5

(472)

H

NO2

H

NO2

۹۳

0.67

Absolute ethanol

syrup

C19H16N7 S2O3Cl

(489)

CH3

CH3

NO2

Cl

۹٤


۱۸۹

Table(۲9): FT-IR absorption bands of the prepared 5-subsituted 1,2,4 triazole 3-thione

other band

n N-H

n C=N

n N=N C=C

n C=S

Substituted

Com. No.

R4

R3

R2

R1

aliph.(C-H) 2915 (C-Br) 836

۳۳٥٥

۱٦۲٦

۱٥٦۷

۱۲۳۱

H

Br

H

CH3

۸۷

(NO2) 1348-1550

۳۳۹۰

۱٦۲۰

۱٥٥۱

۱۲۲۰ H

H

H

NO2

۸۸

(NO2) 1339-1551

Aliph.(C-H) 2910

۳۳۹٤

۱٦۲٥

۱٥۸۳

۱۲۱۰

H

C2H5

H

NO2

۸۹

(NO2) 1328-1572 (C-Cl) 635

۳۳۰٥

۱٦۰٥

۱٥۸۹

۱۲۲۲ H

NH2

NO2

Cl

۹۰

(NO2) 1530,1335 (C-Br) 848 (C-Cl) 641

۳۳۱٥

۱٦۰۰

۱٥۸۸

۱۲۲٥

H

Br

NO2

Cl

۹۱

(NO2) 1346-1533

۳٤۰٤

۱٦۱٥

۱٥۸٤

۱۲۳٥ H

H

NO2

NO2

۹۲

(NO2) 1353-1543

۳۳۲٥

۱٦۳۳

۱٥۸۱

۱۲۱۰ H

NO2

H

NO2

۹۳

(NO2) 1374-1551

aliph.(C-H) 2913 (C-Cl) 641

۳۳۱٥

۱٦۰۸

۱٥۹۰

۱۲۲۲

CH3

CH3

NO2

Cl

۹٤


۱۹۰

Table(30): Ultra violet spectra of the prepared 5-subsituted 1,2,4 diazole 3-thione

Peak

Structure

Fig. No.

Com. No.

ABS l max / nm

Ethanol

1.3 1.06

۲۰۹ ۲۱٥

۱۱٥

۸۸

0.59 0.14

۲۰٦ ۲۷۲

۱۱٦

۸۹

0.85 0.26

۲٦۸ ۳٤۲

۱۱۷

۹۰

1.18 0.41

۲۲۰ ۲۸۲

۱۱۸

۹۱

0.59 0.15

۲۱۸ ۲۷۱

۱۱۹

۹۲


۱۹۱

Peak

Structure

Fig. No.

Com. No.

ABS l max /

nm Ethanol

2.95 2.15

۲۹٥ ۲٥۹

۱۲۰

۹۳

0.54 0.41

۲٥۱ ۳٤۲

۱۲۱

۹٤


۱۹۲

Figure ( 111 ) FTIR spectrum of compound (88)



۱۹۳




۱۹٤




۱۹٥




۱۹٦




۱۹۷



۱۹۸


Figure (123): The expantion of 1H-NMR spectrum of compound (88)


۱۹۹

Figure ( 124 ): 13C-NMR spectrum of compound (88 )


۲۰۰

3-5-5 Substituted 1,3,4-thiadiazoles


benzothiazolyl) substituted phenoxy} N-thiosemicarbazide were added

portion wise to 25mL of conc. sulfuric acid at 0 C with continuous stirring.

The reaction mixture was stirred further for 3 hrs at room temperature.

Then it was poured into an ice-water mixture to precipitate a crude solid.

The crude product was then recrystallized from ethanol, as mention in

chapter two.


features: significant bands at ۳۳۱٥ cm-1, ۱٥٦۰ cm-1 , ۱٦۰٥ cm-1 , ۷٥۰ cm-1

and 1358 cm-1 was attributed to stretching vibrations of v( NH ) amine,

v( N=N ) azo group, v( C=N ) thiazole ring, v( C-S ) thioether group and

v( NO2 ) respectively as shown in Table ( 32 ), Fig. (125).


attributed to (p - p*) . The absorption is listed in Table ( 33 ), Fig. ( 129).


features: significant bands at ۳۳۱٤ cm-1, ۱٥٤۹ cm-1 , ۱٦۰۱ cm-1 , ۷٤٤ cm-1,



v( NO2 ) respectively as shown in Table ( 32 ), Fig. ( 126 ).



( 33 ), Fig. ( 130).


features: significant bands at ۳۳٦٥ cm-1, ۱٥۹٥ cm-1 , ۱٦۰۰ cm-1 , ۷٥٤ cm-1,





۲۰۱



( 33 ), Fig.( 132 ).

FT-IR spectrum of compound [99] showed the following characteristic

features: significant bands at ۳۳۲۲ cm-1, ۱٥٥۷ cm-1 , ۱٦۰۳ cm-1 , ۷٥٥ cm-1,





was attributed to (p -p*) and (n -p*). The absorption is listed in Table ( 33)

Fig.( 133 ).


d6.8 - 8.13 ppm for five aromatic hydrogen , signal at d1.09- 3.31 ppm for

aliphatic hydrogen (3H3, d ), (1H2, m ) and the signal at d4.35 ppm (2H,

singlet ) was attributed to (-NH2) proton, as shown in Table (34), Fig.

( 137).


for aromatic carbons, while the signal at 63 ppm for carbon in thiazole

ring, these and other signals are shown in Fig. (139).


۲۰۲

Table (۳۱): Physical properties of the prepared 2-amino 5(substituted) 1-3-4 thiadiazole

Rf

Solvent used in

the reaction

M.P C0

Molecular formula

Molecular weigh

Substituted

Com. No.

R4

R3

R2

R1

0.54

Absolute ethanol

Syrup

C17H13N7S2O3

(427)

H

H

H

NO2

۹٥

0.93

Absolute ethanol

Syrup

C19H17N7S2O3

(455)

H

C2H5

H

NO2

۹٦

0.81

Absolute ethanol

Syrup

C19H16N7S2O3Cl

(489)

CH3

CH3

NO2

Cl

۹۷

0.65

Absolute ethanol

Syrup

C17H12N8S2O5

(472)

H

NO2

H

NO2

۹۸

0.83

Absolute ethanol

Syrup

C17H12N8S2O5

(444)

H

H

NO2

NO2

۹۹

0.76

Absolute ethanol

Syrup

C18H15N6S2OBr

(484)

H

Br

H

CH3

۱۰۰

0.64

Absolute ethanol

Syrup

C17H13N8S2O3Cl

(476)

H

NH2

NO2

Cl

۱۰۱

0.89

Absolute ethanol

Syrup

C17H11N7S2O3ClBr

(549)

H

Br

NO2

Cl

۱۰۲


۲۰۳

Table(۳۲): FT-IR absorption bands of the prepared 2-amino 5 (substitute) 1-3-4 thiadiazole.

other band

n C-S-

C

n C=N

n N=N C=C

n N-H

Substituted

Com. No.

R4

R3

R2

R1

(NO2) 1358-1543

۷٥۰

۱٦۰٥

۱٥٦۰

۳۳۱٥

H

H

H

NO2

۹٥

alip.(C-H) 2978

(NO2) 1357-1551

۷٤٤

۱٦۰۱

۱٥٤۹

۳۳۱٤

H

C2H5

H

NO2

۹٦

alip.(C-H) 2987

(NO2) 1346-1550 (C-Cl) 643

۷٤۸

۱٦۱٥

۱٥٤٤

۳۳٥۰

CH3

CH3

NO2

Cl

۹۷

(NO2) 1347-1550

۷٥٤

۱٦۰۰

۱٥۹٥

۳۳٦٥

H

NO2

H

NO2

۹۸

(NO2) 1348-1551

۷٥٥

۱٦۰۳

۱٥٥۷

۳۳۲۲

H

H

NO2

NO2

۹۹

alip.(C-H) 2987

(C-Br) 847

۷٥٤

۱٦۲۰

۱٥۸۹

۳۳٤۲

H

Br

H

CH3

۱۰۰

(NO2) 1350-1540 (C-Cl) 645

۷٦۰

۱٦۰۹

۱٥۹۰

۳۳۲۲

H

NH2

NO2

Cl

۱۰۱

(C-Cl) 634 (NO2)

1350-1542 (C-Br) 844

۷٤٥

۱٦۳۷

۱٥٦٥

۳۳۱۹

H

Br

NO2

Cl

۱۰۲


۲۰٤

Table(33): Ultra violet spectra of the prepared 2-amino 5(substitute ) 1-3-4 thiadiazole

Peak

Structure

Fig. No.

Com. No.

ABS l max / nm

Ethanol

0.45

۳۷۰

۱۲۹

۹٥

1.29 1.23

۲۱٥ ۳۸۰

۱۳۰

۹٦

1.30 0.33

۲۷۱ ۳۹۲

۱۳۱

۹۷

2.15 0.15

۲۹٥ ۳٥۳

۱۳۲

۹۸

1.01 0.95

۲۲٥ ۲۳۷

۱۳۳

۹۹


۲۰٥

Peak

Structure

Fig. No.

Com. No.

ABS l max /

nm Ethanol

0.75 0.69

۲۳۷ ۳۲٥

۱۳٤

۱۰۰

1.44 0.28

۲۱۲ ۳٦٤

۱۳٥

۱۰۱

2.1 1.62

225 303

۱۳٦

۱۰۲


۲۰٦

Table(34): The NMR chemical shifts of some of the prepared compounds.

Chemical shifts DMSO

Structure

Fig. No.

Com. No.

d5.201(s, 2H1, NH); d7.400

(d,1H2, H Ar.); d7.952 ( d,

1H3 ,H Ar.); d 8.122(s, 1H4,

H Ar.).

۹

5

d 6.78 (s, 1H1, OH); d7.25 (d,

1H2, H Ar.); d7.45(d, 1H3, H

Ar.); d8.27 (s, 1H4, H Ar.); d

3.45 (s, 2H5, NH2); d8.13 (d,

1H6, H Ar.); d 7.95 (d, 1H7, H

Ar.); d8.75(s, 1H8, H Ar.).

٤٦

۱٦

d1.23 ( t,3H1, CH3); d4.25(m

2H2, CH2 ); d5.19 ( m,1H3,-

CH); d1.63 ( d , 3H4 , CH3)

;d7.15 (d,1H5,HAr.); d7.98

( d, 1H6, H Ar.); d8.05(d,

1H7, H Ar.); d8.45 (d, 1H8, H

Ar.); d7.51 (s, 1H9, H Ar.).

٦۸

٤۷


۲۰۷

NMR Chemical shifts

Structure

Fig. No.

Com. No.

d4.23(s,2H1, NH2); d2.48(m

1H2,CH); d1.19 (d,3H3,CH3)

; d7.19(d,1H4,H Ar.); d7.26

(d, 1H5, H Ar.); d7.76(d, 1H6,

H Ar.); d7.93 (d, 1H7, H

Ar.); d7.69 (s,1H8,H Ar.).

۱۰٦

۸۰

d6.23 (s, 1H1, NH) ; d7.15(s,

1H2,NH);d2.01(m,1H2, CH);

d1.23(d,3H3, CH3); d7.62 (d,

1H5, H Ar.); d7.81 (d, 1H6, H

Ar.); d7.96(d,1H7 ,H Ar.)

d8.31(d, 1H8, H, Ar.); d7.89

(s, 1H9, H Ar.).

۱۱۹

۸۸

d4.35(s, 2H1, NH2); d3.31

(m,1H2,-CH); d1.09 (d, 3H3,

CH3); d6.80 (d, 1H4, H Ar.);

d7.21(d, 1H5, H Ar.); d7.91

(d, 1H6, H Ar.); d8.13(d, 1H7,

H Ar.); d7.01(s, 1H8, H Ar.).

۱۳۳

۹٥


۲۰۸




۲۰۹




۲۱۰




۲۱۱




۲۱۲




۲۱۳




۲۱٤


Figure ( 138 ): The explanation of 1H-NMR spectrum of compound (95)


۲۱٥

Figure ( 139 ): 13C-NMR spectrum of compound (95)

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