Ministry of Higher Education
and Scientific Research
University of Baghdad
College of Science
Department of Chemistry
Synthesis and Characterization
of New Phthalimides linked to
Schiff ’s Bases
A thesis
Submitted to the College of Science University of Baghdad
in Partial Fulfillment of the Requirements for the Degree of Master of
Science in Chemistry
By
Marwa Shawqi Abd Al-Razzak
(B.Sc. 2008)
Supervised by
Dr. Ahlam Marouf Al-Azzawi
1433
2012
‫ﺑﺴﻢ اﷲ اﻟﺮﺣﻤﻦ اﻟﺮﺣﻴﻢ‬
‫أَﻧﺰل ِﻣﻦ اﻟﺴﱠﻤﺎءِ ﻣﺎء ﻓَﺴﺎﻟَﺖ أَو ِ‬
‫ِ‬
‫ِ‬
‫ﺎﺣﺘََﻤ َﻞ‬
‫ـ‬
‫ﻓ‬
‫ﺎ‬
‫ﻫ‬
‫ر‬
‫ﺪ‬
‫ﻘ‬
‫ﺑ‬
‫ﺔ‬
‫ﻳ‬
‫د‬
‫ٌ‬
‫َ‬
‫َ‬
‫َ َ ْ‬
‫َْ َ َ َ َ ً َ ْ ْ َ‬
‫اﻟﺴﱠﻴـﻞ َزﺑﺪا راﺑِﻴـﺎ و ِﻣﻤﱠﺎ ﻳﻮﻗِﺪون ﻋَﻠَﻴ ِﻪ ﻓِﻲ اﻟﻨـﱠﺎرِ اﺑﺘِ‬
‫ﺎء‬
‫ﻐ‬
‫َ‬
‫ْ َ‬
‫ْ ُ ًَ َ ً َ ُ ُ َ ْ‬
‫ﻛﺬَﻟِ‬
‫ﺎع زﺑﺪ ِ‬
‫ِﺣ ْﻠﻴ ٍ‬
‫ِ‬
‫ﻖ‬
‫ﺮ‬
‫ﻀ‬
‫ﻳ‬
‫ﻚ‬
‫ﻪ‬
‫ﻠ‬
‫ـ‬
‫ﺜ‬
‫ﻣ‬
‫ـ‬
‫ﺘ‬
‫ﻣ‬
‫أَو‬
‫ﺔ‬
‫ٍ‬
‫َ‬
‫ب اﻟﻠﱠﻪُ ا ْﻟ َﺤ ﱠ‬
‫ُ‬
‫ْ‬
‫َ‬
‫َ‬
‫َ‬
‫ُ‬
‫َ‬
‫ٌ‬
‫َ ْ‬
‫َ‬
‫َْ ُ‬
‫وا ْﻟﺒـ ِ‬
‫أَ‬
‫ﺄَ‬
‫ﺎس‬
‫ـ‬
‫ﻨ‬
‫اﻟ‬
‫ﻊ‬
‫ﻔ‬
‫ﻨ‬
‫ﻳ‬
‫ﺎ‬
‫ﻣ‬
‫ﺎ‬
‫ﻣ‬
‫و‬
‫ﺎء‬
‫ـ‬
‫ﻔ‬
‫ﺟ‬
‫ﺐ‬
‫ﻫ‬
‫ﺬ‬
‫ﻴ‬
‫ﻓ‬
‫ﺪ‬
‫ﺑ‬
‫ﺰ‬
‫اﻟ‬
‫ﺎ‬
‫ﻣ‬
‫ـ‬
‫ﻓ‬
‫ﻞ‬
‫ﺎﻃ‬
‫ﱠ‬
‫ﱠ‬
‫ﱠ‬
‫ﱠ‬
‫َ‬
‫َ‬
‫ْ‬
‫َ‬
‫َ‬
‫ْ‬
‫َ‬
‫َ‬
‫ُ‬
‫ُ‬
‫َ‬
‫َ َ ُ ُ ًَ‬
‫َ‬
‫َ َ‬
‫َ‬
‫ﻛﺬَﻟِ‬
‫ﺚ ﻓِ‬
‫ِ‬
‫ِ‬
‫َﻣﺜَـﺎلَ )‪(١٧‬‬
‫ﺮ‬
‫ﻀ‬
‫ﻳ‬
‫ﻚ‬
‫ض‬
‫َر‬
‫اﻷ‬
‫ﻲ‬
‫َ‬
‫ﻓَﻴَ ْﻤ ُ‬
‫ْ‬
‫َ‬
‫ﻜُ‬
‫ب اﻟﻠﱠﻪُ ْاﻷ ْ‬
‫ْ‬
‫َْ ُ‬
‫ﺻﺪق اﷲ اﻟﻌﻈﻴﻢ‬
‫ﻮرةُ اﻟﺮﻋﺪ{‬
‫} ُﺳ َ‬
‫» اﻵﻳﺔ‪« ١٧‬‬
Advisor Certification
I certify that this thesis was prepared under my supervision in the University of
Baghdad College of Science, as a partial requirement for the degree of Master of
Science in Chemistry.
Signature :
Advisor : Dr. Ahlam Marouf Al-Azzawi
Date
:
In view of the available recommendation , I forward this thesis for debate by the
examining committee .
Signature :
Name
: Dr. Mohammad Rifat Ahamad
Head of Chemistry Department
College of Science
Baghdad University
Date
:
Examination committee
We , the examining committee , certify that we have read this thesis and
examined the student in its contents and that , in our opinion , it is adequate
with "
" standing as a thesis for the degree of Master of Science
in Chemistry .
Signature :
Signature :
Name
:
Name
:
Date
:
Date
:
Chairman
Member
Signature :
Name
:
Date
:
Member
Signature :
Name
Date
: Dr. Ahlam Marouf Al-Azzawi
:
Supervisor
Approved by the University Committee on Graduate Studies.
Signature
:
Name
: Prof. Dr. Saleh Mahdi Ali
Dean of the College of Science.
Date
:
‫ﺇﻟﻰ ﻣﻦ ﻧﻬﻠﺖ ﻣﻨﻪ ﺍﻟﻌﻠﻢ ﻭﺃﻣﺪﻧﻲ ﺑﻨﺒﻊ ﺍﻟﺤﻴﺎﺓ ﻭﻋﻠﻤﻨﻲ ﺳﺒﻞ ﺍﻟﻌﻄﺎء‪،‬ﺇﻟﻰ ﻣﻦ ﻳﺒﺬﻝ ﻧﻔﺴﻪ‬
‫ﻭﺣﻴﺎﺗﻪ ﻣﻦ ﺍﺟﻠﻲ ‪ ،‬ﺇﻟﻰ ﺍﻟﻘﻠﺐ ﺍﻟﺪﺍﻓﺊ‬
‫‪)..........................................‬ﻭﺍﻟﺪﻱ ﺍﻟﻐﺎﻟﻲ(‪.........................................‬‬
‫ﺇﻟﻰ ﻣﻦ ﻣﺮﺕ ﺑﺤﻴﺎﺗﻲ ﻣﺮﻭﺭ ﺍﻟﺮﺑﻴﻊ ﻓﻲ ﻓﺼﻮﻝ ﺃﻟﺴﻨﻪ‪ ،‬ﻭﻟﻜﻦ ﺍﻟﺮﺑﻴﻊ ﻳﻌﻮﺩ ﻭﻫﻲ ﻟﻦ‬
‫ﺗﻌﻮﺩ‪ ,‬ﺇﻟﻰ ﻣﻦ ﺃﻳﻘﻈﺖ ﻓﻲ ﻧﻔﺴﻲ ﻗﻮﻯ ﺍﻟﺼﺒﺮ‪،‬ﺇﻟﻰ ﻣﻦ ﺭﺣﻠﺖ ﻋﻦ ﺍﻟﺪﻧﻴﺎ ﻭﺗﺮﻛﺖ ﻗﻠﺒﻲ‬
‫ﻳﻜﺴﺮﻩ ﺍﻟﺸﻮﻕ ﻟﻬﺎ‬
‫‪).........................................‬ﺃﻣﻲ ﺭﺣﻤﻬﺎ ﷲ(‪..............................‬‬
‫ﺇﻟﻰ ﺃﻣﻠﻲ ﻓﻲ ﺍﻟﺤﻴﺎﺓ ﻭﺍﻟﻠﺬﻳﻦ ﺃﻋﻄﻮﻧﻲ ﺍﻟﺪﻋﻢ ﻭﺍﻟﻘﻮﻩ ﺩﺍﺋﻤﺎ ‪ ،‬ﻓﺄﺷﺪ ﺑﻬﻢ ﺃﺯﺭﻱ ﻭﺃﻗﻮﻱ ﺑﻬﻢ‬
‫ﻋﺰﻳﻤﺘﻲ‪.‬‬
‫‪)..........................................‬ﺇﺧﻮﺗﻲ ﺣﻔﻈﻬﻢ ﷲ(‪....................................‬‬
‫ﺇﻟﻰ ﻣﻦ ﻧﻘﺸﻮﺍ ﻣﺤﺒﺘﻬﻢ ﻋﻠﻰ ﺟﺪﺭﺍﻥ ﻗﻠﺒﻲ ‪،‬ﻓﻜﺎﻧﻮﺍ ﻟﻮﺣﺎﺕ ﺟﻤﻴﻠﻪ ﺭﺳﻤﺖ ﺑﻴﻦ ﻣﺮﺍﻓﺊ‬
‫ﺍﻟﻮﺟﺪﺍﻥ ﺗﺸﻊ ﺑﺮﻳﻘﺎ ﻭﺟﻤﺎﻻ ﻣﻊ ﻣﺮﻭﺭ ﺍﻷﻳﺎﻡ‬
‫‪)..........................................‬ﺣﻨﺎﻥ‪,‬ﺷﻴﻤﺎء‪,‬ﻋﺬﺭﺍء(‪.................................‬‬
‫ﺇﻟﻰ ﺍﻟﺒﺮﺍﻋﻢ ﺍﻟﺼﻐﻴﺮﻩ‬
‫……………………)ﺳﺎﺭﻩ‪,‬ﺍﺑﺮﺍﻫﻴﻢ‪,‬ﻋﻤﺎﺭ‪,‬ﻋﻠﻲ‪,‬ﻫﺎﻟﻪ‪,‬ﺍﻳﻪ‪ ,‬ﻳﺴﺮ(‪…………...‬‬
ACKNOWLEDGMENTS
First of all , It is with great pleasure that I place my deep sense
of gratitude and heartfelt thanks to my supervisor Dr. Ahlam Marouf
Al-Azzawi for her immense guidance , Kind support , Constant
encouragement throughout the progress of the dissertation work , I wish
her a long life with best health.
My sky high respect with great thanks to Dr. Mohammad Rifat
Ahamad the Head of Chemistry Department , for providing the facilities
which helped in accomplishing .
I sincerely express my gratitude to University of Baghdad , College of
Science, Chemistry Department who helped me in various stages to
complete my project work successfully.
It would not have been possible to realise this work without the
friendly help and advice of several people.
Finally , my sincerest appreciation goes to my beloved family for their
endless love , patience , and having the fortitude to stay by my side during
these years .
Marwa
2012
CONTENTS
Subject
List of Contents
List of Tables
List of Figures
Abstract
Page
i
iv
v
vii
CHAPTER ONE : INTRODUCTION
1.1. Schiffs̕ base
1.2. Synthesis of Schiffs̕ bases
1.3. Applications of Schiffs̕ bases
1.4. Cyclic imides
1.5. Methods for synthesis of cyclic imides
1.5.1. Dehydration of amic acids by using dehydrating agents
1.5.2. Thermal Dehydration
1.5.3. Gabriel Type Synthesis
1.5.4. Diels-Alder Adducts
1.6. Other methods used in preparation of cyclic imides
1.7. Biological Activity of Cyclic Imides
Aim of the Work
i
1
2
8
9
10
10
11
11
12
12
18
22
CHAPTER TWO : EXPERIMENTAL
2.1. Instruments and Chemicals
2.1.1. Instruments
2.1.2. Chemicals
2.2. Part One
2.2.1. Preparation of N-phenyl phthalamic acid [1]
2.2.2. Preparation of N-phenyl phthalimide [2]
2.2.3. Preparation of 4-(N-phthalimidyl) phenyl sulfonyl chloride [3]
2.2.4. Preparation of 4-(N-phthalimidyl)phenyl sulfonyl hydrazine [4]
2.2.5. Preparation of Schiffs̕ Bases [5-18]
2.3. Part Two
2.3.1. Preparation of 4-(4'-(N-phthalimidyl) phenyl sulfonate
acetophenone) [19]
2.3.2. Preparation of 4-(4'-N-phthalimidyl) phenyl sulfonate
methyl benzylidene (Schiffs̕ bases) [20-26]
2.4. Part Three
2.4.1. Preparation of-(4-(4'-N-phthalimidyl) phenyl sulfonate
benzaldehyde) [27]
2.4.2. Preparation of 4-(4'-(N-phthalimidyl) phenyl sulfonate
benzylidene (Schiffs̕ bases) [28-33]
2.5. Part Four
2.5.1. Preparation of phthalimide potassium salt
2.5.2. Preparation of N-(4-phenyl phenacyl) phthalimide [34]
2.5.3. Preparation of Schiffs̕ bases [35-40]
ii
24
24
24
25
26
26
26
27
27
27
28
28
29
29
29
30
30
30
31
CHAPTER THREE : RESULTS AND DISCUSSION
3.1. Part One
3.1.1. N-phenyl phthalamic acid [1]
3.1.2. N-phenyl phthalimide [2]
3.1.3. 4-(N-phthalimidyl) phenyl sulfonyl chloride [3]
3.1.4. 4-(N-phthalimidyl) phenyl sulfonyl hydrazine [4]
3.1.5. N-[4-(N-phthalimidyl) phenylsulfonamido] benzylidene [5-18]
3.2. Part Two
3.2.1. 4-[4'-(N-phthalimidyl) phenyl sulfonate] acetophenone [19]
3.2.2. 4-[4'-(N-phthalimidyl) phenyl sulfonate] methyl
benzylidene [20-26]
3.3. Part Three
3.3.1. 4-[4'-(N-phthalimidyl) phenyl sulfonate] benzaldehyde [27]
3.3.2. 4-[4'-(N-phthalimidyl) phenyl sulfonate] benzylidene [28-33]
3.4. Part Four
3.4.1. N-(4-phenyl phenacyl) phthalimide [34]
3.4.2. N-phthalimidyl-4-phenyl (substituted benzylidene) methane
[35-40]
Biological Activity
Suggestions for Future Work
References
iii
32
32
33
35
36
38
61
61
62
76
76
77
91
91
92
104
105
106
LIST OF TABLES
Table
No.
Title
Page
3-1
Physical properties of compounds [1-4]
41
3-2
Physical properties of Schiffs̕ bases [5-18]
42
3-3
Spectral data of compounds [1-4]
44
3-4
Spectral data of Schiffs̕ bases [5-18]
44
3-5
Physical properties of compounds [20-26]
65
3-6
Spectral data of compounds [20-26]
66
3-7
Physical properties of compounds [28-33]
80
3-8
Spectral data of compounds [28-33]
81
3-9
Physical properties of compounds [35-40]
95
3-10
Spectral data of compounds [35-40]
96
iv
LIST OF FIGURES
Fig.
No.
1
FT-IR spectrum for compound [1]
46
2
FT-IR spectrum for compound [2]
47
3
FT-IR spectrum for compound [3]
48
4
FT-IR spectrum for compound [4]
49
5
FT-IR spectrum for compound [5]
50
6
FT-IR spectrum for compound [6]
51
7
FT-IR spectrum for compound [13]
52
8
1
53
9
13
10
1
11
13
12
1
13
13
14
1
15
13
16
FT-IR spectrum for compound [19]
67
17
FT-IR spectrum for compound [24]
68
18
FT-IR spectrum for compound [26]
69
19
1
70
20
13
21
1
Title
H-NMR spectrum of compound [1]
Page
C-NMR spectrum of compound [1]
54
H-NMR spectrum of compound [2]
55
C-NMR spectrum of compound [2]
56
H-NMR spectrum of compound [4]
57
C-NMR spectrum of compound [4]
58
H-NMR spectrum of compound [5]
59
C-NMR spectrum of compound [5]
H-NMR spectrum of compound [19]
60
C-NMR spectrum of compound [19]
71
H-NMR spectrum of compound [21]
72
v
22
13
23
1
24
13
25
FT-IR spectrum for compound [27]
82
26
FT-IR spectrum for compound [28]
83
27
FT-IR spectrum for compound [31]
84
28
1
85
29
13
30
1
31
13
32
1
33
13
34
FT-IR spectrum for compound [34]
97
35
FT-IR spectrum for compound [35]
98
36
FT-IR spectrum for compound [38]
99
37
1
38
13
39
1
40
13
C-NMR spectrum of compound [21]
73
H-NMR spectrum of compound [24]
74
C-NMR spectrum of compound [24]
H-NMR spectrum of compound [27]
75
C-NMR spectrum of compound [27]
86
H-NMR spectrum of compound [31]
87
C-NMR spectrum of compound [31]
88
H-NMR spectrum of compound [32]
89
C-NMR spectrum of compound [32]
H-NMR spectrum of compound [34]
90
100
C-NMR spectrum of compound [34]
101
H-NMR spectrum of compound [35]
102
C-NMR spectrum of compound [35]
vi
103
Abstract
The present work involved synthesis of new phthalimides linked to
Schiffs̕ bases through different strategies. The work was divided into four
main parts:
1. The first part involved synthesis of phthalimides linked to Schiff bases
through phenyl sulfonamido group [5-18] Scheme(1).
Performing this part include the following steps:
a. Synthesis of N-phenyl phthalamic acid [1] via reaction of phthalic
anhydride with aniline.
b. Dehydration of the synthesized phthalamic acid by acetic anhydride
and anhydrous sodium acetate as dehydrating agent producing Nphenyl phthalimide [2].
c. The
synthesized
chlorosulfonation
N-phenyl
phthalimide
reaction
producing
was
introduced
phthalimidyl
in
phenyl
sulfonyl chloride [3].
d. Phthalimidyl phenyl sulfonyl chloride was treated with hydrazine
hydrate producing phthalimidyl phenyl sulfonyl hydrazine [4].
e.
Reaction of compound [4] with different aromatic aldehydes and
ketones producing the target compounds [5-18].
2. The second part involved synthesis of new phthalimides linked to Schiffs̕
bases through phenyl sulfonate moiety [20-26] Scheme(2).
Performing this part involved the following steps:
a. Synthesis of phthalimidyl phenyl sulfonate acetophenone [19] via
reaction of the synthesized phthalimidyl phenyl sulfonyl chloride
with 4-hydroxy acetophenone.
vii
b. Reaction of compound [19] with different primary aromatic amines
producing the desired compounds [20-26].
3. The third part involved synthesis of new phthalimides linked to Schiffs̕
bases through phenyl sulfonate moiety [28-33]Scheme(3).
This part involved the following steps:
a. Synthesis of phthalimidyl phenyl sulfonate benzaldehyde [27] via
reaction of the synthesized phthalimidyl phenyl sulfonyl chloride
with 4-hydroxy benzaldehyde.
b. Reaction of compound [27] with different primary aromatic amines
producing the desired compounds [28-33].
4. The fourth part involved synthesis of new phthalimides linked to Schiffs̕
bases through methylene group [35-40].
Performing this part includes the following steps:
a. Synthesis of N-[4-phenyl phenacyl] phthalimide [34] via reaction of
phthalimide potassium salt with 4-phenyl phenacyl bromide.
b. Reaction of compound [34] with different primary aromatic amines
producing the desired compounds [35-40] Scheme(4).
All the synthesized compounds were characterized by FT-IR
spectroscopy and 1H-NMR , 13C-NMR spectra for some of them.
5. Antibacterial activity for some of the synthesized imides were evaluated
against two types of bacteria and the results showed that most of them
have a good antibacterial activity.
viii
NH2
O
C
O
COOH
Acetone
+
C
CONH
O
N-phenyl phthalamic acid [1]
Ac2O / NaOAc
reflux
-H2O
O
O
C
SO2Cl
N
C
HSO3Cl
N
C
C
O
O
4-(N-phthalimidyl) phenyl
sulfonyl chloride [3]
N-phenyl phthalimide [2]
reflux 6 hrs. Hydrazine hydrate
O
C
SO2NHNH2
N
C
reflux 6 hrs. Aromatic aldehydes
or ketones
O
4-(N-phthalimidyl) phenyl
sulphonyl hydrazine [4]
O
C
R
SO2 NH N=C
N
C
O
N-[4-(N-phthalimidyl) phenyl sulfonamido]
substituted imine [5-18]
R = (o and p-nitro phenyl,) ,
,
R' = H , CH3 , ph
, (o , m ,and p-hydroxy pheny,l) ,
Cl
,
,
CH3
O
N
H
Scheme (1)
ix
OCH3
R'
O
O
C
+
N
Cl
OH
S
C
O
O
N-phenyl phthalimide [2]
Chlorosulfonic acid
O
O
C
S
N
C
Cl
O
O
4-(N-phthalimidyl) phenyl sulfonyl chloride [3]
4-hydroxy acetophenone
O
O
C
O
C
C
O
S
N
CH3
O
O
4-[4'-(N-phthalimidyl) phenyl sulfonate] acetophenone [19]
Different primary
aromatic amines
O
O
C
CH3
C
C
O
S
N
N
R
O
O
[20-26]
4-[4'-(N-phthalimidyl) phenyl sulfonate] methyl benzylidene
H3C
R=
,
NO2
O2N
,
Cl ,
Cl
S
Cl ,
CH3 ,
N
Scheme (2)
x
CH3
O
O
C
+
N
Cl
C
OH
S
O
O
Chlorosulfonic acid
N-phenyl phthalimide [2]
O
O
C
S
N
C
Cl
O
O
4-(N-phthalimidyl) phenyl sulfonyl chloride [3]
4-hydroxy benzaldehyde
O
O
C
O
C
C
O
S
N
H
O
O
4-[4-'(N-phthalimidyl) phenyl sulfonate] benzaldehyde [27]
Different primary
aromatic amines
O
O
C
H
C
C
O
S
N
N
O
O
[28-33]
4-[4'-(N-phthalimidyl) phenyl sulfonate] benzylidene
H3C
R=
O2N
,
,
Cl
Cl
NO2
Cl ,
CH3 ,
Scheme (3)
xi
R
O
O
C
N
C
KOH (alcoholic)
H
NK
C
C
O
O
phthalimide potassium salt
unsubstituted Phthalimide
4-phenyl phenacyl bromide
O
O
C
N
CH2
C
C
O
N-(4-phenyl phenacyl) phthalimide [34]
Different primary
aromatic amines
O
NR
C
N
CH2
C
C
[35-40]
O
N-phthalimidyl-4-phenyl benzylidene methane
HO
R=
Br
,
,
OH
NO2
Cl ,
CH3 ,
Scheme (4)
xii
Chapter One
Introduction
1-1- Schiffʼs bases
A Schiffs̕ base is a type of chemical compounds containing carbonnitrogen double bond
=C
N=
N
in which nitrogen atom connected to aryl or
alkyl group,these compounds were named after Hugo Schiff
(1)
since their
synthesis was first reported by Schiff , they have the following general
structure.
R1
=N
R3
N R
C=
C
R2
arree aarryll oorr aallk
upss )
kyll grroou
R3 a
R22 , R
R11 , R
(R
The role of R3 group is to stabilize the iminic Schiffs̕ base.
Structurally a Schiffs̕ base (also known as imine or azomethine) is a
nitrogen analogue of an aldehyde or ketone in which the carbonyl group
(C=O) has been replaced by an imine or azomethine group.
Schiffs̕ bases of aliphatic aldehydes are unstable and readily
polymerizable while those of aromatic aldehydes having an effective
conjugation system are more stable(2).
The most common method for preparation of Schiffs̕ bases involved
acid-catalyzed condensation reaction of an amine and aldehyde or ketone
under refluxing conditions(3,4).
The first step in this reaction involved nucleophilic addition which
leads to the formation of unstable carbinol amine intermediate which loses
a molecule of water in the second step forming the corresponding imine.
R1
R2
C=O + R3NH2
O
OH H
C N
R2
R3
H
C N R3
R2
H
R1
R1
Carbinol amine
intermediate
1
R1
R2
C=NR3 + H2O
Chapter One
Introduction
1-2- Synthesis of Schiff ̕ s bases
The first preparation of imines was reported in the 19th century by
Schiffs̕ (1864). Since then a variety of methods for the synthesis of imines
have been described(5).
The classical synthesis reported by Schiffs̕ involves condensation of
carbonyl compound with an amine under azeotropic distillation(6),
molecular sieves are then used to remove the formed water. In 1990s an in
situ method for water elimination was developed using dehydrating
solvents such as tetramethylorthosilicate
or
trimethylorthoformate(7,8).
In 2004,Chakraborti et al.(9) demonstrated that the efficiency of these
methods is dependent on the use of highly electrophilic carbonyl
compounds and strongly nucleophilic amines.
They proposed use of substances that function as Bronsted-Lowry or
Lewis acids to activate the (C=O) of aldehydes , catalyze the nucleophilic
attack by amines and eliminate water as the final step.
Examples of the used Bronsted-Lowry or Lewis acids include :
ZnCl2,
alumina,
TiCl4,
H2SO4,
CH3COOH
and
HCl(10-15).
In the 12 past years a number of innovations and new techniques
have been reported, including solvent-free/ clay/microwave irradiation,
solid-state synthesis, water suspension medium, NaHSO4-SiO2/ microwave/
solvent-free and solvent-free/CaO/microwave(1٦-1۹).
Among these innovations microwave irradiation has been extensively
used due to its operational simplicity, enhanced reaction rates and
selectivity(۲۰).
In 2001 Roman and Andrei(۲۱) synthesized twenty new Schiffs̕ bases
with a potential biological activity resulted from the acid-catalyzed
condensation of orthophenolic aldehydes with several aromatic and hetero
aromatic amines in ethanol.
2
Chapter One
Introduction
OH
R3
R2
OH
R3
CHO
+ ArNH2
CH=N Ar
H2SO4 (Catalyst)
reflux
R1
R1
R2
R1 , R2 , R3 = H, Br, I
CH3
Cl
Cl
,
CH3
Cl
Ar =
,
Cl
Cl
CO2CH3
,
CO2CH3
CO2CH3
Yang et.al(22) performed a microwave-assisted preparation of a series
of Schiffs̕ bases via efficient condensation of salicylaldehyde and aryl
amines without solvent.
R
HO
CH
+
+
H
OH
O
=N
H=
N
CH
avvee
wa
Miccrroow
M
H2N
N
N
N
R
OH
= --CH3 , --Brr
R=
In this method microwave irradiation plays an important role for
promoting condensation reaction of aldehyde and amine thus reaction is
performed within (0.5min.-4mins.).
On the other hand eight new Schiffs̕ bases [2a-h] were prepared in
excellent yields via the condensation of different aromatic amines
and
azoaldehyde
[1]
2-hydroxy-3-methoxy-5-(4-methoxyphenylazo)
benzaldehyde in dry dichlolromethane in the presence of anhydrous
MgSO4(23).
3
Chapter One
Introduction
OCH3
OCH3
N=N
CH3O
OH + ArNH2
MgSO4
N=N
CH3O
OH
CH=N Ar
CHO
[1]
[2a-h]
OH
,
,
CH2
CH3
,
Ar =
H3CO
H3C
,
OCH3
,
OCH3
,
Treatment of two moles of azoaldehyde [1] with one mole of 4,4'diaminodiphenyl ether in refluxing absolute ethanol gave in excellent
yields the two novel compounds [3a-b].
H3
OCH
O
=N
N=
H3O
CH
H +
+ H
OH
H2N
N
O
H2
NH
N
X
X
CHO
= O , SO2)
X=
(X
H3
OCH
O
=N
N=
H3O
CH
H3O
CH
H
OH
O
=N
C=
HO
H
X
X
=N
N=
N
N
H3
OCH
=C
N=
N
=O
X=
3aa X
= SO22
3b X =
The new ten Schiffs̕ bases [2a-h] and [3a-b] showed different
antibacterial activities on testing against five types of bacteria.
Also several Schiffs̕ bases [5a-d] were synthesized by Baluja et al.(24)
via condensation of sulfanilamide [4] with aromatic aldehydes.
SO22NH2
HO
CH
SO22NH22
+
+
NH22
R2
2
R11
R
R2
R
=CH
H
N=
a--d]
[5a
[4]
= --H
= --H
a :: R 1 =
5a
, R2 =
= --H
= --OC H
R1
H
R2
H3 , R
5b :: R
2 =
1 =
=
=
c
:
R
H
H
R
5
S
C
H 3 , R 2 = -H
5c : R 1 = = --OH
= --OCH3 , R2 =
5d :: R1 =
4
R1
Chapter One
Introduction
The same team synthesized several Schiffs̕ bases [7a-d] via refluxing
5-ethyl resacetophenone [6] with aniline derivatives in methanol in the
presence of anhydrous ZnCl2.
H2
NH
N
H
OH
O
HO
H
nCll2 (aan
nh
Zn
h)
Z
+
+
H5C2
H
OH
HO
R3
R
COCH3
R1
R
H55C22
R2
R
[ 77aa--dd]
[6]
=N
C=
CH33
R3
R22
R1
R
= --N
= --H
= --H
R1 =
R2 =
H ,R
R3 =
H
NO2 , R
77aa :: R
= --CH3 , R22 =
= --H , R 3 =
= --CH 3
7b :: R11 =
= --H , R2 =
= --NO2 , R3 == --H
7cc :: R1 =
= --H , R2 =
= --CH3 , R3 =
= --H
7d :: R1 =
These Schiffs̕ bases [5a-d] and [7a-d] showed good antimicrobial
activity against different types of bacteria and fungi.
Since coumarin derivatives are of great interest due to their role in
natural and synthetic organic chemistry and many coumarin containing
products exhibit biological activity, coumarins containing a Schiffs̕ base
are expected to have enhanced biological activities, so according to this
satyanarayana and coworkers(25) synthesized a series of new Schiffs̕ bases
containing coumarin moiety by the condensation of aryl/hetero aromatic
aldehydes with 2-[(4-methyl-2-oxo-2H-chromen-7-yl)oxy]acetohydrazide
[8] under conventional and microwave conditions.
O
H22N--HN
O
C
O
HO
CH
O
O
R
R
+
+
[8]
CH3
R
R
N H
N
N
O
C
[ 9aa--f ]
O
H3
CH
= --H
R=
H , --NO2 , --Cll , --OH
H , --OCH
H3 , --N(CH
H3)2
R
The synthesized compounds have been screened for antimicrobial
activity.
Non classical methods including water based reaction, microwave
and grindstone chemistry were used by Naqvi(26) and coworkers for the
preparation of Schiffs̕ bases [10a-f] from 3-chloro-4-fluoroaniline and
several benzaldehydes.
5
O
Chapter One
Introduction
NH2
Cl
CHO
+
R
Cl
CH=N
method A , B
and C
F
R
F
Schiff bases
R = 3,4-Di OCH3 , 2-Cl , 4-Cl , 2-OH , 4-OH , 3-NO2
[10a-f ]
The key raw materials were allowed to react in water, under
microwave irradiation and grindstone.
These
methodologies
constitute
an
energy
efficient
and
environmentally benign greener chemistry version of the classical
condensation reactions for Schiffs̕ bases formation(27,28).
Water has been proved here as a suitable (green solvent) for the
synthesis of Schiffs̕ bases and increase in %yield is in following order =
Method C < Method B < Method A
(grindstone) < (Microwave) < (Water based synthesis)
S. Kumar et al.(28) synthesized ten Schiffs̕ bases of sulfonamides by
condensing 4-aminobenzene sulfonamide with different aromatic aldehydes
in the presence of glacial acetic acid and ethanol at (50-60)°C.
SO2NH2
CHO
C2H5OH / HOAC glacial
reflux (5-6) hrs
+
R
SO2NH2
NH2
N=CH
R = -H , -Cl , -OH , -N(CH3)2 , OCH3 , NO2 , -(OCH3)3
The antimicrobial activity
of these compounds were examined
against different Gram-positive, Gram-negative bacteria and fungal strains.
The presence of azomethine and sulfonamide functional group is
responsible for antimicrobial activity.
On the other hand G. Kumar et al.(29) synthesized new Schiffs̕ base via
mixing a warm dilute ethanolic solution of thiocarbohydrazide with
2-amino-4-ethyl-5-hydroxy benzaldehyde under reflux for 2hrs.
6
Chapter One
Introduction
S
HN
CHO
HO
2
S
+
H5C2
H2N
NH2
N
H
N
H
NH2
NH
HO
CH=N
N=CH
OH
H5C2
NH2
H2N
C2H5
Reflux
Complex of Cr, Mn and Fe with this Schiffs̕ base were prepared .The
Schiffs̕ base ligand and their complexes were tested for their antimicrobial
against many types of bacteria and fungi. The Cr(III) Complex showed the
best antimicrobial activity but the ligand alone was found to be active
against the fungus trichoderma reesei.
Yang and Sun(30) prepared Schiffs̕ base [9] 4-methyl-N-(3,4,5trimethoxy benzylidene)benzene amine by three different ways.
NH2
CHO
HC=N
CH3
+
OCH3
H3CO
OCH3
H3CO
CH3
OCH3
OCH3
[9]
The first one involved introducing a mixture of p-toluidine, 3,4,5trimethoxy benzaldehyde, neutral alumina and dichloromethane into
microwave oven irradiated for 4 mins.
While in the second way a solution of the two mentioned reactants in
benzene was heated in reflux until no water appear then removing solvent
in vaco.
The third method involved addition of
anhydrous MgSO4 to a
solution of trimethoxy benzaldehyde and p-toluidine in dichloromethane
followed by stirring for 2hrs. at room temperature. Comparison the results
of the three methods shown in Table (1-1) indicated that microwave
method is the most convenient one since it affords higher yields in shorter
reaction time, clean and cheap.
7
Chapter One
Introduction
Table (1-1)
Way
Reaction condition
Time
Yield(%)
1
Microwave irradiation
4 min.
85
2
Reflux
Over 7 hr
72
3
Room temperature stirring
4 hr
75
1-3- Applications of Schiffʼs bases
The chemistry of the carbon-nitrogen double bond plays a vital role in
the progress of chemistry science(31).
Schiffs̕ bases have been widely used in many fields e.g.
biological(32-34), inorganic(35,36), analytical(37,38) drug synthesis and as
bidentate ligand in the field of coordination chemistry.
The Schiffs̕ base complexes have been used in catalytic reactions and
also have been used as fine chemicals and medical substrates(39,40).
Schiffs̕ bases form a significant class of compounds in medicinal and
pharmaceutical chemistry(41-44) with several biological applications that
include antibacterial(45-61), antifungal(62-68), antimalarial(69), anticancer(70-74),
antitubercular(75) , anti-inflammatory(76) , antimicrobial(70) , antiviral(46),
antitumor(78,79) and herbicidal(80) activities.
Also Schiffs̕ bases are important class of ligands due to their synthetic
flexibility, their selectivity and sensitivity towards the central metal
atom(81-83).
The imine group present in such compounds has been shown to be
critical to their biological activities(84).
Anticancer activities of three Schiffs̕ bases N-(1-phenyl-2-hydroxy-2phenyl ethyledine)-2̀̀,4̀-dinitro phenyl hydrazine (PDH), N-(1-phenyl-2hydroxy-2-phenyl ethyledine)-2̀̀-hydroxy phenyl imine (PHP) and N-(2hydroxy benzylidine)-2̀̀-hydroxy phenyl imine (HHP) against Ehrlich
8
Chapter One
Introduction
ascities carcinoma (EAC) cells in Swiss albino mice have been studied(85).
These compounds enhanced life span, reduced average tumor weight
and inhibited tumor cell growth of EAC cell bearing mice.
HC
=N--NH
C=
H
O
OH
O2N
=N
C=
HC OH
NO2
HO
PDH
PHP
=N
H=
N
CH
HO
H
O
H
OH
HH P
1-4- Cyclic imides
Cyclic imides such as maleimide [10], succinimde [11], phthalimide
[12], glutarimide [13], and citraconimide [14] are cyclic organic
compounds, their molecules contain an imide ring and the general structure
(-CO-N(R)-CO-)(86).
N
O
O
O
N
R
N
R
O
O
O
[11]
[10]
R
[12]
O
O
H3C
N
R
N
O
R
O
[13]
[14]
These cyclic imides are an important functionality which have been
found to maintain significant biological activity(87,88).
9
Chapter One
Introduction
1-5- Methods for synthesis of cyclic imides
Synthesis of cyclic imides may be performed by many methods
including
1-5-1- Dehydration of amic acids by using dehydrating agents
The most common method used for preparation of cyclic imides
involved dehydration of amic acids by using different dehydrating agents.
Amic acids are organic compounds containing both carboxyl and
amide groups in their molecules and can be prepared easily with excellent
yields via reaction of cyclic anhydrides with different aliphatic or aromatic
amines(89-95).
Treatment of amic acids with suitable dehydrating agents lead to
dehydration and cyclization producing the corresponding cyclic imides as
shown in Scheme (1-1).
O
COOH
C
O
C
+
RNH2
CONHR
O
O
C
N
R
Suitable dehydrating agent
C
O
Scheme (1-1)
The most important dehydrating agents used in dehydrating of amic
acids to the corresponding imides include:
1-Acetic anhydride with anhydrous sodium acetate(96-104).
2-Thionyl chloride(105-107).
3-Acetyl chloride with triethyl amine(108,109).
4-Phosphorus trichloride(110,111).
5-Phosphorus pentaoxide(112).
10
Chapter One
Introduction
1-5-2- Thermal Dehydration
This method has been used for preparation of imides whenever
dehydration agents failed to do so(113,114).
Al-Azzawi(115) applied this method successfully in the preparation of
several N-substituted citraconimides in high yields (85-90%).
Also Al-Azzawi and Al-Obaidi(116) performed synthesis of several N(hydroxy phenyl)phthalimides by depending on fusion method. Moreover
Al-Azzawi and Ali(117-120) synthesized a series of
N-(hydroxy phenyl)
maleimides and N-(hydroxy phenyl) citracoimides in high yields and purity
by application of this method.
R
COOH
R
Fusion
CONH
O
C
N
C
OH
OH
O
(R = H or CH3)
O
COOH
Fusion
CONH
C
C
OH
N
OH
O
1-5-3- Gabriel Type Synthesis
This method involved treatment of potassium salt of unsubstituted
succinimide and phthalimide with different alkyl halides producing the
corresponding N-substituted imides(121).
O
O
C
NH
C
+
C
KOH
C
O
O
O
C
C
N
O
N K
(CH2)2
OH + KBr
Scheme (1-2)
11
Br(CH2)2OH
Chapter One
Introduction
1-5-4- Diels-Alder Adducts
Maleimide and substituted maleimides can be prepared by heating
maleic anhydride with cyclopentadiene to form Diels-Alder adduct [15]
which was then converted to imide [15] by reaction with amine.
Heating of [16] would produce N-substituted maleimide(122) as
shown in Scheme (1-3)
O
O
+
O
C
C
O
O
C
C
RNH2
N
C
R
C
O
O
[15]
[16]
O
O
C
+
N R
C
O
Scheme (1-3)
1-6- Other methods used in preparation of cyclic imides
The development of simple, relatively mild, efficient and practical
method for the synthesis of N-alkyl and N-arylphthalimides and
succinimides was reported by Langade(123).
This method was performed by using (10 mol%) sulphamic acid
catalyst. Thus a series of N-substituted phthalimides and succinimides were
prepared via reaction of phthalic and succinic anhydride with primary
amines in acetic acid in the presence of (10%) sulphamic acid at (110 °C)
for appropriate time.
12
Chapter One
Introduction
O
O
C
C
O
C
N
C
O
R
O
NH2
or
Sulphamic acid
+
R
O
C
or
O
C
O
C
R = -H , 4-Cl , 4-NO2 , 3-OH , 4-CH3 ,
4-OCH3
N
C
O
R
O
On the other hand N-(4-nitro-2-phenoxy phenyl)methane sulfonamide
or nimesulide [17] a preferential cyclo oxygenase-2(COX-2) inhibitor is
one of the well known non-steroidal anti-inflammatory drugs that has been
utilized to treat pain and other inflammatory diseases.
Reduction of the nitro group in [17] afforded the required amine [18] .
Treatment of [18] with a variety of cyclic anhydrides in refluxing glacial
acetic acid in the presence of sodium acetate afforded a series of novel
nimesulide-based cyclic imides [19-24] as shown in Scheme (1-4).
Some of the synthesized imides showed anti-inflammatory activities
when tested in rats(124).
The prepared new imides and reaction conditions are shown in Table
(1-2) .
O
NHSO2CH3
O
NO2
[17]
C
NHSO2CH3
Sn / HCl
o
90 C , 3h.
O
NH2
C
NHSO2CH3
O
O
Cyclic anhydrides
O
[18]
Scheme (1-4)
13
C
O
N
C O
Imides [19-24]
Chapter One
Introduction
Table (1-2)
Reaction conditions for preparation of imides (19-24)
Comp.
No.
Cyclic
anhydrides
Cyclic imides
O
O
C
C
O
O
C
C
C
O
O
Ph
h
OP
O
O
NO22
O
O
C
O
C
C
C
N
O2N
O
O
C
C
O
O
C
C
C
C
C
H3
HSO2C H
NH
N
C
Ph
h
OP
O
O
O
O
O
24
65
110-120 ºC
15 min
65
110-120 ºC
20 min
65
110-120 ºC
20 min
75
O
O
O
O
C
NH SO22C H33
Phh
OP
O
O
O
O
23
110-120 ºC
15 min
OPPhh
O
N
C
O
O
C
C
HS O2CH
H3
NH
N
O
C
C
C
C
65
O
O
O
22
110-120 ºC
15 min
O
O
O
C
C
HSO2CH
H3
NH
N
C
C
O
N
O2N
O
73
O
O
C
C
21
110-120 ºC
10 min
Phh
OP
O
O
O
O
C
O22
NO
HS O2CH
H3
NH
N
C
C
O
20
Yield(%)
O
O
C
19
Reaction
conditions
O
O
O
O
C
C
C
HSSO
H3
NH
O2C
CH
N
N
N
Phh
OP
O
The unsubstituted cyclic imide is an important functionality which
has been found to maintain significant biological activity(125-129).
A series of un substituted cyclic imides were prepared from cyclic
anhydrides, hydroxylamine hydrochloride and 4-N,N-dimethyl amino
pyridine (DMAP) base catalyst under microwave irradiation(130).
This novel microwave synthesis produced high yields of the
unsubstituted cyclic imides as shown in Table (1-3).
O
O
O
O
C
C
O
C
C
+
+
DM
MA
P
AP
D
waavvee
Miiccrroo w
M
onn
irrrraadaatti o
H2 OH
H..H
HCll
NH
C
H
N H
N
C
O
O
O
14
Chapter One
Introduction
Table (1-۳): Synthesis of unsubstituted imides using NH2OH and DMAP
Imides
Time(min)
Yield(%)
2.68
97
1.82
96
1.57
84
O
O
C
C
H
H
N
N
C
C
O
O
O
O
C
C
C
H
H
N
N
O
O
C
C
C
H
H
N
N
O
On the other hand Mogilaiah and Sakram(131) reported a practical and
efficient method for the synthesis of 1,8-naphthyridinyl phthalimides.
Treatment of 2-amino-3-aryl-1,8-naphthyridines [25a-g]with phthalic
anhydride in the presence of catalytic amount of DMF in absence of
solvent under microwave irradiation afforded the corresponding N-(3-aryl1,8-naphthyridin-2-yl) phthalimides [26a-g] Scheme (1-5) in excellent
yields (92-98%) with short reaction time (3-4 min). The reaction is simple,
clean, rapid and efficient.
O
Ar
C
+
N
N
Ar O
DMF
M.W
O
C
NH2
N
N
O
[25a-g]
N
[26a-g]
a
b
c
d
, Ar = C6H5
, Ar = p-CH3OC6H4
, Ar = o-ClC6H4
, Ar = m-ClC6H4
C
C
O
e , Ar = p-ClC6H4
f , Ar = p-BrC6H4
g , Ar = p-NO2C6H4
Scheme (1-5)
Also a series of phthalimides possessing N-phenoxyalkyl moiety
substituted at position 3 or 4 of the phenyl ring [27-35] was synthesized
and evaluated for anticonvulsant activity(132).
15
Chapter One
Introduction
Synthesis of these imides [27-35] performed by alkylation of
potassium phthalimide with appropriate phenoxyalkylbromide in the
presence of K2CO3 and triethylbenzylammonium chloride (TEBA) in
acetone as shown in Scheme (1-6).
Phenoxyalkyl bromides used in the synthesis of compounds [68-76]
were prepared from reaction between the phenols and an excess of 1,2dibromoethane or 1,3-dibromopropane.
R'
R'
OH +
Br
(CH2)n Br
O
(CH2)n Br
(n = 2 , 3)
(n = 2 , 3)
O
O
C
C
(R = Br)
C
K2CO3 , TEBA
acetone , 6 h reflux
+ R Br
N K
C
N
R
O
O
Scheme (1-6)
Comp.
No.
Comp.
No.
R
R
H3
OC H
27
H2) 2
(C H
O
H3)3
C(CH
32
28
H2) 2
CH
(C
O
O
Cll
C
33
O
O
Cll
29
H2)2
( CH
O
H3
CH
34
O
O
H3)3
C (C H
O
O
Cll
30
H3
OCH
35
O
O
F3
CF
31
O
O
16
O
O
Chapter One
Introduction
Moreover a new series of 2-(1,3-dioxo-2,3-dihydro-1H-2-isoindolyl)
ethyl-2-hydroxy-2-(substituted phenyl) acetates
[39a-e]
have
been
synthesized from the combination of N-(2-hydroxy ethyl)phthalimide [36]
and substituted mandelic acids [38a-e] which resulted in both antiinflammatory and antimicrobial activities(133).
Among the compounds tested for anti-inflammatory activity
compounds [39b] and [39e] showed significant activity and compound
[39b] showed potent antibacterial and antifungal activity.
O
C
O
O +
C
NH2
OH
O
C
Et3N
Toluene
reflux , 4 hr
OH
N
C
O
[36]
OH
OH
+
CHO
COOH
R
COOH
NaOH
o
(0-5 C)
HO
R
[35a-d]
[38a-d]
R = H , CH3 , Cl , OCH3
OH
OH
+
CHO
COOH
COOH
NaOH
o
(0-5 C)
HO
[35e]
[38e]
OH
O
O
C
C
N
C
R
O
OH
O
[39a-d]
[36]
+ [38a-e]
DCC
Dioxane
R.T. 18 hr
OH
O
O
C
C
N
C
O
OH
O
[39e]
Scheme (1-7)
17
Chapter One
Introduction
1-7- Biological Activity of Cyclic Imides
N-substituted cyclic imides represent an important class of bioactive
molecules that show a wide range of pharmacological activities such as
anti-inflammatory, anxiolytic, antifungal , antiviral , antibacterial, analgesic
and antitumor properties(134-142).
Beside these biological effects some phthalimide derivatives
constitute an important class of compounds possessing diverse type of
biological
properties
antimicrobial(143),
including
antimalarial(143),
antihypertensive(144), antiviral(145) and herbicides(146,147) activity.
Also N-phenylphthalimide and its derivatives have been widely
reported to possess beneficial pharmacological effects , they have
been
shown
to
be
anticonvulsant(148,149),
anti-inflammatory
and
hypolipidemic(150,151).
In addition tetrachlorophthalimide has been reported to possess
potent hypoglycemic activity(152-154).
A series of sixteen N-phenylphthalimide derivatives [40-55] was
synthesized by the reaction between phthalic anhydride and different
amines in acetic acid at reflux temperature(155).
The α-glucosidase inhibitory activity of these compounds [40-55] in
microbial and mammalian enzymes was evaluated and the results showed
that N-phenylphthalimide substituted at position 3 of the benzene ring with
NO2 group showed moderate α-glucosidase inhibitory activity, while the
presence of NO2 group at the 2- and 4-positions resulted in the most active
α-glucosidase inhibitor among N-phenylphthalimide derivatives.
R11
R2
O
R
O
C
C
R3
R
N
N
O
18
Chapter One
Introduction
Table (1-4)
Comp. No.
R1
R2
R3
40
H
H
H
41
NO2
H
H
42
H
NO2
H
43
H
H
NO2
44
NO2
H
NO2
45
NH2
H
H
46
H
NH2
H
47
H
H
NH2
48
NH2
H
NH2
49
H
Cl
H
50
H
H
Cl
51
Cl
H
Cl
52
H
Br
H
53
H
OH
H
54
NO2
H
Cl
55
Cl
H
NO2
Also a series of new cyclic imides [56a-b] and [57a-b] with a carbazole
skeleton and a basic side chain at the imide nitrogen were tested in vitro for
tumor cell-growth inhibition(156).
The results showed that compound [56a] is a superior as compared to
[56b] the latter lacking the second methyl group at the aromatic scaffold.
19
Chapter One
Introduction
Likewise when [57a] is compared to its methoxy derivative [57b] the
latter structural modification is clearly beneficial.
R
O
C
N
C
N
H
N(C2H5)2
O
CH3
56a R = CH3
56b R = H
R
CH3
O
C
N
C
N
N(C2H5)2
O
57a R = H
57b R = CH3O
On the other hand a series of N-substitutedmaleimides linked to
benzothiazole moiety [58a-j] were synthesized by Al-Azzawi and
Mehdi(157), via reaction of maleic anhydride with different substituted-2aminobenzothiazoles producing benzothiazol-2-yl maleamic acids followed
by dehydration with acetic anhydride and sodium acetate Scheme (1-8).
Antimicrobial activity study of the synthesized maleimides [58a-j]
against Staphylococcus aureus, Klebsiella pneumonia and Candida
albicans showed that many of the prepared maleimides have good
antimicrobial activity.
Also Al-Azzawi and Hassan(158) synthesized a series of citraconimides
linked to benzothiazole moiety [59a-k], Scheme (1-9) studying their
antimicrobial activity against Staphylococcus aureus, Streptococcus
pyogenes, E.Coli, Pseudomonas aeruginosa and Candida albicans, most
of the tested citraconimides showed good antibacterial and antifungal
activities.
20
Chapter One
Introduction
O
S
C
+
NH2
O
C
N
R
HOOC
S
N
R
N
C
H
O
O
R = H , 6-CH3 , 6-Cl , 6-NO2 ,
4,6-dichloro , 4,6-di CH3 ,
6-OCH3 , 4-NO2-6-Cl ,
6-COOH , 4-Cl-6-NO2
O
S
Ac2O
NaOAc
C
N
C
N
R
O
[58a-j]
Scheme (1-8)
CH3
O
H3C
S
S
C
+
NH2
O
C
N
R
HOOC
N
R
N
C
H
O
O
R = 6-CH3 , 6-Cl , 6-NO2 , 6-COOH ,
4,6-dichloro , 6-OCH3 , 4,6-di CH3 ,
6-COOH-7-OH , 6-NHCO3 , 4-NO2-6-Cl ,
4-Cl-6-NO2
O
S
C
Ac2O / NaOAc
N
R
or Fusion
C
N
CH3
O
[59a-k]
Scheme (1-9)
Moreover Al-Azzawi and Al-Amerri(159) synthesized a series of
phthalimides [60-64] and succinimides [65-69] linked to 1,3,4-oxadiazole
moiety , the new imides showed good antibacterial activity against
Staphylococcus aureus and E. Coli bacteria.
O
R
O
O
C
N
N
O
R
N
C
N
C
N
O
[60-64]
N
[65-49]
(R = 2-OH , H , 4-Cl , 4-OCH3 , 2-NO2)
21
C
O
Chapter One
Introduction
Aim of the Work
Since both phthalimides and Schiffs̕ bases exhibited wide range of
biological activities and have wide spectrum of biological applications the
target of this work involved synthesis of new phthalimides linked to Schiffs̕
bases by using different strategies involving the following parts:
Part One
This part involved synthesis of phthalimides linked to Schiffs̕ base
through phenyl sulfonamido group.
These new imides were synthesized via preparation of N-phenyl
phthalamic acid which introduced subsequently in dehydration reaction
producing N-phenyl phthalimide and this was treated with chloro sulfonic
acid producing phthalimidyl phenyl sulfonyl chloride which in turn was
treated with hydrazine hydrate producing phthalimidyl sulfonyl hydrazine
which represent the main synthones introduced in reaction with different
aldehydes and ketones to afford the desired new phthalimides.
Part Two
This part involved synthesis of new phthalimides linked to Schiffs̕
base through phenyl sulfonate moiety via reaction of phthalimidyl sulfonyl
chloride with 4-hydroxy acetophenone producing phthalimidyl phenyl
sulfonate acetophenone which in turn introduced in reaction with different
primary aromatic amines producing the desired new phthalimides.
Part Three
This part involved synthesis of new phthalimides linked to Schiffs̕
base through phenyl sulfonate moiety via reaction of phthalimidyl sulfonyl
chloride with 4-hydroxy benzaldehyde producing phthalimidyl phenyl
sulfonate benzaldehyde which in turn introduced in reaction with different
primary aromatic amines producing the desired imides.
22
Chapter One
Introduction
Part Four
This part involved synthesis of new phthalimides linked to Schiffs̕
base through methylene group via reaction of 4-phenyl phenacyl bromide
with phthalimide potassium salt producing N-(4-phenyl phenacyl)
phthalimide which in turn introduced in reaction with different primary
aromatic amines to afford the desired imides.
23
Chapter Two
Experimental
2-1- Instruments and Chemicals
2-1-1- Instruments
1. Melting points were determined on Gallenkamp capillary melting point
apparatus.
2. FT-IR spectra were recorded using KBr discs on SHIMADZU FT-IR8400 Fourier Transform Infrared Spectrophotometer, in college of
science, Baghdad University and on SHIMADZU FT-IR-prestige-21
Fourier Transform Infrared Spectrophotometer,in Ibn-Sina Company.
3. 1H-NMR and
13
C-NMR spectra were recorded on near magnetic
resonance Bruker, Ultrasheild 300 MHZ in Jordan, using tetra methyl
silane as internal standard and DMSO-d6 as solvents.
2-1-2- Chemicals
Chemicals used in this work were purchased from BDH, Merck and
Fluka companies and involved the following:
No.
Chemical Compounds
1
Phthalic anhydride
2
Acetic anhydride
3
Different primary aromatic amines
4
Ethanol(abs.)
5
Acetic acid (glacial)
6
Anhydrous sodium acetate
7
Chlorosulfonic acid
8
Acetone
9
Hydrazine hydrate
10
Different aromatic aldehydes and ketones
24
Chapter Two
Experimental
No.
Chemical Compounds
11
Ethanol
12
Methanol
13
Hydrochloric acid
14
4-phenyl phenacyl bromide
15
Unsubstituted Phthalimide
16
Potassium hydroxide
17
Sodium hydroxide
18
Sodium bicarbonate
19
Cyclo hexane
20
Dioxane
The experimental chapter in this work involved the following parts:
2-2- Part One
This part involved synthesis of phthalimides linked to Schiffs̕ bases
through sulfonamido group.
Performing this target involved the following steps:
1. Synthesis of N-phenyl phthalamic acid.
2. Dehydration of the prepared N-phenyl phthalamic acid producing
N-phenyl phthalimide.
3. Chlorosulfonation
of
the
prepared
phthalimide
producing
4-(N-phthalimidyl) phenyl sulfonyl chloride.
4. Treatment of phthalimidyl phenyl sulfonyl chloride with hydrazine
hydrate producing the corresponding sulfonyl hydrazine.
5. Introducing of sulfonyl hydrazine in reaction with different aromatic
aldehydes and ketones producing the desirable new phthalimide.
25
Chapter Two
Experimental
2-2-1- Preparation of N-phenyl phthalamic acid [1]
To a solution of (0.01 mol, 1.48 g) of phthalic anhydride in 25 mL of
acetone, (0.01 mol, 1mL) of aniline was added drop wise with stirring and
cooling(120,160,161,).
Stirring was continued for two hours at room temperature the resulted
precipitate was filtered, dried, recrystallized from ethanol.
The physical properties of compound [1] are listed in Table (3-1).
2-2-2- Preparation of N-phenyl phthalimide [2]
A mixture of (0.01 mol, 2.41 g) of N-phenyl phthalamic acid in 25 mL of
acetic anhydride and (5 %) by weight of anhydrous sodium acetate was
refluxed for two hours with stirring(158,162).
The resulted homogenous solution was cooled to room temperature and
pouring into crushed ice, compound [2] was obtained filtered, dried,
recrystallized from acetone.
The physical properties of compound [2] are listed in Table (3-1).
2-2-3- Preparation of 4-(N-phthalimidyl) phenyl sulfonyl chloride [3]
Chlorosulfonic acid (4 mL) was added drop wise to (0.01 mol, 2.23 g)
of N-phenyl phthalimide during two hours with stirring and keeping
temperature at 0 oC(162).
Stirring was continued for ten hours at room temperature then the
resulted mixture was poured into crushed ice carefully with stirring.
The obtained precipitate was filtered, dried, recrystallized from acetone.
The physical properties of compound [3] are listed in Table (3-1).
26
Chapter Two
Experimental
2-2-4- Preparation of 4-(N-phthalimidyl)phenyl sulfonyl hydrazine [4]
To a solution of (0.01 mol, 3.22 g) of compound [3] in 5 mL of absolute
ethanol, (0.01 mol) of hydrazine hydrate was added drop wise with stirring
and keeping temperature at 0 oC.
The resulted mixture was refluxed for six hours then cooled to room
temperature then pouring on crushed ice with stirring(163).
The resulted precipitate was filtered, washed with cold water, dried and
finally recrystallized from ethanol.
The physical properties of compound [4] are listed in Table (3-1).
2-2-5- Preparation of Schiffs̕ Bases [5-18]
A mixture of 4-(N-phthalimidyl) phenyl sulfonyl hydrazine (0.01 mol,
3.17 g), aromatic aldehyde or ketone (0.01 mol) and (2-3) drops of glacial
acetic acid in absolute ethanol (20 mL) was refluxed for six hours(164).
After cooling the obtained precipitate was filtered then washed with
cold ethanol, dried and recrystallized from a suitable solvent.
Physical properties of compounds [5-18] are listed in Table (3-2).
2-3- Part Two
This part involved synthesis of new phthalimides linked to Schiffs̕ bases
through phenyl sulfonate moiety.
Performing this target involved the following steps:
1. Reaction of 4-(N-phthalimidyl) phenyl sulfonyl chloride with 4hydroxy
acetophenone
producing
4-(4'-(N-phthalimidyl)
phenyl
sulfonate) acetophenone.
2. Introducing of the prepared phthalimidyl sulfonate acetophenone in
reaction with different primary aromatic amines producing the desirable
new imides.
27
Chapter Two
2-3-1- Preparation
Experimental
of
4-(4'-(N-phthalimidyl) phenyl sulfonate)
acetophenone [19]
In a three-necked flask equipped with a stirrer and thermometer a
mixture of (2.04 g, 0.015 mol) of 4-hydroxy acetophenone and (3 mL) of
pyridine was placed.
The flask was surrounded by a bath sufficiently cold to lower the
thermometer of the mixture to 10 oC(164).
4-(N-phthalimidyl)phenyl sulfonyl chloride (0.01 mol, 3.22 g) was
added in portions during 20 minutes with continuous stirring.
The mixture was refluxed for two hours on a water bath then cooled to
room temperature then the reaction mixture was poured into cold water with
stirring until the resulted oily layer solidified.
The solid product was filtered, washed with cold dilute HCl solution
followed by dilute NaHCO3 solution then with distilled water , dried,
recrystallized from ethanol to give pale brown crystals in 70% yield and
m.p.(152-154)oC.
FT-IR: 1739, 1720 cm-1 n(C=O) imide, 1674 cm-1 n(C=O) ketone,1593
cm-1 n(C=C) aromatic , 1361 cm-1 and 1176 cm-1 n(SO2) sulfonate.
2-3-2- Preparation of 4-(4'-N-phthalimidyl) phenyl sulfonate methyl
benzylidene (Schiffs̕ base) [20-26]
In a suitable round bottomed flask (0.01 mol, 4.21 g) of compound [19]
was dissolved in 20 mL of absolute ethanol then (0.01 mol) of primary
aromatic amine was added followed by addition of (2-3) drops of glacial
acetic acid with stirring.
The mixture was refluxed for four hours then cooled to room
temperature and the obtained precipitate was filtered, dried and purified by
28
Chapter Two
Experimental
recrystallization from a suitable solvent.
The physical properties of Schiffs̕ bases [20-26] are listed in Table (3-5).
2-4- Part Three
This part involved synthesis of new phthalimides linked to Schiffs̕ bases
through sulfonate moiety.
Performing this target involved the following steps:
1. Reaction of 4-(N-phthalimidyl) phenyl sulfonyl chloride with
benzaldehyde producing 4-(4'-(N-phthalimidyl) phenyl sulfonate)
benzaldehyde.
2. Introducing of the prepared phthalimidyl sulfonate benzaldehyde in
reaction with different primary aromatic amines producing the desirable
new imides.
2-4-1- Preparation of 4-(4'-N-phthalimidyl) phenyl sulfonate
benzaldehyde [27]
The titled compound [27] was prepared by following the same
procedure used in the preparation of compound [19] except using of
4-hydroxy benzaldehyde instead of 4-hydroxy acetophenone, recrystallized
from ethanol to give pale brown crystals in 72% yield and m.p.(176-178)oC.
FT-IR: 1741 and 1718 cm-1 n(C=O) imide, 1699 cm-1 n(C=O) aldehyde,
1593 cm-1 n(C=C) aromatic and 1360, 1186 cm-1 n(SO2) sulfonate.
2-4-2-
Preparation
of
4-(4'-N-phthalimidyl) phenyl sulfonate
benzylidene (Schiffs̕ bases) [28-33]
The titled compounds were prepared by following the same procedure
used in the synthesis of compounds [20-26] except using of compound [27] as
starting material instead of compound [19].
The physical properties of compounds [28-33] are listed in Table (3-7).
29
Chapter Two
Experimental
2-5- Part Four
This part involved synthesis of new phthalimides linked to Schiffs̕ bases
through methylene (-CH2-).
Performing this target involved the following steps:
1. Preparation of phthalimide potassium salt.
2. Reaction of phthalimide potassium salt with 4-phenyl phenacyl bromide
producing N-(4-phenyl phenacyl) phthalimide.
3. Introducing N-(4-phenyl phenacyl) phthalimide in reaction with
different primary aromatic amines producing the desirable imides.
2-5-1- Preparation of phthalimide potassium salt
Phthalimide (0.01 mol, 1.47 g) was dissolved in 20 mL of absolute
ethanol then was heated in a water bath.
The obtained clear solution was added to alcoholic potassium
hydroxide solution [(0.01 mol) KOH in 25 mL absolute ethanol] with
continuous stirring and cooling, then the obtained precipitate was
filtered and dried.
2-5-2- Preparation of N-(4-phenyl phenacyl) phthalimide [34]
In a suitable round bottomed flask (0.01 mol, 2.75 g) of 4-phenyl
phenacyl bromide was dissolved in 25 mL of absolute ethanol then (0.01 mol,
1.85 g) of phthalimide potassium salt was added gradually with stirring(164).
The resulted mixture was refluxed for six hours with continuous stirring
then was cooled to room temperature and the formed precipitate was filtered,
washed with distilled water and dried.
The solid product was recrystallized from ethanol producing reddish
brown crystals in 65% yield and m.p.(106-108)oC.
30
Chapter Two
Experimental
FT-IR: 1774 and 1716 cm-1 n(C=O) imide, 1689 cm-1 n(C=O) ketone,
1600 cm-1 n(C=C) aromatic and 1392 cm-1 n(C-N) imide.
2-5-3- Preparation of Schiffs̕ Bases [35-40]
A mixture of (0.01 mol, 3.41 g) of N-(4-phenyl phenacyl) phthalimide,
(0.01 mol) of primary aromatic amine in 25 mL of absolute ethanol and (2-3)
drops of glacial acetic acid was refluxed for six hours with stirring.
The resulted mixture was cooled to room temperature and the
precipitate was obtained, filtered, dried, recrystallized from a suitable solvent.
The Physical properties of the prepared Schiffs̕ bases [35-40] are listed
in Table (3-9).
31
Chapter Three
Results and Discussion
Results and Discussion
Among the bicyclic nitrogen heterocycles phthalimides are an
interesting class of compounds with a large range of applications.
Recently phthalimide and some of its derivatives have provide to
have important biological effects similar or even higher than known
pharmacological molecules and so their biological activity is being
a subject of biomedical research(143-151).
Schiffs̕ bases belong to a widely used group intermediates important
for production of specially chemicals like pharmaceuticals or rubber
additives and also have uses in many fields including analytical, inorganic,
medicinal and polymer chemistry(32-38).
According to all these mentioned facts the target of the present work
has been directed toward building of new molecules containing these two
active moieties (phthalimide and Schiffs̕ base) via applying different
strategies, involving the following parts:-
3-1-Part One
3-1-1- N-phenyl phthalamic acid [1]
Compound [1] was prepared via reaction of equimolar amounts of
phthalic anhydride and aniline in acetone.
The reaction was carried out(159) via nucleophilic attack of amino
group of aniline on carbonyl group in phthalic anhydride as shown in
Scheme (3-1).
۳۲
Chapter Three
O
C
O
C
Results and Discussion
O
....
Acceettoonnee
A
+ H2N
+
O
H
C
N
C
H
O
O
O
O
H
C NH
C OH
O
mee (3--1)
Sccheem
The physical properties of compound [1] are listed in Table (3-1).
FT-IR spectra of compound [1] showed strong absorption bands at
3325 cm-1 and at 3136 cm-1 due to n(O-H) carboxylic and n(N-H) amide.
Other absorption bands appeared at 1720 cm-1, 1643 cm-1 and 1600
cm-1 due to n(C=O) carboxylic, n(C=O) amide and n(C=C) aromatic
respectively(165).
1
H-NMR spectrum of this compound showed signals at δ= (7.04-
7.89) ppm due to aromatic protons and (N-H) proton and a clear signal at
δ= 10.33 ppm due to (O-H) carboxylic proton while 13C-NMR spectrum of
the same compound showed signals at δ= (119.9-140) ppm, 167.8 ppm
and 167.92 ppm due to aromatic ring carbons, (C=O) amide and (C=O)
carboxyl respectively(166).
3-1-2- N-phenyl phthalimide [2]
Compound [2] was prepared via dehydration of the prepared
N-phenyl phthalamic acid using acetic anhydride and anhydrous sodium
acetate as dehydrating agent.
Mechanism(159) steps of dehydration reaction are shown in Scheme
(3-2).
۳۳
Chapter Three
Results and Discussion
O
C
O
OH
C
H3 COO N
Naa
++ CH
C
N
N
O H
Naa
ON
++ CH3 COOH
C
N
H
O H
O
C
C
O Naa
O
C
N
++
C
O
C
CH 3
C
H3
CH
C
C
C
CH3
N
O
O
O
H3
CH
C
O
C
....
N
H
H
C
O
O
O H
O
O
O C
H
H 3C
O
O H
O
O
O Naa
O
N
C
H3
CH
++ CH3COO Naa
O H
O
O
O
C
N
C
H3COOH
H
+ CH
+
O
mee (3--2)
Scchheem
The physical properties of compound [2] are listed in Table (3-1) and
its structure was confirmed by FT-IR, 1H-NMR and
13
C-NMR spectral
data. Thus FT-IR spectrum of compound [2] showed disappearance of
n(O-H) and n(N-H)absorption bands proving success of dehydration
reaction and appearance of two bands at 1735 cm-1 and 1708 cm-1 for
asym. and sym. n(C=O) imide , absorption bands of n(C=C) aromatic
and n(C-N) imide appeared
1
at 1593 cm-1 and 1384 cm-1 respectively.
H-NMR spectrum of compound [2] showed disappearance of
(O-H) carboxyl proton signal and appearance of two multiplet signals at
۳٤
Chapter Three
Results and Discussion
δ= (7.44-7.56) ppm and (7.89-7.97) ppm of two aromatic rings protons.
13
C-NMR spectrum of the same compound showed signals at
δ= (123.8-135.1) ppm and δ= 167.4 due to aromatic ring carbons and
(C=O) imide respectively.
3-1-3- 4-(N-phthalimidyl) phenyl sulfonyl chloride [3]
The titled compound was prepared via treatment of N-phenyl
chlorosulfonic acid at 0 oC.
phthalimide with
Mechanism(157) of this reaction involved electrophilic attack by
chlorosulfonic acid on para position of phenyl ring in phthalimide as
described in Scheme (3-3).
O
O
O
Cll
S
C
+
+
H
OH
O
N
C
O
O
O
O
O
O
Cl
S
C
OH
N
H
H
C
O
O
O
O
C ll
OH
C
S
N
N
H
H
C
O
O
O
O
Cl
OH 2
C
N
S
C
O
O
O
--H 2O
O
O
Cl
C
N
S
C
O
O
me
ch
em
e ( 3--3)
he
Sc
۳٥
Chapter Three
Results and Discussion
The physical properties of compound [3] are listed in Table (3-1).
FT-IR spectrum of compound [3] showed absorption bands at 1743
cm-1 and 1720 cm-1 due to asym. and sym. n(C=O) imide, also two clear
absorption bands appeared at 1365 cm-1 and 1188 cm-1 due to asym. and
sym. n(SO2) respectively.
Other absorption bands appeared at 1585 cm-1 and 1300 cm-1 due to
n(C=C) aromatic and n(C-N) imide respectively.
Compound[3] was identified also by application of Lassaigne test(164),
thus the positive results obtained in both tests for sulfur and chlorine gave
another proofs for structure of compound [3].
3-1-4- 4-(N-phthalimidyl) phenyl sulfonyl hydrazine [4]
Compound [4] was prepared via treatment of phthalimidyl phenyl
sulfonyl chloride with hydrazine hydrate.
The mechanism(157) of this nucleophilic substitution reaction was
performed by nucleophilic attack of amino group of hydrazine compound
on sulfur atom in compound [3] followed by elimination of (HCl) molecule
as described in Scheme (3-4).
۳٦
Chapter Three
Results and Discussion
O
C
N
N
C
O
....
Cl ++ H2N
S
NH 2
O
O
O
C
N
C
O
Cl
H2
N NH
S
H
H
O
O
HCll
--H
O
C
N
C
O
O
S
HN
H2
NH
NH
N
O
O
mee (3--4)
Scchheem
The physical properties of compound [4] are listed in Table (3-1) and
its structure was confirmed by FT-IR, 1H-NMR and
13
C-NMR spectral
data.
FT-IR spectrum of compound [4] showed two strong absorption bands at
3359 cm-1 and 3265 cm-1 to (-NH-NH2) group and this is an excellent proof
for the success of hydrazine compound formation.
Other absorption bands appeared at 1718 cm-1, 1710 cm-1, 1595 cm-1,
1390 cm-1, 1338 cm-1 and 1170 cm-1 due to asym. n(C=O) imide, sym.
n(C=O) imide, n(C=C) aromatic, asym. n(SO2), n(C-N) imide and
n(SO2) respectively.
۳۷
sym.
Chapter Three
1
Results and Discussion
H-NMR spectrum of this compound showed signals at δ= (3.5
and 3.8) ppm due to (NH2) and (NH) of hydrazine moiety while
signals
13
of
aromatic
C-NMR
protons
spectrum
of
appeared
compound
at
[4]
δ= (7.39-7.99) ppm.
showed
signals
at
δ= (124-137.9) ppm and 167 ppm due to carbons of aromatic ring and
(C=O) imide respectively.
Details of FT-IR spectral data of compounds [1-4] are listed in Table (3-3).
3-1-5- N-[4-(N-phthalimidyl)phenylsulfonamido]benzylidene[5-18]
The final step in this part involved introducing of compound [4]
phthalimidyl sulfonyl hydrazine in condensation reaction with different
aromatic aldehydes and ketones to afford the desirable phthalimides linked
to Schiffs̕ base through phenyl sulfonamide group.
The first step in condensation reaction between the hydrazine
compound and carbonyl compounds involved nucleophilic addition(167) of
hydrazine compound to carbonyl group producing [I] which eliminate
water molecule in step two to afford the desirable Schiffs̕ base [II] as
shown in Scheme (3-5).
۳۸
Chapter Three
Results and Discussion
O
O
R
1-- R
OH
R ''
C
H
H3COOH
H/H
CH
Prroottoonnaattiioonn
P
O
R'
R
C
C
..
HN H
H2
NH
S
N
C
C
O
O
R
R
C
C
R'
R
++
H3 COO
CH
H
OH
O
C
2--
R
R
OH
++
R
R
R'
R
C
C
O
O
O
C
O2 N
H
NH
SSO
N
H
H
H
OH
N
N
R
C R
C
R'
R
C
H3C
H
OO
OH
CH
CO
C
H
H
O
CH3C OO
Prroottoonnaattioonn
P
C H3C OOH / H
O
O
H2
OH
O
C
C
SO 2 N H
N
N
N
C
C
O
O
H
H
[ I]
R
C R
C
R'
R
CH3 COO
H2O
--H
O
C
R
R
N
H N==C
NH
SO 2 N
C
O
R'
R
H3C
H
OO
OH
CH
CO
C
H2O
H
[ IIII]
=H
H oorr ddiiff ff eerreenntt aallkkyll oorr aarryll grroouupss)
R=
(R
'
= ddiiff ff eerreenntt aallkkyll oorr aarryll grroouupss)
R=
(R
mee (3--55)
Scchheem
Physical properties of compounds [5-18] are listed in Table (3-2)
and their structures are confirmed by FT-IR, 1H-NMR and
spectral data.
۳۹
13
C-NMR
Chapter Three
Results and Discussion
FT-IR spectra of compounds [5-18] showed disappearance of the two
characteristic absorption bands at 3359 and 3265 cm-1 due to (-NH-NH2)
group in hydrazine compound [4] and appearance of new clear absorption
band at (1608-1658) cm-1 due to n(C=N) imine.
These two points are excellent proofs for the success of Schiff base
formation(168).
Besides FT-IR spectra of compounds [5-18] showed clear absorption
bands at (1735-1743) cm-1 and (1706-1720) cm-1 due to asym. and sym.
n(C=O) imide.
Other absorptions appeared at (1573-1604) cm-1, (1373-1388) cm-1,
(1157-1170)cm-1 and (1315-1348) cm-1 due to n(C=C) aromatic, asym.
n(SO2), sym. n(SO2) and n(C-N) imide respectively.
Moreover FT-IR spectra of Schiff bases [6,8,12,15] showed clear
absorption band at (3429-3479) cm-1 n(O-H) phenolic, while compound [7]
showed two absorption bands at (1234 and 1126) cm-1 n(C-O-C) ether and
finally compound [14] showed strong absorption band at 1091 cm-1 due to
n(C-Cl).
All details of FT-IR spectral data of compounds [5-18] are listed in
Table (3-4).
1
H-NMR spectrum of compound [5] showed signal at δ= 1.4 ppm
belong to (CH3) protons, multiplet signals at
δ= (7.39-8.34) ppm due to
aromatic protons and signal at δ= 8.97 ppm due to imine (-CH=N-) proton.
13
C-NMR spectrum of compound [5] showed signals at δ= 24.97
ppm, (123.8-134.4) ppm, 135.3 ppm and 159.1 ppm due to (CH3) group,
aromatic ring carbons, (C=N) imine and (C=O) imide respectively.
1
H-NMR spectrum of compound [7] showed signal at δ= 3.51 ppm
due to (OCH3) protons and four multiplet signals at δ= (6.89-7.96) ppm
due to aromatic protons.
٤۰
Chapter Three
13
Results and Discussion
C-NMR spectrum of compound [7] showed signal at δ= 57 ppm
due to (OCH3) group and signals at δ= (123.9-127.1) ppm, 135.1 ppm and
168 ppm due to aromatic carbons, (C=N) imine
and (C=O) imide
respectively.
Table (3-1): Physical properties of compounds [1-4]
Comp.
No.
Color
Melting
Points °C
Yield
%
Recrystallization
Solvent
White
170-172
88
Ethanol
Off
white
204-205
85
Acetone
SO2Cl
Brown
200 dec.
72
Acetone
SO2NHNH2
White
210 dec.
95
Ethanol
Compound structure
COOH
1
CONH
O
C
2
N
C
O
O
C
3
N
C
O
O
٤
C
N
C
O
٤۱
Chapter Three
Results and Discussion
Table (3-2): Physical properties of Schiffs̕ bases [5-18]
Comp.
No.
Compound structure
Color
O
CH3
C
5
Melting
Yield Recrystallization
Points
%
Solvent
°C
N
H
NH N=C
Pale
yellow
119-120
85
Acetone
Orange
168-170
87
Acetone
Off
white
192-193
81
Ethanol
SO2 NH N=C
H
Deep
yellow
196-198
54
Acetone
CH3
SO2 NH N=C
White
179-181
80
Ethanol
SO2
C
O
O
H
SO2 NH N=C
C
6
N
OH
C
O
O
C
7
N
SO2 NH N=C
OCH3
C
O
O
HO
C
8
N
C
O
O
C
9
N
C
O
٤۲
Chapter Three
Comp.
No.
Results and Discussion
Compound structure
O
Color
O2N
C
10
Melting
Yield Recrystallization
Points
%
Solvent
°C
N
C
Off
white
138-139
66
Ethanol
Off
white
200 dec.
72
Acetone
OH
Off
white
174-175
63
Ethanol
NO2
Pale
yellow
130-132
91
Ethanol
Cl
White
226 dec.
77
Ethanol
Off
white
135-136
83
Acetone
Pale
yellow
> 220
93
Ethanol
White
187-188
90
Acetone
Yellow
198 dec
86
Ethanol
SO2 NH N=C
H
O
O
C
11
N
SO2 NH N=C
C
O
O
C
N
12
CH3
SO2 NH N=C
C
O
O
C
13
N
H
SO2 NH N=C
C
O
O
C
14
N
H
SO2 NH N=C
C
O
O
OH
C
15
N
SO2
H
NH N=C
C
O
O
CH3
SO2 NH N=C
C
N
16
NO2
C
O
O
C
17
N
H
SO2 NH N=C
C
O
18
O
C
N
C
S O2 N H N
H
N H
O
O
٤۳
Chapter Three
Results and Discussion
Table (3-3): Spectral data of compounds [1-4]
Comp.
No.
FTIR spectral data cm-1
Compound structure
n(O-H)
carboxylic
n(N-H) n(C-H)
n(C=O) n(C=O)
amide aromatic carboxylic amide
n(C=C)
aromatic
COOH
1
3325
CONH
O
C
2
3136
3062
1720
1643
1600
n(C-H)
aromatic
n(C=O) imide
n(C=C)
aromatic
n(C-N) imide
3074
1735
1708
1593
1384
n(C-H)
aromatic
n(C=O) n(C=C)
imide aromatic
n(SO2)
asym.
n(SO2)
sym.
n(C-N) imide
1365
1188
1300
n(C=C)
aromatic
n(SO2)
asym.
n(SO2) n(C-N)
sym.
imide
1595
1390
N
C
O
O
C
3
SO2Cl
N
C
1585
n(-NH NH2) n(C-H) n(C=O)
hydrazine aromatic imide
O
C
4
1743
1720
3101
O
SO2NHNH2
N
C
3359
3265
O
3097
1743
1718
1170
1338
Table (3-4): Spectral data of Schiffs̕ bases [5-18]
Comp.
No.
FTIR spectral data cm-1
Compound structure
O
N
others
CH3
C
5
n(N-H) n(C=O) n(C=N) n(C=C) n(SO2) n(SO2) n(C-N)
amide
imide
imine aromatic asym.
sym.
imide
SO2
H
NH N=C
C
3221
1739
1712
1627
1589
1373
1165
1338
-
3221
1739
1716
1608
1589
1373
1165
1338
Phenolic
1743
1716
1651
O
O
C
6
N
H
SO2 NH N=C
OH
C
n(O-H)
3340
O
O
n(C-O-C)
C
7
N
C
O
SO2 NH N=C
OCH3
3417
٤٤
1597
1377
1168
1315
1234
1126
Chapter Three
Results and Discussion
O
HO
C
8
N
C
SO2 NH N=C
H
n(O-H)
1739
1716
1616
3043
1716
1624
1573
1388
1157
1330
-
3030
1741
1706
1610
1595
1386
1166
1340
n(NO2)
1498
3151
1735
1716
1654
1593
1377
1168
1319
-
3209
1739
1716
1627
1604
1377
1168
1342
Phenolic
3221
1739
1716
1651
1589
1373
1165
1338
3377
1741
1716
1625
1595
1375
1170
1330
n(C-Cl)
1091
3221
1739
1716
1627
1589
1373
1165
1338
Phenolic
3232
1740
1716
1658
1593
1373
1165
1342
n(NO2)
1469
1300
3147
1741
1720
1625
1593
1375
1170
1338
-
3400
1741
1718
1620
1593
1380
1170
1348
n(C=O)
Amide
1701
3221
1589
1377
1165
1338
Phenolic
3479
O
O
C
9
N
CH3
SO2 NH N=C
C
O
O
O2N
C
10
N
C
SO2 NH N=C
H
O
O
C
N
11
SO2 NH N=C
C
O
O
C
12
N
CH3
SO2 NH N=C
OH
C
n(O-H)
3460
O
O
C
13
N
H
SO2 NH N=C
NO2
C
n(NO2)
1496
O
O
C
14
N
H
SO2 NH N=C
Cl
C
O
O
OH
C
15
N
SO2
H
NH N=C
C
n(O-H)
3429
O
O
CH3
SO2 NH N=C
C
16
N
NO2
C
O
O
C
17
N
H
SO2 NH N=C
C
O
O
18
C
N
C
SO2 NH N
N H
O
O
٤٥
COOH
CONH
%T
Wave number ( cm-1 )
Fig. No. ( 1 ) : FT-IR spectrum for compound [ 1 ]
46
%T
O
C
N
C
O
Wave number ( cm-1 )
Fig. No. ( 2 ) : FT- IR spectrum for compound [ 2 ]
47
%T
O
C
N
C
SO2Cl
O
Wave number ( cm-1 )
Fig. No. ( 3 ) : FT- IR spectrum for compound [ 3 ]
48
%T
O
C
N
C
SO2NHNH2
O
Wave number ( cm-1 )
Fig. No. ( 4 ) : FT- IR spectrum for compound [ 4 ]
49
%T
O
O
C
N
C
H
O
=
H N=C
S 22 NH
CH3
O
Wave number ( cm-1 )
Fig. No. ( 5 ) : FT-IR spectrum for compound [ 5 ]
50
O
C
N
C
SO2
H
H
=C
NH N=
O
%T
Wave number ( cm-1 )
Fig. No. ( 6 ) : FT- IR spectrum for compound [ 6 ]
51
H
OH
O
O
C
N
C
H
=C
H N=
SO22 NH
O
%T
Wave number ( cm-1 )
Fig. No. ( 7 ) : FT- IR spectrum for compound [ 13 ]
52
N O22
COOH
CONH
Fig. No. ( 8 ) : 1H-NMR spectrum for compound [ 1 ]
53
COOH
CONH
Fig. No. ( 9 ) : 13C-NMR spectrum for compound [ 1 ]
54
O
C
N
C
O
Fig. No. ( 10 ) : 1H-NMR spectrum for compound [ 2 ]
55
O
C
N
C
O
Fig. No. ( 11 ) : 13C-NMR spectrum for compound [ 2 ]
56
O
C
N
C
SO2NHNH2
O
Fig. No. ( 12 ) : 1H-NMR spectrum for compound [ 4 ]
57
O
C
N
C
SO2NHNH2
O
Fig. No. ( 13 ) : 13C-NMR spectrum for compound [ 4 ]
58
O
O
C
N
C
H
SO22 NH
H N==C
CH3
O
Fig. No. ( 14 ) : 1H-NMR spectrum for compound [ 5 ]
59
O
O
C
N
C
H
SO22 NH
H N==C
CH3
O
Fig. No. ( 15 ) : 13C-NMR spectrum for compound [ 5 ]
60
Chapter Three
Results and Discussion
3-2-Part Two
3-2-1- 4-[4'-(N-phthalimidyl) phenyl sulfonate] acetophenone [19]
The titled compound [19] was prepared via reaction between
4-(N-phthalimidyl)
phenyl
sulfonyl
chloride
[3]
and
4-hydroxy
acetophenone.
This reaction represent esterfication between acid chloride
(compound [3]) and substituted phenol (4-hydroxy acetophenone) and the
mechanism(167) was suggested via nucleophilic attack of phenolic hydroxyl
group on sulfur atom in acid chloride followed by elimination of (HCl)
molecule as described in Scheme (3-6).
O
C
N
N
C
O
S
O
....
+ H
Cl +
HO
C
H3
CH
O
O
nee
Pyrridin
O
O
C
N
C
O
O
Cl
S O
O
C
H3
CH
H
O
HCll
--H
O
C
N
C
O
O
O
S
O
O
O
[ 119]
mee (3--6)
Sccheem
٦۱
C
CH3
Chapter Three
Results and Discussion
Compound [19] was recrystallized from ethanol and was obtained as
pale brown crystals in 70% yield with melting point (152-154)oC.
The major FT-IR absorptions in FT-IR spectrum of compound [19]
include absorption bands at 1739 cm-1 and 1720 cm-1 due to asym. and
sym. n(C=O) imide, bands at 1674 cm-1, 1593 cm-1, 1361 cm-1 and 1176
cm-1 due to n(C=O) ketone, n(C=C) aromatic, asym. n(SO2) and
sym.
n(SO2) respectively.
1
H-NMR
δ= 2.569
spectrum of
compound
[19] showed
signal
at
ppm (CH3) group protons and multiplet signals at
(δ= 7.28-8.13) ppm due to aromatic protons, while 13C-NMR spectrum
of the same compound showed signal at δ= 27.2 ppm due to (CH3) group.
Signals at δ= (122.6-153) ppm due to aromatic ring carbons , signal
at δ= 166.8 ppm due to (C=O) imide and signal at δ= 198 ppm due
to
(C=O) ketone.
Chemical test for compound [19] gave positive results in both
(Iodoform test) and general test for carbonyl compounds(169) and these are
good additional proofs for success of compound [19] formation.
3-2-2- 4-[4'-(N-phthalimidyl) phenyl
benzylidene [20-26]
sulfonate]
methyl
The titled Schiffs̕ bases [20-26] were prepared via condensation
reaction of compound [19] with different primary aromatic amines.
Mechanism(167) of this reaction involved nucleophilic attack of
primary amine on carbonyl group in compound [19] producing addition
product [I] which subsequently eliminated water molecule producing the
desirable compound as shown in Scheme (3-7).
٦۲
Chapter Three
Results and Discussion
O
C
N
C
O
1[19]
O
O
O
Protonation
CH3COOH / H
O
O
C
C
O
O
CH3
C
O
O
C
S
N
C
OH
C
O
O
+
CH3COO
CH3
+
RNH2
OH
O
C
C
O
O
C
O
S
N
..
O
O
C
S
N
C
OH H
O
S
N
C
OH H
CH3COOH / H
O
OH2 H
C
O
C
O
O
CH3COOH
Protonation
O
S
R
CH3
C
N
N
C
O
O
O
CH3COO
R
CH3
O
C
H
N
C
O
O
O
O
CH3
O
O
[I]
OH
O
S
N
2-
CH3
C
O
S
CH3COO
N
R
+
CH3COOH
CH3
-H2O
O
C
C
O
O
C N
O
S
N
[20-26]
H3C
,
R=
R
CH3
NO2
O2N
,
Cl ,
Cl
S
Cl ,
CH3 ,
N
Scheme (3-7)
٦۳
CH3
+
H2O
Chapter Three
Results and Discussion
Physical properties of compounds [20-26] are listed in Table (3-5).
FT-IR spectra of compounds [20-26] showed disappearance of
absorption band at 1674 cm-1 which due to n(C=O) ketone and appearance
of clear strong absorption band at (1681-1690) cm-1 due to n(C=N) imine.
FT-IR spectra of
compounds
[20-26]
showed
bands
at
(1725-1743) cm-1, (1710-1726) cm-1, (1593-1595) cm-1, (1361-1385) cm-1
and (1176-1199) cm-1 due to asym. n(C=O) imide, sym. n(C=O) imide,
n(C=C) aromatic, asym. n(SO2) and sym. n(SO2) respectively.
All details of FT-IR spectral data of compounds [20-26] are listed in
Table (3-6).
1
H-NMR spectrum of compound [21] showed two signals at
δ= 2.35 ppm and δ= 2.56 ppm due to two (CH3) groups, while signals at
δ=(7.28-8.12) ppm are due to aromatic ring protons.
13
C-NMR spectrum of the same compound showed signal at
δ= 27.21 ppm due to (CH3) group and signals at δ= (122.5-138.2) ppm
due to
aromatic ring
carbons
and
signals at δ= 152.6 ppm and
δ=166.8 ppm are due to (C=N) imine and (C=O) imide respectively.
1
H-NMR spectrum of compound [24] showed signals at δ= 2.54
ppm and δ= 2.56 ppm due to two (CH3) groups, while signals at δ= (7.288.12) ppm are due to aromatic ring protons.
13
C-NMR spectrum of compound [24] showed signal at δ= 27.2
ppm due to (CH3) groups and signals at δ= (122-135) ppm due to
aromatic ring carbons and signals at δ= 153 ppm and δ= 166 ppm due to
(C=N) imine and (C=O) imide respectively.
٦٤
Chapter Three
Results and Discussion
Table (3-5): Physical properties of compounds [20-26]
Comp.
No.
Melting
Yield Recrystallization
Color Points
%
Solvent
°C
Compound structure
O
CH3
C
N
20
SO2 O
Pale
brown
155-156
72
Ethanol
Off
white
148-150
66
Ethanol
Pale
yellow
159-160
88
Acetone
Cl
Pale
brown
172-173
90
Ethanol
CH3
Off
white
163-164
63
Ethanol
Pale
yellow
180-182
85
Acetone
Pale
brown
167-168
77
Cyclo hexane
C=N
C
O
O
H3C
C
N
21
SO2 O
C=N
C
CH3
O
O
22
NO2
CH3
C
N
SO2 O
C=N
C
O
O
CH3
C
23
N
SO2 O
C=N
C
Cl
O
O
CH3
C
N
24
SO2 O
C=N
C
O
O
CH3
C
N
25
SO2 O
NO2
C=N
Cl
C
O
O
CH3
C
26
N
C
SO2 O
N
C=N
CH3
S
O
٦٥
Chapter Three
Results and Discussion
Table (3-6): Spectral data of compounds [20-26]
FTIR spectral data cm-1
Comp.
No.
Compound structure
n(C-H) n(C=O) n(C=N) n(C=C) n(SO2)
aromatic imide
imine aromatic asym.
n(SO2)
sym.
n(C-N)
imide
others
-
O
CH3
C
20
N
SO2 O
3109
1739
1720
1685
1593
1373
1180
1300
3062
1740
1720
1685
1593
1373
1176
1296
3100
1743
1722
1683
1593
1385
1182
1300
Cl
3100
1739
1726
1687
1593
1369
1182
1355
n(C-Cl)
1078
CH3
3109
1743
1720
1685
1593
1373
1199
1300
-
C=N
C
O
O
H3C
C
21
N
SO2 O
C=N
C
CH3
-
O
O
22
NO2
CH3
C
N
SO2 O
C=N
C
n(NO2)
1496
1355
O
O
CH3
C
23
N
SO2 O
C=N
C
Cl
O
O
CH3
C
24
N
SO2 O
C=N
C
O
O
CH3
C
25
N
SO2 O
C=N
Cl
3080
1725
1710
1690
1595
1372
1185
1300
n(NO2)
1490
1350
n(C-Cl)
1090
CH3
3109
1737
1720
1685
1593
1373
1199
1300
n(C-S)
609
NO2
C
O
O
CH3
C
26
N
C
O
SO2 O
N
C=N
S
٦٦
%T
O
C
N
C
SO 2 O
O
H3
C CH
O
Wave number ( cm-1 )
Fig. No. ( 16 ) : FT-IR spectrum for compound [ 19 ]
67
%T
O
C
N
C
SO2 O
H3
CH
C==N
H3
CH
O
Wave number ( cm-1 )
Fig. No. ( 17 ) : FT-IR spectrum for compound [ 24 ]
68
%T
O
C
N
C
SO2 O
O
CH3 N
N
C==N
S
H3
CH
O
Wave number ( cm-1 )
Fig. No. ( 18 ) : FT-IR spectrum for compound [ 26 ]
69
O
C
N
C
SO2 O
O
H3
C CH
O
Fig. No. ( 19 ) : 1H-NMR spectrum for compound [ 19 ]
70
O
C
N
C
SO2 O
O
H3
C CH
O
Fig. No. ( 20 ) : 13C-NMR spectrum for compound [ 19 ]
71
O
C
N
C
H3C
SO 2 O
C==N
H3
CH
O
Fig. No. ( 21 ) : 1H-NMR spectrum for compound [ 21 ]
72
O
C
N
C
H3C
SO 2 O
=N
C=
H3
CH
O
Fig. No. ( 22 ) : 13C-NMR spectrum for compound [ 21 ]
73
O
C
N
C
SO2 O
H3
CH
C==N
H3
CH
O
Fig. No. ( 23 ) : 1H-NMR spectrum for compound [ 24 ]
74
O
C
N
C
SO2 O
H3
CH
C==N
H3
CH
O
Fig. No. ( 24 ) : 13C-NMR spectrum for compound [ 24 ]
75
Chapter Three
Results and Discussion
3-3-Part Three
3-3-1- 4-[4'-(N-phthalimidyl) phenyl sulfonate] benzaldehyde [27]
Compound [27] was prepared via reaction between 4-(Nphthalimidyl) phenyl sulfonyl chloride [3] and 4-hydroxy benzaldehyde.
Mechanism(167) of reaction involved nucleophilic attack of phenolic
hydroxyl group on sulfur atom in compound [3] followed by elimination of
(HCl) molecule producing the desirable imides as described in Scheme
(3-8).
O
C
N
C
O
S
O
....
+ HO
Cl +
H
H
C
O
O
Pyrriid
diinnee
Py
O
C
N
C
O Cl
S O
O
O
O
O
C
H
H
H
--HCl
O
C
N
C
O
O
S
O
O
O
C
H
O
[ 27]
mee (33--88)
Scchheem
Compound [27] was recrystallized from ethanol and gave pale brown
crystals in 72% yield with melting point (176-178)oC.
FT-IR spectrum of compound [27] showed absorption bands at 1741
cm-1 and 1718 cm-1 asym n(C=O) and sym. n(C=O) imide and a clear
۷٦
Chapter Three
Results and Discussion
strong absorption band at 1699 cm-1 n(C=O) aldehyde.
Other absorption bands appeared at 1593 cm-1, 1370 cm-1, 1186
cm-1 and 1360 cm-1 n(C=C) aromatic, asym. n(SO2) and sym. n(SO2) and
n(C-N) imide respectively.
1
H-NMR spectrum of compound [27] showed signals at δ= (7.37-
8.13) ppm for aromatic protons and signal at δ= 9.99 ppm for aldehyde
O
C H
.
proton
13
C-NMR spectrum of compound [27] showed signals at δ= (123.2-
153.5) ppm due to aromatic ring carbons, signal at δ= 167 ppm due to
n(C=O)
imide and
signal at δ= 193 ppm for n(C=O) aldehyde.
Chemical test compound [27] gave positive result in test for carbonyl
compounds(164) and this is a good additional proof for preparation of
compound [27].
3-3-2- 4-[4'-(N-phthalimidyl) phenyl sulfonate] benzylidene [28-33]
The titled Schiffs̕ bases [28-33] were prepared via condensation
reaction of compound [27] with different primary aromatic amines.
Mechanism(167) of this reaction involved nucleophilic attack of
primary amine on carbonyl group of compound [27] producing [I] which
subsequently eliminated water molecule to afford the desirable compounds
as shown in Scheme (3-9).
۷۷
Chapter Three
1[27]
Results and Discussion
O
C
N
C
O
O
O
O
CH3COOH / H
O
OH
H
C
O
S
N
C
O
O
O
O
C
OH
C
CH3COO
O
O
O
OH
O
C
C
O
O
..
+
H
C
O
S
N
RNH2
O
O
C
OH H
C
O
O
C
OH H
C
CH3COOH / H
O
Protonation
OH2 H
O
C
C
O
S
N
C
O
O
O
CH3COOH
H
O
O
R
N
C
O
S
N
CH3COO
R
H
O
O
H
N
C
O
S
N
CH3COO
R
N
H
-H2O
O
C
S
N
C
O
+
H
C
O
S
N
[I]
Protonation
O
C
2-
H
C
O
S
C
O
N
R
+
CH3COOH
H
O
[28-33]
H3C
O2N
,
R=
,
Cl
Cl
,
NO2
Cl
,
CH3
Scheme(3-9)
۷۸
,
+
H2O
Chapter Three
Results and Discussion
Physical properties of compounds [28-33] are listed in Table (3-7).
FT-IR spectra of compounds [28-33] showed disappearance of
absorption band at 1699 cm-1 n(C=O) aldehyde and appearance of clear
strong absorption band at (1620-1631)
cm-1 due to
n(C=N)
imine.
Other absorption bands appeared at (1740-1741) cm-1, (1720-1722)
cm-1, (1585-1596) cm-1, (1365-1375) cm-1, (1168-1199) cm-1 and (13001355) cm-1 which were attributed to asym. n(C=O) imide, sym. n(C=O)
imide, n(C=C) aromatic, asym. n(SO2), sym. (SO2) and n(C-N) imide
respectively.
All details of FT-IR spectral data of compounds [28-33] are listed
in Table (3-8).
1
H-NMR spectrum of compound [31] showed multiplet signals at δ=
(7.29-8.13) ppm for aromatic protons and clear signal at δ= 8.58 ppm for
imine proton (-N=CH-).
13
C-NMR spectrum of compound [31] showed signals at δ= (122-
151.7) ppm due to aromatic ring carbons, signal at δ= 162.4 ppm for
n(C=N) and signal at δ= 166.83 ppm for (C=O) imide.
1
H-NMR spectrum of compound [32] showed clear singlet signal at
δ= 2.08 ppm due to (CH3) group protons, multiplet signals at δ= (7.278.12) ppm for aromatic protons and singlet signal at δ= 8.61 ppm for imine
proton (-N=CH-), while 13C-NMR spectrum of
the same compound
showed signal at δ= 31.1 ppm (CH3) group, signals at δ= (121.4-151.5)
ppm for aromatic carbons , signal at δ= 159 ppm (C=N) and signal at δ=
166 ppm (C=O) imide.
۷۹
Chapter Three
Results and Discussion
Table (3-7): Physical properties of compounds [28-33]
Comp.
No.
Melting
Yield Recrystallization
Color Points
%
Solvent
°C
Compound structure
O
SO2 O
H
C=N
SO2 O
H
C=N
C
N
28
Off
white
180-182
70
Dioxane
Yellow
270-272
88
Ethanol
Deep
yellow
177-178
76
Acetone
Cl
White
184-186
61
Dioxane
CH3
White
226-228
93
Ethanol
Cl
Yellow
190-191
84
Acetone
C
O
O
C
N
29
CH3
C
O
O
SO2 O
H
C=N
SO2 O
H
C=N
C
N
30
NO2
C
O
O
Cl
C
N
31
C
O
O
C
N
32
SO2 O
H
C=N
C
O
O
C
N
33
SO2 O
ON
H 2
C=N
C
O
۸۰
Chapter Three
Results and Discussion
Table (3-8): Spectral data of compounds [28-33]
Comp.
No.
FTIR spectral data cm-1
Compound structure
n(C-H) n(C=O) n(C=N) n(C=C) n(SO2) n(SO2) n(C-N)
aromatic imide
imine aromatic asym. sym.
imide
others
O
SO2 O
H
C=N
SO2 O
H
C=N
C
28
N
3080
1720
1620
1585
1375
1190
1345
3040
1740
1720
1623
1590
1375
1180
1300
-
C
O
O
C
29
N
CH3
-
C
O
O
C
30
N
SO2 O
NO2
H
C=N
C
n(NO2)
1523
1352
3040
1741
1720
1630
1593
1371
1199
1310
3060
1741
1720
1629
1596
1370
1186
1350
n(C-Cl)
1093
3080
1740
1722
1630
1593
1373
1186
1346
-
O
O
Cl
C
31
N
SO2 O
H
C=N
Cl
C
O
O
C
N
32
SO2 O
H
C=N
CH3
C
O
O
C
N
33
SO2 O
ON
H 2
C=N
Cl
3101
C
O
۸۱
1720
1631
1593
1365
1168
1338
n(NO2)
1504
1404
n(C-Cl)
1068
%T
O
C
N
C
SO 2 O
O
C H
O
Wave number ( cm-1 )
Fig. No. ( 25 ) : FT-IR spectrum for compound [ 27 ]
82
%T
O
C
N
C
O
SO 2 O
H
N
C==N
O
Wave number ( cm-1 )
Fig. No. ( 26 ) : FT-IR spectrum for compound [ 28 ]
83
%T
O
O
C
N
C
SO2 O
H
N
C==N
Cll
Cl
O
Wave number ( cm-1 )
Fig. No. ( 27 ) : FT- IR spectrum for compound [ 31 ]
84
O
C
N
C
SO2 O
O
C H
O
Fig. No. ( 28 ) : 1H-NMR spectrum for compound [ 27 ]
85
O
C
N
C
SO2 O
O
C H
O
Fig. No. ( 29 ) : 13C-NMR spectrum for compound [ 27 ]
86
O
O
C
N
C
SO 2 O
H
=N
N
C=
Cll
Cl
O
Fig. No. ( 30 ) : 1H-NMR spectrum for compound [ 31 ]
87
O
O
C
N
C
SO2 O
H
N
C==N
Cll
Cl
O
Fig. No. ( 31 ) : 13C-NMR spectrum for compound [ 31 ]
88
O
C
N
C
SO2 O
H
H
C==N
H3
CH
O
Fig. No. ( 32 ) : 1H-NMR spectrum for compound [ 32 ]
89
O
C
N
C
SO2 O
H
H
C==N
H3
CH
O
Fig. No. ( 33 ) : 13C-NMR spectrum for compound [ 32 ]
90
Chapter Three
Results and Discussion
3-٤-Part Four
3-4-1- N-(4-phenyl phenacyl) phthalimide [34]
The titled compound was prepared via reaction of phthalimide
potassium salt with 4-phenyl phenacyl bromide according to Gabrial
synthesis.
Unsubstituted phthalimide(170) was converted to its potassium salt
since the
later is the stronger nucleophile which attack the electron-
deficient carbon atom bonded to halogen in para phenyl phenacyl bromide
as shown in Scheme (3-10).
O
O
C
N
C
H
H
K O H (aal coholic)
O
O
O
O
C
K +
NK
+ CH2
C
Brr
B
O
O
C
N
C
O
O
O
C
K
NK
C
O
C
O
H2
CH
C
KB
Brr
+ K
+
4]
[34]
mee (3--110)
heem
Scch
Compound [34] was purified by recrystallization from ethanol and was
obtained as reddish brown crystals in 65% yield with melting point (106108)oC.
FT-IR spectrum of compound [34] showed appearance of clear
absorption band at 1689 cm-1 due to n(C=O) ketone.
۹۱
Chapter Three
Other
1392 cm-1
Results and Discussion
absorption
bands
appeared at 1716 cm-1, 1600 cm-1 and
due to n(C=O)imide, n(C=C) aromatic and n(C-N) imide
respectively.
1
H-NMR spectrum of compound [34] showed signal at δ= 4.95 ppm
due to (-CH2-) protons and signals at δ= (7.44-8.19) ppm due to aromatic
ring protons.
13
C-NMR spectrum of the same compound showed signal at
δ= 34.41 ppm due to (-CH2-) carbon and signals at δ= (123.8-139.1) ppm,
δ= 145.66 ppm and δ= 191.78 ppm due to aromatic ring carbons, (C=O)
imide and (C=O) ketone respectively.
Compound [34] gave positive result in treatment with 2,4-dinitro
phenyl hydrazine(164) and this was a good proof for the formation of this
compound.
3-4-2-N-phthalimidyl-4-phenyl benzylidene methane[35-40]
The titled compounds [35-40] were prepared via reaction between
N-(4-phenyl phenacyl) phthalimide and different primary aromatic amines.
During this reaction the electron-deficient carbon of carbonyl group in
compound [34] was attacked by the strong nucleophile (primary amine)
producing [I] followed by elimination of water molecule(167) producing the
desirable imides [35-40] as shown in Scheme (3-11).
۹۲
Chapter Three
1--
O
C
N
N
C
O
Results and Discussion
H2
CH
C
C H33C OO H / H
n
Prroottoonnaattiioon
P
C
[ 34 ]
....
RN
H2
NH
R
H
OH
H2
CH
C
C
C
O
O
H3 COOH
H
CH
2--
O
C
C
N
C
O
O
C
N
N
C
C
++
O
C
N
N
C
C
++
H
OH
O
H2
CH
C
O
H
OH
O
CH2
C
O
O
C
N CH2
N
C
C
O
O
H
OH
H
C
C
C
H
C
N
N
N
22
C
O
O
H H
OH
O
C
H
H
N
R
R
+ CH3 COO
+
O
H3C
H // H
H
OO
OH
CH
CO
C
O
O
C
C
N CH22
N
C
O
O
H2O
--H
O
O
C
C
N C H22 C
N
C
O
O
N
R
R
H2O
+ CH 3CO OH ++ H
+
[35--40]
HO
R ==
R
Brr
B
,
,
OH
NO22
N
Cl ,
CH3 ,
mee ( 3--9)
Sccheem
۹۳
R
R
H
H3C OO H
++ C H
naattioonn
Prroottoon
P
H2 H
OH
H
C
R
N R
CH 3COO
Chapter Three
Results and Discussion
Physical properties of compounds [35-40] are listed in Table (3-9).
FT-IR spectra of compounds [35-40] showed disappearance of
absorption band at 1689 cm-1 due to n(C=O) ketone and appearance of
absorption
band
at
(1620-1681)
cm-1
due
to
n(C=N)
imine.
Also all spectra showed clear absorption bands at (1697-1725) cm-1,
(1523-1604) cm-1 and (1311-1396) cm-1 due to n(C=O) imide, n(C=C)
aromatic and n(C-N) imide respectively.
All details of FT-IR, spectral data of compounds [35-40] are listed in
Table (3-10).
1
H-NMR spectrum of compound [35] showed signal at δ=5.19
ppm due to (-CH2-) protons and signals at δ=(7.25-8.1)ppm due to
aromatic ring protons.
13
C-NMR spectrum of the same compound showed signal at
δ= 44.9 ppm due to (-CH2-) carbon and signals at δ= (112.8-135.2) ppm
due to aromatic ring carbons and signal at δ= 168ppm due to (C=O)
ketone and (C=N) imine.
۹٤
Chapter Three
Results and Discussion
Table (3-9): Physical properties of compounds [35-40]
Comp.
No.
Compound structure
Color
Melting
Yield Recrystallization
Points
%
Solvent
°C
O
C
35
=
N CH2 C
C
N
O
Pale
green
162-163
92
Acetone
Brown
136-138
77
Ethanol
Yellow
116-117
81
Dioxane
Deep
brown
129-130
90
Ethanol
Red
112-114
64
Acetone
Deep
green
165-167
85
Ethanol
NO2
O
C
36
=
N CH2 C
C
N
O
Br
O
C
37
=
N CH2 C
C
N
O
Cl
O
C
38
=
N CH2 C
C
N
O
OH
O
C
39
=
N CH2 C
C
N
O
CH3
O
C
40
O
=
N CH2 C
C
N
OH
۹٥
Chapter Three
Results and Discussion
Table (3-10): Spectral data of compounds [35-40]
Comp.
No.
FTIR spectral data cm-1
Compound structure
n(C-H) n(C=O) n(C=N) n(C=C) n(C-N)
aromatic imide
imine aromatic imide
others
O
C
3062
1697
1624
1597
1350
n(NO2)
1450
1327
3035
1718
1674
1600
1352
n(C-Br)
688
3059
1725
1701
1631
1600
1311
n(C-Cl)
1083
3055
1716
1681
1647
1361
n(O-H)
Phenolic
3425
3028
1716
1620
1558
1319
-
3000
1720
1703
1681
1590
1396
n(O-H)
Phenolic
3456
=
N CH2 C
35
C
N
O
NO2
O
C
36
C
=
N CH2
C
N
O
Br
O
C
37
=
N CH2 C
C
N
O
Cl
O
C
38
=
N CH2 C
C
N
O
OH
==
O
C
H2 C
N CH
C
N
O
O
39
C H3
O
C
40
O
=
N CH2 C
C
N
OH
۹٦
%T
=
=
O
O
C
N CH2 C
C
O
Wave number ( cm-1 )
Fig. No. ( 34 ) : FT-IR spectrum for compound [ 34 ]
97
%T
==
O
C
N C H2 C
C
N
O
NO2
Wave number ( cm-1 )
Fig. No. ( 35 ) : FT-IR spectrum for compound [ 35 ]
98
%T
C
N
==
O
C
N CH22
C
O
OH
Wave number ( cm-1 )
Fig. No. ( 36 ) : FT- IR spectrum for compound [ 38 ]
99
==
O
C
O
N CH2 C
C
O
Fig. No. ( 37 ) : 1H-NMR spectrum for compound [ 34 ]
100
==
O
O
C
N CH2 C
C
O
Fig. No. ( 38 ) : 13C-NMR spectrum for compound [ 34 ]
101
==
O
C
N CH2 C
C
N
O
N O2
Fig. No. ( 39 ) : 1H-NMR spectrum for compound [ 35 ]
102
==
O
C
N CH2 C
C
N
O
N O2
Fig. No. ( 40 ) : 13C-NMR spectrum for compound [ 35 ]
103
Chapter Three
Results and Discussion
Biological Activity
The synthesized imides in this work were expected to possess
biological activity since they have two active moieties in their molecules
(phthalimide and Schiffs̕ base), thus a prileminary evaluation of antibacterial activity for some of the new imides were tested against two types
of bacteria Staphylococcus aureus (Gram-positive) and Escherichia coli
(Gram-negative).
The results showed that most of the tested imides possess good antibacterial activity as shown in Table (3-11).
Table(3-11):Anti-bacterial activity for some of the Synthesized Schiffs̕ bases
Gram-positive bacteria
Gram-negative bacteria
Staphylococcus aureus
Escherichia coli
5
+++
++
6
++++
-
7
++++
++++
10
++
+++
11
-
++
12
++++
++
14
++
+++
16
++
+++
17
+++
++
18
+++
++++
Comp. No.
Key to symbols = Inactive = (-) inhibition Zone< 6 mm
Slightly active = (+) = inhibition Zone 6-9 mm
Moderately active = (++) inhibition Zone 9-12 mm
Highly active = (+++) inhibition Zone 13-17 mm
Very high activity = (++++) inhibition Zone > 17 mm
104
Chapter Three
Results and Discussion
Suggestions for future work
The following suggestions are found suitable for future work:
1. Synthesis of other new imides linked to Schiffs̕ bases by following
other strategies.
2. Evaluation of antibacterial activity of all the Synthesized imides in
this work against other types of bacteria and comparision the results
with those of known biologically active control compounds.
3. Evaluation of antifungal activity of all Synthesized compounds in
this work against different types of fungi.
4. Synthesis of new carbonyl compounds (or heterocyclic aldehydes
and ketones) and new primary amines (or heterocyclic amines) then
introducing them in synthesis of new imides linked to Schiffs̕ base.
105
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۱۱۷
‫ﺍﻟﺨﻼﺻﺔ‬
‫ﺗﻀ��ﻤﻦ ﺍﻟﺒﺤ��ﺚ ﺗﺤﻀ��ﻴﺮ ﻣﺸ��ﺘﻘﺎﺕ ﻓﺜ��ﺎﻝ ﺍﻳﻤﺎﻳ��ﺪ ﺟﺪﻳ��ﺪﺓ ﻣﺮﺗﺒﻄ��ﺔ ﺑﻘﻮﺍﻋ��ﺪ ﺷ��ﻴﻒ ﺑﺎﺳ��ﺘﺨﺪﺍﻡ ﻁﺮﺍﺋ �ﻖ‬
‫ﺗﺤﻀﻴﺮ ﻣﺨﺘﻠﻔﺔ‪ ،‬ﻟﺬﻟﻚ ﺗﻢ ﺗﻘﺴﻴﻢ ﻫﺬﺍ ﺍﻟﺒﺤﺚ ﺍﻟﻰ ﺃﺭﺑﻌﺔ ﺃﺟﺰﺍء ﺭﺋﻴﺴﻴﺔ ‪:‬‬
‫‪ .۱‬ﺍﻟﺠﺰء ﺍﻻﻭﻝ ﺗﻀﻤﻦ ﺗﺤﻀﻴﺮ ﻣﺸﺘﻘﺎﺕ ﻓﺜﺎﻝ ﺍﻳﻤﺎﻳﺪ ﺟﺪﻳﺪﻩ ﻣﺮﺗﺒﻄﺔ ﺑﻘﻮﺍﻋﺪ ﺷﻴﻒ ﻋﻦ ﻁﺮﻳﻖ‬
‫ﻣﺠﻤﻮﻋﺔ ﻓﻨﻴﻞ ﺳﻠﻔﻮﻥ ﺃﻣﻴﺪ ]‪ [18-5‬ﻣﺨﻄﻂ )‪,(۱‬ﺣﻴﺚ ﺗﻢ ﺗﺤﻀﻴﺮ ﻫﺬﻩ ﺍﻟﻤﺮﻛﺒﺎﺕ ﻋﻦ ﻁﺮﻳﻖ‬
‫ﺍﺗﺒﺎﻉ ﺍﻟﺨﻄﻮﺍﺕ ﺍﻟﺘﺎﻟﻴﺔ‪-:‬‬
‫ﺃ‪ -‬ﺗﺤﻀﻴﺮ ﺣﺎﻣﺾ ‪-N‬ﻓﻨﻴﻞ ﻓﺜﺎﻝ ﺃﻣﻴﻚ ]‪ [1‬ﻣﻦ ﺧﻼﻝ ﺗﻔﺎﻋﻞ ﺍﻧﻬﻴﺪﺭﻳﺪ ﺍﻟﻔﺜﺎﻟﻴﻚ ﻣﻊ ﺍﻻﻧﻴﻠﻴﻦ‪.‬‬
‫ﺏ‪ -‬ﺳﺤﺐ ﺍﻟﻤﺎء ﻣﻦ ﺣﺎﻣﺾ ‪-N‬ﻓﻨﻴﻞ ﻓﺜﺎﻝ ﺃﻣﻴﻚ ﺍﻟﻤﺤﻀﺮ ﻓﻲ ﺍﻟﺨﻄﻮﺓ )ﺃ( ﺑﺎﺳﺘﺨﺪﺍﻡ ﺍﻧﻬﻴﺪﺭﻳﺪ‬
‫ﺍﻟﺨﻠﻴﻚ ﻭﺧﻼﺕ ﺍﻟﺼﻮﺩﻳﻮﻡ ﺍﻟﻼﻣﺎﺋﻴﺔ ﻛﻌﺎﻣﻞ ﺳﺎﺣﺐ ﻟﻠﻤﺎء ﻟﺘﻜﻮﻳﻦ ﺍﻟﻔﺜﺎﻝ ﺍﻳﻤﺎﻳﺪ ﺍﻟﻤﻘﺎﺑﻞ ]‪.[2‬‬
‫ﺝ‪ -‬ﺍﺩﺧﺎﻝ ﺍﻟﻔﺜﺎﻝ ﺃﻳﻤﺎﻳﺪ ﺍﻟﻤﺤﻀﺮ ﻓﻲ ﺍﻟﺨﻄﻮﺓ )ﺏ( ﺑﺘﻔﺎﻋﻞ ﻛﻠﻮﺭﻭﺳﻠﻔﻨﺔ ﻣﻊ ﺣﺎﻣﺾ‬
‫ﺍﻟﻜﻠﻮﺭﻭﺳﻠﻔﻮﻧﻴﻚ ﻟﻠﺤﺼﻮﻝ ﻋﻠﻰ ﻛﻠﻮﺭﻳﺪ ﺳﻠﻔﻮﻧﻴﻞ ﻓﺜﺎﻝ ﺍﻳﻤﺎﻳﺪ ]‪. [3‬‬
‫ﺩ‪ -‬ﺗﻔﺎﻋﻞ ﺍﻟﻤﺮﻛﺐ ]‪ [3‬ﻣﻊ ﺍﻟﻬﻴﺪﺭﺍﺯﻳﻦ ﻫﺎﻳﺪﺭﻳﺖ ﻟﻠﺤﺼﻮﻝ ﻋﻠﻰ ﻓﺜﺎﻝ ﺍﻳﻤﺎﻳﺪ ﻓﻨﻴﻞ ﺳﻠﻔﻮﻧﻴﻞ‬
‫ﻫﻴﺪﺭﺍﺯﻳﻦ ]‪.[4‬‬
‫ﻫ‪ -‬ﺗﺤﻀﻴﺮ ﻋﺪﺩ ﻣﻦ ﻗﻮﺍﻋﺪ ﺷﻴﻒ ]‪ [18-5‬ﻭﺫﻟﻚ ﻋﻦ ﻁﺮﻳﻖ ﺗﻔﺎﻋﻞ ﻓﺜﺎﻝ ﺍﻳﻤﺎﻳﺪ ﻓﻨﻴﻞ ﺳﻠﻔﻮﻧﻴﻞ‬
‫ﻫﻴﺪﺭﺍﺯﻳﻦ ]‪ [4‬ﻣﻊ ﻣﺨﺘﻠﻒ ﺍﻻﻟﺪﻳﻬﺎﻳﺪﺍﺕ ﻭﺍﻟﻜﻴﺘﻮﻧﺎﺕ ﺍﻻﺭﻭﻣﺎﺗﻴﺔ ‪.‬‬
‫‪ .۲‬ﺃﻣﺎ ﺍﻟﺠﺰء ﺍﻟﺜﺎﻧﻲ ﻣﻦ ﺍﻟﺒﺤﺚ ﻓﻴﺘﻀﻤﻦ ﺗﺤﻀﻴﺮ ﻓﺜﺎﻝ ﺍﻳﻤﺎﻳﺪﺍﺕ ﺟﺪﻳﺪﺓ ﻣﺮﺗﺒﻄﺔ ﺑﻘﻮﺍﻋﺪ ﺷﻴﻒ ﻋﻦ‬
‫ﻁﺮﻳﻖ ﻣﻜﻮﻧﺔ ﺍﻟﻔﻨﻴﻞ ﺳﻠﻔﻮﻧﺎﺕ ]‪ [26-20‬ﺣﻴﺚ ﺗﻢ ﺗﺤﻀﻴﺮ ﻫﺬﻩ ﺍﻟﻤﺮﻛﺒﺎﺕ ﺑﺎﺗﺒﺎﻉ ﻣﺎﻳﻠﻲ‪-:‬‬
‫ﺃ‪ -‬ﺗﺤﻀﻴﺮ ﻣﺮﻛﺐ ﻓﺜﺎﻝ ﺍﻳﻤﺎﻳﺪ ﻓﻨﻴﻞ ﺳﻠﻔﻮﻧﺎﺕ ﺍﺳﻴﺘﻮﻓﻴﻨﻮﻥ ]‪ [19‬ﻋﻦ ﻁﺮﻳﻖ ﺗﻔﺎﻋﻞ ﻓﺜﺎﻝ ﺍﻳﻤﺎﻳﺪ‬
‫ﻓﻨﻴﻞ ﺳﻠﻔﻮﻧﻴﻞ ﻛﻠﻮﺭﺍﻳﺪ ]‪ [3‬ﺍﻟﻤﺤﻀﺮ ﻓﻲ ﺍﻟﺠﺰء ﺍﻻﻭﻝ ﻣﻊ ‪ -4‬ﻫﻴﺪﺭﻭﻛﺴﻲ ﺍﺳﻴﺘﻮﻓﻴﻨﻮﻥ‪.‬‬
‫ﺏ‪ -‬ﺍﻟﻤﺮﻛﺐ ]‪ [19‬ﺍﻟﻤﺤﻀﺮ ﻓﻲ ﺍﻟﺨﻄﻮﺓ )ﺃ( ﺑﺘﻔﺎﻋﻠﻪ ﻣﻊ ﻋﺪﺓ ﺃﻣﻴﻨﺎﺕ ﺍﺭﻭﻣﺎﺗﻴﺔ ﺃﻭﻟﻴﺔ ﻣﻌﻮﺿﺔ‬
‫ﺳﻨﺤﺼﻞ ﻋﻠﻰ ﻗﻮﺍﻋﺪ ﺷﻴﻒ ]‪ [26-20‬ﻣﺨﻄﻂ )‪.(۲‬‬
‫‪ .۳‬ﺍﻟﺠﺰء ﺍﻟﺜﺎﻟﺚ ﻣﻦ ﺍﻟﺒﺤﺚ ﻳﺘﻀﻤﻦ ﺗﺤﻀﻴﺮ ﻓﺜﺎﻝ ﺍﻳﻤﺎﻳﺪﺍﺕ ﺟﺪﻳﺪﺓ ﻣﺮﺗﺒﻄﺔ ﺑﻘﻮﺍﻋﺪ ﺷﻴﻒ ﻋﻦ ﻁﺮﻳﻖ‬
‫ﻣﻜﻮﻧﺔ ﺍﻟﻔﻨﻴﻞ ﺳﻠﻔﻮﻧﺎﺕ ]‪ [33-28‬ﻭﺫﻟﻚ ﻋﻦ ﻁﺮﻳﻖ ﺃﺗﺒﺎﻉ ﺍﻟﺨﻄﻮﺍﺕ ﺍﻟﺘﺎﻟﻴﺔ‪-:‬‬
‫ﺃ‪ -‬ﺗﺤﻀﻴﺮ ﻓﺜﺎﻝ ﺍﻳﻤﺎﻳﺪ ﻓﻨﻴﻞ ﺳﻠﻔﻮﻧﺎﺕ ﺑﻨﺰﺍﻟﺪﻳﻬﺎﻳﺪ ]‪ [27‬ﻋﻦ ﻁﺮﻳﻖ ﺗﻔﺎﻋﻞ ﺍﻟﻔﺜﺎﻝ ﺍﻳﻤﺎﻳﺪ ﻓﻨﻴﻞ‬
‫ﺳﻠﻔﻮﻧﻴﻞ ﻛﻠﻮﺭﺍﻳﺪ ]‪ [3‬ﺍﻟﻤﺤﻀﺮ ﻓﻲ ﺍﻟﺠﺰء ﺍﻻﻭﻝ ﻣﻊ ‪ -4‬ﻫﻴﺪﺭﻭﻛﺴﻲ ﺑﻨﺰﺍﻟﺪﻳﻬﺎﻳﺪ‪.‬‬
‫ﺏ‪ -‬ﺗﻔﺎﻋﻞ ﺍﻟﻤﺮﻛﺐ ]‪ [27‬ﺍﻟﻤﺤﻀﺮ ﻓﻲ ﺍﻟﺨﻄﻮﺓ )ﺃ( ﻣﻊ ﻋﺪﺓ ﺍﻣﻴﻨﺎﺕ ﺍﺭﻭﻣﺎﺗﻴﺔ ﺍﻭﻟﻴﺔ ﻣﻌﻮﺿﺔ‬
‫ﺳﻨﺤﺼﻞ ﻋﻠﻰ ﻗﻮﺍﻋﺪ ﺷﻴﻒ]‪ [33-28‬ﻣﺨﻄﻂ )‪.(۳‬‬
‫‪ .٤‬ﺃﻣﺎ ﺍﻟﺠﺰء ﺍﻻﺧﻴﺮ ﻣﻦ ﺍﻟﺒﺤﺚ ﻓﻴﺘﻀﻤﻦ ﺗﺤﻀﻴﺮ ﻓﺜﺎﻝ ﺍﻳﻤﺎﻳﺪﺍﺕ ﺟﺪﻳﺪﺓ ﻣﺮﺗﺒﻄﺔ ﺑﻘﻮﺍﻋﺪ ﺷﻴﻒ ﻋﻦ‬
‫ﻁﺮﻳﻖ ﻣﺠﻤﻮﻋﺔ ﺍﻟﻤﺜﻴﻠﻴﻦ ]‪ [40-35‬ﺗﻢ ﺗﺤﻀﻴﺮ ﻫﺬﻩ ﺍﻟﻤﺮﻛﺒﺎﺕ ﻋﻦ ﻁﺮﻳﻖ ﺍﻟﺨﻄﻮﺍﺕ ﺍﻟﺘﺎﻟﻴﺔ‪-:‬‬
‫ﺃ‪ -‬ﺗﻔﺎﻋﻞ ﻣﻠﺢ ﺍﻟﺒﻮﺗﺎﺳﻴﻮﻡ ﻟﻠﻔﺜﺎﻝ ﺍﻳﻤﺎﻳﺪ ﻣﻊ ‪ -4‬ﻓﻨﻴﻞ ﻓﻴﻨﺎﺳﻴﻞ ﺑﺮﻭﻣﺎﻳﺪ ﻟﺘﻜﻮﻳﻦ ‪ -4‬ﻓﻨﻴﻞ ﻓﻴﻨﺎﺳﻴﻞ‬
‫ﻓﺜﺎﻝ ﺍﻳﻤﺎﻳﺪ ]‪. [34‬‬
‫ﺏ‪ -‬ﺗﻔﺎﻋﻞ ‪ -4‬ﻓﻨﻴﻞ ﻓﻴﻨﺎﺳﻴﻞ ﻓﺜﺎﻝ ﺍﻳﻤﺎﻳﺪ ]‪ [34‬ﺍﻟﻤﺤﻀﺮﻓﻲ ﺍﻟﺨﻄﻮﻩ )ﺃ( ﻣﻊ ﻋﺪﺓ ﺍﻣﻴﻨﺎﺕ ﺍﺭﻭﻣﺎﺗﻴﺔ‬
‫ﺍﻭﻟﻴﺔ ﻣﻌﻮﺿﺔ ﻟﺘﻜﻮﻳﻦ ﻗﻮﺍﻋﺪ ﺷﻴﻒ ﺍﻟﺠﺪﻳﺪﺓ ]‪ [40-35‬ﻣﺨﻄﻂ )‪.(4‬‬
‫ﻋﻴﻨﺖ ﺩﺭﺟﺎﺕ ﺍﻻﻧﺼﻬﺎﺭ ﻟﻠﻤﺮﻛﺒﺎﺕ ﺍﻟﻤﺤﻀﺮﺓ ﻭﺷﺨﺼﺖ ﻁﻴﻔﻴﺎ ﻋﻦ ﻁﺮﻳﻖ ﻣﻄﻴﺎﻓﻴﺔ ﺍﻻﺷﻌﺔ‬
‫ﺗﺤﺖ ﺍﻟﺤﻤﺮﺍء ‪ FT-IR‬ﻛﻤﺎ ﻭﺍﺳﺘﺨﺪﻣﺖ ﻣﻄﻴﺎﻓﻴﺔ ﺍﻟﺮﻧﻴﻦ ﺍﻟﻨﻮﻭﻱ ﺍﻟﻤﻐﻨﺎﻁﻴﺴﻲ ﺑﻨﻮﻋﻴﺔ ‪ 1H-NMR‬ﻭ‬
‫‪ 13C-NMR‬ﻓﻲ ﺗﺸﺨﻴﺺ ﺑﻌﺾ ﺍﻟﻤﺮﻛﺒﺎﺕ ﺍﻟﻤﺤﻀﺮﺓ‪.‬‬
‫ﻛﺬﻟﻚ ﺗﻀﻤﻦ ﺍﻟﺒﺤﺚ ﺩﺭﺍﺳﺔ ﺍﻟﻔﻌﺎﻟﻴﺔ ﺍﻟﺒﺎﻳﻮﻟﻮﺟﻴﺔ ﻟﻌﺪﺩ ﻣﻦ ﺍﻻﻳﻤﺎﻳﺪﺍﺕ ﺍﻟﺠﺪﻳﺪﻩ ﺍﻟﻤﺤﻀﺮﺓ ﺿﺪ‬
‫ﺍﻧﻮﺍﻉ ﻣﻦ ﺍﻟﺒﻜﺘﺮﻳﺎ ﻭﻗﺪ ﺍﻅﻬﺮﺕ ﺍﻟﻨﺘﺎﺋﺞ ﺑﺎﻥ ﻟﻼﻳﻤﺎﻳﺪﺍﺕ ﺍﻟﺠﺪﻳﺪﻩ ﺍﻟﻤﺤﻀﺮﺓ ﻓﻌﺎﻟﻴﺔ ﺟﻴﺪﺓ ﺿﺪ ﺍﻧﻮﺍﻉ‬
‫ﺍﻟﺒﻜﺘﺮﻳﺎ ﻗﻴﺪ ﺍﻟﺪﺭﺍﺳﺔ‪.‬‬
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