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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 اهللا الرحمن الرحيم
بقدرها فـاحتمل اء ماء فسالت أودية أنزل من السم
ل زبدا رابيـا ومما يوقدون عليه في النـار ابتغاء السيـله كذلك يضرب الله الحق حلية أو متـاع زبد مثـ
والبـاطل فـأما الزبد فيذهب جفـاء وأما ما ينفع النـاس )١٧(فيمكث في األرض كذلك يضرب الله األمثـال
صدق اهللا العظيم
}الرعد{ سورة » ١٧ةاآلي «
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 : Dr. Ahlam Marouf Al-Azzawi
Date :
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
إلى القلب الدافئ وحياته من اجلي ، ..............................الغالي)....................................(والدي .................
ولكن الربيع يعود وهي لن ر الربيع في فصول ألسنه،من مرت بحياتي مرو إلى
إلى من أيقظت في نفسي قوى الصبر،إلى من رحلت عن الدنيا وتركت قلبي , تعود يكسره الشوق لها ..........................هللا)....(أمي رحمها .........................................
فأشد بهم أزري وأقوي بهم ، اة واللذين أعطوني الدعم والقوه دائماأملي في الحي إلى
عزيمتي. .........................)...........حفظهم هللا ..........................................(إخوتي
ت جميله رسمت بين مرافئ لوحاإلى من نقشوا محبتهم على جدران قلبي ،فكانوا
ا وجماال مع مرور األيامتشع بريق الوجدان
.............)....................عذراء,شيماء,حنان(..........................................
إلى البراعم الصغيره ...…………يسر) ,ايه,هاله,علي,عمار,ابراهيم,(ساره……………………
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
i
CONTENTS
Subject Page List of Contents i List of Tables iv List of Figures v Abstract vii CHAPTER ONE : INTRODUCTION 1.1. Schiffs base 1 1.2. Synthesis of Schiffs bases 2 1.3. Applications of Schiffs bases 8 1.4. Cyclic imides 9 1.5. Methods for synthesis of cyclic imides 10 1.5.1. Dehydration of amic acids by using dehydrating agents 10 1.5.2. Thermal Dehydration 11 1.5.3. Gabriel Type Synthesis 11 1.5.4. Diels-Alder Adducts 12 1.6. Other methods used in preparation of cyclic imides 12 1.7. Biological Activity of Cyclic Imides 18 Aim of the Work 22
ii
CHAPTER TWO : EXPERIMENTAL 2.1. Instruments and Chemicals 24 2.1.1. Instruments 24 2.1.2. Chemicals 24 2.2. Part One 25 2.2.1. Preparation of N-phenyl phthalamic acid [1] 26 2.2.2. Preparation of N-phenyl phthalimide [2] 26 2.2.3. Preparation of 4-(N-phthalimidyl) phenyl sulfonyl chloride [3] 26 2.2.4. Preparation of 4-(N-phthalimidyl)phenyl sulfonyl hydrazine [4] 27 2.2.5. Preparation of Schiffs Bases [5-18] 27 2.3. Part Two 27 2.3.1. Preparation of 4-(4'-(N-phthalimidyl) phenyl sulfonate acetophenone) [19] 28
2.3.2. Preparation of 4-(4'-N-phthalimidyl) phenyl sulfonate methyl benzylidene (Schiffs bases) [20-26] 28
2.4. Part Three 29 2.4.1. Preparation of-(4-(4'-N-phthalimidyl) phenyl sulfonate benzaldehyde) [27] 29
2.4.2. Preparation of 4-(4'-(N-phthalimidyl) phenyl sulfonate benzylidene (Schiffs bases) [28-33] 29
2.5. Part Four 30 2.5.1. Preparation of phthalimide potassium salt 30 2.5.2. Preparation of N-(4-phenyl phenacyl) phthalimide [34] 30 2.5.3. Preparation of Schiffs bases [35-40] 31
iii
CHAPTER THREE : RESULTS AND DISCUSSION 3.1. Part One 32 3.1.1. N-phenyl phthalamic acid [1] 32 3.1.2. N-phenyl phthalimide [2] 33 3.1.3. 4-(N-phthalimidyl) phenyl sulfonyl chloride [3] 35 3.1.4. 4-(N-phthalimidyl) phenyl sulfonyl hydrazine [4] 36 3.1.5. N-[4-(N-phthalimidyl) phenylsulfonamido] benzylidene [5-18] 38 3.2. Part Two 61 3.2.1. 4-[4'-(N-phthalimidyl) phenyl sulfonate] acetophenone [19] 61 3.2.2. 4-[4'-(N-phthalimidyl) phenyl sulfonate] methyl benzylidene [20-26] 62
3.3. Part Three 76 3.3.1. 4-[4'-(N-phthalimidyl) phenyl sulfonate] benzaldehyde [27] 76 3.3.2. 4-[4'-(N-phthalimidyl) phenyl sulfonate] benzylidene [28-33] 77 3.4. Part Four 91 3.4.1. N-(4-phenyl phenacyl) phthalimide [34] 91 3.4.2. N-phthalimidyl-4-phenyl (substituted benzylidene) methane [35-40] 92
Biological Activity 104 Suggestions for Future Work 105 References 106
iv
LIST OF TABLES
Table No. Title Page
3-1 Physical properties of compounds [1-4] 41
3-2 Physical properties of Schiffs bases [5-18] 42
3-3 Spectral data of compounds [1-4] 44
3-4 Spectral data of Schiffs 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
v
LIST OF FIGURES
Fig. No. Title Page
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 1H-NMR spectrum of compound [1] 53
9 13C-NMR spectrum of compound [1] 54
10 1H-NMR spectrum of compound [2] 55
11 13C-NMR spectrum of compound [2] 56
12 1H-NMR spectrum of compound [4] 57
13 13C-NMR spectrum of compound [4] 58
14 1H-NMR spectrum of compound [5] 59
15 13C-NMR spectrum of compound [5] 60
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 1H-NMR spectrum of compound [19] 70
20 13C-NMR spectrum of compound [19] 71
21 1H-NMR spectrum of compound [21] 72
vi
22 13C-NMR spectrum of compound [21] 73
23 1H-NMR spectrum of compound [24] 74
24 13C-NMR spectrum of compound [24] 75
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 1H-NMR spectrum of compound [27] 85
29 13C-NMR spectrum of compound [27] 86
30 1H-NMR spectrum of compound [31] 87
31 13C-NMR spectrum of compound [31] 88
32 1H-NMR spectrum of compound [32] 89
33 13C-NMR spectrum of compound [32] 90
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 1H-NMR spectrum of compound [34] 100
38 13C-NMR spectrum of compound [34] 101
39 1H-NMR spectrum of compound [35] 102
40 13C-NMR spectrum of compound [35] 103
vii
Abstract
The present work involved synthesis of new phthalimides linked to
Schiffs 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 N-
phenyl phthalimide [2].
c. The synthesized N-phenyl phthalimide was introduced in
chlorosulfonation reaction producing phthalimidyl 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 Schiffs
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.
viii
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 Schiffs
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 Schiffs
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.
ix
CO
CO
OCONH
+
NH2
AcetoneCOOH
CN
CO
O
CN
CO
O
SO2 N=CNHR
R'
Ac2O / NaOAc -H2Oreflux
CN
CO
O
SO2Cl
CN
CO
O
SO2NHNH2
HSO3Cl
reflux 6 hrs. Hydrazine hydrate
reflux 6 hrs. Aromatic aldehydes or ketones
N-phenyl phthalamic acid [1]
N-phenyl phthalimide [2]4-(N-phthalimidyl) phenyl sulfonyl chloride [3]
4-(N-phthalimidyl) phenyl sulphonyl hydrazine [4]
N-[4-(N-phthalimidyl) phenyl sulfonamido] substituted imine [5-18]
R = (o and p-nitro phenyl) , OCH3 (o , m ,and p-hydroxy phenyl) ,
Cl
CH3
,
R = H , CH3 , ph'
Scheme (1)
,NH
O,
, , ,
x
CN
CO
O
S
O
O
Cl
CN
CO
O
+
Chlorosulfonic acid
Cl S
O
O
OH
CN
CO
O
S
O
O
O C
O
CH3
CN
CO
O
S
O
O
O C RN
CH3
[20-26]
4-(N-phthalimidyl) phenyl sulfonyl chloride [3]
4-hydroxy acetophenone
4-[4-(N-phthalimidyl) phenyl sulfonate] acetophenone [19]'
4-[4-(N-phthalimidyl) phenyl sulfonate] methyl benzylidene'
R =
CH3N
S ,
, ,
H3C O2NCl ,
Cl
Cl
NO2
,
Scheme (2)
Different primary aromatic amines
CH3
N-phenyl phthalimide [2]
xi
CN
CO
O
S
O
O
Cl
CN
CO
O
+
Chlorosulfonic acid
Cl S
O
O
OH
CN
CO
O
S
O
O
O C
O
H
CN
CO
O
S
O
O
O C RN
H
[28-33]
4-hydroxy benzaldehyde
4-[4-(N-phthalimidyl) phenyl sulfonate] benzaldehyde [27]'
4-[4-(N-phthalimidyl) phenyl sulfonate] benzylidene'
R =
CH3 ,
, ,
H3C O2NCl
Cl
Cl NO2 ,
Scheme (3)
Different primary aromatic amines
N-phenyl phthalimide [2]
4-(N-phthalimidyl) phenyl sulfonyl chloride [3]
xii
CN
CO
O
CH2
CN
CO
O
C
O
H KOH (alcoholic)
CN K
CO
O
CN
CO
O
CH2 C
NR
4-phenyl phenacyl bromide
N-(4-phenyl phenacyl) phthalimide [34]
[35-40]
N-phthalimidyl-4-phenyl benzylidene methane
R =
CH3 ,
, ,
HO
Cl
NO2
,
Scheme (4)
Different primary aromatic amines
OHBr
unsubstituted Phthalimide phthalimide potassium salt
Chapter One Introduction
1
sbase sʼSchiff -1-1
A Schiffs base is a type of chemical compounds containing carbon-
nitrogen double bond 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.
The role of R3 group is to stabilize the iminic Schiffs base.
Structurally a Schiffs 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.
Schiffs 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 Schiffs 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.
R2
R1C=O + R3NH2 C N R3
R1
R2
O H
HC N
R1
R2
OH H
R3R2
R1C=NR3 H2O+
Carbinol amineintermediate
NN==CC
CC==NN RR33RR22
RR11(( RR11 ,, RR22 ,, RR33 aarree aarryyll oorr aallkkyyll ggrroouuppss ))
Chapter One Introduction
2
bases s Schiff of Synthesis -2-1
The first preparation of imines was reported in the 19th century by
Schiffs (1864). Since then a variety of methods for the synthesis of imines
have been described(5).
The classical synthesis reported by Schiffs 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 Schiffs bases
with a potential biological activity resulted from the acid-catalyzed
condensation of orthophenolic aldehydes with several aromatic and hetero
aromatic amines in ethanol.
Chapter One Introduction
3
Yang et.al(22) performed a microwave-assisted preparation of a series
of Schiffs bases via efficient condensation of salicylaldehyde and aryl
amines without solvent.
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 Schiffs 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).
OHCHOR3
R2R1
ArNH2H2SO4 (Catalyst)
reflux+
OHCH=N ArR3
R2R1
R1 , R2 , R3 = H, Br, I
CH3
CH3
Cl
Cl
Cl
Cl
Cl
CO2CH3
CO2CH3
CO2CH3
, ,
,
Ar =
OOHH
CCHHOO++
OOHH
CCHH==NN
NNHH22NN
RRMMiiccrroowwaavvee NN RR
RR == --CCHH33 ,, --BBrr
Chapter One Introduction
4
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].
The new ten Schiffs bases [2a-h] and [3a-b] showed different
antibacterial activities on testing against five types of bacteria.
Also several Schiffs bases [5a-d] were synthesized by Baluja et al.(24)
via condensation of sulfanilamide [4] with aromatic aldehydes.
SSOO22NNHH22
NNHH22
CCHHOO
RR11
RR22
++
SSOO22NNHH22
NN==CCHH RR11
RR22
[[44]] [[55aa--dd]]
55aa :: RR11 == --HH ,, RR22 == --HH55bb :: RR11 == --OOCCHH33
,, RR22 == --HH55cc :: RR11 == --SSCCHH33 ,, RR22 == --HH55dd :: RR11 == --OOCCHH33 ,, RR22 == --OOHH
CH3O N=N
OCH3
OH
CHO
ArNH2+ CH3O N=N
OCH3
OH
CH=N Ar
Ar =
CH2
OH CH3
H3C H3CO OCH3
OCH3
[1] [2a-h]
, , ,
, , ,
MgSO4
CCHH33OO NN==NN
OOCCHH33
OOHH
CCHHOO
++ XX NNHH22HH22NN
((XX == OO ,, SSOO22))
CCHH33OO NN==NN
OOCCHH33
OOHH
CC==NN XX NN==CC
OOCCHH33HHOO
CCHH33OO
NN==NN
33aa XX == OO33bb XX == SSOO22
Chapter One Introduction
5
The same team synthesized several Schiffs bases [7a-d] via refluxing
5-ethyl resacetophenone [6] with aniline derivatives in methanol in the
presence of anhydrous ZnCl2.
These Schiffs 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 Schiffs base
are expected to have enhanced biological activities, so according to this
satyanarayana and coworkers(25) synthesized a series of new Schiffs 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.
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 Schiffs bases [10a-f] from 3-chloro-4-fluoroaniline and
several benzaldehydes.
++
RR11
RR22
NNHH22RR33
ZZnnCCll22 ((aannhh))CCOOCCHH33
OOHHHHOO
HH55CC22 CC==NN
OOHHHHOO
HH55CC22
CCHH33
RR11
RR22RR33
[[77aa--dd]][[66]]
77aa :: RR11 == --NNOO22 ,, RR22 == --HH ,, RR33 == --HH 77bb :: RR11 == --CCHH33 ,, RR22 == --HH ,, RR33 == --CCHH3377cc :: RR11 == --HH ,, RR22 == --NNOO22 ,, RR33 == --HH77dd :: RR11 == --HH ,, RR22 == --CCHH33 ,, RR33 == --HH
CC
OOOO
HH22NN--HHNNOO OO
CCHH33
HHNNOO OO
CCHH33
NNRR
[[88]] [[99aa--ff ]]
CC
OOOO
++
CCHHOO
RR == --HH ,, --NNOO22 ,, --CCll ,, --OOHH ,, --OOCCHH33 ,, --NN((CCHH33))22
RR
Chapter One Introduction
6
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 Schiffs bases formation(27,28).
Water has been proved here as a suitable (green solvent) for the
synthesis of Schiffs 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 Schiffs 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.
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 Schiffs base via
mixing a warm dilute ethanolic solution of thiocarbohydrazide with
2-amino-4-ethyl-5-hydroxy benzaldehyde under reflux for 2hrs.
+R
Cl
FCH=NCHO
R
NH2
ClF
method A , Band C
[10a-f]Schiff bases
R = 3,4-Di OCH3 , 2-Cl , 4-Cl , 2-OH , 4-OH , 3-NO2
SO2NH2
NH2
+
SO2NH2
N=CH
C2H5OH / HOAC glacialreflux (5-6) hrs
CHO
R = -H , -Cl , -OH , -N(CH3)2 , OCH3 , NO2 , -(OCH3)3
R
Chapter One Introduction
7
Complex of Cr, Mn and Fe with this Schiffs base were prepared .The
Schiffs 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 Schiffs base [9] 4-methyl-N-(3,4,5-
trimethoxy benzylidene)benzene amine by three different ways.
The first one involved introducing a mixture of p-toluidine, 3,4,5-
trimethoxy 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.
NH2
CH3
+
CHO
OCH3
H3CO
HC=N
OCH3OCH3
H3CO
CH3
[9]
OCH3
+CHOHO
H5C2 NH2
H2NNH
S
NH
NH2
HN
S
NH
CH=N N=CHHO
H5C2 NH2
OH
H2N C2H5
2 Reflux
Chapter One Introduction
8
bases sʼSchiff Applications of -3-1
The chemistry of the carbon-nitrogen double bond plays a vital role in
the progress of chemistry science(31).
Schiffs 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 Schiffs base complexes have been used in catalytic reactions and
also have been used as fine chemicals and medical substrates(39,40).
Schiffs 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 Schiffs 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 Schiffs bases N-(1-phenyl-2-hydroxy-2-
phenyl ethyledine)-2,4-dinitro phenyl hydrazine (PDH), N-(1-phenyl-2-
hydroxy-2-phenyl ethyledine)-2-hydroxy phenyl imine (PHP) and N-(2-
hydroxy benzylidine)-2-hydroxy phenyl imine (HHP) against Ehrlich
Way Reaction condition Time Yield(%)
1 Microwave irradiation 4 min. 85
2 Reflux Over 7 hr 72
3 Room temperature stirring 4 hr 75
Table (1-1)
Chapter One Introduction
9
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.
Cyclic imides -4-1
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).
These cyclic imides are an important functionality which have been
found to maintain significant biological activity(87,88).
O
O
N R
O
O
N R
O
O
N R
O
O
N R
O
O
N R
H3C
[10] [12]
[13] [14]
[11]
CC==NNHHCC
NNHH--
OO22NN
NNOO22 CC==NN
HHOO
OOHH
CCHH==NN
HHOO
HHHHPP
PPDDHH PPHHPP
OOHH HHCC OOHH
Chapter One Introduction
10
Methods for synthesis of cyclic imides -5-1 Synthesis of cyclic imides may be performed by many methods
including agentsdehydrating of amic acids by using ydration Deh -1-5-1
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).
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).
C
O
C
O
O + RNH2
COOH
CONHR
Suitable dehydrating agentC
O
C
O
N R
Scheme (1-1)
Chapter One Introduction
11
ydrationhThermal De -2-5-1
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.
Gabriel Type Synthesis -3-5-1
This method involved treatment of potassium salt of unsubstituted
succinimide and phthalimide with different alkyl halides producing the
corresponding N-substituted imides(121).
C
O
C
O
NH + KOHC
O
C
O
N K
Br(CH2)2OHC
O
C
O
N OH(CH2)2 + KBr
Scheme (1-2)
COOHR
CONH
OH
C
O
C
O
NFusion
R
OH
COOH
CONH
OH
Fusion C
O
C
O
N
OH
(R = H or CH3)
Chapter One Introduction
12
AdductsAlder -Diels -4-5-1
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)
lic imidescher methods used in preparation of cyOt -6-1
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.
C
O
C
O
O+C
O
C
O
OC
O
C
O
N RRNH2
C
O
C
O
N R+
Scheme (1-3)
[15] [16]
Chapter One Introduction
13
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
NO2
NHSO2CH3
O
NHSO2CH3
NH2
CO
CO
O
Sn / HCl90 C , 3h.o O
NHSO2CH3
Cyclic anhydrides
[17] [18]N
CO
C OImides [19-24]
Scheme (1-4)
C
O
C
O
O
C
O
C
O
O
or Sulphamic acid
C
O
C
O
N
C
O
C
O
or
N
+
NH2
R = -H , 4-Cl , 4-NO2 , 3-OH , 4-CH3 , 4-OCH3
R
R
R
Chapter One Introduction
14
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).
Comp. No.
Cyclic anhydrides
Cyclic imides Reaction
conditions Yield(%)
19
110-120 ºC
10 min 73
20
110-120 ºC
15 min 65
21
110-120 ºC
15 min 65
22
110-120 ºC
15 min 65
23
110-120 ºC
20 min 65
24
110-120 ºC
20 min 75
Table (1-2)
CC
OO
CC
OO
OOCC
OO
CC
OO
NN HH++ NNHH22OOHH..HHCCllDDMMAAPP
MMiiccrroo wwaavveeiirrrraaddaattiioonn
Reaction conditions for preparation of imides (19-24)
CC
OO
CCOO
OOCC
OO
CCOO
NN NNHHSSOO22CCHH33
OOPPhh
CC
OO
CCOO
OO
NNOO22
CC
OO
CCOO
NN NNHHSSOO22CCHH33
OOPPhhNNOO22
CC
OO
CCOO
OOOO22NN OO22NN
CC
OO
CCOO
NN NNHHSSOO22CCHH33
OOPPhh
CC
OO
CCOO
OOCC
OO
CCOO
NN NNHHSSOO22CCHH33
OOPPhh
CC
OO
CCOO
OOCC
OO
CCOO
NN NNHHSSOO22CCHH33
OOPPhh
CC
OO
CCOO
OO NN NNHHSSOO22CCHH33
OOPPhh
CC
OO
CCOO
Chapter One Introduction
15
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-aryl-
1,8-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.
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).
Imides Time(min) Yield(%)
2.68 97
1.82 96
1.57 84
Table (1-۳): Synthesis of unsubstituted imides using NH2OH and DMAP
NN
Ar
NH2
+ C
O
C
O
O DMFM.W
C
O
C
O
NNN
Ar
[26a-g][25a-g]
a , Ar = C6H5 e , Ar = p-ClC6H4b , Ar = p-CH3OC6H4 f , Ar = p-BrC6H4c , Ar = o-ClC6H4 g , Ar = p-NO2C6H4 d , Ar = m-ClC6H4
Scheme (1-5)
CC
OO
CCOO
NN HH
CC
OO
CCOO
NN HH
CC
OO
CCOO
NN HH
Chapter One Introduction
16
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 1,2-
dibromoethane or 1,3-dibromopropane.
Comp. No.
R Comp. No.
R
27
32
28
33
29
34
30
35
31
R
OH (CH2)n BrBr+
(n = 2 , 3)
' R
O
'
Br(CH2)n (R = Br)
(n = 2 , 3)
C
O
C
O
N K + R Br K2CO3 , TEBAacetone , 6 h reflux
C
O
C
O
N R
Scheme (1-6)
OO CC((CCHH33))33((CCHH22))22 OO
OOCCHH33
OO CCll((CCHH22))22 OO CCll
OO CCHH33((CCHH22))22 OO CC((CCHH33))33
OO
CCll
OO
OOCCHH33
OO
CCFF33
Chapter One Introduction
17
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 anti-
inflammatory 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.
[36] + [38a-e] DCCDioxaneR.T. 18 hr
C
O
C
O
N
OH
ROC
O
OH
[39a-d]
C
O
C
O
N
OH
OC
O
OH
[39e]Scheme (1-7)
C
O
C
O
O +NH2 OH
Et3NToluene
reflux , 4 hr
C
O
C
O
NOH
[36]
OH
R+
CHO
COOH
NaOH(0-5 oC)
OH
COOH
HOR
[35a-d] [38a-d]
OH
+ CHO
COOH
NaOH(0-5 oC)
HO
OH
COOH
[35e] [38e]
R = H , CH3 , Cl , OCH3
Chapter One Introduction
18
Biological Activity of Cyclic Imides -7-1
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 including antimicrobial(143), 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.
CC
OO
CCOO
NN
RR11 RR22
RR33
Chapter One Introduction
19
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.
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
Table (1-4)
Chapter One Introduction
20
Likewise when [57a] is compared to its methoxy derivative [57b] the
latter structural modification is clearly beneficial.
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-2-
aminobenzothiazoles 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.
C
O
N
N
C
O
H
N(C2H5)2
56a R = CH356b R = H
C
O
N
N
C
O
57a R = H57b R = CH3O
R
CH3
CH3
N(C2H5)2
R
Chapter One Introduction
21
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.
C
O
C
O
NO
NN
R
C
O
C
O
NO
NN
R
[60-64] [65-49]
(R = 2-OH , H , 4-Cl , 4-OCH3 , 2-NO2)
S
NR
NH2
C
O
C
O
O+S
NR
N C
O
HOOC
H
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
S
NRC
O
C
O
N
[58a-j]
Ac2O
S
NR
NH2
C
O
C
O
O+S
NR
N C
O
HOOC
H
H3C
CH3
Ac2O / NaOAcor Fusion
S
NRC
O
C
O
N
[59a-k]
CH3
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
Scheme (1-9)
NaOAc
Scheme (1-8)
Chapter One Introduction
22
Aim of the Work
Since both phthalimides and Schiffs 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 Schiffs
bases by using different strategies involving the following parts:
Part One
This part involved synthesis of phthalimides linked to Schiffs 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 Schiffs
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 Schiffs
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.
Chapter One Introduction
23
Part Four
This part involved synthesis of new phthalimides linked to Schiffs
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.
Chapter Two Experimental
24
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-IR-
8400 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 13C-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
Chapter Two Experimental
25
The experimental chapter in this work involved the following parts:
2-2- Part One
This part involved synthesis of phthalimides linked to Schiffs 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.
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
Chapter Two Experimental
26
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).
Chapter Two Experimental
27
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 Schiffs 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 Schiffs bases
through phenyl sulfonate moiety.
Performing this target involved the following steps:
1. Reaction of 4-(N-phthalimidyl) phenyl sulfonyl chloride with 4-
hydroxy 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.
Chapter Two Experimental
28
2-3-1- Preparation 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 (Schiffs 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
Chapter Two Experimental
29
recrystallization from a suitable solvent.
The physical properties of Schiffs bases [20-26] are listed in Table (3-5).
2-4- Part Three This part involved synthesis of new phthalimides linked to Schiffs 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 (Schiffs 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).
Chapter Two Experimental
30
2-5- Part Four
This part involved synthesis of new phthalimides linked to Schiffs 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.
Chapter Two Experimental
31
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 Schiffs 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 Schiffs bases [35-40] are listed
in Table (3-9).
Chapter Three Results and Discussion
۳۲
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).
Schiffs 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 Schiffs 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).
Chapter Three Results and Discussion
۳۳
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).
1H-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).
CCOO
CC
OO
OO
++....HH22NN
AAcceettoonneeCC
OO
NN
CCOO
OOHH
HH
NNHHCC
OO
CCOO
OOHH
SScchheemmee ((33--11))
Chapter Three Results and Discussion
۳٤
The physical properties of compound [2] are listed in Table (3-1) and
its structure was confirmed by FT-IR, 1H-NMR and 13C-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 at 1593 cm-1 and 1384 cm-1 respectively.
1H-NMR spectrum of compound [2] showed disappearance of
(O-H) carboxyl proton signal and appearance of two multiplet signals at
CC
CCOO
OO
NNHH
OOHH
++ CCHH33CCOOOO NNaa
CC
CCOO
OO
NNHH
OO NNaa
++ CCHH33CCOOOOHH
CC
CCOO
OO
NNHH
OO NNaaCC
OOCCOO
OOCCHH33
CCHH33
++CC
CCOO
OO
NNHH
OO CC OO CC CCHH33
OOOO NNaa
CC
CCOO
OO
NNHH
OO CC CCHH33
OO
....++ CCHH33CCOOOO NNaa
CC
CCOO
NN
OO CC CCHH33
OOOO
HH
CCNN
CC
OO
OO
++ CCHH33CCOOOOHH
SScchheemmee ((33--22))
HH33CC
Chapter Three Results and Discussion
۳٥
δ= (7.44-7.56) ppm and (7.89-7.97) ppm of two aromatic rings protons. 13C-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
phthalimide with chlorosulfonic acid at 0 oC.
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).
CCll SS
OO
OO
OOHH
CCNN
CC
OO
OO
++
CCll SS
OO
OO
OOHH
CCNN
CC
OO
OO
HH
CCNN
CC
OO
OO
HH
CCll SS
OO
OO
CCNN
CC
OO
OO
CCll SS
OO
OO
OOHH
OOHH22
CCNN
CC
OO
OO
CCll SS
OO
OO
SScchheemmee ((33--33))
--HH22OO
Chapter Three Results and Discussion
۳٦
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).
Chapter Three Results and Discussion
۳۷
The physical properties of compound [4] are listed in Table (3-1) and
its structure was confirmed by FT-IR, 1H-NMR and 13C-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 sym.
n(SO2) respectively.
CCNN
CC
OO
OO
SS
OO
OO
CCll ++ HH22NN NNHH22
....
CCNN
CC
OO
OO
SS
OO
OO
NN NNHH22
CCll
HH HH
--HHCCll
CCNN
CC
OO
OO
SS
OO
OO
NNHHNNHH22
SScchheemmee ((33--44))
Chapter Three Results and Discussion
۳۸
1H-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 of aromatic protons appeared at δ= (7.39-7.99) ppm. 13C-NMR spectrum of compound [4] 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 Schiffs 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 Schiffs base [II] as
shown in Scheme (3-5).
Chapter Three Results and Discussion
۳۹
Physical properties of compounds [5-18] are listed in Table (3-2)
and their structures are confirmed by FT-IR, 1H-NMR and 13C-NMR
spectral data.
CC
OO
RR RR''11-- CC
OOHH
RR RR'' CC
OOHH
RR RR ''
22--CC
NNCC
OO
OO
SS
OO
OO
NNHHNNHH22
....CC
OOHH
RR RR''
CC
NN
CC
OO
OO
SSOO22 CCNNHH RRRR''
OOHH
NN
HH
HH
CC
NN
CC
OO
OO
SSOO22 CCNNHH RR
RR''
OOHH22
NN
HH
SScchheemmee ((33--55))
CC
NN
CC
OO
OO
SSOO22 NN==CCNNHHRR
RR''
[[II]]
[[IIII]]
--HH22OO
((RR == HH oorr ddiiff ffeerreenntt aallkkyyll oorr aarryyll ggrroouuppss))((RR == ddiiffffeerreenntt aallkkyyll oorr aarryyll ggrroouuppss))''
HH22OO
CCHH33CCOOOOHH // HHPPrroottoonnaattiioonn
CCHH33CCOOOO++
CCHH33CCOOOO
CCHH33CCOOOOHH
PPrroottoonnaattiioonnCCHH33CCOOOOHH // HH
CCHH33CCOOOO
CCHH33CCOOOOHH
++
Chapter Three Results and Discussion
٤۰
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).
1H-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.
13C-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.
1H-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.
Chapter Three Results and Discussion
٤۱
13C-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.
Comp. No. Compound structure Color Melting
Points °C Yield
% Recrystallization
Solvent
1 CONH
COOH
White 170-172 88 Ethanol
2 C
NCO
O
Off white 204-205 85 Acetone
3 C
NCO
O
SO2Cl
Brown 200 dec. 72 Acetone
٤ C
NCO
O
SO2NHNH2
White 210 dec. 95 Ethanol
Table (3-1): Physical properties of compounds [1-4]
Chapter Three Results and Discussion
٤۲
Table (3-2): Physical properties of Schiffs bases [5-18]
Comp. No. Compound structure Color
Melting Points
°C
Yield %
Recrystallization Solvent
5 C
NCO
O
SO2 N=CNH
CH3H
Pale yellow 119-120 85 Acetone
6 C
NCO
O
SO2 N=CNHH
OH
Orange 168-170 87 Acetone
7 CN
CO
O
SO2 N=CNH OCH3
Off white 192-193 81 Ethanol
8 C
NCO
O
SO2 N=CNHH
HO
Deep yellow 196-198 54 Acetone
9 C
NCO
O
SO2 N=CNHCH3
White 179-181 80 Ethanol
Chapter Three Results and Discussion
٤۳
Comp. No. Compound structure Color
Melting Points
°C
Yield %
Recrystallization Solvent
10 C
NCO
O
SO2 N=CNH
O2N
H
Off white 138-139 66 Ethanol
11 CN
CO
O
SO2 N=CNH
Off white 200 dec. 72 Acetone
12 C
NCO
O
SO2 N=CNH OHCH3
Off white 174-175 63 Ethanol
13 C
NCO
O
SO2 N=CNHH
NO2
Pale yellow 130-132 91 Ethanol
14 C
NCO
O
SO2 N=CNHH
Cl
White 226 dec. 77 Ethanol
15 C
NCO
O
SO2 N=CNH
OHH
Off white 135-136 83 Acetone
16 C
NCO
O
SO2 N=CNH NO2
CH3
Pale yellow > 220 93 Ethanol
17 C
NCO
O
SO2 N=CNHH
White 187-188 90 Acetone
18
Yellow 198 dec 86 Ethanol NN HH
OOCC
NNCC
OO
OO
SSOO22 NNNNHH
Chapter Three Results and Discussion
٤٤
Table (3-3): Spectral data of compounds [1-4]
Comp. No. Compound structure
FTIR spectral data cm-1
n(O-H) carboxylic
n(N-H) amide
n(C-H) aromatic
n(C=O) carboxylic
n(C=O) amide
n(C=C) aromatic
1 CONH
COOH
3325 3136 3062 1720 1643 1600
2 C
NCO
O
n(C-H) aromatic n(C=O) imide n(C=C)
aromatic n(C-N) imide
3074 1735 1708 1593 1384
3 C
NCO
O
SO2Cl
n(C-H) aromatic
n(C=O) imide
n(C=C) aromatic
n(SO2) asym.
n(SO2) sym. n(C-N) imide
3101 1743 1720 1585 1365 1188 1300
4 C
NCO
O
SO2NHNH2
n(-NH NH2) hydrazine
n(C-H) aromatic
n(C=O) imide
n(C=C) aromatic
n(SO2) asym.
n(SO2) sym.
n(C-N) imide
3359 3265 3097 1743
1718 1595 1390 1170 1338
Table (3-4): Spectral data of Schiffs bases [5-18]
Comp. No. Compound structure
FTIR spectral data cm-1
n(N-H) amide
n(C=O) imide
n(C=N) imine
n(C=C) aromatic
n(SO2) asym.
n(SO2) sym.
n(C-N) imide others
5 C
NCO
O
SO2 N=CNH
CH3H
3221 1739 1712 1627 1589 1373 1165 1338 -
6 C
NCO
O
SO2 N=CNHH
OH
3221 1739 1716 1608 1589 1373 1165 1338
n(O-H) Phenolic
3340
7 CN
CO
O
SO2 N=CNH OCH3
3417 1743 1716 1651 1597 1377 1168 1315
n(C-O-C) 1234 1126
Chapter Three Results and Discussion
٤٥
8 C
NCO
O
SO2 N=CNHH
HO
3221 1739 1716 1616 1589 1377 1165 1338
n(O-H) Phenolic
3479
9 C
NCO
O
SO2 N=CNHCH3
3043 1716 1624 1573 1388 1157 1330 -
10 CN
CO
O
SO2 N=CNH
O2N
H
3030 1741 1706 1610 1595 1386 1166 1340
n(NO2) 1498
11 CN
CO
O
SO2 N=CNH
3151 1735 1716 1654 1593 1377 1168 1319 -
12 C
NCO
O
SO2 N=CNH OHCH3
3209 1739 1716 1627 1604 1377 1168 1342
n(O-H) Phenolic
3460
13 C
NCO
O
SO2 N=CNHH
NO2
3221 1739 1716 1651 1589 1373 1165 1338
n(NO2) 1496
14 C
NCO
O
SO2 N=CNHH
Cl
3377 1741 1716 1625 1595 1375 1170 1330 n(C-Cl)
1091
15 C
NCO
O
SO2 N=CNH
OHH
3221 1739 1716 1627 1589 1373 1165 1338
n(O-H) Phenolic
3429
16 C
NCO
O
SO2 N=CNH NO2
CH3
3232 1740 1716 1658 1593 1373 1165 1342
n(NO2) 1469 1300
17 C
NCO
O
SO2 N=CNHH
3147 1741 1720 1625 1593 1375 1170 1338 -
18 N H
OCN
CO
O
SO2 NNH
3400 1741 1718 1620 1593 1380 1170 1348
n(C=O) Amide 1701
46
% T
Wave number ( cm-1 )
Fig. No. ( 1 ) : FT-IR spectrum for compound [ 1 ]
CCOONNHH
CCOOOOHH
47
% T
Wave number ( cm-1 )
Fig. No. ( 2 ) : FT- IR spectrum for compound [ 2 ]
CCNN
CC
OO
OO
48
% T
Wave number ( cm-1 )
Fig. No. ( 3 ) : FT- IR spectrum for compound [ 3 ]
CCNN
CC
OO
OO
SSOO22CCll
49
% T
Wave number ( cm-1 )
Fig. No. ( 4 ) : FT- IR spectrum for compound [ 4 ]
CCNN
CC
OO
OO
SSOO22NNHHNNHH22
50
% T
Wave number ( cm-1 )
Fig. No. ( 5 ) : FT-IR spectrum for compound [ 5 ]
CCNN
CC
OO
OO
SSOO22 NN==CCNNHH
CCHH33HH
51
% T
Wave number ( cm-1 )
Fig. No. ( 6 ) : FT- IR spectrum for compound [ 6 ]
CCNN
CC
OO
OO
SSOO22 NN==CCNNHHHH
OOHH
52
% T
Wave number ( cm-1 )
Fig. No. ( 7 ) : FT- IR spectrum for compound [ 13 ]
CCNN
CC
OO
OO
SSOO22 NN==CCNNHHHH
NNOO22
53
] 1 [ compound for spectrum NMR-H1 : ) 8 ( No. Fig.
CCOONNHH
CCOOOOHH
54
] 1 [ compound for mpectrus NMR-C13 : ) 9 ( No. Fig.
CCOONNHH
CCOOOOHH
55
] 2 [ compound for spectrum NMR-H1 : ) 01 ( No. Fig.
CCNN
CC
OO
OO
56
] 2 [ compound rfo spectrum NMR-C13 : ) 11 ( No. Fig.
CCNN
CC
OO
OO
57
] 4 [ compound for spectrum NMR-H1 : ) 21 ( No. Fig.
CCNN
CC
OO
OO
SSOO22NNHHNNHH22
58
] 4 [ compound for spectrum NMR-C13 : ) 31 ( No. Fig.
CCNN
CC
OO
OO
SSOO22NNHHNNHH22
59
] 5 [ compound for spectrum NMR-H1 : ) 41 ( No. Fig.
CCNN
CC
OO
OO
SSOO22 NN==CCNNHH
CCHH33HH
60
] 5 [ compound for spectrum MRN-C13 : ) 51 ( No. Fig.
CCNN
CC
OO
OO
SSOO22 NN==CCNNHH
CCHH33HH
Chapter Three Results and Discussion
٦۱
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).
CCNN
CC
OO
OO
SS
OO
OO
CCNN
CC
OO
OO
SS
OO
OO
OO CC
OO
CCHH33
CCNN
CC
OO
OO
SS
OO
OO
OO CC
OO
CCHH33
++ HHOO CC
OO
CCHH33CCll
PPyyrriiddiinnee
....
HH
CCll
--HHCCll
[[1199]]SScchheemmee ((33--66))
Chapter Three Results and Discussion
٦۲
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.
1H-NMR spectrum of compound [19] showed signal at
δ= 2.569 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 sulfonate] methyl benzylidene [20-26]
The titled Schiffs 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).
Chapter Three Results and Discussion
٦۳
CN
CO
O
S
O
O
O C
O
CH3
[19]
CN
CO
O
S
O
O
O C
OH
CN
CO
O
S
O
O
O C
OH
1-
RNH2
..
CN
CO
O
S
O
O
O C
OH
CN
CO
O
S
O
O
O C
OH
NR
H
H
CN
CO
O
S
O
O
O C
CH3
N
HOH
R
[I]
CN
C
O
O
S
O
O
O C
CH3
N
OH2
R
H
-H2O
H2OC
NCO
O
S
O
O
O C
CH3
N R
[20-26]
2-
Scheme (3-7)
+ +
CH3COOH / H Protonation
CH3COOH / H Protonation
CH3COOH
CH3COOH
CH3COO
CH3COO
CH3COO+
+
CH3
CH3
CH3
CH3
R =
CH3N
S ,
, ,
H3C O2N
Cl ,
Cl
Cl
NO2
,CH3
Chapter Three Results and Discussion
٦٤
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).
1H-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.
13C-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.
1H-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= (7.28-
8.12) ppm are due to aromatic ring protons.
13C-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.
Chapter Three Results and Discussion
٦٥
Comp. No. Compound structure Color
Melting Points
°C
Yield %
Recrystallization Solvent
20 C
NCO
O
SO2 OCH3
C=N
Pale brown 155-156 72 Ethanol
21 C
NCO
O
SO2 OCH3
C=N
H3C
Off white 148-150 66 Ethanol
22 C
NCO
O
SO2 OCH3
C=N
NO2
Pale yellow 159-160 88 Acetone
23 C
NCO
O
SO2 OCH3
C=N Cl
Cl
Pale brown 172-173 90 Ethanol
24 C
NCO
O
SO2 OCH3
C=N CH3
Off white 163-164 63 Ethanol
25 C
NCO
O
SO2 OCH3
C=N Cl
NO2
Pale yellow 180-182 85 Acetone
26 S
N
CH3CN
CO
O
SO2 OCH3
C=N
Pale brown 167-168 77 Cyclo hexane
Table (3-5): Physical properties of compounds [20-26]
Chapter Three Results and Discussion
٦٦
Table (3-6): Spectral data of compounds [20-26]
Comp. No. Compound structure
FTIR spectral data cm-1
n(C-H) aromatic
n(C=O) imide
n(C=N) imine
n(C=C) aromatic
n(SO2) asym.
n(SO2) sym.
n(C-N) imide others
20 C
NCO
O
SO2 OCH3
C=N
3109 1739 1720 1685 1593 1373 1180 1300 -
21 C
NCO
O
SO2 OCH3
C=N
H3C
3062 1740 1720 1685 1593 1373 1176 1296 -
22 C
NCO
O
SO2 OCH3
C=N
NO2
3100 1743 1722 1683 1593 1385 1182 1300
n(NO2) 1496 1355
23 C
NCO
O
SO2 OCH3
C=N Cl
Cl
3100 1739 1726 1687 1593 1369 1182 1355 n(C-Cl)
1078
24 C
NCO
O
SO2 OCH3
C=N CH3
3109 1743 1720 1685 1593 1373 1199 1300 -
25 C
NCO
O
SO2 OCH3
C=N Cl
NO2
3080 1725 1710 1690 1595 1372 1185 1300
n(NO2) 1490 1350
n(C-Cl) 1090
26 S
N
CH3CN
CO
O
SO2 OCH3
C=N
3109 1737 1720 1685 1593 1373 1199 1300 n(C-S)
609
67
% T
Wave number ( cm-1 )
Fig. No. ( 16 ) : FT-IR spectrum for compound [ 19 ]
CCNN
CC
OO
OO
SSOO22 OO CC
OOCCHH33
68
% T
Wave number ( cm-1 )
Fig. No. ( 17 ) : FT-IR spectrum for compound [ 24 ]
CCNN
CC
OO
OO
SSOO22 OO
CCHH33CC==NN CCHH33
69
% T
Wave number ( cm-1 )
Fig. No. ( 18 ) : FT-IR spectrum for compound [ 26 ]
SS
NN
CCHH33CCNN
CC
OO
OO
SSOO22 OO
CCHH33CC==NN
70
] 19 [ compound for spectrum NMR-H1 : ) 19 ( No. Fig.
CCNN
CC
OO
OO
SSOO22 OO CC
OOCCHH33
71
] 19 [ compound for spectrum NMR-C13 : ) 20 ( No. Fig.
CCNN
CC
OO
OO
SSOO22 OO CC
OOCCHH33
72
] 21 [ compound for spectrum NMR-H1 : ) 21 ( No. Fig.
CCNN
CC
OO
OO
SSOO22 OOCCHH33
CC==NN
HH33CC
73
] 21 [ compound for mspectru NMR-C13 : ) 22 ( No. Fig.
CCNN
CC
OO
OO
SSOO22 OOCCHH33
CC==NN
HH33CC
74
] 24 [ compound for spectrum NMR-H1 : ) 23 ( No. Fig.
CCNN
CC
OO
OO
SSOO22 OO
CCHH33CC==NN CCHH33
75
] 24 [ compound for spectrum NMR-C13 : ) 24 ( No. Fig.
CCNN
CC
OO
OO
SSOO22 OO
CCHH33CC==NN CCHH33
Chapter Three Results and Discussion
۷٦
3-3-Part Three
3-3-1- 4-[4'-(N-phthalimidyl) phenyl sulfonate] benzaldehyde [27]
Compound [27] was prepared via reaction between 4-(N-
phthalimidyl) 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).
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
CCNN
CC
OO
OO
SS
OO
OO
CCNN
CC
OO
OO
SS
OO
OO
OO CC
OO
HH
CCNN
CC
OO
OO
SS
OO
OO
OO CC
OO
HH
++ HHOO CC
OO
HHCCll
PPyyrriiddiinnee
....
HH
CCll
--HHCCll
[[2277]]
SScchheemmee ((33--88))
Chapter Three Results and Discussion
۷۷
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.
1H-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
proton .
13C-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].
33]-[28 benzylidene sulfonate] phenyl phthalimidyl)-(N-[4'-4 -2-3-3
The titled Schiffs 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).
CC
OOHH
Chapter Three Results and Discussion
۷۸
CN
CO
O
S
O
O
O C
O
H
[27]
CN
CO
O
S
O
O
O C
OH
CN
CO
O
S
O
O
O C
OH
1-
RNH2
..
CN
CO
O
S
O
O
O C
OH
CN
CO
O
S
O
O
O C
OH
NR
H
H
CN
CO
O
S
O
O
O C
H
N
HOH
R
[I]
CN
C
O
O
S
O
O
O C
H
N
OH2
R
H
-H2O
H2OC
NCO
O
S
O
O
O CH
N R
[28-33]
2-
R =
CH3 ,
, ,
H3C O2N
Cl ,
Cl
Cl NO2
,
Scheme(3-9)
+ +
CH3COOH / H Protonation
CH3COOH / H Protonation
CH3COOH
CH3COOH
CH3COO
CH3COO
CH3COO+
+
H
H
H
H
Chapter Three Results and Discussion
۷۹
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 (1300-
1355) 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).
1H-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-).
13C-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.
1H-NMR spectrum of compound [32] showed clear singlet signal at
δ= 2.08 ppm due to (CH3) group protons, multiplet signals at δ= (7.27-
8.12) 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.
Chapter Three Results and Discussion
۸۰
Table (3-7): Physical properties of compounds [28-33]
Comp. No. Compound structure Color
Melting Points
°C
Yield %
Recrystallization Solvent
28 C
NCO
O
SO2 OHC=N
Off white 180-182 70 Dioxane
29 C
NCO
O
SO2 OHC=N
CH3
Yellow 270-272 88 Ethanol
30 C
NCO
O
SO2 OHC=N
NO2
Deep yellow 177-178 76 Acetone
31 C
NCO
O
SO2 OHC=N Cl
Cl
White 184-186 61 Dioxane
32 C
NCO
O
SO2 OHC=N CH3
White 226-228 93 Ethanol
33 C
NCO
O
SO2 OHC=N Cl
O2N
Yellow 190-191 84 Acetone
Chapter Three Results and Discussion
۸۱
Table (3-8): Spectral data of compounds [28-33]
Comp. No. Compound structure
FTIR spectral data cm-1
n(C-H) aromatic
n(C=O) imide
n(C=N) imine
n(C=C) aromatic
n(SO2) asym.
n(SO2) sym.
n(C-N) imide others
28 C
NCO
O
SO2 OHC=N
3080 1720 1620 1585 1375 1190 1345 -
29 C
NCO
O
SO2 OHC=N
CH3
3040 1740 1720
1623 1590 1375 1180 1300 -
30 CN
CO
O
SO2 OHC=N
NO2
3040 1741 1720 1630 1593 1371 1199 1310
n(NO2) 1523 1352
31 CN
CO
O
SO2 OHC=N Cl
Cl
3060 1741 1720 1629 1596 1370 1186 1350 n(C-Cl)
1093
32 C
NCO
O
SO2 OHC=N CH3
3080 1740 1722 1630 1593 1373 1186 1346 -
33 C
NCO
O
SO2 OHC=N Cl
O2N
3101 1720 1631 1593 1365 1168 1338
n(NO2) 1504 1404
n(C-Cl) 1068
82
% T
Wave number ( cm-1 )
Fig. No. ( 25 ) : FT-IR spectrum for compound [ 27 ]
CCNN
CC
OO
OO
SSOO22 OO CC
OOHH
83
% T
Wave number ( cm-1 )
Fig. No. ( 26 ) : FT-IR spectrum for compound [ 28 ]
CCNN
CC
OO
OO
SSOO22 OO
HHCC==NN
84
% T
Wave number ( cm-1 )
Fig. No. ( 27 ) : FT- IR spectrum for compound [ 31 ]
CCNN
CC
OO
OO
SSOO22 OOHHCC==NN CCll
CCll
85
] 27 [ compound for spectrum NMR-H1 : ) 28 ( No. Fig.
CCNN
CC
OO
OO
SSOO22 OO CC
OOHH
86
] 27 [ compound for spectrum NMR-C13 : ) 29 ( No. Fig.
CCNN
CC
OO
OO
SSOO22 OO CC
OOHH
87
] 31 [ compound for spectrum NMR-H1 : ) 30 ( No. Fig.
CCNN
CC
OO
OO
SSOO22 OOHHCC==NN CCll
CCll
88
] 31 [ compound for mspectru NMR-C13 : ) 31 ( No. Fig.
CCNN
CC
OO
OO
SSOO22 OOHHCC==NN CCll
CCll
89
] 32 [ compound for spectrum NMR-H1 : ) 32 ( No. Fig.
CCNN
CC
OO
OO
SSOO22 OO
HHCC==NN CCHH33
90
] 32 [ compound for spectrum NMR-C13 : ) 33 ( No. Fig.
CCNN
CC
OO
OO
SSOO22 OO
HHCC==NN CCHH33
Chapter Three Results and Discussion
۹۱
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).
Compound [34] was purified by recrystallization from ethanol and was
obtained as reddish brown crystals in 65% yield with melting point (106-
108)oC. FT-IR spectrum of compound [34] showed appearance of clear
absorption band at 1689 cm-1 due to n(C=O) ketone.
CCNN
CC
OO
OO
HHKKOOHH ((aallccoohhoolliicc))
CCNN KK
CC
OO
OO
CCHH22 CC
OO
BBrrCC
NN KKCC
OO
OO
++
CCNN
CC
OO
OO
CCHH22 CC
OO
[[3344]]
SScchheemmee ((33--1100))
KKBBrr++
Chapter Three Results and Discussion
۹۲
Other absorption bands appeared at 1716 cm-1, 1600 cm-1 and
1392 cm-1 due to n(C=O)imide, n(C=C) aromatic and n(C-N) imide
respectively.
1H-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.
13C-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).
Chapter Three Results and Discussion
۹۳
CCNN
CC
OO
OO
CCHH22 CC
OO
[[3344]]
11--CC
NNCC
OO
OO
CCHH22 CC
OOHH
CCNN
CC
OO
OO
CCHH22 CC
OOHH
RRNNHH22
....22--
CCNN
CC
OO
OO
CCHH22 CC
OOHH
CCNN
CC
OO
OO
CCHH22 CC
OOHH
NNRR
HH
HH
CCNN
CCOO
OO
CCHH22 CC
OOHH
NNHH
RR
CCNN
CCOO
OO
CCHH22 CC
OOHH22
NN
HH
RR--HH22OO
CCNN
CCOO
OO
CCHH22 CC NN RR
[[3355--4400]]
SScchheemmee ((33--99))
RR ==
CCHH33 ,,
,, ,,
HHOO
CCll
NNOO22
,,
OOHHBBrr
CCHH33CCOOOOHHCCHH33CCOOOO++
++
++
++
CCHH33CCOOOOHH
CCHH33CCOOOOHH++ ++ HH22OO
CCHH33CCOOOOHH // HH PPrroottoonnaattiioonn
CCHH33CCOOOO
CCHH33CCOOOOHH // HHPPrroottoonnaattiioonn
Chapter Three Results and Discussion
۹٤
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).
1H-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.
13C-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.
Chapter Three Results and Discussion
۹٥
Table (3-9): Physical properties of compounds [35-40]
Comp. No. Compound structure Color
Melting Points
°C
Yield %
Recrystallization Solvent
35 CN
CO
O
CH2 C=
N
NO2
Pale green 162-163 92 Acetone
36 CN
CO
O
CH2 C=
N
Br
Brown 136-138 77 Ethanol
37 CN
CO
O
CH2 C=
N
Cl
Yellow 116-117 81 Dioxane
38 CN
CO
O
CH2 C=
N
OH
Deep brown 129-130 90 Ethanol
39 CN
CO
O
CH2 C=
N
CH3
Red 112-114 64 Acetone
40 CN
CO
O
CH2 C=
NOH
Deep green 165-167 85 Ethanol
Chapter Three Results and Discussion
۹٦
Table (3-10): Spectral data of compounds [35-40]
Comp. No. Compound structure
FTIR spectral data cm-1
n(C-H) aromatic
n(C=O) imide
n(C=N) imine
n(C=C) aromatic
n(C-N) imide others
35 CN
CO
O
CH2 C=
N
NO2
3062 1697 1624 1597 1350 n(NO2) 1450 1327
36 CN
CO
O
CH2 C=
N
Br
3035 1718 1674 1600 1352 n(C-Br) 688
37 CN
CO
O
CH2 C=N
Cl
3059 1725 1701 1631 1600 1311 n(C-Cl)
1083
38 CN
CO
O
CH2 C=
N
OH
3055 1716 1681 1647 1361 n(O-H)
Phenolic 3425
39
3028 1716 1620 1558 1319 -
40 CN
CO
O
CH2 C=
NOH
3000 1720 1703 1681 1590 1396
n(O-H) Phenolic
3456
CCNN
CC
OO
OO
CCHH22 CC==
NN
CCHH33
97
% T
Wave number ( cm-1 )
Fig. No. ( 34 ) : FT-IR spectrum for compound [ 34 ]
CCNN
CC
OO
OO
CCHH22 CC
==OO
98
% T
Wave number ( cm-1 )
Fig. No. ( 35 ) : FT-IR spectrum for compound [ 35 ]
CCNN
CC
OO
OO
CCHH22 CC==
NN
NNOO22
99
% T
Wave number ( cm-1 )
Fig. No. ( 36 ) : FT- IR spectrum for compound [ 38 ]
CCNN
CC
OO
OO
CCHH22 CC==
NN
OOHH
100
] 34 [ compound for spectrum NMR-H1 : ) 73 ( No. Fig.
CCNN
CC
OO
OO
CCHH22 CC
==OO
101
] 34 [ compound for spectrum NMR-C13 : ) 83 ( No. Fig.
CCNN
CC
OO
OO
CCHH22 CC
==OO
102
] 53 [ compound for spectrum NMR-H1 : ) 93 ( No. Fig.
CCNN
CC
OO
OO
CCHH22 CC==
NN
NNOO22
103
] 53 [ compound for mspectru NMR-C13 : ) 04 ( No. Fig.
CCNN
CC
OO
OO
CCHH22 CC==
NN
NNOO22
Chapter Three Results and Discussion
104
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 Schiffs base), thus a prileminary evaluation of anti-
bacterial 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 anti-
bacterial activity as shown in Table (3-11).
Table(3-11):Anti-bacterial activity for some of the Synthesized Schiffs bases
Comp. No. Gram-positive bacteria Gram-negative bacteria
Staphylococcus aureus Escherichia coli
5 + + + + +
6 + + + + -
7 + + + + + + + +
10 + + + + +
11 - + +
12 + + + + + +
14 + + + + +
16 + + + + +
17 + + + + +
18 + + + + + + + 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
Chapter Three Results and Discussion
105
Suggestions for future work
The following suggestions are found suitable for future work:
1. Synthesis of other new imides linked to Schiffs 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 Schiffs base.
References
۱۰٦
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الخالصة
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: هذا البحث الى أربعة أجزاء رئيسية تحضير مختلفة، لذلك تم تقسيم
ف عن طريق مرتبطة بقواعد شيفثال ايمايد جديده اتشتقالجزء االول تضمن تحضير م .۱
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-اتباع الخطوات التالية:
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الخطوة (أ) باستخدام انهيدريد في فنيل فثال أميك المحضر-N ء من حامضسحب الما - ب
[2].المائية كعامل ساحب للماء لتكوين الفثال ايمايد المقابل لالخليك وخالت الصوديوم ا
سلفنة مع حامض كلورو (ب) بتفاعلادخال الفثال أيمايد المحضر في الخطوة - ج
. [3]فثال ايمايد للفونيك للحصول على كلوريد سلفونيالكلوروس
مع الهيدرازين هايدريت للحصول على فثال ايمايد فنيل سلفونيل [3]عل المركب اتف - د
[4]. هيدرازين
فثال ايمايد فنيل سلفونيل وذلك عن طريق تفاعل [5-18]تحضير عدد من قواعد شيف -ه
.الروماتيةديهايدات والكيتونات االلمع مختلف ا [4] هيدرازين
د شيف عن أما الجزء الثاني من البحث فيتضمن تحضير فثال ايمايدات جديدة مرتبطة بقواع .۲
-يلي:احيث تم تحضير هذه المركبات باتباع م [20-26] طريق مكونة الفنيل سلفونات
عن طريق تفاعل فثال ايمايد [19]اسيتوفينون فنيل سلفوناتتحضير مركب فثال ايمايد - أ
.هيدروكسي اسيتوفينون 4-الجزء االول مع المحضر في [3]سلفونيل كلورايد فنيل
مع عدة أمينات اروماتية أولية معوضة هالمحضر في الخطوة (أ) بتفاعل [19]المركب - ب
.)۲مخطط ( [20-26]سنحصل على قواعد شيف
الجزء الثالث من البحث يتضمن تحضير فثال ايمايدات جديدة مرتبطة بقواعد شيف عن طريق .۳
-وذلك عن طريق أتباع الخطوات التالية: [28-33] اتمكونة الفنيل سلفون
فنيل عن طريق تفاعل الفثال ايمايد [27]بنزالديهايد تاسلفونفنيل تحضير فثال ايمايد - أ
.هيدروكسي بنزالديهايد 4-المحضر في الجزء االول مع [3]سلفونيل كلورايد
اولية معوضة الخطوة (أ) مع عدة امينات اروماتية المحضر في [27]تفاعل المركب - ب
.)۳مخطط ([28-33] سنحصل على قواعد شيف
البحث فيتضمن تحضير فثال ايمايدات جديدة مرتبطة بقواعد شيف عن أما الجزء االخير من .٤
-تم تحضير هذه المركبات عن طريق الخطوات التالية: [35-40]لين يطريق مجموعة المث
فنيل فيناسيل -4فنيل فيناسيل برومايد لتكوين 4-تفاعل ملح البوتاسيوم للفثال ايمايد مع - أ
. [34]فثال ايمايد
ماتية ومع عدة امينات ار (أ) في الخطوهالمحضر [34]فنيل فيناسيل فثال ايمايد -4تفاعل - ب
.)4مخطط ( [35-40]اولية معوضة لتكوين قواعد شيف الجديدة
مطيافية االشعة عن طريق وشخصت طيفيا درجات االنصهار للمركبات المحضرة تعين
و 1H-NMRمطيافية الرنين النووي المغناطيسي بنوعية استخدمت وكما FT-IRتحت الحمراء 13C-NMR في تشخيص بعض المركبات المحضرة.
المحضرة ضد ية البايولوجية لعدد من االيمايدات الجديدهكذلك تضمن البحث دراسة الفعال
المحضرة فعالية جيدة ضد انواع وقد اظهرت النتائج بان لاليمايدات الجديدهانواع من البكتريا
البكتريا قيد الدراسة.
العراق جمهورية وزارة التعليم العالي والبحث العلمي
كلية العلوم -جامعة بغداد Áقسم الكيميا
ℌⅬ℞ℂ₧ Ⅵ ℘Ⅼ℆№₧ ₆ ⅕₍€ℱ Ⅱ℈Ⅻ℈₯ ₥₌℈Ⅻ₍⅜Ⅻ
ℰⅬℕ ℈℩₌Ⅶℶ₡ Ⅲ⅘ℚ₨⅛
جزء من متطلبات نيل درجة الماجستير وهي جامعة بغداد -رسالة مقدمة إلى كلية العلوم العضويةكيمياء / الكيمياء الفي علوم
هاتقدم
مروة شوقي عبد الرزاق الجبوري ٢٠٠٨بكالوريوس علوم الكيمياء
بإشراف
الدكتورة أحالم معروف العزاوي
1433å ٢٠١٢ã
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