This document provides details of a thesis submitted for a Doctor of Philosophy degree in Chemistry. It describes the objectives of the thesis which are to synthesize and characterize N-phenyl succinimides, glutarimides, chalcones, pyrazoles, amino-pyrimidines and malononitriles and test their biological activities. It outlines the materials and methods used which involve synthesizing cyclic imides, chalcone derivatives from the imides, and then pyrazoles, amino-pyrimidines and malononitriles from the chalcones. It also provides an abstract that summarizes the key points of the thesis and introduces the topics to be covered.

1. THESIS
SUBMITTED TO THE
SHRI JAGDISH PRASAD JHABARMAL
TIBREWALA UNIVERSITY,
FOR THE DEGREE
OF
DOCTOR OF PHILOSOPHY
IN
CHEMISTRY
Year -2016

2. Name of scholar : Ravindra Shenfadu Dhivare
Registration Number : 15712276
Subject : Chemistry
Guide : Dr. Rajendrasingh Yadav
Co-Guidance of : Dr. Rajput Shankarsing Sardarsing
Year: 2016

3. The Thesis Has Been Divided Into The Following
Points
Abstract
Introduction
Justification
Literature Survey
Objective of the plan work
Chapter wise Synthesis & Results
Concluding Remarks
Future Scope

4. ABSTRACT
Formylation is a fundamental route of organic synthesis
subsequently the formation of aldehyde which plays an
intermediate role. The formyl chalcones are very important
intermediates and building blocks widely employed in the synthesis
of diverse pyrazole and pyrimidine systems. Bis-chalcones are the
synthestic and naturally occurring flavonoids present in the variety
of food stuffs. These are recently focused as a pharmacological,
medicinal, and several synergistic groups of biological activities.
Chalcone based pyrazoles and pyrimidines show the wide range of
applications in medicines. Pyrimidino-pyrazoles are being studied
in the combact against cancer so on. Malononitriles is a versatile
active methylene group used as initial constituent in the synthesis
of nitrile groups in the Knoevenagel condensation reaction of cyclic
imides by eco-friendly route. All the compounds in the research
scheme were synthesized by conventional and microwave
synthetic methods.

5. ABSTRACT Cont.…
The synthesis of N-phenyl-pyrrolidine-2, 5-dione (2a-j) and N-
phenyl-piperidine-2, 6-dione (4a-j) has been developed. The
method involves in the first step; the treatment of substituted
anilines and succinic anhydrides in benzene which form N-
phenylcarbamoyl propanoic acid and then further cyclization with
acetyl chloride. Some of N-phenyl succinimides and N-phenyl
glutarimides are so far unknown. All these synthesized cyclic
imides may by use for preparation of various heterocyclic systems
such as chalcones, pyrazoles, pyrimidines and malononitriles. The
development of bis-chalcone (5a-j and 7a-j) involves in the
treatment of cyclic imides and vanillin in neutral alumina in
microwave solvent free method. Correspondingly the synthesis of
pyrazole (6a-j and 8a-j) derivatives has been obtained by the
treatment of substituted chalcones and hydrazine hydrate with
neutral alumina.

6. ABSTRACT Cont.…
Similarly the substituted amino-pyrimidines (9a-j and 10a-j) were
also prepared by bis-chalcones and guanidine nitrate with neutral
alumina in microwave solvent free synthesis. As a final point the
Knoevenagel condensation of malononitrile derivatives (11a-j and
12a-j) was consistently prepared thru the same method by using
cyclic imides and di-cyanomethane in presence of neutral alumina.
All the synthesized compounds were found reasonable
antibacterial activities counter to Bacillus subtilis gram +ve and
Escherichia coli gram -ve bacterial strains. Likewise they showed
significant to good activities against fungal strains Candida
albicans and Aspergillus niger. Out of these, some of the
compound exhibited synergistic antifungal activities.

7. INTRODUCTION
The science of assembling heterocyclic ring has made
enormous strides in recent years. The proper arrangement of
such assemblies has general novel molecular species.
Heterocycles provide the various beneficial resource routes for
the construction of the heterocyclic systems in various kinds of
synthetic policies including aldol-condensation, cyclo-addition,
cyclo-condensation and molecular-rearrangement so on

8. INTRODUCTION Cont….
The chemistry of chalcones created the challenges of scientific
studies all over the globe. They are especially remarkable for their
biological, pharmaceutical and industrial relevance due to their multi-
coloured characteristics. Basically they are benzylidene-
acetophenones but they are popularly known as “Chalcone”
specified by the scientist S.V. Kostanecki and J. Tambor in the year
1899. Aldol-condensation is the significant variety of scheme
available for the synthesis of chalcones. Various naturally occurring
antibiotics and amino-chalcones possess their biological activity
which exist an unsaturated carbonyl group. Chalcones were
illustrated by their tenure structure along with two aromatic rings.

9. INTRODUCTION Cont….
Pyrazole is a simple aromatic five membered ring compound has
very important class of heterocycles due to its biological and
pharmacological activities which exhibit an anti-inflammatory,
herbicidal, plant growth regulating, fungicidal, bactericidal, anti-
pyretic and protein kinase inhibitors. In the crop production
chemistry, there is a great significance of pyrazole derivatives due
to their biological potency amongst herbicidal, fungicidal and
insecticidal action found with their stroke of synthetic routes and the
mode of action. Pyrazole derivatives can be used as an inhibitor
action in blood platelet aggregation in recent times and also very
important in the field of enzyme inhibition. The types of pyrazole
nucleus are,

10. INTRODUCTION Cont….
Pyrimidine is the most important and essential diazine which is
useful for all types of life processes on the mother earth. It
occupies a great role in the heterocyclic compounds because of
its therapeutic, pesticidal, insecticidal and fungicidal actions. It
also possesses good pharmacological properties. Almost all the
derivatives of pyrimidine based chalcones demonstrated excellent
anti-microbial activities.

11. INTRODUCTION Cont….
Malononitrile (MDN) is vital and prevalently acknowledged reagent
which is helpful for the heterocyclic synthesis. It shows versatile
moiety and its reactivity is broadly spread in chemical, biological,
medicinal and industrial fields due to its pesticidal, fungicidal,
pharmaceutical, dyestuff making, charge transfer, semiconductor,
organic conductor and electrochemical transformation activities. A
malononitrile derivative also gives remarkable stability and electrical
properties which is well suitable to organic conductors for the
charge transfer development systems. Due to its electron
withdrawing groups; it is also efficient electron acceptors for the
semiconductor devices. Hence, the malononitrile builds a significant
chemical property in medicinal research and chemical synthesis.
The malononitrile nucleuses are;

12. INTRODUCTION Cont….
Cyclic-imides are the part of cyclic amide ring compounds which
is having the molecular structure -CO-V(R)-CO- imide ring and
are hydrophobic as well as neutral in nature but they can traverse
the biological membranes. Some general structures of cyclic
imides are;

13. JUSTIFICATION
Rationale – The main validating aim of the present research is to
demonstrate the importance of the organic synthesis and its
scope with the numerous properties against biological, medicinal,
pharmacological, agriculture as well as industrial fields. By
interpreting the endurance of current situation; here the
researcher is going to prepare some of the important compounds
such as pyrazoles, amino-pyrimidines and malononitriles
derivatives from chalcones and expecting to examine their
biological activities.

14. LITERATURE SURVEY
1 Gilchrist T. L.
(1999)
reported of new and improved methods of aromatic
building blocks of heterocycles by ring compounds
2 Doan T.N., Dao
T.T. (2011)
reported chalcones i.e. synthetic flavonids
3 Shibata S.
(1994)
Anti-tumorigenic Chalcones, Stem Cells
4 Jamal H. et al.
(2009)
Chalcones: Differential effects on glycogen contents of
liver, brain and spinal cord in rats
5 Sharma B. et al.
(2010)
Chalcones a New Class of Potential Non- Azo Dyes
6 Werner et al.
(2003)
A Convenient Synthesis of 4-Aminoaryl Substituted Cyclic
Imides
7 Prado et al.
(2004)
Biological evaluation of some selected Cyclic Imides:
Mitochondrial Effects and in vitro Cytotoxicity

15. 8 Kolyamshin
O.A., Danilov
V.A. (2004)
N-Aryl-2-dialkylaminosuccinimides
9 Shetgiri N.P.,
Nayak B.K.
(2005)
Synthesis and antimicrobial activity of some succinimides
10 Guevara-Salazar
et al. (2007)
The Electronic Influence on the Active Site-Directed
Inhibition of Acetylcholinesterase by N-aryl-Substituted
Succinimides
11 Wang et al.
(2008)
Efficient Synthesis of 4,5-Disubstituted-3-toluenesulfonyl
Glutarimides Application to the Formal Synthesis of
Mappicine Ketone
12 Michalska et al.
(2000)
Glutarimide: A Carrier Transporting Drug Through Cell
Membranes
13 Corradi et al.
(2007)
New “Green” Approaches to the Synthesis of Pyrazole
Derivatives
14 Radi S.
(2010)
Synthesis and Preliminary Biological Activity of Some New
Pyrazole Derivatives as Acyclonucleoside Analogues
LITERATURE SURVEY
Cont…

16. 14 Bole S.B.
(2011)
Synthesis and biological evaluation of novel pyrazole
derivatives as urease inhibitors
15 Yuvaraj S.
(2009)
Analysis and Antibacterial Evaluation of Pyrazole Derivative
16 Sharma R.N.
(2010)
Synthesis, Characterization, and Biological activities of
Some New Arylazopyrazoles
17 Solankee et al.
(2009)
Chalcones, pyrazolines and aminopyrimidines as
antibacterial agents
18 Mohebbi S.
(2011)
"Synthesis route-based hit identification approach" as a tool
in medicinal chemistry and its application in investigating
the anti-proliferative and antimicrobial effects of 2-
aminopyrimidine derivatives
19 Nofal Z.M.
(2011)
Synthesis of new pyrimidine derivatives with evaluation of
their anti-inflammatory and analgesic activities
20 Suneel Kumar
K.(2011)
Synthesis and characterization of some novel Pyrimidines
via Aldol Condensation
LITERATURE SURVEY
Cont…

17. 21 Singh K. et al.
(2012)
2-Aminopyrimidine based 4-aminoquinoline anti-plasmodial
agents, Synthesis, biological activity, structure-activity
relationship and mode of action studies
22 Sharma V. &
Sharma K.V.
(2011)
Synthesis and biological activity of some 2-amino-4,6-
substituted-diarylpyrimidines: reaction of substituted
chalcones with guanidinium carbonate
23 Kim B.R. et al.
(2009)
Efficient Synthesis of 4,5,6-Trisubstituted-2-
aminopyrimidines
24 El-Zahar M.I.
(2011)
Synthesis, Antitumor Activity and Molecular Docking Study
of Novel Benzofuran-2-yl Pyrazole Pyrimidine Derivatives
25 Sidhu et al.
(2010)
Chemoselective reaction of malononitrile with imine-ones
and antifungal potential of products
26 Helmy N.M. et
al.
(2011)
A route to dicyanomethylene pyridines and substituted
benzonitriles utilizing malononitrile dimer as a precursor
27 Bhuiyan et al.
(2012)
Microwave assisted knoevenagel condensation: synthesis
and antimicrobial activities of some arylidene-
malononitriles
LITERATURE SURVEY
Cont…

18. LITERATURE SURVEY
Cont…
28 Ameta K.L. et al.
(2011)
Synthesis of some novel chalcones and their facile one-pot
conversion to 2-aminobenzene-1, 3-dicarbonitriles using
malononitrile
29 Deng H. et al.
(2011)
Discovery of 2-(4-Methylfuran-2(5H)-ylidene)malononitrile
and Thieno[3,2-b]thiophene-2-carboxylic Acid Derivatives
as G Protein-Coupled Receptor 35 (GPR35) Agonists
30 Hosni H.M. and
Abdulla M.M.
(2008)
Anti-Inflammatory and Analgesic Activities of some newly
Synthesized Pyridinedicarbonitrile and
Benzopyranopyridine Derivatives
31 Rajput S.S.
(2012)
Synthesis and Characterization of Bis-Heteroyclic
Derivatives of 1-(3-Chlorophenyl)-Pyrrolidine-2, 5-Dione
32 Kumar R.
(2008)
Synthesis and Biological Evaluation of some Novel
Analogue of p-Hydroxyaniline
33 Rajput A.P. and
Girase P.D.
(2011)
Synthesis, Characterization and Microbial Screening of
Pyrazoline Derivatives of 2, 6-Dichloro-1-(N-Substituted
Phenyl)-1, 4-Dihydropyridine-3, 5-Dicarbaldehyde
34 Rajput A.P. and
Bhadane S.J.
(2012)
Synthesis of 2, 5-dichloro 3, 4-diformyl (N-substituted
phenyl) pyrroles and their synthetic utility

19. 1) To prepare N-substituted phenyl-succinimides and
glutarimides from succinic anhydride and glutaric
anhydride using substituted aniline and their
characterization.
2) To synthesize prazoles from N–phenyl-succinimides and
glutarimides and scrutinize their characterization.
3) To synthesize amino-pyrimidines from N–phenyl-
succinimides and glutarimides and examine their
characterization.
4) To synthesize the malononitrile derivatives from N–phenyl-
succinimides and glutarimides and assess their
characterization.
5) The entire synthesized compound series will be tested for
their biological potencies.
RESEARCH OBJECTIVES

20. MATERIALS AND METHODS
Synthesis of Cyclic Imides
Synthesis of Chalcone Derivatives from imides
Synthesis of pyrazole derivatives
Synthesis of Amino-pyrimidines
Synthesis of Malononitriles
Characterization of all of the compounds
Biological Activities of all synthesized derivatives

21. MATERIALS AND METHODS

22. SYNTHESIS, CHARACTERIZATION AND BIOLOGICAL
ACTIVITIES OF N-PHENYL SUCCINIMIDE AND N-PHENYL
GLUTARIMIDE DERIVATIVES
CHAPTER-3
A comprehensive literature review discloses that the chemistry of
N-substituted phenyl succinimides and glutarimides have not been
studied significantly. To achieve our aim we have developed
efficient and economical two step synthesis followed by acid
intermediates by using succinic anhydride and glutaric anhydride
as a starting compounds for the construction of N-substituted
phenyl succinimides and glutarimides. In this method Succinic
anhydride or glutaric anhydride was treated with substituted
aromatic primary amines in presence of benzene which gives acid
intermediates. The acid intermediates further refluxed with acetyl
chloride furnished N-substituted phenyl succinimides (2a-j) and N-
phenyl glutarimides (4a-j) as visualized in (Scheme-I).

23. CHAPTER-3 Cont.…..
NH2
Acetyl Chloride
Acetyl Chloride
1
2
3
SCHEME - I
HOOC-H2C-H2C-OC-HN NH-CO-CH2-CH2-CH2-COOH
®
®
®
®
®
N O
O
N
O
O
O
O
O
O
O
O
4

24. The researcher has developed the convenient method for the
synthesis of N-phenyl succinimide & Glutarimide derivatives.
The experimental method is demonstrated in the fig.
CHAPTER-3 Cont.…..
O
O O
NH2
O
Cl
N O
O
HCl fumes
Escape
30 ml
90 mmole
NH
O
O
OH
10 mmole
10 mmole
Refluxed at 90-110 ºC up to 15 - 20 minutes for both conditions
After dried
completely
then reflux
next step

25. To accomplish the research objective benzene (10 mmole) was
added in succinic anhydride and heated under reflux with
constant stirring for 15 to 20 minutes till the solution becomes
clear. Into this solution the primary aromatic amines and α-
napthyl amine ‘A’ (10 mmole) in 5 ml benzene was slowly
poured with constant stirring for 15 to 20 minutes till the
solution becomes homogenized. Upon evaporation of benzene
the whitish amorphous powder of 3-(N-phenyl or
napthylcarbamoyl) propanoic acid 1a-j was obtained.
The mixture of 3-(N-phenyl or napthylcarbamoyl) propanoic
acid 1a-j and acetyl chloride (90 mmole) was refluxed with
constant stirring at the temperature 90-110 ºC for 15 to 20
minutes till the complete evolution of HCl gas. The mixture was
then became cool at room temp accomplished the solid
products 2a-j. Thus the crude product was washed 2 to 3 times
by lukewarm distilled water and filtered off; the resulting solids
were recrystallized from ethanol (Scheme–Ia).
CHAPTER-3 Cont.…..

26. CHAPTER-3 Cont.…..
O
O
O
N
O
O
NH2 NHCOCH2CH2COOH
® ®
®
+
S A 1a-j
2a-j
Benzene
Reflux
90-110 ºC
Reflux
90-110 ºC
Acetyl
Chloride
Scheme -Ia: Preparation of N-phenyl Succinimides
® , a = -H, b = -4Br, c = -4Cl, d = -4CH3, e = -4OCH3,
f = -4F, g = -4NO2, h = -phenyl, i = -3Cl,-4F, j = -2,4,5Cl

27. CHAPTER-3 Cont.…..
Sr.
No.
Substituted
Aniline
Compound
Code
Molecular
Formula
M.W.
Practical
Yield
M.P. Range
(ºC)
Product
Colour
(Crude)
1 -H 2a C10H9NO2 175.06 79.91% 154-156 ºC
Cream
White
2 4-Br
2b
C10H8BrNO2 254.08 89.78% 174-176 ºC
Whitish
Brown
3 4-Cl
2c
C10H8ClNO2 209.63 76.60% 159-161 ºC
Whitish
Lavender
4 4-CH3
2d
C11H11NO2 189.21 62.73% 150-152 ºC
Cream
5 4-OCH3
2e
C11H11NO3 205.21 78.91% 160-162 ºC
Brown
6 4-F
2f
C10H8FNO2 193.17 62.90% 176-178 ºC
Brownish
7 4-NO2
2g
C10H8N2O4 220.18 88.86% 219-221 ºC
Cream
Yellow
8 α-Napthyl
2h
C14H11NO2 225.24 99.11% 148-150 ºC
Dark
Lavender
9 3-Cl,4-F
2i
C10H7ClFNO2 227.62 84.60% 158-160 ºC
Pinkish
White
10 2,4,5-Cl
2j
C10H6Cl3NO2 278.52 75.56% 196-198 ºC
Pure
White
Physical Characteristics of 2a-j

28. CHAPTER-3 Cont.…..
N
NH2 NHCO(CH2)3COOH
® ®
®
+
G A
3a-j 4a-j
Benzene
Reflux
90-110 ºC
Reflux
90-110 ºC
Acetyl
Chloride
Scheme -Ib: Preparation of N-phenyl Glutarimides
O
O
O
O O
® , a = -H, b = -4Br, c = -4Cl, d = -4CH3, e = -4OCH3,
f = -4F, g = -4NO2, h = -phenyl, i = -3Cl,-4F, j = -2,4,5Cl

29. CHAPTER-3 Cont.…..
Physical Characteristics of 4a-j
Sr.
No.
Substituted
Aniline
Compound
Code
Molecular
Formula
M.W.
Practical
Yield
M.P. Range
(ºC)
Product
Colour
(Crude)
1 -H 4a C11H11NO2 189.21 77.92% 120-122 ºC
Cream
Colour
2 4-Br 4b C11H10BrNO2 268.11 82.94% 144-146 ºC
Whitish
Brown
3 4-Cl 4c C11H10ClNO2 223.66 86.70% 123-125 ºC
Faint
Lavender
4 4-CH3 4d C12H13NO2 203.24 77.07% 179-181 ºC
Marble
Colour
5 4-OCH3 4e C12H13NO3 219.24 76.66% 138-140 ºC
Brownish
6 4-F 4f C11H10FNO2 207.2 76.35% 119-121 ºC
Brownish
7 4-NO2 4g C11H10N2O4 234.21 84.01% 168-170 ºC
Cream
Yellow
8 α-Napthyl 4h C15H13NO2 239.37 83.61% 153-155 ºC
Dark
Lavender
9 3-Cl,4-F 4i C11H9ClFNO2 241.65 91.30% 104-106 ºC
Whitish
Brown
10 2,4,5-Cl 4j C11H8Cl3NO2 292.55 85.73% 138-140 ºC
Pure
White

30. CHAPTER-3 Cont.…..
Spectral Analysis of 2a-j & 4a-j
These title derivatives were characterized by their spectral analysis. Elemental
analysis the series of these compounds were found closely around the given
ranges of C: 57.83, H: 3.59, N: 2.50. These compounds in its IR spectrum
observed and showed the frequency bands at 1800 cm-1 to 1665 cm-1 typical
range for cyclic anhydride carbonyl carbon groups, bands between 3000 cm-1
to 2800 cm-1 for –CH2−CH2− and –CH2−CH2−CH2− stretching for cyclic group,
array frequency bands at 1350 cm-1 to 1300 cm-1 for cyclic imine groups, bands
at 1650 cm-1 to 1450 cm-1 three peaks for aromatic ring and a single band of Ar-
Br between 1075 cm-1- 1030 cm-1, Ar-Cl between 1035 cm-1- 1100 cm-1, Ar-F
between 1250 cm-1- 1100 cm-1, Ar-NO2 between 1550 cm-1- 1500 cm-1, Ar-
OCH3 between 1350 cm-1- 1100 cm-1 in the starting substituted phenyl
succinimides was found, verified and confirmed the formation of cyclic imides.
The 1HNMR spectrum of the compounds 2a-j and 4a-j in CDCl3 solvent showed
typical signals of aromatic (7.16-7.36 δ) multiplets 4H atoms, napthyl group
(7.30-8.03 δ) multiplet signals of seven protons and imide group signal (2.94 δ)
four protons. Based on these data the probable structures of 2a-j and 4a-j were
predicted.

31. CHAPTER-3 Cont.…..
Spectra of 2a-j

32. CHAPTER-3 Cont.…..
Spectra of 4a-j

33. CHAPTER-3 Cont.…..
Antimicrobial Activities of N-Phenyl Succinimide and N-
Phenyl Glutarimide Series: 2a-j & 4a-j
S
t
d
2
a
2
b
2
c
2
d
2
e
2
f
2
g
2
h
2
i
2
j
4
a
4
b
4
c
4
d
4
e
4
f
4
g
4
h
4
i
4
j
C
t
r
l
0
5
1 0
1 5
2 0
2 5
3 0
0 %
2 0 %
4 0 %
6 0 %
8 0 %
1 0 0 %
 C o m p o u n d se rie s 
C h a r t 0 1 : A n tib a cte rial ac tiv ities o f 2 a -j an d 4 a -j (B .S .) M ea n ± S D
Z
o
n
e
o
f
in
h
i
b
iti
o
n
in
m
m
%
o
f
i
n
h
i
b
it
io
n
100 g/ml
200 g/ml
300 g/ml
S
t
d
2
a
2
b
2
c
2
d
2
e
2
f
2
g
2
h
2
i
2
j
4
a
4
b
4
c
4
d
4
e
4
f
4
g
4
h
4
i
4
j
C
t
r
l
0
5
1 0
1 5
2 0
2 5
3 0
0 %
2 0 %
4 0 %
6 0 %
8 0 %
1 0 0 %
 C o m p o u n d se rie s 
C h a r t 0 2 : A n tib a cterial a ctiv itie s o f 2 a-j a n d 4 a-j (E .C .) M ea n ± S D
Z
o
n
e
o
f
in
h
i
b
iti
o
n
in
m
m
%
o
f
i
n
h
i
b
it
io
n
1 0 0 g /m l
2 0 0 g /m l
3 0 0 g /m l
Antibacterial Activities of
2a-j & 4a-j

34. CHAPTER-3 Cont.…..
Antimicrobial Activities of N-Phenyl Succinimide and N-
Phenyl Glutarimide Series: 2a-j & 4a-j
Antifungal Activities of
2a-j & 4a-j
S
t
d
2
a
2
b
2
c
2
d
2
e
2
f
2
g
2
h
2
i
2
j
4
a
4
b
4
c
4
d
4
e
4
f
4
g
4
h
4
i
4
j
C
t
r
l
0
5
1 0
1 5
2 0
2 5
3 0
0 %
2 0 %
4 0 %
6 0 %
8 0 %
1 0 0 %
 C o m p o u n d se rie s 
Z
o
n
e
o
f
in
h
i
b
iti
o
n
in
m
m
%
o
f
i
n
h
i
b
it
io
n
1 0 0 g /m l (C .A .)
1 0 0 g /m l (A .N .)
C h a r t 0 3 : A n tifu n g al activ ities o f 2 a-j an d 4 a-j (C .A . an d A .N .) M ean ± S D

35. CHAPTER-3 Cont.…..
Result & Discussion of 2a-j & 4a-j
The compounds 2a-j and 4a-j were found moderately active against
gram +ve Bacillus subtilis and gram -ve Escherichia coli bacterial
strains. In the same way only a few compounds 2a, 2f, 2i were showed
significant potency against Aspergillus niger and Candida albicans
fungal strains and compound 2j was found moderate activity against
Candida albicans.

36. CHAPTER- 4
SYNTHESIS, CHARACTERIZATION AND BIOLOGICAL
ACTIVITIES OF PYRAZOLE DERIVATIVES
Pyrazole derivatives have concerned a great deal of consideration on
account of their wide range of application in biological, pharmaceutical and
medicinal domains. To accomplish the objective we have designed
ecofriendly, efficient and economical solvent free synthesis followed by
chalcone intermediates. The substituted bis-chalcones 5a-j and 7a-j were
prepared initially irradiation of substituted phenyl succinimides (2a-j) and
glutarimides (4a-j) with vanillin using neutral alumina in microwave.
Subsequently to accomplish the pyrazole synthones, the afforded
chalcones were reacted with hydrazine hydrates in presence of neutral
alumina in solvent free microwave condition furnishes the (6a-j) and (8a-j)
compounds foreseen in the (Scheme-II).

37. CHAPTER- 4 Cont.…..
SCHEME - II
5
7
7
6
7
4
7
2
7
®
N
O
O
®
N
O
O
Ar
Ar
®
N N
NH
HN
N
Ar Ar
®
N O
O
®
N O
O
®
N
Ar
Ar
N
NH
HN
N
Ar
Ar
ArCHO
ArCHO
NH2NH2.H2O
NH2NH2.H2O
8
7

38. CHAPTER- 4 Cont.…..
Material Method: Melting points were noted and uncorrected by open-glass
capillaries. IR spectra in (KBr pallets) were note down via Shimadzu FṮIṞ꞉8400Ṡ
and ATR Brucker alpha FṮ-IṞ spectrophotometer. 13C NMR and 1H NMR spectras
were monitored on 500.13 MHz, 400 MHz and 125.77 MHz by Brucker
spectrophotometer. The reactions were monitored by TLC executed by using pre
coated silica-gel aluminium plates with mixture of diethyl ether and ethyl acetate
7:3 proportion or benzene. All the compounds 5a-j, 6a-j, 7a-j and 8a-j were
synthesized in the domestic microwave oven Electrolux Nutrition in hours from
the corresponding commercially available 4-hydroxy-3-methoxy benzaldehyde
(vanillin), hydrazine hydrate, neutral alumina (Al2O3) and ethanol as shown in the
fig.
N N
NH
HN
N
HO OH
O
CH3
O
H3C
N
OH
HO
O
O
O
O
H3C
CH3
®
N O
O
CHO
OH
OCH3
+
®
NH2NH2.H2O
®
MW
Neutral
Al2O3
Neutral
Al2O3
Fig 15: Experimental display of pyrazole synthesis
2

39. CHAPTER- 4 Cont.…..
General Procedure for the Synthesis of Bis-chalcones by using N-Phenyl
Succinimides 5a-j:
N
OH
HO
O
O
O
O
H3C
CH3
®
Neutral Al2O3
N
O
O
CHO
OH
OCH3
+
®
MW
640W
5-8 min
Scheme -IIa: (3Z,4Z)-3,4-bis-(-4-hydroxy-3-methoxy-benzylidene)-N-phenyl-pyrrolidine-2,5-dione (5a-j)
® , a = -H, b = -4Br, c = -4Cl, d = -4CH3, e = -4OCH3,
f = -4F, g = -4NO2, h = -phenyl, i = -3Cl,-4F, j = -2,4,5Cl
2 a-j V
5 a-j
1 2
The bis-chalcones (5a-j) are synthesized by the mixture of 5 mmole of
phenyl substituted succinimides (2a-j) and 10 mmole of 4-hydroxy-3-
methoxy-benzaldehyde (V) in 2 gm of neutral Al2O3 under microwave
assisted solvent free conditions at 640W powers for 5-8 minutes. The
afforded coloured compounds were recovered and recrystallized by ethanol
(Scheme – IIa)

40. CHAPTER-4 Cont.…..
Physical Characteristics of 5a-j
Sr.
No.
Substituted
Aniline
Compd
Code
Molecular
Formula
MW Pr.
Yield
M.P. Range
(ºC)
Product Colour
(Crude)
1 -H 5a C26H21NO6 443.45 84.56% 112-114 ºC White Crystals
2 4-Br
5b
C26H20BrNO6
522.34
97.59% 91-93 ºC Whitish Brown
3 4-Cl
5c
C26H20ClNO6
477.89
94.93% 109-111 ºC
Whitish Brown
4 4-CH3
5d
C27H23NO6
457.47
68.28% 99-101 ºC
Whitish Yellow
5 4-OCH3
5e
C27H23NO7
473.47
71.48% 108-110 ºC
Muddy White
6 4-F
5f
C26H20FNO6
461.44
64.62% 148-150 ºC
Dark Yellow
7 4-NO2
5g
C26H20N2O8
488.45
84.42% 152-154 ºC
Dark Yellow
8 α-Napthyl
5h
C30H23NO6
493.51
83.26% 89-91 ºC
Dark Brown
9 3-Cl,4-F
5i
C26H19ClFNO6
495.88
74.39% 98-100 ºC
Pinkish
10 2,4,5-Cl
5j
C26H18Cl3NO6
546.78
71.06% 137-139 ºC
Whitish Yellow

41. CHAPTER- 4 Cont.…..
General Procedure for the Synthesis of Bis-chalcones by using N-Phenyl
Glutarimides 7a-j:
The bis-chalcones (7a-j) are synthesized by the mixture of 5 mmole of phenyl
substituted glutarimides (4a-j) and 10 mmole of 4-hydroxy-3-methoxy-
benzaldehyde (V) in 2 gm of neutral Al2O3 under microwave assisted solvent
free conditions take place on 640W powers for 3-6 minutes. The afforded
coloured compounds were recovered by and recrystallized by ethanol as shown
in the scheme – IIc.
Neutral Al2O3
CHO
OH
OCH3
+
®
MW
N
®
4a-j
O O N O
O
HO
O O
OH
CH3 CH3
7a-j
V
2
Scheme -IIc: (3Z,5Z)-3,5-bis(4hydroxy3methoxybenzylidene)-N-phenyl-piperidine-2,6dione (7a-j)
® , a = -H, b = -4Br, c = -4Cl, d = -4CH3, e = -4OCH3,
f = -4F, g = -4NO2, h = -phenyl, i = -3Cl,-4F, j = -2,4,5Cl
640W
3-6 min

42. CHAPTER-4 Cont.…..
Physical Characteristics of 7a-j
Sr.
No.
Substituted
Aniline
Compd
Code
Molecular
Formula
MW Pr.
Yield
M.P.
Range(ºC)
Product Colour
(Crude)
1 -H 7a C27H23NO6 457.47 79.91% 78-80ºC Pale Yellow
2 4-Br
7b
C27H22BrNO6
536.37
94.37% 94-96ºC Dark Yellow
3 4-Cl
7c
C27H22ClNO6
491.92
82.25% 76-78ºC Dark Yellow
4 4-CH3
7d
C28H25NO6
471.5
83.98% 95-97ºC Yellow
5 4-OCH3
7e
C28H25NO7
487.5
69.41% 68-70ºC Brown
6 4-F
7f
27H22FNO6
475.47
90.84% 85-87ºC Yellow
7 4-NO2
7g
C27H22N2O8
502.47
78.33% 93-95ºC Yellow
8 α-Napthyl
7h
C31H25NO6
507.53
91.74% 88-90ºC Brown
9 3-Cl,4-F
7i
C27H21ClFNO6
509.91
82.23% 74-76ºC Dark Yellow
10 2,4,5-Cl
7j
C27H20Cl3NO6
560.81
83.03% 103-105ºC Yellowish white

43. CHAPTER-4 Cont.…..
Spectral Analysis of 5a-j & 7a-j
These intermediate derivatives were characterized by their spectral analysis.
Elemental analysis series of these compounds were found closely around the
given ranges of C: 57.83, H: 3.59, N: 2.50. These compounds in its IR
spectrum observed and showed the frequency bands at 1800 cm-1 to 1665 cm-1
typical range for cyclic anhydride carbonyl carbon groups, a single band found
between 3100 cm-1 to 3000 cm-1 for =CH stretching for cyclic group, ranges the
frequency broad band at 3600 cm-1 to 3200 cm-1 for aromatic alcohol group,
bands at 1650 cm-1 to 1450 cm-1 for aromatic ring three peaks and a single
band of Ar-Br between 1075 cm-1- 1030 cm-1, Ar-Cl between 1035 cm-1- 1100
cm-1, Ar-F between 1250 cm-1- 1100 cm-1, Ar-NO2 between 1550 cm-1- 1500
cm-1, Ar-OCH3 between 1350 cm-1- 1100 cm-1 in the intermediary substituted
chalcones were found, verified and confirmed the formation of bis-chalcones.
The 1HNMR spectrum of the compounds 5a-j and 7a-j in CDCl3 and DMSO-d6
solvents showed the signals typical of aromatic (6.80-7.42 δ) multiplets 8H
atoms and =CH group, methoxy group (3.86 δ) singlet signal of three protons
and aromatic alcoholic -OH group signal (9.77 δ) singlet for a single proton.
Founded these data the possible structures of 5a-j and 7a-j were confirmed.

44. CHAPTER-4 Cont.…..
Spectra of 5a-j

45. CHAPTER-4 Cont.…..
Spectra of 7a-j

46. CHAPTER-4 Cont.…..
Antimicrobial Activities of Bis-chalcones: 5a-j & 7a-j
Antibacterial Activities of
5a-j & 7a-j
S
t
d
5
a
5
b
5
c
5
d
5
e
5
f
5
g
5
h
5
i
5
j
7
a
7
b
7
c
7
d
7
e
7
f
7
g
7
h
7
i
7
j
C
t
r
l
0
5
1 0
1 5
2 0
2 5
3 0
0 %
2 0 %
4 0 %
6 0 %
8 0 %
1 0 0 %
 C o m p o u n d se rie s 
C h a r t 0 4 : A n tib a cte rial ac tiv ities o f 5 a -j an d 7 a -j (B .S .) M ea n ± S D
Z
o
n
e
o
f
in
h
i
b
iti
o
n
in
m
m
%
o
f
i
n
h
i
b
it
io
n
1 0 0 g /m l
2 0 0 g /m l
3 0 0 g /m l
S
t
d
5
a
5
b
5
c
5
d
5
e
5
f
5
g
5
h
5
i
5
j
7
a
7
b
7
c
7
d
7
e
7
f
7
g
7
h
7
i
7
j
C
t
r
l
0
5
1 0
1 5
2 0
2 5
3 0
0 %
2 0 %
4 0 %
6 0 %
8 0 %
1 0 0 %
 C o m p o u n d se rie s 
C h a r t 0 5 : A n tib a cterial a ctiv itie s o f 5 a-j a n d 7 a-j (E .C .) M ea n ± S D
Z
o
n
e
o
f
in
h
i
b
iti
o
n
in
m
m
%
o
f
i
n
h
i
b
it
io
n
1 0 0 g /m l
2 0 0 g /m l
3 0 0 g /m l

47. CHAPTER-4 Cont.…..
Antimicrobial Activities of Bis-chalcones 5a-j & 7a-j
Antifungal Activities of
5a-j & 7a-j
S
t
d
5
a
5
b
5
c
5
d
5
e
5
f
5
g
5
h
5
i
5
j
7
a
7
b
7
c
7
d
7
e
7
f
7
g
7
h
7
i
7
j
C
t
r
l
0
5
1 0
1 5
2 0
2 5
3 0
0 %
2 0 %
4 0 %
6 0 %
8 0 %
1 0 0 %
 C o m p o u n d se rie s 
C h a r t 0 6 : A n tifu n g al activ ities o f 5 a-j an d 7 a-j (C .A . an d A .N .) M ean ± S D
Z
o
n
e
o
f
in
h
i
b
iti
o
n
in
m
m
%
o
f
i
n
h
i
b
it
io
n
1 0 0 g /m l (C .A .)
1 0 0 g /m l (A .N .)

48. CHAPTER- 4 Cont.…..
General Procedure for the Synthesis of Bi-pyrazoles by using Bis-
chalcones derived from N-phenyl succinimides 6a-j:
The pyrazole (6a-j) derivatives were synthesized by the mixture of 2 mmole of
bis-chalcones (5a-j) and 4 mmole of hydrazine hydrate in 2 gm of neutral Al2O3
under microwave assisted solvent free conditions on 640 W powers for 4-7
minutes. The afforded coloured compounds were recovered by ethyl acetate
and recrystallized by ethanol (Scheme – IIb)
N N
NH
HN
N
HO OH
O
CH3
O
H3C
N
OH
HO
O
O
O
O
H3C
CH3
®
2 NH2NH2.H2O
®
Neutral Al2O3
MW
640W
4-7 min
Scheme -IIb: (3Z,4Z)-3,4-bis-(4-hydroxy-3-methoxy-benzylidene)-7-(N-phenyl)-3,3a,3b,4,5,7-
hexahydro- 2H-pyrrolo[2,3-c,5,4-c] dipyrazole (6a-j)
® , a = -H, b = -4Br, c = -4Cl, d = -4CH3, e = -4OCH3,
f = -4F, g = -4NO2, h = -phenyl, i = -3Cl,-4F, j = -2,4,5Cl
5 a-j
6 a-j

49. CHAPTER-4 Cont.…..
Physical Characteristics of 6a-j
Sr.
No.
Substituted
Aniline
Comp
d
Code
Molecular
Formula MW
Pr.
Yield
M.P. Range
(ºC)
Product Colour
(Crude)
1 -H 6a C26H25N5O4 471.51 91.48% 172-174ºC Yellowish brown
2 4-Br 6b C26H24BrN5O4 550.4 60.36% 207-209ºC Brownish yellow
3 4-Cl 6c C26H24ClN5O4 505.95 95.61% 194-196ºC Brown chilly
4 4-CH3 6d C27H27N5O4 485.53 78.83% 197-199ºC Yellow
5 4-OCH3 6e C27H27N5O5 501.53 67.87% 179-181ºC Dark yellow
6 4-F 6f C26H24FN5O4 489.5 88.88% 202-204ºC Yellow
7 4-NO2 6g C26H24N6O6 516.51 92.63% 173-175ºC Yellow
8 α-Napthyl 6h C30H27N5O4 521.57 96.52% 128-130ºC Brown
9 3-Cl,4-F 6i C26H23ClFN5O4 523.94 76.15% 177-179ºC Pale Yellow
10 2,4,5-Cl 6j C26H22Cl3N5O4 574.84 84.66% 169-171ºC Pale Yellow

50. CHAPTER- 4 Cont.…..
General Procedure for the Synthesis of Bi-pyrazoles by using Bis-
chalcones derived from N-Phenyl Glutarimides 8a-j:
The pyrazole (8a-j) derivatives were synthesized by the mixture of 2 mmole of
afforded bis-chalcones (7a-j) and 4 mmole of hydrazine hydrate in 2 gm of
neutral Al2O3 under microwave assisted solvent free conditions on 640W
powers for 3-6 minutes. The afforded coloured compounds were recovered by
ethyl acetate and recrystallized by ethanol (Scheme – IId)
Neutral Al2O3
®
MW
N O
O
HO
O O
OH
CH3 CH3
8a-j
Scheme -IId:
® , a = -H, b = -4Br, c = -4Cl, d = -4CH3, e = -4OCH3,
f = -4F, g = -4NO2, h = -phenyl, i = -3Cl,-4F, j = -2,4,5Cl
640W
3-6 min
N N
NH
HN
N
HO OH
O
CH3
O
H3C
2 NH2NH2 . H2O
7a-j
®
(3Z,4Z)-3,4-bis-(4-hydroxy-3-methoxy-benzylidene)-7-(1-phenyl)-3,3a,3b,4,5,7-hexahydro-
2H- piperidine-[2,3-c,5,4-c] dipyrazole (8a-j)

51. CHAPTER-4 Cont.…..
Physical Characteristics of 8a-j
Sr.
No.
Substituted
Aniline
Compd
Code
Molecular
Formula MW
Pr.
Yield
M.P. Range
(ºC)
Product Colour
(Crude)
1 -H 8a C27H27N5O4 485.53 82.57% 151-153ºC Yellow granules
2 4-Br 8b C27H26BrN5O4 564.43 78.01% 157-159ºC Yellow granules
3 4-Cl 8c C27H26ClN5O4 519.98 75.37% 155-157ºC Yellow
4 4-CH3 8d C28H29N5O4 499.56 81.04% 158-160ºC Yellow
5 4-OCH3 8e C28H29N5O5 515.56 82.81% 148-150ºC Greenish muddy
6 4-F 8f C27H26FN5O4 503.52 75.20% 152-154ºC Pale Yellow
7 4-NO2 8g C27H26N6O6 530.53 83.01% 147-149ºC Yellow
8 α-Napthyl 8h C31H29N5O4 535.59 84.96% 149-151ºC Greenish brown
9 3-Cl,4-F 8i C27H25ClFN5O4 537.97 87.26% 148-150ºC Pale Yellow
10 2,4,5-Cl 8j C27H24Cl3N5O4 588.87 76.53% 144-146ºC Dark yellow

52. CHAPTER-4 Cont.…..
Spectral Analysis of 6a-j & 8a-j
Elemental analysis series of these compounds were found much close
around the given ranges of C: 57.83, H: 3.59, N: 2.50. These compounds in
its IR spectrum observed and showed the frequency band at 3400 cm-1 to
3100 cm-1 typical range for the presence of primary amine (−NH) groups,
ranges the frequency broad band at 3600 cm-1 to 3200 cm-1 for aromatic
alcohol group, bands at 1650 cm-1 to 1450 cm-1 for aromatic ring three peaks
and a single band of Ar-Br stuck between 1075 cm-1- 1030 cm-1, Ar-Cl
between 1035 cm-1- 1100 cm-1, Ar-F between 1250 cm-1- 1100 cm-1, Ar-NO2
between 1550 cm-1- 1500 cm-1, Ar-OCH3 between 1350 cm-1- 1100 cm-1 in
the confirmatory pyrazoles nucleus were found, proved and validated the
formation of bi-pyrazoles. The 1HNMR spectrum of the compounds 6a-j and
8a-j in CDCl3 and DMSO-d6 solvents showed the signals typical of aromatic
(6.71-8.04 δ) multiplets 8H atoms, a single peak observed in the presence of
–NH group (8.60 δ) singlet 1H, singlet signal of –CH group of 1H (4.53 δ),
singlet of –CH2 value (3.40 δ) two protons, methoxy group (3.84 δ) singlet
signal of three protons and aromatic alcoholic −OH group signal (9.73 δ)
singlet for a single proton. 13C NMR spectral values 55.99, 110.55, 115.95,
123.91, 125.97, 130.88, 148.45, 150.33 and 161.03 also observed.
Detecting these validated data the possible structures of 6a-j and 8a-j were
confirmed.

53. CHAPTER-4 Cont.…..
Spectra of 6a-j

54. CHAPTER-4 Cont.…..
Spectra of 8a-j

55. CHAPTER-4 Cont.…..
Antimicrobial Activities of Bi-pyrazoles: 6a-j & 8a-j
Antibacterial Activities of
6a-j & 8a-j
S
t
d
6
a
6
b
6
c
6
d
6
e
6
f
6
g
6
h
6
i
6
j
8
a
8
b
8
c
8
d
8
e
8
f
8
g
8
h
8
i
8
j
C
t
r
l
0
5
1 0
1 5
2 0
2 5
3 0
0 %
2 0 %
4 0 %
6 0 %
8 0 %
1 0 0 %
 C o m p o u n d se rie s 
C h a r t 0 7 : A n tib a cte rial ac tiv ities o f 6 a -j an d 8 a -j (B .S .) M ea n ± S D
Z
o
n
e
o
f
in
h
i
b
iti
o
n
in
m
m
%
o
f
i
n
h
i
b
it
io
n
1 0 0 g /m l
2 0 0 g /m l
3 0 0 g /m l
S
t
d
6
a
6
b
6
c
6
d
6
e
6
f
6
g
6
h
6
i
6
j
8
a
8
b
8
c
8
d
8
e
8
f
8
g
8
h
8
i
8
j
C
t
r
l
0
5
1 0
1 5
2 0
2 5
3 0
0 %
2 0 %
4 0 %
6 0 %
8 0 %
1 0 0 %
 C o m p o u n d se rie s 
C h a r t 0 8 : A n tib a cterial a ctiv itie s o f 6 a-j a n d 8 a-j (E .C .) M ea n ± S D
Z
o
n
e
o
f
in
h
i
b
iti
o
n
in
m
m
%
o
f
i
n
h
i
b
it
io
n
1 0 0 g /m l
2 0 0 g /m l
3 0 0 g /m l

56. CHAPTER-4 Cont.…..
Antimicrobial Activities of Bi-pyrazoles 6a-j & 8a-j
Antifungal Activities of
6a-j & 8a-j
S
t
d
6
a
6
b
6
c
6
d
6
e
6
f
6
g
6
h
6
i
6
j
6
a
8
b
8
c
8
d
8
e
8
f
8
g
8
h
8
i
8
j
C
t
r
l
0
5
1 0
1 5
2 0
2 5
3 0
0 %
2 0 %
4 0 %
6 0 %
8 0 %
1 0 0 %
 C o m p o u n d se rie s 
C h a r t 0 9 : A n tifu n g al activ ities o f 6 a-j an d 8 a-j (C .A . an d A .N .) M ean ± S D
Z
o
n
e
o
f
in
h
i
b
iti
o
n
in
m
m
%
o
f
i
n
h
i
b
it
io
n
1 0 0 g /m l (C .A .)
1 0 0 g /m l (A .N .)

57. CHAPTER-4 Cont.…..
Result & Discussion of 6a-j & 8a-j
The compounds 5a-j, 6a-j, 7a-j and 8a-j were found considerable active
against gram +ve Bacillus subtilis and gram -ve Escherichia coli bacterial
strains. Similarly the compounds 5a-j and 7a-j showed superior activity
and compound 6i and 8j showed moderate activity against Candida
albicans fungal strain and 6c and 8j showed moderate activity against
Aspergillus niger.

58. CHAPTER- 5
SYNTHESIS, CHARACTERIZATION AND BIOLOGICAL ACTIVITIES OF
AMINO-PYRIMIDINES DERIVED FROM N-PHENYL SUCCINIMIDES
By considering the versatile application of pyrimidines in biological and
medicinal fields, it was planned to synthesize the new substituted amino-
pyrimidine derivatives with the hope to get potential antimicrobial agents.
To attain the target work substituted bis-chalcones derived from N-phenyl
succinimides were treated with guanidine nitrate forms the final amino-
pyrimidines respectively as shown in the Scheme - III.
N
N N N
N
Ar
H2N NH2
Ar
SCHEME - III
9
7
®
5
2
7
®
N
O
O
®
N
O
O
Ar
Ar
ArCHO
NH
NH2
H2N .HNO3

59. CHAPTER- 5 Cont.…..
General Procedure for the Synthesis of Amino-pyrimidines by using Bis-
chalcones derived from N-Phenyl Succinimides 9a-j:
The researcher has developed the convenient ecofriendly microwave method
used for the synthesis of amino-pyrimidine derivatives. To achieve the research
objective amino-pyrimidine (9a-j) derivatives were synthesized by the mixture of
2 mmole of afforded bis-chalcones (5a-j) and 4 mmole of guanidine nitrate in 2
gm of neutral Al2O3 under microwave assisted solvent free conditions on 640W
power for 4-7 minutes. The afforded coloured compounds were recovered by
ethyl acetate and recrystallized by ethanol (Scheme – IIIa)
N
N
OH
HO
O
O
O
O
H3C
CH3
®
®
Neutral Al2O3
MW 640W
4-7 min
Scheme -IIIa: 9-(N-phenyl)-4,5-(2","'-methoxyphenol)-9H-1,3,6,8,9-penta-azo-fluorene-2,7-diamine (9a-j)
® , a = -H, b = -4Br, c = -4Cl, d = -4CH3, e = -4OCH3,
f = -4F, g = -4NO2, h = -phenyl, i = -3Cl,-4F, j = -2,4,5Cl
5 a-j
9 a-j
N
N
N
N
OH
OH
O
H3C
O
CH3
NH2
H2N
NH
NH2
H2N .HNO3
2

60. CHAPTER-5 Cont.…..
Physical Characteristics of 9a-j
Sr.
No.
Substituted
Aniline
Compd
Code
Molecular
Formula MW
Pr.
Yield
M.P.
Range(ºC)
Product Colour
(Crude)
1 -H 9a C28H23N7O4 521.53 92.30% 179-181ºC White
2 4-Br 9b C28H22BrN7O4 600.42 79.66% 117-119ºC Wheat
3 4-Cl 9c C28H22ClN7O4 555.97 76.81% 104-106ºC Dark Yellow
4 4-CH3 9d C29H25N7O4 535.55 80.45% 108-110ºC Wheat
5 4-OCH3 9e C29H25N7O5 551.55 67.88% 105-107ºC Whitish
6 4-F 9f C28H22FN7O4 539.52 81.34% 114-116ºC Yellow
7 4-NO2 9g C28H22N8O6 566.52 55.83% 113-115ºC Pale Yellow
8 α-Napthyl 9h C32H25N7O4 571.59 100-102ºC Dark Brown
9 3-Cl,4-F 9i C28H21ClFN7O4 573.96 83.50% 117-119ºC White
10 2,4,5-Cl 9i C28H20Cl3N7O4 624.86 73.71% 149-151ºC White

61. CHAPTER- 6
SYNTHESIS, CHARACTERIZATION AND BIOLOGICAL ACTIVITIES OF
AMINO-PYRIMIDINES DERIVED FROM N-PHENYL GLUTARIMIDES
In view of the multipurpose application of pyrimidines in pharmacological,
biological medicinal arenas and in our work continuance for the synthesis of
amino-pyrimidines, it was deliberated to synthesize the new substituted
amino-pyrimidine derivatives with the confidence to get potential
antimicrobial agents. To attain the target work substituted bis-chalcones
derived from N-phenyl glutarimides were treated with guanidine nitrate forms
the final amino-pyrimidines respectively as shown in the Scheme - IV.
N
N N N
N
Ar
H2N NH2
Ar
9
7
®
NH
NH2
H2N .HNO3
7
7
4
7
®
N O
O
®
N O
O
Ar
Ar
ArCHO
SCHEME - IV

62. CHAPTER- 6 Cont.…..
General Procedure for the Synthesis of Amino-pyrimidines by using
Bis-chalcones derived from N-Phenyl Glutarimides 10a-j:
The researcher has developed the convenient ecofriendly microwave method
used for the synthesis of amino-pyrimidine derivatives. To achieve the research
objective amino-pyrimidine (10a-j) derivatives were synthesized by the mixture
of 2 mmole of afforded bis-chalcones (7a-j) and 4 mmole of guanidine nitrate in
2 gm of neutral Al2O3 under microwave assisted solvent free conditions on
640W power for 4-7 minutes. The afforded coloured compounds were
recovered by ethyl acetate and recrystallized by ethanol (Scheme – IVa)
N
®
Neutral Al2O3
MW 640W
4-7 min
Scheme -IVa: 9-(N-phenyl)-4,5-(2","'-methoxyphenol)-9H-1,3,6,8,9-hexa-azo-fluorene-2,7-diamine (10a-j)
® , a = -H, b = -4Br, c = -4Cl, d = -4CH3, e = -4OCH3,
f = -4F, g = -4NO2, h = -phenyl, i = -3Cl,-4F, j = -2,4,5Cl
10 a-j
N
N
N
N
OH
OH
O
H3C
O
CH3
NH2
H2N
NH
NH2
H2N .HNO3
2
N
®
7 a-j
HO
O O
OH
CH3
CH3

63. CHAPTER-6 Cont.…..
Physical Characteristics of 10a-j
Sr.
No.
Substitute
d
Aniline
Compd
Code
Molecular
Formula MW
Pr.
Yield
M.P. Range
(ºC)
Product Colour
(Crude)
1 -H 10a C29H25N7O4 535.55 80.45% 89-91ºC Dark Yellow
2 4-Br 10b C29H24BrN7O4 614.45 76.54% 99-101ºC Dark Yellow
3 4-Cl 10c C29H24ClN7O4 570.00 83.03% 88-90ºC Yellow
4 4-CH3 10d C30H27N7O4 549.58 79.12% 108-110ºC Yellow
5 4-OCH3 10e C30H27N7O5 565.58 67.25% 88-90ºC Yellowish Brown
6 4-F 10f C29H24FN7O4 553.54 80.00% 91-93ºC Dark Yellow
7 4-NO2 10g C29H24N8O6 580.55 70.68% 123-125ºC Pale Yellow
8 α-Napthyl 10h C33H27N7O4 585.61 64.60% 103-105ºC Dark Brown
9 3-Cl,4-F 10i C29H23ClFN7O4 587.99 72.60% 84-86ºC Yellow
10 2,4,5-Cl 10j C29H22Cl3N7O4 638.89 72.10% 128-130ºC White

64. CHAPTER-5 & 6 Cont.…..
Spectral Analysis of 9a-j & 10a-j
Elemental analysis series of these compounds were found much close
around the given ranges of C: 57.83, H: 3.59, N: 2.50. These compounds in
its IR spectrum observed and showed the frequency band at 3400 cm-1 to
3100 cm-1 typical range for the presence of primary amine (−NH) groups,
ranges the frequency broad band at 3600 cm-1 to 3200 cm-1 for aromatic
alcohol group, bands at 1650 cm-1 to 1450 cm-1 for aromatic ring three peaks
and a single band of Ar-Br stuck between 1075 cm-1- 1030 cm-1, Ar-Cl
between 1035 cm-1- 1100 cm-1, Ar-F between 1250 cm-1- 1100 cm-1, Ar-NO2
between 1550 cm-1- 1500 cm-1, Ar-OCH3 between 1350 cm-1- 1100 cm-1 in
the confirmatory pyrazoles nucleus were found, proved and validated the
formation of bi-pyrazoles. The 1HNMR spectrum of the compounds 6a-j and
8a-j in CDCl3 and DMSO-d6 solvents showed the signals typical of aromatic
(6.71-8.04 δ) multiplets 8H atoms, a single peak observed in the presence of
–NH group (8.60 δ) singlet 1H, singlet signal of –CH group of 1H (4.53 δ),
singlet of –CH2 value (3.40 δ) two protons, methoxy group (3.84 δ) singlet
signal of three protons and aromatic alcoholic −OH group signal (9.73 δ)
singlet for a single proton. 13C NMR spectral values 55.99, 110.55, 115.95,
123.91, 125.97, 130.88, 148.45, 150.33 and 161.03 also observed.
Detecting these validated data the possible structures of 6a-j and 8a-j were
confirmed.

65. CHAPTER-5 & 6 Cont.…..
Spectra of 9a-j

66. CHAPTER-5 & 6 Cont.…..
Spectra of 10a-j

67. CHAPTER-5 & 6 Cont.…..
Antimicrobial Activities of Amino-pyrimidines: 9a-j
Antibacterial Activities of
9a-j
S
t
d
9
a
9
b
9
c
9
d
9
e
9
f
9
g
9
h
9
i
9
j
C
t
r
l
0
5
1 0
1 5
2 0
2 5
3 0
0 %
2 0 %
4 0 %
6 0 %
8 0 %
1 0 0 %
 C o m p o u n d serie s 
C h a r t N o .-1 0 : A n tib ac te ria l a c tiv itie s o f 9 a -j (B .S .) M e an ± S D
Z
o
n
e
o
f
in
h
i
b
iti
o
n
in
m
m
%
o
f
i
n
h
i
b
it
io
n
1 0 0 g /m l
2 0 0 g /m l
3 0 0 g /m l
S
t
d
9
a
9
b
9
c
9
d
9
e
9
f
9
g
9
h
9
i
9
j
C
t
r
l
0
5
1 0
1 5
2 0
2 5
3 0
0 %
2 0 %
4 0 %
6 0 %
8 0 %
1 0 0 %
 C o m p o u n d se rie s 
C h a r t N o .-1 1 : A n tib a cteria l ac tiv ities o f 9 a-j (E .C .) M ea n ± S D
Z
o
n
e
o
f
in
h
i
b
iti
o
n
in
m
m
%
o
f
i
n
h
i
b
it
io
n
1 0 0 g /m l
2 0 0 g /m l
3 0 0 g /m l

68. CHAPTER-5 & 6 Cont.…..
Antimicrobial Activities of Amino-pyrimidines: 10a-j
Antibacterial Activities of
10a-j
S
t
d
1
0
a
1
0
b
1
0
c
1
0
d
1
0
e
1
0
f
1
0
g
1
0
h
1
0
i
1
0
j
C
t
r
l
0
5
1 0
1 5
2 0
2 5
3 0
0 %
2 0 %
4 0 %
6 0 %
8 0 %
1 0 0 %
 C o m p o u n d se rie s 
C h a r t N o .-1 3 : A n tib a c te rial a c tiv ities o f 1 0 a-j (B .S .) M ea n ± S D
Z
o
n
e
o
f
in
h
i
b
iti
o
n
in
m
m
%
o
f
i
n
h
i
b
it
io
n
1 0 0 g /m l
2 0 0 g /m l
3 0 0 g /m l
S
t
d
1
0
a
1
0
b
1
0
c
1
0
d
1
0
e
1
0
f
1
0
g
1
0
h
1
0
i
1
0
j
C
t
r
l
0
5
1 0
1 5
2 0
2 5
3 0
0 %
2 0 %
4 0 %
6 0 %
8 0 %
1 0 0 %
 C o m p o u n d se rie s 
C h a r t N o .-1 4 : A n tib a c te ria l ac tiv itie s o f 1 0 a -j (E .C .) M e a n ± S D
Z
o
n
e
o
f
in
h
i
b
iti
o
n
in
m
m
%
o
f
i
n
h
i
b
it
io
n
1 0 0 g /m l
2 0 0 g /m l
3 0 0 g /m l

69. CHAPTER-4 Cont.…..
Antimicrobial Activities of Amino-pyrimidines 9a-j & 10a-j
Antifungal Activities of
9a-j & 10a-j
S
t
d
9
a
9
b
9
c
9
d
9
e
9
f
9
g
9
h
9
i
9
j
C
t
r
l
0
5
1 0
1 5
2 0
2 5
3 0
0 %
2 0 %
4 0 %
6 0 %
8 0 %
1 0 0 %
 C o m p o u n d se rie s 
C h a r t N o .-1 2 : A n tifu n g al activ ities o f 9 a-j (C .A . an d A .N .) M ean ± S D
Z
o
n
e
o
f
in
h
i
b
iti
o
n
in
m
m
%
o
f
i
n
h
i
b
it
io
n
1 0 0 g /m l (C .A .)
1 0 0 g /m l (A .N .)
S
t
d
1
0
a
1
0
b
1
0
c
1
0
d
1
0
e
1
0
f
1
0
g
1
0
h
1
0
i
1
0
j
C
t
r
l
0
5
1 0
1 5
2 0
2 5
3 0
0 %
2 0 %
4 0 %
6 0 %
8 0 %
1 0 0 %
 C o m p o u n d se rie s 
C h a r t N o .-1 5 : A n tifu n g al activ ities o f 1 0 a-j (C .A . an d A .N .) M ean ± S D
Z
o
n
e
o
f
in
h
i
b
iti
o
n
in
m
m
%
o
f
i
n
h
i
b
it
io
n
1 0 0 g /m l (C .A .)
1 0 0 g /m l (A .N .)

70. CHAPTER-5 & 6 Cont.…..
Result & Discussion of 9a-j & 10a-j
Results: The compounds 9a-j were found adequate results practicing
against gram +ve Bacillus subtilis and gram -ve Escherichia coli bacterial
strains. In the same way these compounds exhibited the significantly
superior antifungal activity against Aspergillus niger and Candida albicans
fungal strains.
Results: The compounds 10a-j attained the reasonably active against
gram +ve Bacillus subtilis and gram -ve Escherichia coli bacterial strains.
Similarly some of these compounds validated the synergistic antifungal
activity against Candida albicans and Aspergillus niger fungal strains.

71. CHAPTER- 7
SYNTHESIS, CHARACTERIZATION AND BIOLOGICAL ACTIVITIES
OF MALONONITRILE DERIVATIVES
A wide-ranging literature review discloses that the chemistry of
malononitrile have not been explored extensively. Various synthetic
practices were reported for the synthesis of malononitrile derivatives but
the majority of the processes experience from limitations such as
availability of the precursors, multi-steps, lengthy reaction conditions,
tolerance of functional group and comparatively low yield. The chemical
and pharmacological importance and inconvenient and inefficient
procedures encouraged us to develop a short, candid and inexpensive and
ecofriendly route for the construction of malononitrile derivatives. Thus, we
planned to synthesize the novel malononitrile derivatives from substituted
N-phenyl succinimides and N-phenyl glutarimides as a final target
visualized in the Scheme – V.

72. CHAPTER- 7 Cont.…..
5
7
7
4
7
2
7
®
N
O
O
®
N
®
N O
O
®
N
CH2(CN)2
CN
CN
CN
NC
CN
CN
NC
NC
CH2(CN)2
SCHEME - V

73. CHAPTER- 7 Cont.…..
General Procedure for the Synthesis of Malononitriles by using N-Phenyl
Succinimides 11a-j:
The researcher has developed the convenient ecofriendly microwave method
used for the synthesis of malononitrile derivatives. To achieve the research
objective malononitriles (11a-j) derivatives were synthesized by the mixture of
2 mmole of afforded N-phenyl succinimides (2a-j) and 4 mmole of
dicyanomethane in 2 gm of neutral Al2O3 under the microwave assisted solvent
free conditions on 640W power for 4-7 minutes. The afforded brownish and
coffee coloured compounds were recovered and recrystallized by ethanol.
(Scheme – Va)
Neutral Al2O3
MW
640W
4-7 min
Scheme -Va: 2-(5-dicyanomethylene-N-phenyl-pyrrolidin-2-ylidene)-malononitrile (11a-j)
® , a = -H, b = -4Br, c = -4Cl, d = -4CH3, e = -4OCH3,
f = -4F, g = -4NO2, h = -phenyl, i = -3Cl,-4F, j = -2,4,5Cl
2 a-j 11 a-j
®
N
O
O
®
N
CN
CN
NC
NC
H2C
C
C
N
N
+ 2

74. CHAPTER-7 Cont.…..
Physical Characteristics of 11a-j
Sr.
No.
Substituted
Aniline
Compd
Code
Molecular
Formula MW
Pr.
Yield
M.P. Range
(ºC)
Product Colour
(Crude)
1 -H 11a C16H9N5 271.28 55.55% 138-140 ºC Dark Brown
2 4-Br 11b C16H8BrN5 350.17 45.71% 130-132ºC Brown
3 4-Cl 11c C16H8ClN5 305.72 65.57% 105-107ºC Brownish yellow
4 4-CH3 11d C17H11N5 285.3 59.29% 113-115ºC Whitish brown
5 4-OCH3 11e C17H11N5O 301.3 26.91% 118-120ºC Brownish yellow
6 4-F 11f C16H8FN5 289.27 47.05% 129-131ºC Brownish yellow
7 4-NO2 11g C16H8N6O2 316.27 28.48% 160-162ºC Brownish yellow
8 α-Napthyl 11h C20H11N5 321.33 72.89% 80-82ºC Violet
9 3-Cl,4-F 11i C16H7ClFN5 323.71 63.46% 143-145ºC Yellowish white
10 2,4,5-Cl 11j C16H6Cl3N5 374.61 53.47% 175-177ºC White

75. CHAPTER- 7 Cont.…..
General Procedure for the Synthesis of Malononitriles by using N-Phenyl
Glutarimides 12a-j:
To achieve the research objective malononitriles (12a-j) derivatives were
synthesized by the mixture of 2 mmole of afforded N-phenyl glutarimides (4a-j)
and 4 mmole of dicyanomethane in 2 gm of neutral Al2O3 under the microwave
assisted solvent free conditions on 640W power for 4-7 minutes. The afforded
brownish and coffee coloured compounds were recovered and recrystallized by
ethanol. (Scheme – Va)
Neutral Al2O3
MW
640W
4-7 min
Scheme -Vb: 2-(6-dicyanomethylene-N-phenyl-piperidin-2-ylidene)-malononitrile (12a-j)
® , a = -H, b = -4Br, c = -4Cl, d = -4CH3, e = -4OCH3,
f = -4F, g = -4NO2, h = -phenyl, i = -3Cl,-4F, j = -2,4,5Cl
4 a-j 12 a-j
H2C
C
C
N
N
+ 2
®
N O
O
®
N
CN
CN
CN
NC

76. CHAPTER-7 Cont.…..
Physical Characteristics of 12a-j
Sr.
No.
Substituted
Aniline
Compd
Code
Molecular
Formula MW
Pr.
Yield
M.P. Range
(ºC)
Product Colour
(Crude)
1 -H 12a C17H11N5 285.3 61.40% 97-99ºC Coffee
2 4-Br 12b C17H10BrN5 364.2 35.71% 133-135ºC Whitish mud
3 4-Cl 12c C17H10ClN5 319.75 74.60% 80-82ºC muddy
4 4-CH3 12d C18H13N5 299.33 48.49% 164-166ºC Cream
5 4-OCH3 12e C18H13N5O 315.33 40.95% 107-109ºC Lavender mud
6 4-F 12f C17H10FN5 303.29 67.65% 119-121ºC Yellowish
7 4-NO2 12g C17H10N6O2 330.3 28.78% 115-117ºC Brown mud
8 α-Napthyl 12h C21H13N5 335.36 28.05% 95-97ºC Dark violet
9 3-Cl,4-F 12i C17H9ClFN5 337.74 54.89% 91-93ºC Brown
10 2,4,5-Cl 12j C17H8Cl3N5 388.64 38.65% 109-111ºC Cream

77. CHAPTER-7 Cont.…..
Spectral Analysis of 11a-j & 12a-j
The malononitrile derivatives were characterized by their spectral analysis.
Elemental analysis the series of these compounds were found closely nearby
given default ranges of C: 57.83, H: 3.59, N: 2.50. The IR spectrum observed of
these compounds which showed the frequency bands at 2300 cm-1 to 2100 cm-
1 typical range for nitrile C≡N group, bands between 3000 cm-1 to 2800 cm-1 for
–CH2−CH2− and –CH2−CH2−CH2− stretching for cyclic group, ranges the
frequency bands at 1350 cm-1 to 1300 cm-1 for cyclic imine groups, bands at
1650 cm-1 to 1450 cm-1 three peaks for aromatic ring and a single band of Ar-Br
between 1075 cm-1- 1030 cm-1, Ar-Cl between 1035 cm-1- 1100 cm-1, Ar-F
between 1250 cm-1- 1100 cm-1, Ar-NO2 between 1550 cm-1- 1500 cm-1, Ar-
OCH3 between 1350 cm-1- 1100 cm-1 in the substituted malononitriles was
found, verified and confirmed the formation of malononitriles. The 1HNMR
spectrum of the compounds 11a-j and 12a-j in CDCl3 and DMSO-d6 solvents
showed the representative signals of aromatic (7.02-7.58 δ) multiplets 5H
atoms, napthyl group (7.30-8.03 δ) multiplet signals of seven protons and imide
group signal (2.28 δ) multiplet two protons of 11a-j and multiplet signals 2H
(1.81 δ) in 12a-j. 13C NMR detected the values 16.90, 20.57, 24.66, 32.77,
39.80, 39.97, 40.15, 112.50, 118.99, 124.36, 125.39, 131.01 and 173.10 and
the molecular weight of 11b also confirmed by HRMS. Based on these data the
probable structures of 11a-j and 12a-j were predicted.

78. CHAPTER-7 Cont.…..
Spectra of 11a-j

79. CHAPTER-7 Cont.…..
Spectra of 12a-j

80. CHAPTER- 7 Cont.…..
Antimicrobial Activities of Malononitriles: 11a-j & 12a-j
Antibacterial Activities of
11a-j & 12a-j
S
t
d
1
1
a
1
1
b
1
1
c
1
1
d
1
1
e
1
1
f
1
1
g
1
1
h
1
1
i
1
1
j
1
2
a
1
2
b
1
2
c
1
2
d
1
2
e
1
2
f
1
2
g
1
2
h
1
2
i
1
2
j
C
t
r
l
0
5
1 0
1 5
2 0
2 5
3 0
0 %
2 0 %
4 0 %
6 0 %
8 0 %
1 0 0 %
 C o m p o u n d se rie s 
C h a r t 1 6 : A n tib ac te ria l a c tiv itie s o f 1 1 a -j a n d 1 2 a -j (B .S .) M e an ± S D
Z
o
n
e
o
f
in
h
i
b
iti
o
n
in
m
m
%
o
f
i
n
h
i
b
it
io
n
1 0 0 g /m l
2 0 0 g /m l
3 0 0 g /m l
S
t
d
1
1
a
1
1
b
1
1
c
1
1
d
1
1
e
1
1
f
1
1
g
1
1
h
1
1
i
1
1
j
1
2
a
1
2
b
1
2
c
1
2
d
1
2
e
1
2
f
1
2
g
1
2
h
1
2
i
1
2
j
C
t
r
l
0
5
1 0
1 5
2 0
2 5
3 0
0 %
2 0 %
4 0 %
6 0 %
8 0 %
1 0 0 %
 C o m p o u n d se rie s 
C h a r t N o .-1 7 : A n tib a cteria l ac tiv ities o f 1 1 a-j a n d 1 2 a -j (E .C .) M ea n ± S D
Z
o
n
e
o
f
in
h
i
b
iti
o
n
in
m
m
%
o
f
i
n
h
i
b
it
io
n
1 0 0 g /m l
2 0 0 g /m l
3 0 0 g /m l

81. CHAPTER-7 Cont.…..
Antimicrobial Activities of Malononitrile 11a-j & 12a-j
Antifungal Activities of
11a-j & 12a-j
S
t
d
1
1
a
1
1
b
1
1
c
1
1
d
1
1
e
1
1
f
1
1
g
1
1
h
1
1
i
1
1
j
1
2
a
1
2
b
1
2
c
1
2
d
1
2
e
1
2
f
1
2
g
1
2
h
1
2
i
1
2
j
C
t
r
l
0
5
1 0
1 5
2 0
2 5
3 0
0 %
2 0 %
4 0 %
6 0 %
8 0 %
1 0 0 %
 C o m p o u n d se rie s 
C h a r t N o .-1 8 : A n tifu n g al activ ities o f 1 1 a-j an d 1 2 a-j (C .A . an d A .N .) M ean ± S D
Z
o
n
e
o
f
in
h
i
b
iti
o
n
in
m
m
%
o
f
i
n
h
i
b
it
io
n
1 0 0 g /m l (C .A .)
1 0 0 g /m l (A .N .)

82. CHAPTER- 7 Cont.…..
Result & Discussion of 11a-j & 12a-j
Results: The compounds 11a-j and 12a-j were found moderately active
against gram +ve Bacillus subtilis and gram -ve Escherichia coli bacterial
strains. Similarly these compounds exhibited the significantly superior
antifungal activity against Aspergillus niger and Candida albicans fungal
strains.

83. CHAPTER- 8
CONCLUDING REMARKS AND FUTURE SCOPE
Chapter wise conclusions:
Chap-3: Synthesis, Characterization and Biological Activities of
N-Phenyl Succinimide and N-Phenyl Glutarimide Derivatives
The synthesized compounds 2a-j and 4a-j were evaluated in–vitro
antimicrobial activities by using gram +ve Bacillus subtilis and gram -ve
Escherichia coli bacterial strains. Similarly antifungal, activity against
Aspergillus niger and Candida albicans fungal strains. Almost all the
compounds indicated moderate antibacterial activities and significant
antifungal activities equated with standard drug. These synthones were used
as a title compounds for further preparation of chalcones, pyrazoles,
pyrimidines and malononitrile derivatives.
Some of N-phenyl succinimides and N-phenyl glutarimides
are so far unknown. All these synthesized cyclic imides
may by use for preparation of various heterocyclic
systems such as chalcones, pyrazoles, pyrimidines so on.
CONCLUSION

84. CHAPTER- 8 Cont.…..
Chap-4: Synthesis, Characterization and Biological Activities of
Pyrazole Derivatives
Overall method for the synthesis of bis-chalcones 5a-j and 7a-j has been
developed by using different substituted phenyl succinimides and glutarimides
with di-substituted aromatic aldehyde vanillin in the solvent-free microwave
method. Correspondingly further treatment on bis-chalcones with hydrazine
hydrate gave substituted pyrazoles 6a-j and 8a-j. Bis-chalcones and pyrazoles
both were screened their antimicrobial activities. As a result, they showed
moderate to good activities against Bacillus subtilis and Escherichia coli strains.
Similarly some bis-chalcones showed superior antifungal activities bu only few
pyrazoles showed good antifungal activities against Candida albicans and
Aspergillus niger strains.
1. Over-all method for the synthesis of bis–chalcone derivatives has been
developed. The method consists of the treatment of afforded cyclic imides
and vanillin in neutral alumina in microwave solvent free method.
2. Correspondingly the synthesis of pyrazole derivatives has been obtained by
the treatment of substituted chalcones and hydrazine hydrate with neutral
alumina.
3. The ecofriendly microwave method can be used for the preparation of
different substituted heterocyclic synthones.
CONCLUSION

85. CHAPTER- 8 Cont.…..
Chap-5 & 6: Synthesis, Characterization and Biological Activities of
Amino-Pyrimidines derived from N-phenyl Sucinimides.
Substituted amino-pyrimidines 9a-j and 10a-j was synthesized from bis-chalcones
and guanidine nitrate by eco-friendly rout of the microwave irradiated solvent-free
method. These synthones were evaluated in vitro antimicrobial activities against
Bacillus subtilis and Escherichia coli with different concentrations found
considerable activity. Similarly they exhibited significantly synergistic antifungal
activity against Candida albican and Aspergillus niger strains as compared to
standard drugs.
1) General method for the synthesis of substituted amino-pyrimidines
was developed which consists of the treatment of afforded
bis-chalcones and guanidine nitrate with neutral alumina in
microwave solvent free synthesis.
2) The amino-pyrimidines formed 9a-j so far novel synthones
and might be used for the preparation of innumerable heterocyclic
schemes such as Schiff’s bases and condensation products so on.
3) Common method for the synthesis of substituted amino-pyrimidines
was prepared by consisting treatment of synthesized bis-chalcones
derived from N-phenyl glutarimides and guanidine nitrate
with neutral alumina in microwave solvent free method.
4) These amino-pyrimidines may be used for the synthesis
of various heterocycles.
CONCLUSION

86. CHAPTER- 8 Cont.…..
Chap- 7: Synthesis, Characterization and Biological Activities of
Malononitrile Derivatives
At the end of all the sections, malononitrile 11a-j and 12a-j derivatives were
developed by the title compounds with the mixture of dicyanomethane in
microwave method. These synthesized active methylene malononitrile
analogs were evaluated against the same bacterial and fungal strains. Almost
all the compounds showed moderately active against bacterial strains but
superior and synergistic activity showed on fungal strains.
CONCLUSION
1. A general method for the properties of malononitrile
derivatives 11a-j and 12a-j has been developed.
2. The compounds 11a-j and 12a-j may be used for
properties of various heterocyclic syntheses.

87. FUTURE
SCOPE
The contents of this thesis are research centered by continuing testimony and the views
of the heterocyclic synthesis group. There is a considerable amount of activities in the
area of the development of eco-friendly and sophisticated chemical synthesis. There are
a number of syntheses and novel synthones with their antimicrobial activities were
successfully reported in the current situations. Here the researcher was developed some
novel heterocyclic compounds and screened their biological activities as well as put the
future scope of these newly synthesized compounds.
1) The different substituted N-phenyl succinimides may be used for the synthesis of heterocyclic
analogs.
2) The substituted N-phenyl glutarimides may be used for the development of heterocyclic
derivatives.
3) These cyclic imides may be used as stiffning agent in the production of vulcanized rubber.
4) Chalcones from succinimides may be used for the synthesis of novel heterocyclic synthones.
5) Chalcones derived from glutarimides may be used for the preparation of the novel hetero
compounds.
6) Pyrazoles derived fro the chalcones may be used for the different and new heterocyclic
synthesis.
7) Some of these pyrazoles can also be used for making the dyes or pigments in dye industries.
8) Amino-pyrimidines from the chalcones may be used for the preparation of different types of
heterocyclic analogs.
9) Some amino-pyrimidine derivatives might be suitable for the fungicides and fungal infection
against human being due to their greater potency towards fungi species.
10) Malononitrile derivatives derived from the succinimides and glutarimides may be used for the
development of novel heterocyclic and cyano groups.

89. Prepared By,
Name of scholar : Dhivare Ravindra S.
Registration Number: 15712276
Subject : Chemistry