SYNTHESIS OF VARIOUS DERIVATIVES OF

BENZYLIDENEMALANONITRILE BY USING KNOEVENAGEL

CONDENSATION

Report on a project carried out as a part of curriculum for the degree of “Master of Science in
Organic Chemistry” at Department of Chemistry, Agasti Arts, Commerce & Dadasaheb Rupwate
Science College, and Akole. Tal. - Akole, Dist.- Ahmednagar, (422 601).
Submitted by
Wakchaure Sayali sanjay
M. Sc. II (Organic Chemistry)
Department of Chemistry
Agasti Arts, Commerce & Dadasaheb Rupwate Science College, Akole
Tal. - Akole, Dist.- Ahmednagar 422601
2024-2025
Under the guidance of
Prof. Amruta Sanjay Ankaram

Department of Chemistry,
Agasti Arts, Commerce & Dadasaheb Rupwate Science College, Akole
Tal. - Akole, Dist.- Ahmednagar (422 601)

SAVITRIBAI PHULE PUNE UNIVERSITY

Nov- 2024

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 CANDIDATES DECLARATION

I hereby declared that, project entitled “Synthesis of various derivatives of

benzylidenemalanonitrile by using Knoevenagel condensation,” submitted to the
Department of Chemistry, Agasti Arts, Commerce & Dadasaheb Rupwate Science College,
Akole. Tal. - Akole, Dist.- Ahmednagar 422 601, in partial fulfilment of degree of Master of
Science, has not been submitted to any other University or institution. This Work carried out
at the Department of Chemistry, Agasti Arts, Commerce & Dadasaheb Rupwate Science
College, Akole. Tal. - Akole, Dist.- Ahmednagar, 422 601.

Miss. Wakchaure Sayali Sanjay

M. Sc. II (Organic Chemistry)

Department of Chemistry,

Agasti Arts, Commerce & Dadasaheb Rupwate Science College, Akole

Tal. - Akole, Dist.- Ahmednagar 422 601

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 CERTIFICATE

This is to certify that the work incorporated in this project entitled “Synthesis
of various derivatives of benzylidenemalanonitrile by using Knoevenagel condensation”
being submitted to Department of Chemistry, Agasti Arts, Commerce And Dadasheb
Rupwate Science College, Akole as partial fulfilment of requirement for the degree of
Master of Science in Organic Chemistry by Miss. Sayali Sanjay Wakchaure is carried
out under my supervision at Department of Chemistry, Agasti Arts, Commerce And
Dadasaheb Rupwate Science College, Akole. Tal. - Akole, Dist.- Ahmednagar, (422 601)
during the academic year 2024-2025.

Prof. Amruta Sanjay Ankaram

Department of Chemistry,

Agasti Arts, Commerce & Dadasaheb Rupwate Science College, Akole

Tal.- Akole, Dist. - Ahmednagar (422 601)

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 Department of Chemistry
Agasti Arts, Commerce & Dadasaheb Rupwate Science College, Akole.

Tal.- Akole, Dist.- Ahmednagar (422 601)

CERTIFICATE

This is to certified that, the work incorporated in the project report entitled
“Synthesis of various derivatives of benzylidenemalanonitrile by using Knoevenagel
condensation” being submitted by Miss.Sayali Sanjay Wakchaure for the award of the
degree of Master of Science in Organic Chemistry to Department of Chemistry, Agasti
Arts, Commerce and Dadasaheb Rupwate Science College Akole, was carried out by the
candidate under the supervision of Prof. Amruta Ankaram, (Department of Chemistry),
Agasti Arts, Commerce and Dadasaheb Rupwate Science College, Akole. Tal.
- Akole, Dist.- Ahmednagar, (422 601) during the academic year 2024-2025.

Dr. S. M. Sonawane Examiner

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 Acknowledgment

It is my great pleasure to thank many people who

have assisted me through this short journey. First and foremost, I wish to thank my
advisor Prof. Amruta Sanjay Ankaram, for his guidance, support, encouragement, and
inspiration to my project studies. She is a fantastic mentor who was influential for my
interest, and my ability to grasp the essence of organic chemistry. She teaches me
everything she knows and always encourages me to think creatively and be prepared to
learn new scientific method . I am grateful to him for all the way in which he has
prepared me to move forward in my career and life .
I was very fortunate to work with a fantastic group of Chemistry Department, Akole College.
My thanks to Dr. S. M. Sonawane, Prof. Mrs. S. M. Bangal, Prof. S. G. Muthe, Prof. A.
L. Wakchaure, Prof. Mrs. J. S. Shinde, Dr .P.H.Naikwadi, for devoting their precious
time and made much valuable suggestion which indeed helped me during this project work.
I also take this opportunity to thank all respected teachers
from the department who always helped me to move ahead and were always source for
motivation and spiritual energy. Along with them I sincerely thanks to all my friend,
colleagues in M. Sc- I, Lab asst. Mr. K. D. Bhalerao, Lab. Attendant Mrs. S. A. Shewale,
Mrs. P. B. Nawale, Mr. V. P. Deshmukh for their constant support and continuous
motivation. My apologies to all those who have helped me but I forgot to acknowledge.

Wakchuare Sayali Sanjay

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 INDEX

Sr. No. Title Page No.

1 Introduction 9

2 Literature Review 10

3 Optimization of Reaction Conditions 14

4 Scheme 15

5 Experimental section 18

6 Thin Layer Chromatographic Data 25

7 Spectroscopic Data 27

8 Conclusion 30

9 Reference 31

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 List of Abbreviations

Unit

oC Degree Celsius

mg Milligram

hr Hour

mL Milliliter

Hz Hertz

MHz Megahertz

Mmol Millimole

Chemical group

Aq. Aqueous

Ac. Acetyl

CDCl3 Deuterated chloroform

DCM Dichloromethane

DME 1,2-Dimethoxyethane

DMF Diethylformamide

Et Ethyl

Me Methyl

Tf Trifluromethane sulfonyl

Ph Phenyl

THF Tetrahydrofuran

TMS Trimethylsilyl

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Other Notations
Cat. Catalytic

δ Chemical Shift

d Doublet

equiv Equivalent

e.q. Example

J Coupling Constant in NMR

m.p. Melting point

M.W. Molecular weight

m multiplate

NMR Nuclear Magnetic resonance

% Percentage

rt Room temperature

s Singlet

TLC Thin layer chromatography

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 1. INTRODUCTION
Knoevenagel Condensation reaction is named after Knoevenagel Emil (1922). It is an important
reaction for alpha C C bond formation. Nielsen, A. T. & Houlihan W. J. (1986) have shown that
Knoevenagel Condensation reaction is the modification of an Aldol Condensation Reaction
Benzylidenemalononitrile derivatives are generally synthesized by the Knoevenagel condensation
reaction of aromatic aldehydes with active methylene compounds. Scientists have developed great
interest in these compounds as they serve as valuable organic key intermediates for synthesis of drugs
and various products of importance. They have shown that products formed by reaction of malononitriles
have antifungal activity.

The use of benzylidenemalononitriles in the synthesis of cyclopentene derivatives. Most of the

Knoevenagel reactions have been carried out in presence of pyridine as solvent and piperidine as catalyst.
However, pyridine being toxic, have high risk and involves tedious workup procedure. To overcome
these difficulties, focus is on alternative green methods of synthesis which are more efficient. In our
present work, we are reporting environmentally friendly method for synthesis of benzylidenemalonitrile
derivatives of aromatic aldehydes which is clean, efficient and gives excellent yields at room
temperature. This reaction has been carried out using principles of Green Chemistry. We have
synthesized these compounds by Ultrasonic method reported by Novellin, Robert (1997) and Suslick
Kenneth S. (ed.) (1998). the applications of Ultrasonic waves (>20 kHz) that irradiate the liquid samples.
Seyedali A. A., Ramam, A. A. A., Parthasarthy, R. & Sajjadi, B. (2016) have explained Sustainable
methods. Reactions have been carried out in sonicator using ammonium acetate as catalyst. Ultrasonic
energy increases the rate of reaction, by using cavitational effects and reducing reaction temperature,
need of solvent and thus provides eco-friendly method. We have also synthesised these derivatives using
already existing microwave synthesis techniques and compared the yields and reaction time in
microwave and sonicator.

General Reaction:

CN

CHO
N N Ammonium acetate
CN
R.T.5-7 mins
malononitrile H
Benzaldehyde Benzylidene malononitrile

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 2. OPTIMIZATION OF REACTION CONDITION

Synthesis of Benzylidene Malononitrile

CHO
N Ammonium acetate
R.T.5-7 mins
malononitrile H
Benzaldehyde Benzylidene malononitrile

Take a mixture of benzaldehyde (2.68 ml) in 25 ml of dil.water and malononitrile (1.65 gm)in 10 ml of
dil.water, add both the beaker in conical flask. Add a pinch of ammonium acetate with constant stirring
with glass rod. The reaction mixture is sonicated at room temp.for about 5 to 7 mins. The amount of crude
is obtained. Filter the product, dry and record the yield, M.P. and TLC.

Entry Catalytic amount Temperature Yield

Catalyst
No. (0.47 mmol) (oC) (%)
20 mg
1 LiOH 50 64
(0.47 mmol)
25 mg
2 NH4Cl 60 72
(0.47 mmol)
64 mg
3 ZnCl2 60 82
(0.47 mmole)
64 mg
4 ZnCl2 80 85
(0.47 mmole)
64 mg
5 ZnCl2 90 85
(0.47 mmole)
64 mg
6 Ammonium 90 86
acetate (0.47 mmole)

After optimizing reaction condition entry no. 6 parameters are used for the further synthesis.

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 3. SCHEME

Take a mixture of benzaldehyde (2.68 ml) in 25 ml of dil.water and malononitrile (1.65 gm) in 10 ml of

dil.water, add both the beaker in conical flask. Add a pinch of ammonium acetate with constant stirring with

glass rod. The reaction mixture is sonicated at room temp.for about 5 to 7 mins. The amount of crude is

obtained. Filter the product, dry and record the yield, M.P. and TLC

AROMATIC ALDEHYDES:

1) Benzaldehyde
2) Salicyldehyde
3) p-Chlorobenzaldehyde
4) 4 hydroxy benzaldehyde
5) 3,4-dimethoxy benzaldehyde

Scheme- 1. Synthesis of Benzylidene Malononitrile

CN

CHO
N N
Ammonium acetate CN
R.T.5-7 mins
malononitrile H
Benzaldehyde Benzylidene malononitrile

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 Scheme- 2. Synthesis of salicylidene Malononitrile

CHO OH CN

N N Ammonium acetate
CN
R.T.5-7 mins
malononitrile H
Salicyladehyde Salicylidene malononitrile

Scheme- 3. Synthesis p-chloro benzylidene Malononitrile

CHO Cl

N N Ammonium acetate
CN
malononitrile
H
p- chloro benzylidene
malononitrile
P-chloro benzaldehyde

Scheme 4: Synthesis of 4 hydroxybenzyledine malononitrile

CHO

HO

N N
Ammonium acetate
R.T.5-7 mnis CN
malononitrile
H
OH
4 Hydroxy benzaldehyde 4 Hydroxy benzylidene
malononitrile

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Scheme-5 Synthesis of 3,4 Dimethoxy benzylidene malononitrile

Ome
CHO
Ome
CN
N N
R.T.5-7 mins
Ome malononitrile CN

H
3,4 dimethoxy benzylidene malononitrile
3,4 dimethoxy benzaldehyde

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 4. EXPERIMENTAL SECTION

General Reaction:

CN

CHO
N N Ammonium acetate
CN
R.T.5-7 mins
malononitrile H
Benzaldehyde Benzylidene malononitrile

Procedure:

Take a mixture of aldehyde (0.65 gm) in 25 ml of dil.water and malononitrile ( ) in 10 ml of

dil.water, add both the beaker in conical flask. Add a pinch of ammonium acetate with constant stirring with
glass rod. The reaction mixture is sonicated at room temp.for about 5 to 7 mins. The amount of crude is
obtained. Filter the product, dry and record the yield, M.P. and TLC

1]Synthesis of benzylidene malononitrile

CHO
N

malononitrile H
Benzaldehyde Benzylidene malononitrile

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 Take a mixture of benzaldehyde (2.68 ml) in 25 ml of dil.water and malononitrile (1.65gm) in 10
ml of dil.water, add both the beaker in conical flask. Add a pinch of ammonium acetate with
constant stirring with glass rod. The reaction mixture is sonicated at room temp.for about 5 to 7
mins. The amount of crude is obtained. Filter the product, dry and record the yield, M.P. and TLC

Physical Constant
Colour TLC
Melting Point (0C) Yield
Time of the
product Rf Rf
Observed Reported Solvent
Reactant Product
Ethyl
acetate
5-7 Crystallin 840 C 860 C 0.64 0.82 86.66%
+
min. e white n-hexane
(8:2)

1] Synthesis of Salicylidene Malononitrile

CHO OH CN

OH
N N Ammonium acetate
CN
R.T.5-7 mins
malononitrile H
Salicyladehyde Salicylidene malononitrile

Take a mixture of salicylaldehyde (3.05 gm) in 25 ml of dil.water and malononitrile (1.65gm) in

10 ml of dil.water, add both the beaker in conical flask. Add a pinch of ammonium acetate with constant
stirring with glass rod. The reaction mixture is sonicated at room temp.for about 5 to 7 mins. The
amount of crude is obtained. Filter the product, dry and record the yield, M.P. and TLC

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 Physical Constant
Colour TLC
Melting Point (0C) Yield
Time of the
Rf Rf
product Observed Reported Solvent
Reactant Product
Ethyl
acetate 69.22%
5-7 Brown 1200 C 1250 C 0.69 0.30
+
min.
n-hexane (8:2)

1] Synthesis of P-chloro benzylidene malononitrile

CHO Cl

CN
malononitrile
H
p- chloro benzylidene
malononitrile
P-chloro benzaldehyde

Take a mixture of P- chloro benzaldehyde (3.51gm) in 25 ml of dil.water and malononitrile (1.65gm)

in 10 ml of dil.water, add both the beaker in conical flask. Add a pinch of ammonium acetate with
constant stirring with glass rod. The reaction mixture is sonicated at room temp.for about 5 to 7 mins.
The amount of crude is obtained. Filter the product, dry and record the yield, M.P. and TLC

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 Physical Constant
Colour TLC
Melting Point (0C) Yield
Time of the
product Rf Rf
Observed Reported Solvent
Reactant Product
Ethyl
acetate 71.14%
5-7 Brownish 920 C 940 C 0.68 0.73
+
min. white
n-hexane (8:2)

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 2] Synthesis of 4 hydroxy benzylidene malononitrile

CHO

HO

N N
Ammonium acetate
R.T.5-7 mnis CN
malononitrile
H
OH
4 Hydroxy benzaldehyde 4 Hydroxy benzylidene
malononitrile

Take a mixture of 4- hydroxybenzaldehyde (3.51gm) in 25 ml of dil.water and malononitrile

(1.65gm) in 10 ml of dil.water, add both the beaker in conical flask. Add a pinch of ammonium acetate
with constant stirring with glass rod. The reaction mixture is sonicated at room temp.for about 5 to 7 mins.
The amount of crude is obtained. Filter the product, dry and record the yield, M.P. and TLC
.

Physical Constant
Colour TLC
Melting Point (0C) Yield
Time of the
Rf Rf
product Observed Reported Solvent
Reactant Product
Ethyl
acetate 73.03%
5-7 Brown 1880 C 1900 C 0.44 0.72
+
min.
n-hexane
(6:4)

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3] Synthesis of 3,4 Dimethoxy benzylidene malononitrile

Ome
CHO
Ome
CN
N N Ammonium acetate
R.T.5-7 mins
Ome malononitrile CN

Ome H
3,4 dimethoxy benzylidene malononitrile
3,4 dimethoxy benzaldehyde

Take a mixture of 3,4 dimethoxybenzaldehyde (2gm) in 25 ml of dil.water and malononitrile

(0.27gm) in 10 ml of dil.water, add both the beaker in conical flask. Add a pinch of ammonium
acetate with constant stirring with glass rod. The reaction mixture is sonicated at room temp.for
about 5 to 7 mins. The amount of crude is obtained. Filter the product, dry and record the yield,
M.P. and TLC

Physical Constant
Colour TLC
Melting Point (0C) Yield
Time of the
Rf Rf
product Observed Reported Solvent
Reactant Product
Ethyl
Dark acetate 73.19%
5-7min. 1420 C 1480 C 0.65 0.75
yello +
w n-hexane
(8:2)

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 5. THIN LAYER CHROMATOGRAPHIC DATA

Sr.
Name of the product TLC Product
No.

Benzylidene
1
malononitrile

Salicylidene
Malononitrile
2

P-chloro benzylidene
3 Malononitrle

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4
4 hydroxy benzylidene
malononitrile

3,4 Dimethoxy
5 benzylidenemalononitrile

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6. Spectroscopic Data

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 6. CONCLUSION

1. In this report, we have described a very simple, inexpensive, high yielding, non- toxic,
environment friendly method.

2. Knoevenagel Condensation of aromatic aldehyde with active methylene compounds were

carried out by using sonicator at room temperature simply and efficiently in presence of
catalytic amount of benign ammonium acetate and high percentage yields of corresponding
benzylidenemalononitriles were obtained in environmentally friendly way. Thus, we have
developed greener method of Knoevenagel condensation using sonicator.
 3. REFERENCES

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English). 2010, 49, 1730–1734.
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Lipoxygenase. J. Med. Chem. 1991, 34, 1503–1505.
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Intermolecular Knoevenagel Reactions. Macromolecules . 2004, 37, 2021–2025.
4. Nokami, J.; Kataoka, K.; Shiraishi, K.; Osafune, M.; Hussain, I.; Sumida, S. Convenient
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9. Pawar, H.S.; Wagh, A.S.; Lali, A.M. Triethylamine: A Potential N-Base Surrogate for
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Chem. 2016, 40, 4962–4968.