PROJECT REPORT

FINAL YEAR B. PHARM

SYNTHESIS OF PYRAZOLE FROM GREEN CATALYST
A PROJECT SUBMITTED TO THE
UNIVERSITY OF MUMBAI
FOR THE DEGREE OF
BACHELOR OF PHARMACY
(FINAL YEAR B. PHARM)

SUBMITTED BY
SHIVAM CHATURVEDI -03
SUDHIR GUPTA -20
ASHRAF KHAN -31
RIZWAN PATHAN -52
AFZAL SHAIKH-67

UNDER THE GUIDENCE OF

MS. SAYLI SAWANT

H K COLLEGE OF PHARMACY
Jogeshwari West, Mumbai Maharashtra 400102
1
 STATEMENT BY CANDIDATE
We state that the work embodied in the project titled “SYNTHESIS OF
PYRAZOLONE FROM GREEN CATALYST” forms our own contribution to
work carried out under the guidance of Ms. Sayli Sawant at H K College of
Pharmacy. This work wasn’t submitted for any other Degree or to any other
University. Whenever references have been made to previous works of others, it
has been clearly noted and mentioned in the Bibliography.

Sr No. Name of student Signature Roll No.

1 Shivam Chaturvedi 03
2 Sudhir Gupta 20
3 Ashraf khan 31
4 Rizwan Pathan 52
5 Afzal shaikh 67

STATEMENT BY GUIDE
I certify that the project entitled titled “SYNTHESIS OF PYRAZOLONE
FROM GREEN CATALYST” being submitted by Shivam Chaturvedi, Sudhir
Gupta, Ashraf Khan, Rizwan Pathan, Afzal Shaikh under my guidance as a part of
“Final Year B. Pharm Project” is carried out at HK College of Pharmacy.

Ms. Sayli Sawant

Assistant Professor
H. K. College of Pharmacy.

2
 ACKNOWLEDGEMENT

The work of some unknown person makes our lives easier every day. I believe it is
appropriate to acknowledge all of those unknown persons, but it is also necessary
to acknowledge those people who have directly shaped our lives and work.

I profusely express my undying gratitude towards my guide Ms. Sayli Sawant,

Assistant Professor (Department of Pharmaceutical Chemistry), H.K.COLLEGE
OF PHARMACY who stood by us throughout the project work and for spending
her valuable time for giving us knowledge, encouragement and helping us for
successful completion of our research work.

I am deeply indebted to non teaching staffs of the department who are always a
source of knowledge and inspiration to us, I would like to thank Mr. Santosh for
their prompt assistance and co-operation.

3
SR. NO. CONTENT PG NO.

1 INTRODUCTION 5

2 AIM AND OBJECTIVE 11

3 LITERATURE SURVEY 12

4 MATERIAL AND METHOD 16

5 RESULTS AND DISCUSSIONS 20

6 CONCLUSION 23

7 REFERENCES 24

INDEX

4
INTRODUCTION
Hetero-cyclic compounds are acquiring more importance in recent years because
of their pharmacological activities. Pyrazolones have a particular value due to their
broad spectrum of biological activity and their wide-ranging utility as synthetic
tools in the design of various bioactive molecules.

Pyrazolone is a five membered lactum ring, containing two nitrogen and one
ketonic group in its structure in addition, pyrazolones possess antimicrobial,
antifungal, anti-mycobacterial, antibacterial, anti-inflammatory, antitumor, gastric
secretion stimulatory, antidepressant and antifilarial activities. They also serve as
precursors for dyes, pigments, pesticides and chelating agents, besides finding
applications in the extraction and separation of various metal ions. The high
therapeutic properties of the pyrazolone related drugs have encouraged the
medicinal chemists to synthesize a large number of novel chemotherapeutic agents.
Numerous methods for the synthesis of pyrazolone and also their various structure
reactions offer enormous scope in the field of medicinal chemistry.

Figure 1: Structure of Pyrazolone

5
When pyrazolones were discovered, they were only known as NSAIDs but in
recent times they play a versatile role in several complications like cerebral
ischemia, cardiovascular diseases, antibacterial, antioxidant, anticancer and several
other pharmacological activities. Over the last few decades, pyrazolone derivatives
have been used for various biochemical applications. Some of these derivatives
such as metamizole, phenazone, aminopyrine, and propyphenazone, are widely
used as anti-inflammatory and analgesics. The chemistry of pyrazolone has gained
increasing attention due to its diverse pharmacological properties such as
anticancer, analgesic, anti-inflammatory, antimicrobial, antioxidant, antifungal,
antiviral, antidiabetic, and several other biological activities.

Thus, keeping because of their importance, synthetic strategies for existing as well
as novel pyrazolone derivatives have been developed and explored their
biochemical utility. This review deals with the various pharmacological properties
of different pyrazolone derivatives and puts chemical synthetic schemes.

Disadvantages of pyrazolone by using conventional method:-

However, the synthesis of pyrazoline derivatives using conventional methods had

many problems, one of which is the product yield, which was <70%.

However, there are some disadvantages to this conventional method, for example,
higher temperatures, longer reaction times, general inspection procedures, the
formation of by-products, and environmental influences.

Green chemistry used benign synthetic procedures that were very efficient and
environment friendly to synthesize a variety of bioactive heterocyclic frameworks
that were useful for the synthesis of drugs, plastics, petrochemicals, agricultural
chemicals, cosmetics, and many more.

6
Reaction time in conventional methods was longer than in other methods.

A decrease in reaction time was carried out in line with the increase in the resulting
product.

The results of products in conventional methods tended to be less good compared

to other methods due to high heating, a longer time, and more solvent
consumption.

Pyrazolone derivative available in the market:

NAME IUPAC NAME BRAND NAME USES

Antipyrine 1,2 dihydro-5,5- Phenzone Analgesic,
dimethyl 2- Analgesine Antipyretic
phenyl-3 H
pyrazol-3-one
Amino phenazone 4-dimethylamino- Phenzone Analgesic
1,5-dimethyl1-2- Analgesic Anti-inflammatory
phenylpyrazol-3-
one
Propyphenazone 1,5-dimethyl-2- Pyramidone Analgesic
phenyl-4- Anodymin Anti-inflammatory
propan2yl-3-one
Phenylbutazone 4-butyl-1,2- Atropan Azdid Analgesic
diphenyl- Butazolidin Anti-inflammatory
pyrazolidine- Phanyzone Rheutism
3,5dione
 7
GREEN CHEMISTRY
Paul Anastas and John C. Warner (1998) states that green chemistry is the
utilization of a set of principles that reduces or eliminates the use of hazardous
substances in the design of reaction mechanism, prevention of waste, maximize the
atom economy, use of safer solvents, reduce derivatization and design for energy
efficiency.

Over the last two centuries, new approaches to the synthesis of heterocycles have
had an enormous impact on both organic and inorganic chemistry. In this
perspective, the Research Topic “Green Synthesis of Heterocycles” encompasses a
collection of research and review articles focusing on heterocyclic compounds
synthetized according to Green Chemistry principles. The focal point was to build
on efficient catalytic methodologies aiming at high process performances by means
of non-toxic/green and biodegradable chemicals.

PRINCIPLES OF GREEN CHEMISTRY

1. Prevent waste: Design chemical syntheses to prevent waste. Leave no waste to

treat or clean up.

2. Maximize atom economy: Design syntheses so that the final product contains
the maximum proportion of the starting materials. Waste few or no atoms.

3. Design less hazardous chemical syntheses: Design syntheses to use and

generate substances with little or no toxicity to either humans or the environment.

4. Design safer chemicals and products: Design chemical products that are fully
effective yet have little or no toxicity.
 8

5. Use safer solvents and reaction conditions: Avoid using solvents, separation
agents, or other auxiliary chemicals. If you must use these chemicals, use safer
ones.

6. Increase energy efficiency: Run chemical reactions at room temperature and

pressure whenever possible.

7. Use renewable feedstocks: Use starting materials (also known as feedstocks)

that are renewable rather than depletable. The source of renewable feedstocks is
often agricultural products or the waste of other processes.

8. Avoid chemical derivatives: Avoid using blocking or protecting groups or any

temporary modifications if possible.

9. Use catalysts, not stoichiometric reagents: Minimize waste by using catalytic

reactions. Catalysts are effective in small amounts and can carry out a single
reaction many times.

10. Design chemicals and products to degrade after use: Design chemical
products to break down to innocuous substances after use so that they do not
accumulate in the environment

11. Analyze in real time to prevent pollution: Include in-process, real-time

monitoring, and control during syntheses to minimize or eliminate the formation of
byproducts.
12. Minimize the potential for accidents: Design chemicals and their physical
forms (solid, liquid, or gas) to minimize the potential for chemical accidents
including explosions, fires, and releases to the environment.

9
 Figure 2: Principles of Green Chemistry

10

AIM AND OBJECTIVES:

AIM: -

To synthesize pyrazalone by using green catalyst (Boric acid).

OBJECTIVES: -

Green chemistry is the need of today and hence it was planned to synthesize some
heterocyclic compounds in an eco-friendly way.

 To understand the basic concepts of Thin layer Chromatography (TLC).

 To perform TLC of products.
 To understand the basic concepts of Infrared Spectroscopy (IR).
 To interpret IR spectra of the compound.
 11
LITERATURE SURVEY:

1. Mariyappan, B.P Saha, L Suthersan, AHalder 1 The basic principles of

green synthesis are that they are simple methods, require a short time, and involve
easy product separation and purification. These advantages encouraged us to
develop an easy green methodology to synthesize 2-pyrazoline-5-one derivatives.

Reaction 1

2. Pankaj Kumar Sonar, Shailendra Saraf K2., Synthesis of Some

Pyrazalone Derivatives and Evaluation of its Antibacterial and Cytotoxic Activity

Reaction 2
 12

3. Shaik Abdul Rahaman et al /Int.J.PharmTechRe3 Pyrazalone’s are

conventionally synthesized by the treatment of β-keto esters with hydrazine
substrates under acidic conditions at elevated temperature however, these authors
reported a novel and environmentally safe procedure for rapid preparation of
various pyrazalone derivatives using ultrasound irradiation.

Reaction 3

Various methods have been developed for the synthesis of pyrazole ring systems
(18–21). In most of these methods, diverse organic solvents such as ethanol,
toluene, CH2Cl2, acetone and acetonitrile have

been used (22–31). The obtained product yields of most of these reactions are
significant, but the solvents used are not compatible with the environment or cost
savings. For these reasons, the development of efficient and operationally simple
procedures for the synthesis of pyrazole ring systems under environment-friendly
conditions is highly appreciated. Due to the harmful effects of organic solvents on
the environment and humans, solvent-free reactions have received wide-spread
attention. Furthermore, solvent-free reactions have several benefits compared with
solvents ‘technique reaction, such as faster reaction rate, reduced reaction time,
less energy usage, easy separation, formation of product with fewer impurities and
high yield.
 13

4. Bottomley, W.E.; Boyd4 Various methods have been developed for the syn-
thesis of pyrazole ring systems (18–21). In most of these methods, diverse organic
solvents such as ethanol, toluene, CH2Cl2, acetone and acetonitrile have been used
(22–31). The obtained product yields of most of these reactions are significant, but
the solvents used are not compatible with the environment or cost savings.

5. Laszlo5, P. In this paper, we offered a green, environment-friendly, novel,

and inexpensive method for the synthesis of a series of pyrazole derivatives. The
reaction took place in the presence of tetrabutylammonium bromide, a
commercially available organic ionic salt, at room temperature under solvent-free
conditions. All products were confirmed by infrared radiation, nuclear magnetic
resonance, and elemental analysis. The yields of products were 75–86%.

6. RISHIRAM PARAJULI6 novel approach to the synthesis of pyrazole

derivatives from tosylhydrazones of alpha, beta-unsaturated carbonyl compounds
possessing a beta-hydrogen is proposed, exploiting microwave (MW) activation
coupled with solvent free reaction conditions. The cycloaddition was studied on
three ketones (trans-4-phenyl-3-buten-2-one, beta-ionone and trans-chalcone).
 14
PLAN OF WORK:-

Literature Survey

Selection of Scheme

Synthesis of molecules

Purification and characterization

 15

EXPERIMENT(MATERIAL AND METHOD) :-

Scheme Of Synthesis (Boric Acid)

Boric Acid

CHEMICAL PROCUREMENT: -

Chemical Name Batch No CAS No Vendor Name

Ethanol - - Government
warehouse
Petroleum Ether - 8032-32-4 Vishal Chem
Ethyl Acetate 1174-A-25 141-78-6 Vishal Chem
Boric Acid 10043-35-3 Ozone India
Ethyl 017-A-25 141-97-9 Vishal Chem
Acetoacetate
Phenyl Hydrazine - 100-63-0 Ozone India
Chloroform - 67-66-3 Ozone India
Methanol - - Ozone India
 16
SYNTHESIS OF PYRAZOLONE FROM BORIC ACID

PROCEDURE
1.Reagents and Catalyst:
• Ethyl acetoacetate (0.130 g) and
phenyl hydrazine (0.108 g) are
added to a 25-mL round-bottom
flask.
• Add citric acid as a catalyst, in
distilled water (10 mL).
2.Reaction:
• Stir the mixture at 80°C to induce
the condensation reaction between ethyl acetoacetate and phenyl hydrazine,
with citric acid promoting the reaction.
• The reaction can be monitored using Thin Layer Chromatography (TLC) to
check for the formation of the desired pyrazalone product.
3.Cooling and Precipitation:
• Once the reaction is complete (as monitored by TLC), allow the mixture to
cool to room temperature.
• The product should precipitate as it cools, indicating the formation of the
pyrazolone.
4.Filtration and Washing:
• Filter the precipitated product to separate it from the reaction mixture.
• Wash the filtered product with ethyl acetate to remove any organic
impurities.
• Rinse with distilled water to remove traces of citric acid and other water-
soluble impurities.
17
5.Drying and characterization:
• Dry the filtered and washed product.
• Analyze the final product using appropriate characterization techniques like,
IR, or mass spectrometry to ensure you have synthesized 3-methyl-1-phenyl-
pyrazol-5-one

SYNTHESIS OF PYRAZOLONES FROM BETA CYCLODEXTRINE

(STANDARD)

1. Ethyl acetoacetate (0.130 g) and

phenyl hydrazine (0.108 g) were
added to a 25-mL round bottom
flask containing beta-cyclodextrin
(12% by moles) in distilled water
(10 ml).
2. The mixture was then stirred at
80oC. After completion of reaction
(as monitored by TLC), the
reaction mixture was cooled to
room temperature and the crude product was allowed to precipitate.
3. The crude product was filtered off. Later, washed with ethyl acetate and
water, 93%, yellow powder was obtained.

18
PURIFICATION AND CHARACTERIZATION: -
TLC (Using Catalyst: -Boric acid)

1. TLC of compounds were obtained by using mobile phase as Chloroform:

Methanol (9:1)
2. The compound clearly show the formation of product (same RF value) with
presence of reactants and side products.
S-standard product (using beta-cyclodextrin as a catalyst)
TLC (Single Spot of Boric acid)

TLC of compounds were obtained by using mobile phase as Chloroform:

Methanol (9:1)

19
RESULT AND DISCUSSION: -
The basic principles of green syntheses are that they are simple methods, require a
short time, and involve easy product separation and purification. These advantages
encouraged us to develop an easy green methodology to synthesize pyrazolone.

PHYSICAL PROPERTIES OF BORIC ACID

PHYSICAL Molecular formula

CHARACTERISTICS
Molecular weight 174.20 gm/mol
Nature Yellow amorphous
Melting point 108°C
% Yield 92%
Mobile Phase Chloroform: Methanol (9:1)
Visualization U.V Chamber

20
IR SPECTRUM OF BORIC ACID:-
 21
NMR SPECTRA: -
 22
CONCLUSION: -
 • The synthesized compounds were purified and characterized using IR.

• In the synthesis of pyrazolone derivatives, various synthesis methods could

be used. One of the simplest synthetic methods was the conventional
method. However, the conventional method was not as superior as the green
synthesis method because it produced a product yield of <70%. This became
a challenge in the world of synthetic chemistry to optimize reaction
conditions by considering various parameters to obtain good-resulting
products.

• Parameters that needed to be considered were temperature, reaction time,

energy source, and product yield. One of the efforts to optimize the reaction
conditions was to modify the variation in the concentration of solvent,
temperature, and catalyst used during the reaction.

23
REFRENCES
1. Aricò, F., 2020. Green synthesis of heterocycles. Frontiers in Chemistry, 8,
p.74.
2. Hisar, B.C., 2017. Green methods for synthesis of various Heterocycles:
Sustainable approach. IJCS, 5(6), pp.479-485.
3. Ameta, K.L. and Dandia, A. eds., 2014. Green chemistry: synthesis of bioactive
heterocycles. Springer. || .
4. Sharma, S., Gangal, S. and Rauf, A., 2008. Green chemistry approaches the
sustainable advancement to the synthesis of heterocyclic chemistry. Rasayan J.
Chem, 1(4), pp.693-717.

5. Bhadke, P.K., Pahelkar, A.R., Gadkari, Y.U., Naik, J.M. and Telvekar, V.N.,
2022. Eco-Friendly and Efficient Greener Process for the Synthesis of
Chalcones and Pyrazolones Using the Supramolecular Catalyst β-
Cyclodextrin. Organic Preparations and Procedures International, 54(4),
pp.363-369.

6. Pal, S., Mareddy, J. and Devi, N.S., 2008. High speed synthesis of pyrazolones
using microwave-assisted neat reaction technology. Journal of the Brazilian
Chemical Society, 19, pp.1207-1214.

7. Shaikh, M.S., Chandrasekaran, B., Palkar, M.B., Kanhed, A.M., Kajee, A.,
Mlisana, K.P., Singh, P., Ghai, M., Cleopus Mahlalela, M. and Karpoormath,
R., 2020. Synthesis and biological evaluation of novel carbazole hybrids as
promising antimicrobial agents. Chemistry & Biodiversity, 17(5), p.e1900550.

8. Anshu, D., Vijay, P., Gupta, S.L. and Rathore, K.S., 2013. Suitability of cobalt
doped ZnS nanoparticles for recyclable photocatalysts. J. Mol. Catal., 373,
pp.61-71.
24